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  • 1.
    Aarnio, Mikko
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Hall, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Ängeby-Möller, Kristina
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Evaluation of  PET tracers [11C]D-deprenyl, [11C]L-dideuteriumdeprenyl and [18F]FDG for Visualization of Acute Inflammation in a Rat Model of Pain - Preliminary Findings.Manuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: Positron emission tomography with the radioligand [11C]D-deprenyl has shown an increased signal at the location of pain in patients with ankle sprains, rheumatoid arthritis and chronic whiplash injury, but the mechanism of this tracer uptake and its exact binding site in inflammation or tissue injury is still unclear. The aim of this study was to further evaluate [11C]D-deprenyl´s usefulness as a marker of acute inflammation.

    Methods: An animal PET/CT study was performed three days after the induction of a rat model of inflammatory or surgical pain. Fourteen adult male Sprague-Dawley rats and three tracers [11C]D-deprenyl, [11C]L-dideuterumdeprenyl and [18F]fluorodeoxyglucose were used.

    Results: No [11C]D-deprenyl accumulation was seen in a rat model of musculoskeletal pain. In the rat model of inflammatory pain all three ligands were shown to visualize the inflamed ankle joint with much lower uptake in the control ankle joint. The uptake was largest with [11C]D-deprenyl and [11C]L- dideuteriumdeprenyl, where approximately 1 % of the injected dose could be found in the affected ankle joint during the first minutes, whereas the uptake of [18F]FDG was approximately 0.5 % of the injected dose. However, the ratio of uptake of the injected ankle joint versus the control ankle joint was much higher for [18F]FDG (around 10 fold increase) than for the two deprenyl enantiomers (2 – 3 fold increase). The uptake pattern of [11C]D-deprenyl and [11C]L-dideuteriumdeprenyl did not show signs of specific binding or irreversible trapping.

    Conclusions: Contrary to our expectations, of the three tracers only [18F]FDG may be used as markers of peripheral inflammation in a rat model of inflammatory pain. However, as a high site-specificity is required, [11C]D-deprenyl and [11C]L-dideyteriumdeprenyl deserve further exploration regarding sensitivity, specificity and uptake mechanisms in human pain syndromes.

  • 2. Aarons, L
    et al.
    Karlsson, MO
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Mentre, F
    Rombout, F
    Steimer, JL
    van Peer, A
    Role of modelling and simulation in Phase I drug development.2001In: Eur J Pharm Sci, Vol. 13, p. 115-Article in journal (Refereed)
  • 3.
    Abass Abdulkadir, Sazan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    The Use of a Clinical Decision Support System to Identify Potential Drug-Related Problems: Focused on the Types of Alerts for Pediatric Patients2022Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Background: Sweden is among the top countries with the greatest use of e-prescriptions at a national level. A clinical decision support system called Electronic Expert Support (EES) is available at all pharmacies in Sweden to examine e-prescriptions in connection with the dispensing to prevent drug related problems (DRPs). DRPs result in patient suffering and substantial costs for society. The types of alerts generated for pediatric patients at Swedish pharmacies using EES-system has not been studied before, to the best of our knowledge. Aim: The aim of this research is to study the use of EES at pharmacies in Sweden for the pediatric population (ages 0-12 years), by describing what types of alerts for potential DRPs are generated, how they are handled and how the use of EES has changed over time. Method: Data on the number and categories of EES analyses, alerts, and resolved alerts was provided by the Swedish eHealth Agency. Results: The study shows that the use of EES has increased. The most common type of generated alert for a potential DRP among pediatric was high dose pediatric (30,3% of all alerts generated). The most common type of alert for a potential DRP that was resolved among pediatrics was therapy duplication (45,8%). The most common reason for closing an alert was dialogue with patient for verification of the treatment (66,3% of all closed alerts). Conclusion: Knowledge of which type of alerts that are the most common may contribute to increased prescriber awareness of important potential DRPs. Future studies should investigate the clinical relevance of the generated alerts for the pediatric population.

  • 4.
    Abass Abdulkadir, Sazan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala Univ, Fac Pharm, Dept Pharm, S-75237 Uppsala, Sweden..
    Wettermark, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala Univ, Fac Pharm, Dept Pharm, S-75237 Uppsala, Sweden..
    Hammar, Tora
    Linnaeus Univ, eHlth Inst, Dept Med & Optometry, S-39182 Kalmar, Sweden..
    Potential Drug-Related Problems in Pediatric Patients-Describing the Use of a Clinical Decision Support System at Pharmacies in Sweden2023In: Pharmacy, E-ISSN 2226-4787, Vol. 11, no 1, article id 35Article in journal (Refereed)
    Abstract [en]

    The clinical support system Electronic Expert Support (EES) is available at all pharmacies in Sweden to examine electronic prescriptions when dispensing to prevent drug-related problems (DRPs). DRPs are common, and result in patient suffering and substantial costs for society. The aim of this research was to study the use of EES for the pediatric population (ages 0-12 years), by describing what types of alerts are generated for potential DRPs, how they are handled, and how the use of EES has changed over time. Data on the number and categories of EES analyses, alerts, and resolved alerts were provided by the Swedish eHealth Agency. The study shows that the use of EES has increased. The most common type of alert for a potential DRP among pediatric patients was regarding high doses in children (30.3% of all alerts generated). The most common type of alert for a potential DRP that was resolved among pediatrics was therapy duplication (4.6% of the alerts were resolved). The most common reason for closing an alert was dialogue with patient for verification of the treatment (66.3% of all closed alerts). Knowledge of which type of alerts are the most common may contribute to increased prescriber awareness of important potential DRPs.

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  • 5.
    Abass, Ahmed
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Syntes av MPro-inhibitor2020Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    December 2019 the new pandemic Covid-19 sweeps the world and impose unmatched challenges on modern humanity, the virus started from Wuhan China and in just a few months the virus had spread to other countries and WHO (World Health Organization) called the disease a pandemic, Covid-19 is caused by the virus SARS-CoV -2 (severe acute respiratory syndrome-Coronavirus2), the virus is largely spread through human-to-human transmission, today more than 263 million people have been infected with the virus while more than 5 million have died.

    SARS-CoV-2 is closely related to other viruses of the genus Betacoronavirus such as bat coronavirus BatCoV RaTG13 (~ 96% sequence identity) and SARS-CoV (~ 80% sequence identity), Coronavirus such as SARS-CoV and SARS-CoV -2 need main protease MPro (3CLPro), MPro is interesting as there are no similar proteases in humans, and it is vital for virus survival as it has essential role in processing and replicating polyproteins of viral RNA.

    ML188 is a SARS-CoV MPro inhibitor, SARS-CoV and SARS-CoV -2 have 80% sequence identity, ML188 can be used as a starting point to analyze and improve MPro inhibitors that can be used against SARS-CoV -2.

    In this study with the use of UGI reaction to synthesized and modified analog to ML188 by exchanging 3-pyridialkarboxaldehyd which is one of the 4 starting material the compound with 4-pyridilkarboxaldehyd. By changing the nitrogen position in the aromatic ring, we want to see if this change can increase or decrease the compound effectiveness and if it has deferent effect on SARS-CoV2.  

    TLC and LC-MS are analysis method that is used to monitor the reaction and determine the purity of the reaction, column chromatography is used to purify the reaction mixture, NMR analysis both proton and carbon NMR is used to confirm the structure of our synthesized product. Result from the LCMS-Analyze showed a clear high peak with the exact mass of our Sought product but it also showed that the purification of the mixture didn’t happen fully thus we still had some impurities in the mixture. both the proton and carbon NMR results data were consistent with our compound structure. Now we need to test if this new compound can result to better inhibition in SARS-CoV2.

  • 6.
    Abass, mariam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Mortalitet bland covid-19 antikoagulantia användare patienter och icke-antikoagulantia användare: en systematisk översikt2022Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Covid-19 is a serious infectious disease that was first discovered in China in 2019. The disease spread very quickly, infecting over 40 million globally and leading to more than a million deaths. The damage caused by the corona infection led to severe thromboembolic conditions that led to death. Therefore, anticoagulants were used in connection with corona to prevent the thromboembolic conditions. But has the use of anticoagulants in covid-19 patients really affected mortality?    Aim: To make a systematic review that explores whether anticoagulant use among COVID-19 patients affect mortality.    Methods: A systematic search was conducted September in 2022 of published studies on PubMed associated with mortality and use of anticoagulants in covid-19 patients. The articles reviewed were selected based on defined PICO and inclusion and exclusion criteria. Types of studies reviewed were cohort and case-control studies.    Results & conclusions:   A total of 20 different studies were studied and based on them it is concluded that anticoagulant treatment associated with lower mortality in severely ill covid-19 patients has been demonstrated. However, bleeding risk was observed in other covid-19 patients due to use of anticoagulants.

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  • 7.
    Abbas, Nasir
    et al.
    Univ Karachi, Int Ctr Chem & Biol Sci, HEJ Res Inst Chem, Karachi 75270, Pakistan..
    Ali, Arslan
    Univ Karachi, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan..
    Kumari, Sindhia
    Univ Karachi, Int Ctr Chem & Biol Sci, HEJ Res Inst Chem, Karachi 75270, Pakistan..
    Iqbal, Ayesha
    Univ Karachi, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan..
    Husain, Adnan
    Kuwait Inst Sci Res KISR, Environm & Life Sci Res Ctr, Safat 13109, Kuwait..
    Saeed, Talat
    Kuwait Inst Sci Res KISR, Environm & Life Sci Res Ctr, Safat 13109, Kuwait..
    Al-Ballam, Zainab Abdulamer
    Kuwait Inst Sci Res KISR, Environm & Life Sci Res Ctr, Safat 13109, Kuwait..
    Ahmed, Nisar
    Kuwait Inst Sci Res KISR, Environm & Life Sci Res Ctr, Safat 13109, Kuwait..
    El-Seedi, Hesham R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi. Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China..
    Musharraf, Syed Ghulam
    Univ Karachi, Int Ctr Chem & Biol Sci, HEJ Res Inst Chem, Karachi 75270, Pakistan.;Univ Karachi, Dr Panjwani Ctr Mol Med & Drug Res, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan.;Univ Karachi, Ind Analyt Ctr, Int Ctr Chem & Biol Sci, Halal Testing Labs, Karachi 75270, Pakistan..
    Untargeted-metabolomics differentiation between poultry samples slaughtered with and without detaching spinal cord2020In: Arabian Journal of Chemistry, ISSN 1878-5352, E-ISSN 1878-5379 , Vol. 13, no 12, p. 9081-9089Article in journal (Refereed)
    Abstract [en]

    Chicken meat is among the common and relatively inexpensive source of protein consumed worldwide from the poultry industry. Many communities show concern regarding the procedure of slaughtering animals for meat consumption due to ethical, religious, or cultural reasons. Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) based untargeted metabolomics of 40 chicken meat samples were evaluated to differentiate meat samples based on slaughtering methods. Samples were grouped into, Zabiha (cutting neck without detaching spinal cord) and Non-Zabiha (completely detaching neck). A volcano plot reveals at least 150 features found significantly different between the two groups having >= 2-fold changes in intensities with p-values <= 0.05. Among them 05 identified and 25 unidentified metabolites have clear differences in peak intensities. The identified features can be employed to differentiate meat obtained from different slaughtering methods. A characteristic pattern based on principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) was observed among the groups. The results will benefit Halal certification, food safety, and security agencies to curb food fraud. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of King Saud University.

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  • 8.
    Abbasi, Mina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Translational aspects of unbound brain to plasma concentration ratios2012Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Introduction:  The unbound brain-to-plasma concentration ratio (Kp,uu,brain) is one of the most important indicators for brain penetration in the area of CNS drug discovery and development. Kp,uu,brain can be calculated by combining the total brain-to-plasma concentration ratio (Kp,brain),  the brain free fraction (fu,brain) and  the plasma free fraction (fu,p).

    Aim:  This study has three purposes, to calculate Kp,uu,brain from publications in humans,  to collect data regarding species differences in Kp,uu,brain and to see whether Kp,uu,brain in humans differs in different  brain regions or not.

    Materials and Methods:  The values of Kp, brain were derived from positron emission tomography (PET), MRS (Magnetic Resonance Spectroscopy), and brain surgery for tumor removal. fu,brain and fu,p were collected from brain homogenate, equilibrium dialysis and ultrafiltration studies.

    Results:  Data on Kp,brain was sparse in the literature. Kp,uu,brain was calculated for sixteen different drugs in humans. According to the calculation, nine of these sixteen compounds were found to be actively influxed into the brain, six were actively effluxed from the BBB and one had a passive diffusion. Depending on the compound, Kp,uu,brain was higher or smaller in humans compared to mice and rats.  Kp,uu,brain for five compounds were calculated for different brain regions. Four compounds had a higher Kp,uu,brain value in almost all other regions than the cerebellum and one had a higher Kp,uu,brain in cerebellum than in the other regions.

    Conclusions:  No definite conclusion on Kp,uu,brain in humans, species differences in Kp,uu,brain  or Kp,uu,brain  in different human brain regions could be reached in this study. In view of the importance of Kp,uu,brain  in CNS drug discovery and development, more studies on Kp,uu,brain in humans and in the other species are required.

  • 9.
    Abberud, Madelene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Time to first antibiotic administration in The Alfred Emergency and Trauma Centre for suspected febrile neutropenia: a retrospective chart review2012Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Introduction: Febrile neutropenia (FN) is a frequent complication of chemotherapy use in cancer patients. There is evidence to suggest that the time to antibiotic administration is associated with increase survival and effective clinical outcome. The Australian consensus guidelines for the management of FN in adult cancer patients recommends treatment within 30 minutes to patients with features of systemic compromise. A study performed at The Alfred Hospital in 2010 revealed a median time of 145 minutes to first antibiotic administration. A new guideline was therefore developed and education was implemented. This study was conducted to evaluate the intervention. Aim: To determine time to first antibiotic prescribing and administration for patients with suspected FN presenting to the Alfred Emergency and Trauma centre. Materials and Methods: The electronic medical record of 112 episodes of suspected FN presenting between March and August 2012 were reviewed.  Data were retrospective collected according to a FN data spreadsheet. An observational study were also performed at  The Alfred Emergency and Trauma centre during October and November 2012 to determine time to first antimicrobial prescribing, because this data could not be collected from the electronic medical record. Results: The median time from presentation to antibiotic prescribing was 68 minutes. The median time from presentation to antibiotic administration was 121 minutes. Conclusions: The implementation of the new guidelines has reduced the time with 16.6%, but the target first antibiotic administration within 30 minutes has not been reached.

  • 10.
    Abd El-Gaber, Amira S.
    et al.
    Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm, Egypt.
    El Gendy, Abdel Nasser G.
    Natl Res Ctr, Med & Aromat Plants Res Dept, 33 El Bohouth St,PO 12622, Giza, Egypt.
    Elkhateeb, Ahmed
    Natl Res Ctr, Phytochem & Plant Systemat Dept, 33 El Bohouth St,PO 12622, Giza, Egypt.
    Saleh, Ibrahim A.
    Natl Res Ctr, Phytochem Dept, 33 El Bohouth St,PO 12622, Giza, Egypt.
    El-Seedi, Hesham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi. Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm, Egypt;Univ Karachi, ICCBS, Karachi 75270, Pakistan.
    Microwave Extraction of Essential Oil from Anastatica hierochuntica (L): Comparison with Conventional Hydro-Distillation and Steam Distillation2018In: Journal of Essential Oil-Bearing Plants (JEOBP), ISSN 0972-060X, E-ISSN 0976-5026, Vol. 21, no 4, p. 1003-1010Article in journal (Refereed)
    Abstract [en]

    This article stands to introduce microwave assisted extraction (MAE) as a more effective method for extraction of Anastatica hierochuntica (L) essential oils (EOs) compared to traditional hydrodistillation (HD) and steam distillation (SD) methods. Analysis of EOs by gas chromatography-mass spectrometry (GC/MS) showed significant differences in the constituents and percentages of the obtained oils. Using MAE and HD obtained oxygenated monoterpenes 50.79 % whereas SD obtained sesquiterpene hydrocarbons 79.84 % as major contents of the extracted oils. This is the first report of EO composition of the aerials parts of A. heirochunatica. It offered several advantages of MAE technique as a green method with shorter extraction time (60 min) and better yield.

  • 11.
    Abd El-Wahed, Aida A.
    et al.
    Agr Res Ctr, Plant Protect Res Inst, Dept Bee Res, Giza 12627, Egypt..
    Farag, Mohamed A.
    Cairo Univ, Coll Pharm, Pharmacognosy Dept, Kasr El Aini St, Cairo 11562, Egypt.;Amer Univ Cairo, Sch Sci & Engn, Dept Chem, New Cairo 11835, Egypt..
    Eraqi, Walaa A.
    Cairo Univ, Fac Pharm, Dept Microbiol & Immunol, Cairo 11562, Egypt..
    Mersal, Gaber A. M.
    Taif Univ, Coll Sci, Chem Dept, At Taif 21944, Saudi Arabia..
    Zhao, Chao
    Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Fujian, Peoples R China..
    Khalifa, Shaden A. M.
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden..
    El-Seedi, Hesham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm 32512, Egypt.;Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China..
    Unravelling the beehive air volatiles profile as analysed via solid-phase microextraction (SPME) and chemometrics2021In: JOURNAL OF KING SAUD UNIVERSITY SCIENCE, ISSN 1018-3647, Vol. 33, no 5, article id 101449Article in journal (Refereed)
    Abstract [en]

    Objective: Beehive air therapy is recognized as a potential remedy for treating asthma, bronchitis, lung fibrosis, and respiratory tract infections. Developed countries in which beehive air therapy is currently authorized include Germany, Hungary, Slovenia, and Austria. However, scientific proof of its efficacy is lacking which warrants further chemical and biological analyses as a proof of concept. In this study, bee-hive air volatile profile was determined for the first time along with its individual components (bees, venom, honey, and beeswax).

    Methods: Volatile compounds were collected from beehive air using solid phase micro-extraction (SPME) coupled to gas chromatography-mass spectrometry (GC-MS). Antimicrobial assay of the air released from 4 beehive products was further performed against Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and multi drug-resistant Staphylococcus aureus (MRSA) using the in vitro agar-well diffusion and microtiter plate assays.

    Results and conclusions: A total of 56 volatile compounds were identified from beehive air, venom, bee insect and wax air including 6 fatty acids, 6 alcohols, 10 aldehydes, 5 esters, 1 ether, 9 hydrocarbons, 1 phenol, 7 ketones, 1 nitrogenous compound and 10 terpenes. The most abundant constituents were short-chain fatty acids (26.32%) while the lowest were the nitrogenous compounds (0.82%). The principal component analysis (PCA) scores plot of the UPLC/MS dataset showed the similarity of the beehive air to the insect bee's aroma profile. With regards to antimicrobial assay, beehive air and venom exerted the strongest antimicrobial activity among the examined bee products against S. aureus, K. pneumoniae, A. baumannii, and MRSA in agar-well diffusion assay but failing to exert an effect using microtiter plate assay as in case of bee venom against the aforementioned bacteria.

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  • 12.
    Abd El-Wahed, Aida A.
    et al.
    Agr Res Ctr, Plant Protect Res Inst, Dept Bee Res, Giza 12627, Egypt..
    Khalifa, Shaden A. M.
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden..
    Elashal, Mohamed H.
    Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt..
    Musharraf, Syed G.
    Univ Karachi, Int Ctr Chem & Biol Sci, HEJ Res Inst Chem, Karachi 75270, Pakistan..
    Saeed, Aamer
    Quaid I Azam Univ, Dept Chem, Islamabad 45320, Pakistan..
    Khatib, Alfi
    Int Islamic Univ Malaysia, Pharmacognosy Res Grp, Dept Pharmaceut Chem, Kulliyyah Pharm, Kuantan 25200, Pahang Darul Ma, Malaysia.;Airlangga Univ, Fac Pharm, Surabaya 60155, Indonesia..
    Tahir, Haroon Elrasheid
    Jiangsu Univ, Sch Food & Biol Engn, Zhenjiang 212013, Jiangsu, Peoples R China..
    Zou, Xiaobo
    Jiangsu Univ, Sch Food & Biol Engn, Zhenjiang 212013, Jiangsu, Peoples R China..
    Al Naggar, Yahya
    Martin Luther Univ Halle Wittenberg, Inst Biol, Gen Zool, Hoher Weg 8, D-06120 Halle, Germany.;Tanta Univ, Dept Zool, Fac Sci, Tanta 31527, Egypt..
    Mehmood, Arshad
    Beijing Technol & Business Univ, Beijing Engn & Technol Res Ctr Food Addit, Beijing 100048, Peoples R China..
    Wang, Kai
    Chinese Acad Agr Sci, Inst Apicultural Res, Beijing 100093, Peoples R China..
    El-Seedi, Hesham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi. Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt.;Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China..
    Cosmetic Applications of Bee Venom2021In: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 13, no 11, article id 810Article, review/survey (Refereed)
    Abstract [en]

    Bee venom (BV) is a typical toxin secreted by stingers of honeybee workers. BV and BV therapy have long been attractive to different cultures, with extensive studies during recent decades. Nowadays, BV is applied to combat several skin diseases, such as atopic dermatitis, acne vulgaris, alopecia, vitiligo, and psoriasis. BV is used extensively in topical preparations as cosmetics and used as dressing for wound healing, as well as in facemasks. Nevertheless, the safety of BV as a therapeutic choice has always been a concern due to the immune system reaction in some people due to BV use. The documented unfavorable impact is explained by the fact that the skin reactions to BV might expand to excessive immunological responses, including anaphylaxis, that typically resolve over numerous days. This review aims to address bee venom therapeutic uses in skin cosmetics.

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  • 13.
    Abd El-Wahed, Aida
    et al.
    Agr Res Ctr, Plant Protect Res Inst, Dept Bee Res, Giza 12627, Egypt.;Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt..
    Yosri, Nermeen
    Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt.;Jiangsu Univ, Sch Food & Biol Engn, Zhenjiang 212013, Jiangsu, Peoples R China..
    Sakr, Hanem H.
    Menoufia Univ, Dept Zool, Fac Sci, Shibin Al Kawm 32512, Egypt..
    Du, Ming
    Dalian Polytech Univ, Sch Food Sci & Technol, Natl Engn Res Ctr Seafood, Dalian 116034, Peoples R China..
    Algethami, Ahmed F. M.
    Alnahalaljwal Fdn Saudi Arabia, POB 617, Al Jumum 21926, Makkah, Saudi Arabia..
    Zhao, Chao
    Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China.;Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Control Chinese Med, Taipa, Macao, Peoples R China..
    Abdelazeem, Ahmed H.
    Beni Suef Univ, Dept Med Chem, Fac Pharm, Bani Suwayf 62514, Egypt.;Riyadh Elm Univ, Dept Pharmaceut Sci, Coll Pharm, Riyadh 11681, Saudi Arabia..
    Tahir, Haroon Elrasheid
    Jiangsu Univ, Sch Food & Biol Engn, Zhenjiang 212013, Jiangsu, Peoples R China..
    Masry, Saad H. D.
    Abu Dhabi Food Control Author, Al Ain 52150, U Arab Emirates.;City Sci Res & Technol Applicat, Arid Lands Cultivat Res Inst ALCRI, Dept Plant Protect & Biomol Diag, Alexandria 21934, Egypt..
    Abdel-Daim, Mohamed M.
    Suez Canal Univ, Dept Pharmacol, Fac Vet Med, Ismailia 41522, Egypt..
    Musharraf, Syed Ghulam
    Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan..
    El-Garawani, Islam
    Menoufia Univ, Dept Zool, Fac Sci, Shibin Al Kawm 32512, Egypt..
    Kai, Guoyin
    Zhejiang Chinese Med Univ, Coll Pharm, Lab Med Plant Biotechnol, Hangzhou 310053, Peoples R China..
    Al Naggar, Yahya
    Martin Luther Univ Halle Wittenberg, Inst Biol, Gen Zool, Hoher Weg 8, D-06120 Halle, Saale, Germany.;Tanta Univ, Fac Sci, Zool Dept, Tanta 31527, Egypt..
    Khalifa, Shaden A. M.
    Stockholm Univ, Dept Mol Biosci, Wenner Gren Inst, SE-10691 Stockholm, Sweden..
    El-Seedi, Hesham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi. Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt.;Stockholm Univ, Dept Mol Biosci, Wenner Gren Inst, SE-10691 Stockholm, Sweden.;Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China..
    Wasp Venom Biochemical Components and Their Potential in Biological Applications and Nanotechnological Interventions2021In: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 13, no 3, article id 206Article, review/survey (Refereed)
    Abstract [en]

    Wasps, members of the order Hymenoptera, are distributed in different parts of the world, including Brazil, Thailand, Japan, Korea, and Argentina. The lifestyles of the wasps are solitary and social. Social wasps use venom as a defensive measure to protect their colonies, whereas solitary wasps use their venom to capture prey. Chemically, wasp venom possesses a wide variety of enzymes, proteins, peptides, volatile compounds, and bioactive constituents, which include phospholipase A2, antigen 5, mastoparan, and decoralin. The bioactive constituents have anticancer, antimicrobial, and anti-inflammatory effects. However, the limited quantities of wasp venom and the scarcity of advanced strategies for the synthesis of wasp venom's bioactive compounds remain a challenge facing the effective usage of wasp venom. Solid-phase peptide synthesis is currently used to prepare wasp venom peptides and their analogs such as mastoparan, anoplin, decoralin, polybia-CP, and polydim-I. The goal of the current review is to highlight the medicinal value of the wasp venom compounds, as well as limitations and possibilities. Wasp venom could be a potential and novel natural source to develop innovative pharmaceuticals and new agents for drug discovery.

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  • 14.
    Abdaljaleel, Ghofran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Tablettillverkning genom användning av torrgranulering (valspressning)2020Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 15.
    Abdalla, Souad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Hjälpämnens påverkan på läkemedelsabsorption.2022Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Hjälpämne definieras som de inaktiva ingredienserna som tillsätts till läkemedel och som inte är avsedda att utöva terapeutiska effekter. Majoriteten av läkemedelsprodukter innehåller hjälpämne där hjälpämnena utgör ca. 50% av totala vikten av de fasta beredningsformerna. Hjälpämnen används för att överkomma de begränsningar som den farmaceutiska substansen har men även för att möjliggör hantering och användning av en läkemedelsberedning samt underlätta frisättningsegenskaper. Forskning har visat att hjälpämne är mer än inerta komponenter, utan hjälpämne har förmågan att reagera med andra ingredienser i formuleringen och påverka läkemedelsabsorptionen. Syftet: Att beskriva med hjälp av exempel hur hjälpämne kan påverka läkemedelsabsorptionen. Uppsatsen kommer att fokusera på vissa delprocesser av absorptionen. Metod: En allmän litteraturstudie där 18 artiklar inkluderades. Analysen av artiklarna resulterade i teman. Resultat: Tre huvudteman formulerades. Hjälpämnes effekter på absorptionsvariabler utifrån dess egenskaper där studier har visat att egenskaper hos hjälpämne kan avspegla om dessa kommer att bidra till en förbättrad eller försämrad absorption. Hjälpämnes effekter på transportproteiner där det framkom att hjälpämne modulerar aktiviteter av en del effluxtransportörer. Koncentrationsberoende effekter av hjälpämne på läkemedelsabsorption där koncentrationen av hjälpämne är en avgörande faktor för en förbättrad respektive försämrad absorption. Diskussion: Hjälpämnens effekter kan inte generaliseras, även inom en viss läkemedelsklass. Mycket forskning i in-vivo är nödvändigt för att förbättra förståelsen och utveckling av hjälpämne samt deras inverkan på läkemedelsabsorption.

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  • 16.
    Abdallah, Nadia Younous
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Rekommenderade dygnsdoser för barn - Går det att beräkna?2021Independent thesis Basic level (degree of Bachelor), 12 HE creditsStudent thesis
    Abstract [en]

    Background: Defined daily dose (DDD) is a unit that gives an estimate of drug utilization. The DDDs that are developed today are only based on adult’s drug use. That means that the DDDs for adults may not necessarily apply to children. 

    Aim: To calculate recommended daily dose for boys and girls in different ages and compare it with DDD for adults for paracetamol, phenoxymethylpenicillin, desloratadine and melatonin.  

    Methods: This descriptive cross-sectional study was conducted September-October 2021. Boys and girls in ages 1, 5, 12 and 16 years were included. Data was retrieved from FASS.se, tillväxtkurvor.se and WHO Collaborating Centre for Drug Statistics Methodology. 

    Results: The children’s daily doses are lower than DDD for adults for paracetamol for all ages, phenoxymethylpenicillin for ages 1, 5 and 12 and desloratadine for ages 1 and 5. The daily doses of phenoxymethylpenicillin aged 16 are higher than DDD for adults. Daily doses for melatonin and desloratadine age 12 and 16 were the same as DDD for adults. Paracetamol and phenoxymethylpenicillin have variations in the daily doses for the children. Girls in all ages except from 12 years and the youngest children had lowers doses. Desloratadine ages 1 and 5 had the same dose and ages 12 and 16 had the same dose. For melatonin the children received the same doses. 

    Conclusion: The calculated recommended daily doses for children are to some extent in line with WHO DDDs. In order to use WHO DDDs in children, it is important to have knowledge of which drugs and ages they can be applied for.  

     

     

     

  • 17.
    Abd-El Azeem, Hoda H.
    et al.
    Menoufia Univ, Fac Sci, Dept Zool, Shibin Al Kawm 32512, Egypt..
    Osman, Gamalat Y.
    Menoufia Univ, Fac Sci, Dept Zool, Shibin Al Kawm 32512, Egypt..
    El-Seedi, Hesham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi. Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China.;Jiangsu Univ, Jiangsu Educ Dept, Int Joint Res Lab Intelligent Agr & Agriprod Proc, Zhenjiang 212013, Jiangsu, Peoples R China.;Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm 32512, Egypt..
    Fallatah, Ahmed M.
    Taif Univ, Coll Sci, Dept Chem, POB 11099, Taif 21944, Saudi Arabia..
    Khalifa, Shaden A. M.
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, SE-10691 Stockholm, Sweden..
    Gharib, Mohamed M.
    Menoufia Univ, Fac Sci, Dept Bot, Shibin Al Kawm 32512, Egypt..
    Antifungal Activity of Soft Tissue Extract from the Garden Snail Helix aspersa (Gastropoda, Mollusca)2022In: Molecules, ISSN 1431-5157, E-ISSN 1420-3049, Vol. 27, no 10, article id 3170Article in journal (Refereed)
    Abstract [en]

    Gastropods comprise approximately 80% of molluscans, of which land snails are used variably as food and traditional medicines due to their high protein content. Moreover, different components from land snails exhibit antimicrobial activities. In this study, we evaluated the antifungal activity of soft tissue extracts from Helix aspersa against Candida albicans, Aspergillus flavus, and Aspergillus brasiliensis by identifying extract components using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Two concentrations of three extracts (methanol, acetone, and acetic acid) showed antifungal activity. Both acetone (1 g/3 mL) and acetic acid extracts (1 g/mL) significantly inhibited C. albicans growth (p = 0.0001, 5.2 +/- 0.2 mm and p = 0.02, 69.7 +/- 0.6 mm, respectively). A. flavus and A. brasiliensis growth were inhibited by all extracts at 1 g/mL, while inhibition was observed for acetic acid extracts against A. brasiliensis (p = 0.02, 50.3 +/- 3.5 mm). The highest growth inhibition was observed for A. flavus using acetic acid and acetone extracts (inhibition zones = 38 +/- 1.7 mm and 3.1 +/- 0.7 mm, respectively). LC-MS-MS studies on methanol and acetone extracts identified 11-alpha-acetoxyprogesterone with a parent mass of 372.50800 m/z and 287.43500 m/z for luteolin. Methanol extracts contained hesperidin with a parent mass of 611.25400 m/z, whereas linoleic acid and genistein (parent mass = 280.4 and 271.48900 m/z, respectively) were the main metabolites.

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  • 18.
    Abdelmoniem, Amr M.
    et al.
    Cairo Univ, Dept Chem, Fac Sci, Giza, Egypt.
    Elnagdi, Mohamed H.
    Cairo Univ, Giza, Egypt;Kuwait Univ, Safat, Kuwait.
    Elsehemy, Mohamed S.
    Cairo Univ, Dept Chem, Fac Pharm, Giza, Egypt.
    El-Seedi, Hesham R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi. Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt.
    Abdelhamid, Ismail A.
    Cairo Univ, Dept Chem, Fac Sci, Giza, Egypt.
    Synthesis, Chemistry and Utilities of Diaminoazoles with Special Reference to 3,5-Diaminopyrazoles2018In: Current Organic Synthesis, ISSN 1570-1794, E-ISSN 1875-6271, Vol. 15, no 4, p. 487-514Article, review/survey (Refereed)
    Abstract [en]

    Background: Although the chemistry of heteroaromatic monoamino azoles has been surveyed more than once in the last decade, the chemistry of the di- and triaminoazoles has not been reviewed. In this article we will survey the synthesis, chemistry and utility of the diaminoazoles. In this review, the chemistry of the diaminoazoles as well as their most important utilities will be surveyed. Objective: The review focuses on recent progress in diaminoazoles (i.e. diaminopyrazoles, diaminoimidazoles, diaminotriazoles and diaminothiazole) with especial references to diaminopyrazoles. The synthesis as well as pharmaceutical utilities are reported. There are several methods for synthesis of diaminopyrazoles. 3,5-Diaminopyrazole and its derivatives are prepared through the reaction of malononitrile or arylhydrazononitrile with hydrazine derivatives. 3,4-Diaminopyrazoles are prepared via nitration of 3-aminopyrazole with subsequent reduction of the produced compound. The diaminopyrazoles have several applications in cosmetic and pharmaceutical industries. They also have useful utilities as a constituent in oxidative hair dyes. Conclusion: We managed to report the common methods for the synthesis of diaminoazoles with especial reference to aminopyrazoles that are prepared through the reaction of malononitrile or hydrazononitriles with hydrazine derivatives. Some important applications that include pharmaceutical utilities such as hair dye constituents are reported.

  • 19.
    AbdelRehim, M
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Karlen, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Zhang, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Kamel, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Hassan, M
    Enantiomer separation of underivatized tocainide and related compounds by CGC using ammonia as carrier gas1996In: JOURNAL OF MICROCOLUMN SEPARATIONS, Vol. 8, p. 151-Article in journal (Refereed)
  • 20.
    Abdel-Rehim, Mohamed
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy.
    Influence of ammonia as carrier gas on separation and detection performance in capillary gas chromatography 1994Doctoral thesis, comprehensive summary (Other academic)
  • 21.
    Abdel-Rehim, Mohamed
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Hassan, Moustapha
    Capillary gas chromatography of trichlorophenols using ammonia as carrier gas2000In: Journal of High Resolution Chromatography, Vol. 23, p. 156-Article in journal (Refereed)
  • 22.
    Abdelwahab, Mahmoud Tareq
    et al.
    Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa..
    Court, Richard
    Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa..
    Everitt, Daniel
    Global Alliance TB Drug Dev, New York, NY USA..
    Diacon, Andreas H.
    Stellenbosch Univ, Dept Med, Tygerberg, South Africa.;Task Appl Sci, Bellville, South Africa..
    Dawson, Rodney
    Univ Cape Town, Div Pulmonol, Lung Inst, Cape Town, South Africa.;Univ Cape Town, Dept Med, Lung Inst, Cape Town, South Africa..
    Svensson, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.;Uppsala Univ, Dept Pharm, Uppsala, Sweden..
    Maartens, Gary
    Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa.;Univ Cape Town, Wellcome Ctr Infect Dis Res Africa, Inst Infect Dis & Mol Med, Cape Town, South Africa..
    Denti, Paolo
    Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa..
    Effect of Clofazimine Concentration on QT Prolongation in Patients Treated for Tuberculosis2021In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 65, no 7, article id e02687-20Article in journal (Refereed)
    Abstract [en]

    Clofazimine is classified as a WHO group B drug for the treatment of rifampin-resistant tuberculosis. QT prolongation, which is associated with fatal cardiac arrhythmias, is caused by several antitubercular drugs, including clofazimine, but there are no data quantifying the effect of clofazimine concentration on QT prolongation. Our objective was to describe the effect of clofazimine exposure on QT prolongation. Fifteen adults drug-susceptible tuberculosis patients received clofazimine monotherapy as 300mg daily for 3 days, followed by 100mg daily in one arm of a 2-week, multiarm early bactericidal activity trial in South Africa. Pretreatment Fridericia-corrected QT (QTcF) (105 patients, 524 electrocardiograms [ECGs]) and QTcFs from the clofazimine monotherapy arm matched with clofazimine plasma concentrations (199 ECGs) were interpreted with a nonlinear mixed-effects model. Clofazimine was associated with significant QT prolongation described by a maximum effect (Emax) function. We predicted clofazimine exposures using 100-mg daily doses and 2 weeks of loading with 200 and 300mg daily, respectively. The expected proportions of patients with QTcF change from baseline above 30 ms (DQTcF. 30) were 2.52%, 11.6%, and 23.0% for 100-, 200-, and 300-mg daily doses, respectively. At steady state, the expected proportion with Delta QTcF of >30 ms was 23.7% and with absolute QTcF of >450 ms was 3.42% for all simulated regimens. The use of loading doses of 200 and 300mg is not predicted to expose patients to an increased risk of QT prolongation, compared with the current standard treatment, and is, therefore, an alternative option for more quickly achieving therapeutic concentrations.

  • 23.
    Abdelwahab, Mahmoud Tareq
    et al.
    Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa..
    Wasserman, Sean
    Univ Cape Town, Dept Med, Div Infect Dis & HIV Med, Cape Town, South Africa.;Univ Cape Town, Wellcome Ctr Infect Dis Res Africa, Inst Infect Dis & Mol Med, Cape Town, South Africa..
    Brust, James C. M.
    Albert Einstein Coll Med, Div Gen Internal Med, New York, NY USA.;Albert Einstein Coll Med, Div Infect Dis, New York, NY USA..
    Gandhi, Neel R.
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA.;Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA.;Emory Univ, Emory Sch Med, Dept Med Infect Dis, Atlanta, GA USA..
    Meintjes, Graeme
    Univ Cape Town, Dept Med, Div Infect Dis & HIV Med, Cape Town, South Africa.;Univ Cape Town, Wellcome Ctr Infect Dis Res Africa, Inst Infect Dis & Mol Med, Cape Town, South Africa..
    Everitt, Daniel
    Global Alliance TB Drug Dev, New York, NY USA..
    Diacon, Andreas
    Task Appl Sci, Bellville, South Africa.;Stellenbosch Univ, Dept Med, Cape Town, South Africa..
    Dawson, Rodney
    Univ Cape Town, Lung Inst, Cape Town, South Africa.;Univ Cape Town, Div Pulmonol, Dept Med, Cape Town, South Africa..
    Wiesner, Lubbe
    Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa..
    Svensson, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.
    Maartens, Gary
    Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa.;Univ Cape Town, Wellcome Ctr Infect Dis Res Africa, Inst Infect Dis & Mol Med, Cape Town, South Africa..
    Denti, Paolo
    Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa..
    Clofazimine pharmacokinetics in patients with TB: dosing implications2020In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 75, no 11, p. 3269-3277Article in journal (Refereed)
    Abstract [en]

    Background: Clofazimine is in widespread use as a key component of drug-resistant TB regimens, but the recommended dose is not evidence based. Pharmacokinetic data from relevant patient populations are needed to inform dose optimization. Objectives: To determine clofazimine exposure, evaluate covariate effects on variability, and simulate exposures for different dosing strategies in South African TB patients. Patients and methods: Clinical and pharmacokinetic data were obtained from participants with pulmonary TB enrolled in two studies with intensive and sparse sampling for up to 6 months. Plasma concentrations were measured by LC-MS/MS and interpreted with non-Linear mixed-effects modelling. Body size descriptors and other potential covariates were tested on pharmacokinetic parameters. We simulated different dosing regimens to safely shorten time to average daily concentration above a putative target concentration of 0.25 mg/L. Results: We analysed 1570 clofazimine concentrations from 139 participants; 79 (57%) had drug-resistant TB and 54 (39%) were HIV infected. Clofazimine pharmacokinetics were well characterized by a three-compartment model. Clearance was 11.5 L/h and peripheral volume 10500 L for a typical participant. Lower plasma exposures were observed in women during the first few months of treatment, explained by higher body fat fraction. Model-based simulations estimated that a Loading dose of 200 mg daily for 2 weeks would achieve average daily concentrations above a target efficacy concentration 37 days earlier in a typical TB participant. Conclusions: Clofazimine was widely distributed with a Long elimination half-Life. Disposition was strongly influenced by body fat content, with potential dosing implications for women with TB.

  • 24.
    abdi, bahja omar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Double-checking advanced drug reconstitution in pediatric care2021Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Background 

    An evidence-and experience-based pediatric drug information system, ePed, was developed in Sweden to gather pediatric drug therapy information. Recently a database, Advanced Reconstitution Module (ARM), was designed to detect errors in the reconstitution of high-risk drugs. ARM is integrated with ePed and has a front-end system called ReVal that facilitates communication between the database and DrugLog (an ultraviolet spectrophotometer).  

    Aim 

    The study’s main aim was to ensure correct drug management of high-risk drugs in the neonatal units at Karolinska University Hospital. The study had three objectives; (1) Determination of the prevalence of dilution error for high-risk drugs, (2) Evaluation of the staff experiences with the ARM-system, (3) Investigation of the adsorption of insulin on plastic material.  

    Methods

    Stage 1: Random samples of nine different diluted high-risk drugs used in clinical practice were collected and measured with DrugLog. Stage 2: Recruited participants prepared insulin using ARM. The reconstituted insulin from stage 2 was further studied. 

    Results

    Stage 1: Out of 168 samples, 44.6 % (95 %CI 37.3 %-52.2 %) contained concentrations outside of the acceptable limit (± 10 %). Stage 2: None of the participants found the ARM process difficult, and 34 % of the insulin prepared was outside of the acceptable range. No difference in adsorption (PVC vs. PVC-free lines) was found for insulin.  

    Conclusions

    The first objective of this study was to determine the prevalence of dilution error. With an overall rate of error of 44,6 % the main conclusion that can be drawn from this study is the need for a system that can help minimize this rate of error. The second objective was to evaluate the staff experiences with ARM which was identified to be a simple method according to the participants. More profound studies have to be performed in order to investigate insulins adsorption to plastic which was the studies third objective.  

  • 25.
    Abdi, Hafsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Finns det någon koppling mellan Alzheimers sjukdom och Diabetes Mellitus?2014Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Alzheimers sjukdom är en neurodegenerativ sjukdom vars orsak är okänd, kännetecknas av en gradvis försämring av kognitiva funktioner. Alzheimers sjukdom och Diabetes Mellitus har flera gemensamma patofysiologiska samband, bland annat insulinresistens. Försämrad insulinsignalering kan leda till kognitiv funktionsförsämring, som i sin tur kan leda till Alzheimers sjukdom. Båda insulin och amyloid-β metaboliseras av insulinnedbrytande enzym (IDE), defekt i IDE kan delvis orsaka amyloid-β ansamlingar. Syftet med detta arbete är att undersöka om försämrad insulinsignalering kan leda till kognitiv försämring och påskynda utvecklingen av Alzheimers sjukdom.

    Jag har gjort en systematisk litteraturöversikt för att undersöka detta. Det är större risk att drabbas av Alzheimers sjukdom om man har Diabetes Mellitus. Man såg ett samband mellan försämrad insulinsignalering och försämrad kognitiv funktion. Förhöjda glukosnivåer var förenade med kognitiv försämring, medan nedsatt glukosnivå inte hade någon betydelse vid kognitiv försämring. Dessutom påskyndar en hög glukosnivå omvandlingen från MCI (mild kognitivs vikt) till Alzheimers sjukdom. Trots detta resultat krävs det mer forskning inom området eftersom olika metoder användes på de olika studierna vilket kan ge ett falskt samband.

  • 26.
    Abdillahi, Suado M.
    et al.
    Lund Univ, Div Infect Med, Dept Clin Sci, Tornavagen 10, S-22184 Lund, Sweden.
    Maass, Tobias
    Univ Cologne, Fac Med, Ctr Biochem, Ctr Mol Med Cologne, D-50931 Cologne, Germany.
    Kasetty, Gopinath
    Lund Univ, Div Resp Med & Allergol, Dept Clin Sci, S-22184 Lund, Sweden.
    Strömstedt, Adam A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi.
    Baumgarten, Maria
    Lund Univ, Div Infect Med, Dept Clin Sci, Tornavagen 10, S-22184 Lund, Sweden.
    Tati, Ramesh
    Lund Univ, Div Infect Med, Dept Clin Sci, Tornavagen 10, S-22184 Lund, Sweden.
    Nordin, Sara L.
    Lund Univ, Div Infect Med, Dept Clin Sci, Tornavagen 10, S-22184 Lund, Sweden.
    Walse, Björn
    Sarom Biostruct AB, S-22363 Lund, Sweden.
    Wagener, Raimund
    Univ Cologne, Fac Med, Ctr Biochem, Ctr Mol Med Cologne, D-50931 Cologne, Germany.
    Schmidtchen, Artur
    Lund Univ, Div Dermatol & Venereol, Dept Clin Sci, S-22184 Lund, Sweden;Univ Copenhagen, Bispebjerg Hosp, Dept Biomed Sci, Copenhagen Wound Healing Ctr, DK-2400 Copenhagen, Denmark.
    Mörgelin, Matthias
    Lund Univ, Div Infect Med, Dept Clin Sci, Tornavagen 10, S-22184 Lund, Sweden;Colzyx AB, S-22381 Lund, Sweden.
    Collagen VI Contains Multiple Host Defense Peptides with Potent In Vivo Activity2018In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 201, no 3, p. 1007-1020Article in journal (Refereed)
    Abstract [en]

    Collagen VI is a ubiquitous extracellular matrix component that forms extensive microfibrillar networks in most connective tissues. In this study, we describe for the first time, to our knowledge, that the collagen VI von Willebrand factor type A like domains exhibit a broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria in human skin infections in vivo. In silico sequence and structural analysis of VWA domains revealed that they contain cationic and amphipathic peptide sequence motifs, which might explain the antimicrobial nature of collagen VI. In vitro and in vivo studies show that these peptides exhibited significant antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa through membrane disruption. Our findings shed new light on the role of collagen VI derived peptides in innate host defense and provide templates for development of peptide-based antibacterial therapies.

  • 27.
    Abdiwoli, Abdisalam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    pH-responsive release of proteins from colloidal capsules for oral drug delivery2020Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Biologics are an important part of modern healthcare and are mostly administered parenterally due to the fact that it is the route of administration that avoids degradation of biologics and ensures their systemic exposure. However, there is a need to develop oral drug delivery formulations for local treatment of diseases in the gastrointestinal tract (GI). Colloidal capsules is a formulation that can potentially facilitate oral administration of biologics. There have been studies on colloidal capsules and the various ways of manufacturing them, one of which is “Emulsion-based method”. The aim of this study was to produce colloidal capsules made of silica nanoparticles through emulsion-based method, coat them to study their pH-responsive release and characterize them. Encapsulation of a model protein in the silica colloidal capsules was also attempted. pH-responsive release was not studied due to limited access to the laboratory and, a literature study of articles about colloidal capsules was conducted instead, regarding different aspects of colloidal capsule synthesis and encapsulation of various compunds. Web of science was the database used to find scientific studies that specifically produced colloidal capsules. Colloidal capsules were synthesized using a Pickering-emulsion method. Commercially available SiO2 nanoparticles were used to form the capsules by ultrasonication.  The hydrodynamic size and capsule morphology were analyzed using dynamic light scattering (DLS) and scanning electron microscopy (SEM), respectively. Zeta potential was measured through electrophoretic light scattering (ELS). Articles for the literature study were found using the “web of science” database. Colloidal capsules were successfully produced, coated and characterized. Additionally, the literature study shows that there diverse colloidal capsule synthesis conditions, model proteins and applications for colloidal capsules.

  • 28.
    Abdo, Chirine Hussein
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Lund universitet.
    Kombination och koncentration av toxiska substanser hos personer obducerade på grund av narkotika relaterade dödsfall i Skåne2023Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Opioidförgiftningar är ett framträdande folkhälsoproblem i många länder runt om i världen. Det misstänks att kombinationen mellan opioider och sederande läkemedel ökar risken för död även vid lägre doser opioider. Syftet med denna studie var att studera hur andra sederande läkemedel, bensodiazepiner, hypnotika, antiepileptika, antidepressiva och antihistaminer skulle kunna öka risken för opioidförgiftningar även vid lägre doser. Samt att identifiera andra möjliga riskfaktorer för opioidöverdos. 

     

    Metod: Detta är en retrospektiv registerstudie som analyserar forensiska och toxikologiska data för samtliga personer obducerade inom rättsmedicin, avlidna i Skåne mellan 2011–2018 (N= 1395) på grund av intoxikation av minst en opioid. Datan analyserades med hjälp av independet sample t-test samt frekvensberäkningar för att analysera gruppskillnader. 

     

    Resultat: Majoriteten av dödsfallen (84,6%) var relaterade till kombination mellan opioider och minst ett sederande läkemedel. Morfin/heroin var den vanligaste opioid i studien (36,2%) och bensodiazepiner (65,7%) var den mest frekventa sederande läkemedel i studien. Bensodiazepiner, hypnotika samt antiepileptika ledde till att signifikant lägre doser av morfin/heroin, fentanyl respektive tramadol krävdes till död på grund av överdos. Vissa grupper identifierades för att kunna tillhöra riskzonen. 

     

    Slutsats: Den studerade populationen kännetecknades av omfattande kombination mellan opioider och bensodiazepiner. Dessutom rapporterades ett signifikant samband mellan förskrivning av bensodiazepiner, hypnotika samt antiepileptika och ökad risk för överdosdödsfall vid lägre doser opioider. Därför bör förskrivning av dessa läkemedel begränsas till opioidanvändare. 

  • 29.
    Abdu, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Betydelsen av PDGF vid Trippelnegativ Bröstcancer2022Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Triple negative breast cancers (TNBC) are defined by the absence of estrogen andprogesterone receptors and the absence of HER2 protein overexpression. TNBC cancersrepresent a heterogeneous breast cancer subtype with poor prognosis. The heterogeneity of thedisease has limited the successful development of targeted therapy in unselected patientpopulations. Currently there are no approved targeted therapies for TNBC. However, intenseresearch is ongoing to identify specific targets and develop additional and better systemictreatment options. Recently researchers have found that the PDGF pathway plays a significantpart in communication between cancer cells and cells in the surrounding tissue. In thisliterature study evaluated if the PDGFR inhibition is a treatment strategy for triple negativebreast cancer. Method: literature original articles from database Pubmed was used in thisstudy. Results: results show that PDGF is more overexpressed in tissue cells than tumor cells.PDGF isoforms like PDGFRalfa and PDGF-C can increase the risk of distant recurrence tocentral nervsystem and early recurrence of primary breast cancer. The TNBC subtype (MES)is more likely to overexpress PDGF and inhibition with PDGF specific aptamer have shownsignificantly decreased tumor cell growth. Triple combination treatment with MEK1/2 and(JAK2) inhibitors resulted in significant reduction of cell growth and immunological inducedcell death through CD8+ t-cells. Single treatment with PDGFR inhibitors like Ponatinib andSunitinib reduced cell growth and cell migration in TNBC, but a combination treatment withDoxorubicin showed far greater inhibitor effect on cell growth and migration it also causedcell death. Chemotherapy Doxorubicin combination with a PDGFR- inhibitor resulted inbetter treatment compared to a single PDGFR- inhibitor to treat TNBC.Conclusion: It has been proven that PDGF isoforms have different significance in thedevelopment of TNBC. The PDGFC ligand is significantly more expressed in TNBCcompared to other PDGF isoforms. Ligand and receptor binding PDGFC-PDGFRα expressionis increased during breast cancer progression. PDGFRbeta signaling pathway plays a crucialrole in mediating vascular properties and therefore may be a good marker for reducing newvessel formation in endothelial cells. Combination therapy appears to be promising drugtreatment in TNBC. PDGFR inhibitors combined with cytostatic drugs or JAK & MEK1/2inhibitors can provide a pharmacological synergistic effect or activate the immune systemCD8+ T cells. Combination therapy reduces emergence of resistance mechanisms, howeverthere is a lack of studies on toxicity side effects. Nyckelord: Trippelnegativ bröstcan

  • 30.
    Abdul Amir, Meys
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Kvalitetsgranskning av utskrivningsinformation från fyra kirurgavdelningar på Akademiska sjukhuset2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Kvalitetesgranskning av utskrivningsinformation från fyra kirugavdelningar på Akademiska sjukhuset

    Meys Abdul Amir

    Introduktion: Vid utskrivning från kirurgavdelningar förekommer ofta brister i utskrivningsinformation gällande patientens läkemedelsbehandling, vilket medför läkemedelsrelaterad sjuklighet. För att åtgärda detta krävs utdelning av uppdaterad läkemedelslista, fullständig och tydlig information till patienter vid utskrivning samt införande av läkemedelsberättelse i utskrivningsmeddelandet. Läkemedelsberättelse genomförs när läkemedelsförändring utförs under vårdtiden på sjukhuset. Syfte: Syftet med arbetet var att undersöka i vilken utsträckning utskrivningsmeddelande med läkemedelsberättelse skrivs till patienter vid kirurgavdelningar på Akademiska sjukhuset, samt undersöka i vilken utsträckning läkemedelslista skickas med till patienter vid utskrivning och även kontrollera om läkemedelslistorna uppdateras vid utskrivning. Material och metoder: Retrospektiv observationsstudie genom journalgranskning och telefonintervju av alla patienter i alla åldrar utskrivna från alla kirurgavdelningar på Akademiska sjukhuset under december 2015. Resultat: Av 332 patienter som ingick i studien hade läkemedelsförändringar utförts för 176 patienter, och utskrivningsningsmeddelande upprättades till drygt 6,3 % av dessa 176 patienter. Av de 332 patienterna erhöll 60% en uppdaterad läkemedelslista. Telefonintervju genomfördes med 107 patienter och av dessa hade 37% fått en läkemedelslista. Förbättrade resultat observerades hos patienter som fått läkemedelsgenomgång av klinikapotekare vid utskrivning. Konklusion: Rutinen för utskrivningsinformationen är fortfarande bristfällig på de kirurgiska avdelningarna. Flera apotekare behövs på dessa avdelningar, för att kunna minska antal läkemedelsfel efter utskrivning från sjukhuset.

  • 31.
    Abdul Sattar Mehdi, Katrelneda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Läkemedelsgenomgång för äldrepatienter med demenssjukdom på ettsärskilt boende i region Dalarna2019Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Demens orsakas av hjärnskador som främst drabbar äldre. Antalet dementa personer i Sverige uppgår idag till ca. 150 000 och beräknas fördubblas de kommande 30 åren i och med den allt äldre befolkningen. De äldre har ofta flera diagnoser. Detta samt åldersrelaterade förändringar i fysiologiska funktioner leder till stor läkemedelsanvändning, vilket i sin tur ger upphov till läkemedelsrelaterade problem (LRP) i form av exempelvis biverkningar, interaktioner, avsaknad av indikation, indikation utan behandling, olämplig läkemedelsbehandling eller doseringsfel. LRP kan upptäckas, åtgärdas, minskas eller förebyggas med hjälp av läkemedelsgenomgång.

    Syfte: Syftet med detta arbete var att genomföra läkemedelsgenomgång för äldre patienter med demenssjukdom och med minst fem eller fler ordinerade läkemedel för att analysera förekomsten av LRP bland patienterna.

    Metod: Läkemedelsgenomgång för 20 patienter utfördes i ett särskilt demensboende genom avidentifierade patientdata i form av läkemedelslista, senaste labprover samt diagnoslista. Även frågeställningar baserade på en lathund för läkemedelsgenomgång besvarades. Aktuella frågeställningar var att rätt och uppdaterad läkemedelslista fanns i journalen, läkemedelsinteraktioner, olämpliga läkemedel för äldre, dosering anpassad till njur-, och leverfunktion, laboratorievärden, diagnos utan aktuell/rimlig behandling, läkemedel utan aktuell/rimlig indikation samt biverkningar. Även användningen av icke-farmakologisk behandling kontrollerades.

    Resultat: Studien visade att samtliga patienter hade korrekt och uppdaterad läkemedelslista registrerad i journalen. 55% av patienterna hade minst en läkemedelsinteraktion. 10% hade olämpliga läkemedel för äldre. 20% hade ett eller fler feldoserade läkemedel. 25% behövde åtgärder i form av komplettering av blodprover eller insättning av läkemedel efter utvärdering av labvärden i samband med existerande diagnos. 50% hade minst en diagnos registrerad, men saknade aktuell läkemedelsbehandling och 10% tog läkemedel utan att det fanns aktuell eller rimlig indikation registrerad i deras journal.Slutsats: Projektet tyder på att flera olika LRP upptäcktes bland dementa patienter i boendet där de vanligast förekommande är läkemedelsinteraktioner samt registrerad diagnos utan aktuellt läkemedel. Åtgärder utfördes i form av dosjustering av läkemedel, insättning av läkemedel, borttagning av olämpligt läkemedel, kontroll av diagnos som saknade behandling samt att ytterligare blodprover beställdes för en del patienter. Detta indikerar att läkemedelsgenomgång är en viktig procedur och därmed bör tillämpas på alla äldre patienter som använder sig av flera läkemedel för att upptäcka och åtgärda LRP. Målet med detta är i sin tur att förbättra livskvaliteten, välmåendet samt patientsäkerheten för äldre dementa patienter.

  • 32.
    Abdulahad, Noor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    The effects of short-term use of proton pump inhibitors on plasma and salivary nitrate/nitrite and exhaled NO in patients with established coronary artery disease2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Introduction: Recent studies have suggested several vasoprotective/cardioprotective effects of dietary nitrate (NO3-) and nitrite (NO2-), including blood pressure regulating, antiplatelet effect, enhanced endothelial function and increased oxygen supply in healthy volunteers. There is, on the other hand, concern that an increase in gastric pH may blunt these beneficial effects due to the low pH requirement (pH< 2) for nitric oxide (NO) generation from nitrate in the stomach. This effect has not previously been investigated in 'real life' patients. Aim: To investigate the effects of an increased gastric pH caused by short-term (5 days) use of esomeprazole, a proton pump inhibitor, on plasma and salivary nitrate/nitrite and exhaled NO in patients with established coronary artery disease (CAD). Methods: A total of seven patients with CAD were enrolled in the study. An on-line method was used to determine fractional exhaled concentration of NO (FeNO) at multiple flow rates, data was modeled to estimate alveolar airways NO concentration (Calv) and bronchial NO flux (JNO). Plasma and salivary nitrate/nitrite levels were also analyzed. Results: There was a statistically (P = 0.0469) significant reduction in Calv in the overall patient group after treatment with esomeprazole. There was a trend toward an increase, albeit non-statistically significant (P = 0.0781) in salivary nitrate after treatment with esomeprazole. Conclusion: The major finding in this study is the significant reduction in the alveolar NO concentration in the overall patient group after treatment with esomeprazole. Further research is needed in this area.

  • 33.
    Abdulameer, Shams
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Test och utvärdering av Janusmed Riskprofil i valideringssystemet SAPVAL vid Akademiska sjukhuset i Uppsala (System Assisted Pharmaceutical VALidation)2022Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 34.
    Abdulfattah, Amenah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Variation in blood pressure target achievement in primary care centers2021Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Background: High blood pressure (BP) or hypertension is defined as a systolic and diastolic pressure over 140/90 mmHg. High blood pressure increases the risk for premature death, and previous research has shown that many patients do not reach targets and that there are differences between primary healthcare centers in the proportion of patient reaching targets. The reasons for these variations, however, are unknown. Aim: To investigate variations in blood pressure target achievement between primary care centers in Stockholm county and how different factors such as practice size, ownership, socioeconomic and antihypertensive drug treatment can influence this diversity. Method(s): This study was designed as a cross-sectional register study with a descriptive quantitative perspective. Data was collected from three sources: National Primary Care Quality register, Care Need Index for healthcare in Stockholm region and Stockholm County Council data warehouse VAL. The study included 179 out of all 227 primary care centers in the region. The proportion of all patients with hypertension reaching targets was assessed each year during 2019-2021, and correlations studied for potential predictors. Results: there was a variation between primary care centers in target blood pressure fulfillment, ranging from 22-66% during 2021, 23-63% during 2020 and 33-66% during 2019, respectively. There was no overall difference between public and private centers in the proportion of patients reaching targets, but a larger practice variation among private centers. No correlation was found between the other studied factors and target blood pressure fulfillment during 2021. Conclusion: There was a variation between primary care centers in the proportion of patients reaching blood pressure targets. Different practices may change ranking between years and other factors than practice size, ownership and socioeconomic appears to explain the variation.

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  • 35.
    Abdulhameed, Ingi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bedömning av njurfunktionen hos cancerpatinter vid dosering av karboplatin2014Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Introduktion: Vid behandling av ett flertal cancertyper används läkemedlet karboplatin som doseras efter njurfunktionen. Karboplatin utsöndras huvudsakligen via njurarna och elimineringen bestäms framför allt av den glomerulära filtrationshastigheten (GFR). Därför krävs det en noggrann bedömning av njurfunktionen för en korrekt behandling. GFR kan både mätas till exempel med iohexolclearance eller skattas med hjälp av matematiska formler. Det råder en osäkerhet om vilka GFR-metoder som är lämpligast för att skatta njurfunktionen hos cancerpatienter som behandlas med karboplatin.

    Syfte: Att undersöka vilken eller vilka av följande sex GFR skattnings metoder, Cockcroft -Gault med okompenserat kreatinin (CGold), Cockcroft–Gault (CG) med kompenserat kreatinin, cystatin C-GFR, Modification of Diet in Renal Disease Study (MDRD4), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) samt Lund-Malmö formeln (LM-reviderad), som bäst korrelerar till ”gold standard” metoden iohexolclearance, för att bättre kunna dosera karboplatin till cancerpatienter.

    Material och metoder: Femtioåtta cancerpatienter från Radiumhemmet som under 2013 genomfört iohexolclearance innan behandlingsstart med karboplatin inkluderades. GFR hos dessa patienter beräknades med ovanstående formler. Överensstämmelse mellan iohexolclearance och övriga GFR metoder bestämdes med bland annat linjär regression, bias och precision.

    Resultat: CGold och Cystatin C tenderar att underskatta GFR medan MDRD4, CKD-Epi och CG tenderar att överskatta GFR. LM-reviderad överensstämmer med iohexolclearance.

    Konklusion: Lund-Malmö formeln (LM-reviderad) är den metod som bäst korrelerar till ”gold standard” metoden iohexolclearance.

  • 36.
    Abdulla Karim, Dana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Ersättning av två aminosyror i 9S-dioxygenas-allenoxidsyntas av Colletotrichum graminicola samt förkortning av dioxygenasdomänen för 3D-strukturanalys2015Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Oxylipiner är oxiderade metaboliter av fleromättade fettsyror. Hos svampar är dessa inblandade i kommunikation, reproduktion, reglering av mykotoxinproduktion och modulering av växtförsvarssystemet vid infektion. Colletotrichum graminicola tillhör de mest kända och viktigaste svampar som orsakar skador på grödor. Genen EFQ_27323 från C. graminicola kodar för 9S-dioxygenas-allenoxidsyntas (9S-DOX-AOS) och vid inkubation med linolsyra bildar hydroperoxyoctadekadiensyra (9-HPODE).

     

    Syftet med projektet är dels att ändra kiraliteten av 9S-DOX-AOS i genen EFQ_27323 genom att ersätta aminosyrorna Ile590 och Leu601 mot Gly590 och Phe601, respektive, och dels att förkorta DOX-domänen av enzymet för vidare 3D-strukturanalyser.

     

    Site directed mutagenesis används för mutationer av gener genom PCR-tekniken. Mutanten både transformeras och uttrycks i E.coli (BL21) med hjälp av expressionsvektorn pET101D-TOPO. De uttryckta enzymerna inkuberas med linolsyra (18:2n-6) och aktiviteten och dess kiralitet analyseras med hjälp av LC-MS/MS.

     

    Ersättningen av Ile590 med Gly590 ändrade kiraliteten av 9S-HPODE till 9R-HPODE med 20 % medan dubbelmutanten, d.v.s. Gly590 och Phe601 ändrade kiraliteten med 58 %. Enzymet förlorar sin 9-HPODE aktivitet när en förkortning av DOX-domän utan CYP-domän genomförs.

     

    Specifika aminosyrasubstitutioner i aktivt centrum påverkar regio- och stereoselektiviteten. Aminosyrorna i genen EFQ_27323, Gly590 och Phe601 istället för Ile590 med Leu601 ändrar kiraliteten från 9S-DOX-AOS till 9R-DOX-AOS

  • 37.
    Abdullah, Sarah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Validering av narkotikahanteringen för morfin, oxikodon och ketobemidon vid Astrid Lindgrens Barnsjukhus2016Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Validering av narkotikahanteringen för morfin, oxikodon och ketobemidon vid Astrid Lindgrens Barnsjukhus

    Sarah Abdullah

    Fördjupningsprojekt i farmakoterapi 30 hp, Apotekarprogrammet

    Institution för farmaceutisk biovetenskap, Handledare: Per Nydert, Examinator: Margareta Hammalund- Udenaes

    Introduktion: Kontrollerad narkotikaanvändning leder till mindre risk för läkemedelshanteringsfel vilket bidrar till ökad personal- och patientsäkerhet. Syfte: Validering av datauttag från TakeCare samt validering av hanteringen av morfin, oxikodon och ketobemidon på avdelning Q84 och B78 på Astrid Lindgrens Barnsjukhus. Material och metoder: Uttag i narkotikaloggen jämfördes med administreringar i journalsystemet TakeCare. Detta utfördes retrospektivt under 11,5 månader i den kvantitativa studien och prospektivt under ca. en månad i den kvalitativa studien där även orsaker till avvikelserna har studerats. Dessutom jämfördes den dokumenterade kassationen mot den uppskattade kassationen. Resultat: I den retrospektiva studieperioden ingick 93 patienter. Av alla doser i narkotikaloggen fanns på Q84 78,6 % (95 % KI 73,5-83,2) och på B78 85,9 % (95 % KI 81,8-89,4) av doserna i TakeCare. Av totala antalet doser saknades på Q84 21 % (95 % KI 17,0-25,6)* och på B78 5,2 % (95 % KI 3,2-7,99) av doserna i narkotikaloggen. Dessutom förekom det under den retrospektiva studien 38 avvikelser i behållningen vilket var signifikant högre jämfört med fem avvikelser på B78. De huvudsakliga orsakerna till avvikelser mellan uttag och administrering var vård utanför avdelningen (29 % resp. 36 % av alla avvikelser), administrering skedde ur tidigare patientuttag (14 % resp. 14 %), opioidinfusion (34 % resp. 0 %) och behov saknades (0 % resp. 36 %) för Q84 resp. B78. Under hela studieperioden utgjorde den dokumenterade kassationen 0,39 % på Q84 och 0,93 % på B78 av den uppskattade kassationen. Konklusion: Antal doser i TakeCare av alla doser i narkotikaloggen var inte signifikant skild mellan avdelningarna. Däremot var antalet doser som saknades i narkotikaloggen av alla doser signifikant högre på Q84. Detta indikerar att narkotikaloggen var mer välskött på B78. Antalet avvikelser i behållningen var signifikant högre på Q84, vilket indikerar att läkemedelsautomaten på B78 leder till en mer kontrollerad narkotikahantering. Både på avdelning Q84 och B78 var kassationen bristfälligt dokumenterad.

  • 38.
    Abdulmahdi, Rasha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Statinanvändning hos äldre hypertonipatienter med nedsatt njurfunktion2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Statinanvändning hos äldre hypertonipatienter med nedsatt njurfunktion

    Rasha Abdulmahdi

    Handledare: Björn Wettermark, Docent, Apotekare, Utvecklingsavdelningen, SLL. Yvonne Freund-Levi, MD PhD Överläkare KI. Tero Shemiekka, överläkare Avdelningen för E-hälsa, SLL. Examinator: Margareta Hammarlund-Udenaes, Professor i farmakokinetik och farmakodynamik. Institutionen för farmaceutisk biovetenskap. Examensarbete i Farmakoterapi D, 30hp, Uppsala universitet.

     

    Introduktion: Äldre patienter löper större risk att utveckla läkemedelsbiverkningar p.g.a. avtagande njurfunktion. Flera publicerade studier tyder på att många patienter läggs in akut på sjukhus för att de använder läkemedel som inte anpassas efter deras njurfunktion. Syfte: Att kartlägga förskrivning av statiner hos äldre hypertonipatienter med avseende på njurfunktion i Skaraborg och sydvästra Stockholms Län. Material och metoder: En tvärsnittstudie baserad på data hämtade från SPCCD (Swedish Primary Care Cardiovascular Database). Patienter ≥ 65 år som hade minst ett registrerat S-kreatinin under år 2006-2008 inkluderades och andelen som hämtade ut statiner under perioden 2006-2009 analyserades. GFR (Glomerular Filtration Rate) beräknades med CKD-EPI-formeln (Chronic Kidney Disease Epidemiology Collaboration). Läkemedelssubstanserna lämplighet eller behov av dosjustering i relation till njurfunktion granskades enligt RenBase, en databas med dokumentation av läkemedel vid nedsatt njurfunktion. Resultat. Totalt identifierades 38 239 individer och av dessa hade 23,8 % behandlats med statiner. De mest förskrivna statinerna var simvastatin (84,2 %) och atorvastatin (10,5 %). Det var signifikant färre (95 % C.I.) som behandlades med de båda statinerna vid en jämförelse mellan GFR < 30 och >30. Det fanns ingen korrelation mellan snittdosering (mg/dag) och njurfunktion. Konklusion: Många äldre hypertonipatienter i primärvården med nedsatt njurfunktion får statinbehandling. Det förefaller dock som om simvastatin inte dosjusteras hos patienter med svårt nedsatt njurfunktion.

                 

  • 39.
    Abdulrahim, Souad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Evaluation of UTLAM PDMS with Rotating Membrane Diffusion Cell for In Vitro Lipolysis Assay of Felodipine Loaded LBF2021Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The number of poorly water-soluble drugs acquiring a high lipophilicity (BCS class II) have increased tremendously in the pharmaceutical development pipeline over the past decades. One of the solutions that has been conducted to overcome the low aqueous solubility problem was to co-administer these drugs with lipids or fats as lipid-based formulations (LBF). In vitro lipid digestion assays for drug loaded LBF have been used to predict the behaviour of these drugs in vivo in the GI tract. The aim of this study was to examine the feasibility of using Ultra-Thin Large Area PDMS membrane of (~10 μm) thickness with Rotating Membrane Diffusion Cell (RMDC) for in vitro lipolysis-permeation experiments for Felodipine loaded Lipid-based Formulation. Membrane fabrication was done using Sylgard 184 elastomer kit and spin-coater device to get the ultra-thin membranes of approximately 10 μm thickness. Felodipine loaded LBF (22mg/g Felodipine, LBF type: MC-IIIA) was digested in the RMDC at 100 rpm speed for 60 min at 37°C. 75 μl of Lucifer Yellow (10 mM) was used as a membrane integrity marker and was added to the donor chamber of (225 mL) volume prior to digestion to check for mass transfer through the membrane in the receiver chamber (70 mL). During the digestion phase, the maximum ionised fatty acids was 0.402 mmol at 59.6 min, however, the unionised fatty acids during back titration have reached 0.86 at 61.4 min. Lucifer Yellow mass transfer graphs showed a steady increase in the area under the curve at the time point 20 min, where it reached approximately 75 nmol min cm-2. The experiment needs to be repeated to be able to identify a more rigorously justified leak criterion for LY-PDMS. It should be noted that PDMS-LY partition experiments were planned, so that the partitioning affinity could be determined to predict the flux of Lucifer Yellow through PDMS. This secondary method would provide a priority leak criterion.

  • 40.
    Abdulrasul, Ali
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Neurosteroids and Alzheimer’s disease: Mechanistic studies of neuroprotection and neurogenesis2015Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Alzheimer’s disease (AD) and its consequent memory and cognitive impairments continue to be unhaltable and incurable to this day. Yet, recent studies demonstrating neuroprotective effects of some neurosteroids have shown a potential of these steroids to modulate AD progression in vitro and in vivo. In the present study, the effects of neurosteroids were studied on hydrogen peroxide (H2O2), as well as staurosporine-induced toxicity in SH-SY5Y neuroblastoma cells. Moreover, underlying mechanisms were investigated. Cell viability was measured with MTT-assay. The results demonstrated that the neurosteroids investigated reduced hydrogen peroxide-induced toxicity. One of the neurosteroid even reduced staurosporine-induced toxicity. Moreover, the present study also showed neurogenic properties for one of the neurosteroid studied.  In conclusion, this report demonstrates that neurosteroids act neuroprotective against hydrogen peroxide-induced toxicity and that one of the neurosteroids studied even acts neuroprotective against staurosporine-induced toxicity and possesses neurogenic effects. 

  • 41. Abela, D
    et al.
    Ritchie, H
    Ababneh, D
    Gavin, C
    Nilsson, Mats F
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Niazi, M Khalid Khan
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis.
    Carlsson, K
    Webster, WS
    The effect of drugs with ion channel-blocking activity on the early embryonic rat heart2010In: Birth defects research. Part B. Developmental and reproductice toxicology, ISSN 1542-9733, E-ISSN 1542-9741, Vol. 89, no 5, p. 429-440Article in journal (Refereed)
    Abstract [en]

    This study investigated the effects of a range of pharmaceutical drugs with ion channel-blocking activity on the heart of gestation day 13 rat embryos in vitro. The general hypothesis was that the blockade of the IKr/hERG channel, that is highly important for the normal functioning of the embryonic rat heart, would cause bradycardia and arrhythmia. Concomitant blockade of other channels was expected to modify the effects of hERG blockade. Fourteen drugs with varying degrees of specificity and affinity toward potassium, sodium, and calcium channels were tested over a range of concentrations. The rat embryos were maintained for 2 hr in culture, 1 hr to acclimatize, and 1 hr to test the effect of the drug. All the drugs caused a concentration-dependent bradycardia except nifedipine, which primarily caused a negative inotropic effect eventually stopping the heart. A number of drugs induced arrhythmias and these appeared to be related to either sodium channel blockade, which resulted in a double atrial beat for each ventricular beat, or IKr/hERG blockade, which caused irregular atrial and ventricular beats. However, it is difficult to make a precise prediction of the effect of a drug on the embryonic heart just by looking at the polypharmacological action on ion channels. The results indicate that the use of the tested drugs during pregnancy could potentially damage the embryo by causing periods of hypoxia. In general, the effects on the embryonic heart were only seen at concentrations greater than those likely to occur with normal therapeutic dosing.

  • 42.
    Abelo, A
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Eriksson, UG
    Karlsson, MO
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Larsson, H
    Gabrielsson, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    A turnover model of irreversible inhibition of gastric acid secretion byomeprazole in the dog.2000In: J Pharmacol Exp Ther, Vol. 295, p. 662-Article in journal (Refereed)
  • 43.
    Abelo, A
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Gabrielsson, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Holstein, B
    Eriksson, UG
    Holmberg, J
    Karlsson, MO
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Pharmacodynamic modelling of reversible gastric acid pump inhibition indog and man.2001In: Eur J Pharm Sci, Vol. 14, p. 339-Article in journal (Refereed)
  • 44.
    Abelo, A
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Holstein, B
    Eriksson, UG
    Gabrielsson, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Karlsson, MO
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Gastric acid secretion in the dog: a mechanism-based pharmacodynamic modelfor histamine stimulation and irreversible inhibition by omeprazole.2002In: J Pharmacokinet Pharmacodyn, Vol. 29, p. 365-Article in journal (Refereed)
  • 45.
    Abiri, Pojan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Användandet av webbsajten Sil Online – Svenska informationstjänster för läkemedel: En enkät- och intervjustudie2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Introduktion: Sil, Svenska informationstjänster för läkemedel, tillhandahåller kvalitetssäkrad läkemedelsinformation till aktörer inom hälso- och sjukvård. Sil Online (www.silonline.se) möjliggör åtkomsten till informationen i Sil databasen.

    Syfte: Att utvärdera vilka som är användare av Sil Online, i vilket ändamål användningen sker samt vilken information som söks på Sil Online för att skapa underlag för framtidsutveckling av webbsajten.

    Material och metoder: En deskriptiv tvärsnittsstudie bestående av en kvantitativ webbenkätundersökning (tidsperiod: 2015-03-05 till 2015-04-02) och en kvalitativ intervjuerundersökning bland frivilliga respondenter på webbenkäten.

    Resultat: Den största användargruppen bland respondenterna av webbenkäten var farmacevter (67 %), följt av systemutvecklare (16 %) varav majoriteten (43 %) jobbade inom hälso- och sjukvård eller förvaltning och administration inom landsting och kommuner (24 %). Aktuell läkemedelsinformation söktes av majoriteten av användarna (78 %) och mer än hälften (77 %) tyckte att det var lätt att hitta på webbsajten. Intervjurespondenterna saknade information om syftet med Sil Online men tyckte att det var en informativ sajt med unik information om licensläkemedel och listor med landstingens rekommenderade läkemedel. Tydligare instruktioner skulle förbättra användarvänlighet och marknadsföring skulle vidga användarkretsen.

    Konklusion: Sil Online upplevs vara en användarvänlig och informativ webbsajt. Studien visar att det finns potential för utveckling inom presentation och marknadsföring av webbsajten.

  • 46.
    Abood, Ekhlas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Identifying Medication History Errors at Iraqi Hospital Admissions Using The Swedish-LIMM model2016Independent thesis Advanced level (degree of Master (One Year)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    Abstract

    Background and Objective: An accurate medication history list is an integral part of the patient assessment at hospital admission. The objective of the study was to describe the frequency, type, and predictors of unintentional medication errors and to evaluate the quality of the clinical pharmacy services focusing on the acceptance of the recommendations made by the clinical pharmacist.

    Setting and methods: A descriptive study was conducted at two internal medicine wards at Baghdad Teaching Hospital in Iraq using Lund Integrated Medicines Management (LIMM)-based medication reconciliation. The study pharmacist conducted medication interviews for patients shortly after hospital admission to obtain the most accurate pre-admission medication history list. This list was compared with the medication list in the patient’s medical chart. Intended addition, withdrawal of a drug, or changes to the dose/ dosage form in the patient’s medical list was considered as medication discrepancies. However, medication discrepancies were considered as medication errors based on no identified clinical reason.

    Results: A total of 114 patients were included in this study. Over two-thirds of the study patients (73.7%) experienced 215 medication errors identified by a clinical pharmacist conducting medication reconciliation. Most errors were omission (87.9%). Cardiovascular agents followed by NSAID were commonly in error (53%) and (10.2%) respectively. In a logistic regression model, age (odds ratio (OR), 1.055: 95% confidence interval (CI) 1.010 - 1.102), female gender (OR, 3.468: 95% CI 1.232- 9.761) and number of medications at admission (OR, 0.810: 95% CI 0.681-0.963) were predictors for medication history errors at admission.

    Conclusions: Medication errors at the time of hospital admission are common and undetected.  A structured approach like the LIMM-based medication reconciliation at Iraqi hospital is needed to detect these errors.

    Download full text (pdf)
    Abstract
  • 47.
    Abosedera, Dalia A.
    et al.
    Univ Sadat City, Environm Studies & Res Inst, Dept Nat Resources, Sadat City, Egypt..
    Emara, S. A.
    Univ Sadat City, Fac Vet Med, Dept Cytol & Histol, Sadat City, Egypt..
    Tamam, Omar A. S.
    Univ Sadat City, Environm Studies & Res Inst, Dept Nat Resources, Sadat City, Egypt..
    Badr, Osama M.
    Univ Sadat City, Anim Biotechnol Dept, Genet Engn & Biotechnol Inst GEBRI, Sadat City, Egypt..
    Khalifa, Shaden A. M.
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden..
    El-Seedi, Hesham
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. BJiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China.;Jiangsu Univ, Jiangsu Educ Dept, Int Joint Res Lab Intelligent Agr & Agriprod Proc, Zhenjiang, Jiangsu, Peoples R China.;Menoufia Univ, Fac Sci, Dept Chem, Menoufia 32511, Egypt..
    Refaey, Mohamed S.
    Univ Sadat City, Fac Pharm, Dept Pharmacognosy, Menoufia 32897, Egypt..
    Metabolomic profile and in vitro evaluation of the cytotoxic activity of Asphodelus microcarpus against human malignant melanoma cells A3752022In: Arabian Journal of Chemistry, ISSN 1878-5352, E-ISSN 1878-5379 , Vol. 15, no 10, article id 104174Article in journal (Refereed)
    Abstract [en]

    Melanoma is a huge worldwide health problem that must be handled more effectively with better therapeutic options. As a result, new treatment drugs are required to treat this condition. The goal of this study was to investigate the cytotoxic activity of the anthraquinone-rich fractions obtained from Asphodelus microcarpus against human melanoma cell A375. On these melanoma cell lines; the cytotoxicity of these fractions had never been studied before. Liquid chromatography linked to mass spectrometry (LC-MS-MS) and Nuclear Magnetic Resonance was used to determine the chemical profiles of these fractions. The cytotoxicity of the fractions studied was determined by measuring cell viability and calculating IC50 values. Both ethyl acetate (EtOAC) and the precipitate fractions (PPT) exhibited selective cytotoxicity on human melanoma A 375 cell line with IC50 values of 83 and 65 mu g/mL, respectively. The antiproliferative properties of EtOAc fraction and PPT were supported by a noticeable decrease in cell numbers during the G2/M cell cycle arrest. Our findings suggest that the anthraquinone content of A. microcarpus tubers is responsible for its anti-proliferative and apoptotic properties and that further in vivo investigations should be conducted to establish the viability of using them to treat human melanomas.

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    fulltext
  • 48.
    Abouzayed, Ayman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Theranostic Targeting of GRPR and PSMA in Prostate Cancer2023Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is based on five original articles that investigated the theranostics of prostate cancer by gastrin-releasing peptide receptor (GRPR) and prostate-specific membrane antigen (PSMA) targeting. GRPR and PSMA are two extensively evaluated prostate cancer cell markers due to their overexpression in the majority of prostate cancer samples. Theranostic targeting of GRPR and PSMA is an attractive strategy to improve the management of prostate cancer patients.

    Papers I and II focused on the dual targeting of GRPR and PSMA. The effect of linker modification on the affinity for GRPR and PSMA and the pharmacokinetic profile was evaluated. In Paper III, the effect of the GRPR antagonist RM26 conjugation to an albumin-binding domain on the pharmacokinetic profile and its potential use in therapy was investigated. Paper IV focused on developing a GRPR antagonist that was suitable for single-photon emission computed tomography (SPECT) using technetium-99m. In Paper V, the GRPR antagonist developed in Paper IV was translated into a phase I clinical trial to assess safety and dosimetry.

    Modifying the linkers in GRPR and PSMA heterodimers can largely impact the affinity for both targets. This modification influenced the in vivo targeting specificity and biodistribution, with [125I]I-BO530 in Paper I and [111In]In-BQ7812 in Paper II outperforming other analogues. Our findings in Paper III indicated that the conjugation of an albumin-binding domain to RM26 increased the blood concentration of the radiotracer. This increase led to elevated and stable tumour uptake of [111In]In-DOTA-ABD-RM26 after several days of injection. However, [111In]In-DOTA-ABD-RM26 was also increasingly taken up by various healthy organs. The GRPR antagonist [99mTc]Tc-maSSS-PEG2-RM26, studied in Paper IV, showed high specificity and affinity for GRPR. This resulted in elevated GRPR-mediated uptake. Additionally, maSSS-PEG2-RM26 could be radiolabelled via a straightforward radiolabelling protocol. Clinical evaluation of [99mTc]Tc-maSSS-PEG2-RM26 in prostate and breast cancer patients (Paper V) demonstrated the safety and tolerability of the radiotracer, with favourable dosimetry and no side effects.

    In conclusion, this thesis evaluated different tools for the theranostic targeting of GRPR and PSMA. The findings warrant further investigation to optimise the reported radiotracers.

    List of papers
    1. Synthesis and Preclinical Evaluation of Radio-Iodinated GRPR/PSMA Bispecific Heterodimers for the Theranostics Application in Prostate Cancer
    Open this publication in new window or tab >>Synthesis and Preclinical Evaluation of Radio-Iodinated GRPR/PSMA Bispecific Heterodimers for the Theranostics Application in Prostate Cancer
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    2019 (English)In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 11, no 7, article id 358Article in journal (Refereed) Published
    Abstract [en]

    Gastrin-releasing peptide receptor (GRPR) and prostate-specific membrane antigen (PSMA) are overexpressed in most prostate cancers. GRPR expression is higher in early stages while PSMA expression increases with progression. The possibility of targeting both markers with a single theranostics radiotracer could improve patient management. Three GRPR/PSMA-targeting bispecific heterodimers (urea derivative PSMA-617 and bombesin-based antagonist RM26 linked via X-triazolyl-Tyr-PEG2, X = PEG2 (BO530), (CH2)(8) (BO535), none (BO536)) were synthesized by solid-phase peptide synthesis. Peptides were radio-iodinated and evaluated in vitro for binding specificity, cellular retention, and affinity. In vivo specificity for all heterodimers was studied in PC-3 (GRPR-positive) and LNCaP (PSMA-positive) xenografts. [I-125]I-BO530 was evaluated in PC-3pip (GRPR/PSMA-positive) xenografts. Micro single-photon emission computed tomography/computed tomography (microSPECT/CT) scans were acquired. The heterodimers were radiolabeled with high radiochemical yields, bound specifically to both targets, and demonstrated high degree of activity retention in PC-3pip cells. Only [I-125]I-BO530 demonstrated in vivo specificity to both targets. A biodistribution study of [I-125]I-BO530 in PC-3pip xenografted mice showed high tumor activity uptake (30%-35%ID/g at 3 h post injection (pi)). Activity uptake in tumors was stable and exceeded all other organs 24 h pi. Activity uptake decreased only two-fold 72 h pi. The GRPR/PSMA-targeting heterodimer [I-125]I-BO530 is a promising agent for theranostics application in prostate cancer.

    Keywords
    prostate cancer, GRPR, PSMA, bispecific heterodimers, theranostics, radio-iodine
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-393138 (URN)10.3390/pharmaceutics11070358 (DOI)000478995100060 ()31340483 (PubMedID)
    Funder
    Swedish Research Council, 2015-02509Swedish Research Council, 2015-02353Swedish Cancer Society, CAN 2017/425Swedish Cancer Society, CAN2015/350Swedish Cancer Society, CAN 2018/436
    Available from: 2019-09-23 Created: 2019-09-23 Last updated: 2023-05-06Bibliographically approved
    2. Heterodimeric Radiotracer Targeting PSMA and GRPR for Imaging of Prostate Cancer-Optimization of the Affinity towards PSMA by Linker Modification in Murine Model
    Open this publication in new window or tab >>Heterodimeric Radiotracer Targeting PSMA and GRPR for Imaging of Prostate Cancer-Optimization of the Affinity towards PSMA by Linker Modification in Murine Model
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    2020 (English)In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 12, no 7, article id 614Article in journal (Refereed) Published
    Abstract [en]

    Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) are promising targets for molecular imaging of prostate cancer (PCa) lesions. Due to the heterogenic overexpression of PSMA and GRPR in PCa, a heterodimeric radiotracer with the ability to bind to both targets could be beneficial. Recently, our group reported the novel heterodimer BQ7800 consisting of a urea-based PSMA inhibitor, the peptide-based GRPR antagonist RM26 and NOTA chelator. The study reported herein, aimed to improve the affinity of BQ7800 towards PSMA by changing the composition of the two linkers connecting the PSMA- and GRPR-targeting motifs. Three novel heterodimeric analogues were synthesized by incorporation of phenylalanine in the functional linker of the PSMA-binding motif and/or shortening the PEG-linker coupled to RM26. The heterodimers were labeled with indium-111 and evaluated in vitro. In the competitive binding assay, BQ7812, featuring phenylalanine and shorter PEG-linker, demonstrated a nine-fold improved affinity towards PSMA. In the in vivo biodistribution study of [In-111]In-BQ7812 in PC3-pip tumor-bearing mice (PSMA and GRPR positive), the activity uptake was two-fold higher in the tumor and three-fold higher in kidneys than for [In-111]In-BQ7800. Herein, we showed that the affinity of a bispecific PSMA/GRPR heterodimer towards PSMA could be improved by linker modification.

    Place, publisher, year, edition, pages
    MDPI, 2020
    Keywords
    prostate cancer, PSMA, GRPR, heterodimer, molecular imaging, SPPS
    National Category
    Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-420766 (URN)10.3390/pharmaceutics12070614 (DOI)000556488600001 ()32630176 (PubMedID)
    Funder
    Swedish Research Council, 2019-00986Swedish Cancer Society, 2017/425
    Available from: 2020-10-06 Created: 2020-10-06 Last updated: 2023-05-06Bibliographically approved
    3. Preclinical Evaluation of the GRPR-Targeting Antagonist RM26 Conjugated to the Albumin-Binding Domain for GRPR-Targeting Therapy of Cancer
    Open this publication in new window or tab >>Preclinical Evaluation of the GRPR-Targeting Antagonist RM26 Conjugated to the Albumin-Binding Domain for GRPR-Targeting Therapy of Cancer
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    2020 (English)In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 12, no 10, article id 977Article in journal (Refereed) Published
    Abstract [en]

    The targeting of gastrin-releasing peptide receptors (GRPR) was recently proposed for targeted therapy, e.g., radiotherapy. Multiple and frequent injections of peptide-based therapeutic agents would be required due to rapid blood clearance. By conjugation of the GRPR antagonist RM26 (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) to an ABD (albumin-binding domain), we aimed to extend the blood circulation of peptides. The synthesized conjugate DOTA-ABD-RM26 was labelled with indium-111 and evaluated in vitro and in vivo. The labelled conjugate was stable in PBS and retained specificity and its antagonistic function against GRPR. The half-maximal inhibitory concentration (IC50) of In-nat-DOTA-ABD-RM26 in the presence of human serum albumin was 49 +/- 5 nM. [In-111]In-DOTA-ABD-RM26 had a significantly longer residence time in blood and in tumors (without a significant decrease of up to 144 h pi) than the parental RM26 peptide. We conclude that the ABD-RM26 conjugate can be used for GRPR-targeted therapy and delivery of cytotoxic drugs. However, the undesirable elevated activity uptake in kidneys abolishes its use for radionuclide therapy. This proof-of-principle study justified further optimization of the molecular design of the ABD-RM26 conjugate.

    Place, publisher, year, edition, pages
    MDPI, 2020
    Keywords
    prostate cancer, gastrin-releasing peptide receptor, RM26, albumin-binding domain, targeted therapy, gastrin-releasing peptide receptors (GRPR) antagonist
    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-425851 (URN)10.3390/pharmaceutics12100977 (DOI)000585297400001 ()33081166 (PubMedID)
    Funder
    Vinnova, 2019/00104Swedish Cancer Society, CAN 2017/425Swedish Cancer Society, 2018/436Swedish Cancer Society, 19 0212 Pj 01HSwedish Research Council, 2019-00986Swedish Research Council, 2015-02353Swedish Research Council, 2016-05207
    Note

    De två första författarna delar förstaförfattarskapet.

    De två sista författarna delar sistaförfattarskapet.

    Available from: 2020-11-23 Created: 2020-11-23 Last updated: 2023-05-06Bibliographically approved
    4. Preclinical Evaluation of 99mTc-Labeled GRPR Antagonists maSSS/SES-PEG2-RM26 for Imaging of Prostate Cancer
    Open this publication in new window or tab >>Preclinical Evaluation of 99mTc-Labeled GRPR Antagonists maSSS/SES-PEG2-RM26 for Imaging of Prostate Cancer
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    2021 (English)In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 13, no 2, article id 182Article in journal (Refereed) Published
    Abstract [en]

    Background: Gastrin-releasing peptide receptor (GRPR) is an important target for imaging of prostate cancer. The wide availability of single-photon emission computed tomography/computed tomography (SPECT/CT) and the generator-produced 99mTc can be utilized to facilitate the use of GRPR-targeting radiotracers for diagnostics of prostate cancers.

    Methods: Synthetically produced mercaptoacetyl-Ser-Ser-Ser (maSSS)-PEG2-RM26 and mercaptoacetyl-Ser-Glu-Ser (maSES)-PEG2-RM26 (RM26 = d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) were radiolabeled with 99mTc and characterized in vitro using PC-3 cells and in vivo, using NMRI or PC-3 tumor bearing mice. SPECT/CT imaging and dosimetry calculations were performed for [99mTc]Tc-maSSS-PEG2-RM26.

    Results: Peptides were radiolabeled with high yields (>98%), demonstrating GRPR specific binding and slow internalization in PC-3 cells. [99mTc]Tc-maSSS-PEG2-RM26 outperformed [99mTc]Tc-maSES-PEG2-RM26 in terms of GRPR affinity, with a lower dissociation constant (61 pM vs 849 pM) and demonstrating higher tumor uptake. [99mTc]Tc-maSSS-PEG2-RM26 had tumor-to-blood, tumor-to-muscle, and tumor-to-bone ratios of 97 ± 56, 188 ± 32, and 177 ± 79, respectively. SPECT/CT images of [99mTc]Tc-maSSS-PEG2-RM26 clearly visualized the GRPR-overexpressing tumors. The dosimetry estimated for [99mTc]Tc-maSSS-PEG2-RM26 showed the highest absorbed dose in the small intestine (1.65 × 10−3 mGy/MBq), and the effective dose is 3.49 × 10−3 mSv/MBq.

    Conclusion: The GRPR antagonist maSSS-PEG2-RM26 is a promising GRPR-targeting agent that can be radiolabeled through a single-step with the generator-produced 99mTc and used for imaging of GRPR-expressing prostate cancer.

    Place, publisher, year, edition, pages
    MDPI, 2021
    Keywords
    prostate cancer, gastrin-releasing peptide receptor antagonist, technetium-99m, single-photon emission computed tomography, RM26
    National Category
    Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-438735 (URN)10.3390/pharmaceutics13020182 (DOI)000622994100001 ()33573232 (PubMedID)
    Funder
    Swedish Research Council, 2019-00986Swedish Cancer Society, 2017/425Swedish Cancer Society, 20 0815 PjFSwedish Cancer Society, 20 0814 UsF
    Available from: 2021-03-29 Created: 2021-03-29 Last updated: 2024-01-15Bibliographically approved
    5. Phase I Trial of [Tc-99m]Tc-maSSS-PEG(2)-RM26, a Bombesin Analogue Antagonistic to Gastrin-Releasing Peptide Receptors (GRPRs), for SPECT Imaging of GRPR Expression in Malignant Tumors
    Open this publication in new window or tab >>Phase I Trial of [Tc-99m]Tc-maSSS-PEG(2)-RM26, a Bombesin Analogue Antagonistic to Gastrin-Releasing Peptide Receptors (GRPRs), for SPECT Imaging of GRPR Expression in Malignant Tumors
    Show others...
    2023 (English)In: Cancers, ISSN 2072-6694, Vol. 15, no 6, article id 1631Article in journal (Refereed) Published
    Abstract [en]

    The gastrin-releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PCa) and in hormone-driven breast cancer (BCa). The aim of this phase I clinical trial was to evaluate safety, biodistribution, and dosimetry after the administration of the recently developed GRPR-targeting antagonistic bombesin analogue [Tc-99m]Tc-maSSS-PEG(2)-RM26 in PCa and BCa patients. Planar and whole-body SPECT/CT imaging was performed in six PCa patients and seven BCa patients 2, 4, 6, and 24 h post the intravenous administration of 40 mu g of [Tc-99m]Tc-maSSS-PEG(2)-RM26 (600-700 MBq). No adverse events or pathological changes were observed. The rapid blood clearance of [Tc-99m]Tc-maSSS-PEG(2)-RM26 was observed with predominantly hepatobiliary excretion. The effective doses were 0.0053 +/- 0.0007 for male patients and 0.008 +/- 0.003 mSv/MBq for female patients. The accumulation of [Tc-99m]Tc-maSSS-PEG(2)-RM26 in tumors was observed in four out of six PCa and in seven out of seven BCa patients. In four BCa patients, a high uptake of the agent into the axillary lymph nodes was detected. Immunohistochemistry revealed positive GRPR expression in 60% of primary PCa, 71.4% of BCa tumors, and 50% of examined BCa lymph nodes. In conclusion, a single administration of [Tc-99m]Tc-maSSS-PEG(2)-RM26 was safe and well tolerated. [Tc-99m]Tc-maSSS-PEG(2)-RM26 SPECT may be useful for tumor detection in PCa and BCa patients, pending further studies.

    Place, publisher, year, edition, pages
    MDPI, 2023
    Keywords
    GRPR, antagonist, 99mTc, phase I trial
    National Category
    Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-500596 (URN)10.3390/cancers15061631 (DOI)000957432700001 ()36980517 (PubMedID)
    Funder
    Swedish Cancer Society, 20-0815 PjFSwedish Cancer Society, 20 0814 UsFSwedish Research Council, 2019-00986Swedish Research Council, 2022-00556
    Available from: 2023-04-21 Created: 2023-04-21 Last updated: 2023-05-06Bibliographically approved
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  • 49.
    Abouzayed, Ayman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Borin, Jesper
    KTH Royal Inst Technol, Dept Prot Sci, S-11417 Stockholm, Sweden..
    Lundmark, Fanny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Rybina, Anastasiya
    Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Med, Tomsk 634009, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia..
    Hober, Sophia
    KTH Royal Inst Technol, Dept Prot Sci, S-11417 Stockholm, Sweden..
    Zelchan, Roman
    Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Med, Tomsk 634009, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia..
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer precision medicine.
    Chernov, Vladimir
    Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Med, Tomsk 634009, Russia..
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The GRPR Antagonist [99mTc]Tc-maSSS-PEG2-RM26 towards Phase I Clinical Trial: Kit Preparation, Characterization and Toxicity2023In: Diagnostics, ISSN 2075-4418, Vol. 13, no 9, article id 1611Article in journal (Refereed)
    Abstract [en]

    Gastrin-releasing peptide receptors (GRPRs) are overexpressed in the majority of primary prostate tumors and in prostatic lymph node and bone metastases. Several GRPR antagonists were developed for SPECT and PET imaging of prostate cancer. We previously reported a preclinical evaluation of the GRPR antagonist [99mTc]Tc-maSSS-PEG2-RM26 (based on [D-Phe6, Sta13, Leu14-NH2]BBN(6-14)) which bound to GRPR with high affinity and had a favorable biodistribution profile in tumor-bearing animal models. In this study, we aimed to prepare and test kits for prospective use in an early-phase clinical study. The kits were prepared to allow for a one-pot single-step radiolabeling with technetium-99m pertechnetate. The kit vials were tested for sterility and labeling efficacy. The radiolabeled by using the kit GRPR antagonist was evaluated in vitro for binding specificity to GRPR on PC-3 cells (GRPR-positive). In vivo, the toxicity of the kit constituents was evaluated in rats. The labeling efficacy of the kits stored at 4 °C was monitored for 18 months. The biological properties of [99mTc]Tc-maSSS-PEG2-RM26, which were obtained after this period, were examined both in vitro and in vivo. The one-pot (gluconic acid, ethylenediaminetetraacetic acid, stannous chloride, and maSSS-PEG2-RM26) single-step radiolabeling with technetium-99m was successful with high radiochemical yields (>97%) and high molar activities (16–24 MBq/nmol). The radiolabeled peptide maintained its binding properties to GRPR. The kit constituents were sterile and non-toxic when tested in living subjects. In conclusion, the prepared kit is considered safe in animal models and can be further evaluated for use in clinics.

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  • 50.
    Abouzayed, Ayman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Kanellopoulos, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. NCSR Demokritos, Mol Radiopharm, INRaSTES, Athens 15310, Greece..
    Gorislav, Alisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Maina, Theodosia
    NCSR Demokritos, Mol Radiopharm, INRaSTES, Athens 15310, Greece..
    Nock, Berthold A.
    NCSR Demokritos, Mol Radiopharm, INRaSTES, Athens 15310, Greece..
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Preclinical Characterization of a Stabilized Gastrin-Releasing Peptide Receptor Antagonist for Targeted Cancer Theranostics2023In: Biomolecules, E-ISSN 2218-273X, Vol. 13, no 7, article id 1134Article in journal (Refereed)
    Abstract [en]

    Radiolabeled gastrin-releasing peptide receptor (GRPR) antagonists have shown great promise for the theranostics of prostate cancer; however, their suboptimal metabolic stability leaves room for improvements. It was recently shown that the replacement of Gly(11) with Sar(11) in the peptidic [D-Phe(6),Leu(13)-NHEt,des-Met(14)]BBN(6-14) chain stabilized the [Tc-99m]Tc-DB15 radiotracer against neprilysin (NEP). We herein present DOTAGA-PEG(2)-(Sar(11))RM26 (AU-RM26-M1), after Gly(11) to Sar(11)-replacement. The impact of this replacement on the metabolic stability and overall biological performance of [In-111]In-AU-RM26-M1 was studied using a head-to-head comparison with the unmodified reference [In-111]In-DOTAGA-PEG(2)-RM26. In vitro, the cell uptake of [In-111]In-AU-RM26-M1 could be significantly reduced in the presence of a high-excess GRPR-blocker that demonstrated its specificity. The cell uptake of both radiolabeled GRPR antagonists increased with time and was superior for [In-111]In-AU-RM26-M1. The dissociation constant reflected strong affinities for GRPR (500 pM for [In-111]In-AU-RM26-M1). [In-111]In-AU-RM26-M1 showed significantly higher stability in peripheral mice blood at 5 min pi (88 & PLUSMN; 8% intact) than unmodified [In-111]In-DOTAGA-PEG(2)-RM26 (69 & PLUSMN; 2% intact; p < 0.0001). The administration of a NEP inhibitor had no significant impact on the Sar(11)-compound (91 & PLUSMN; 2% intact; p > 0.05). In vivo, [In-111]In-AU-RM26-M1 showed high and GRPR-mediated uptake in the PC-3 tumors (7.0 & PLUSMN; 0.7%IA/g vs. 0.9 & PLUSMN; 0.6%IA/g in blocked mice) and pancreas (2.2 & PLUSMN; 0.6%IA/g vs. 0.3 & PLUSMN; 0.2%IA/g in blocked mice) at 1 h pi, with rapid clearance from healthy tissues. The tumor uptake of [In-111]In-AU-RM26-M1 was higher than for [In-111]In-DOTAGA-PEG(2)-RM26 (at 4 h pi, 5.7 & PLUSMN; 1.8%IA/g vs. 3 & PLUSMN; 1%IA/g), concordant with its higher stability. The implanted PC-3 tumors were visualized with high contrast in mice using [In-111]In-AU-RM26-M1 SPECT/CT. The Gly(11) to Sar(11)-substitution stabilized [In-111]In-DOTAGA-PEG(2)-(Sar(11))RM26 against NEP without negatively affecting other important biological features. These results support the further evaluation of AU-RM26-M1 for prostate cancer theranostics after labeling with clinically relevant radionuclides.

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