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  • 1. Abelson, K.
    et al.
    Jacobsen, K. R.
    Kalliokoski, O.
    Teilmann, C.
    Sundbom, Renée
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, J.
    Limitations of the Usefulness of Fecal Corticosterone as Biomarker for Stress in Mice2012In: Journal of the American Association for Laboratory Animal Science, ISSN 1559-6109, Vol. 51, no 5, p. 639-639Article in journal (Refereed)
  • 2.
    Abelson, Klas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Adem, Bashir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Royo, Felix
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    High plasma corticosterone levels persist during frequent automatic blood sampling in rats2005In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 19, no 5, p. 815-19Article in journal (Refereed)
    Abstract [en]

    Corticosterone levels in blood may be used as a marker of stress in rodents, provided that the blood sampling procedure itself is non-stressful. Automated blood sampling equipment (Accusampler®) allows blood sampling without any interference with the animal and might be useful as a tool for an on-line measurement of stress markers in blood. However, the impact of the blood sampling itself on the corticosterone levels in blood is unknown. The present study was designed to evaluate whether the frequency of blood sampling influences the plasma corticosterone levels in male and female rats. During anaesthesia, a catheter was placed in the jugular vein and attached to an Accusampler®. Blood samples (200 μl) were withdrawn with a high (24 samples) or low frequency (3 samples) during a six-hour period immediately after the catheter insertion. The corticosterone levels in the plasma were quantified with ELISA. The corticosterone levels persisted at high post-operation concentrations when blood was collected frequently, while the levels steadily declined significantly during low-frequency sampling. The corticosterone levels were higher in female than in male rats, but the curves were similar. The present study elucidates the importance of considering the frequency of blood withdrawal during automated blood sampling. This parameter may have an impact on the experimental results when using blood corticosterone levels as a stress marker, but also during any in vivo study where blood is collected, since high corticosterone levels may affect the normal physiology of the animals.

  • 3.
    Abelson, Klas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Undergraduate and postgraduate students' responses to mandatory courses (FELASA category C) in laboratory animal science 1997-20032005In: Internationalisation and Harmonisation of Laboratory Animal Care and Use Issues: Proceedings of the Ninth FELASA Symposium 14-17 June 2004, Nantes, France / [ed] M. R. Gamble, 2005Conference paper (Other academic)
  • 4.
    Abelson, Klas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Höglund, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats2002In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 317, no 2, p. 93-6Article in journal (Refereed)
    Abstract [en]

    The local anesthetic lidocaine suppresses different pain conditions when administered systemically. Part of the antinociceptive effect appears to be mediated via receptor mechanisms. We have previously shown that muscarinic and nicotinic agonists that produce antinociception increase the intraspinal release of acetylcholine. In the present study it was hypothesized that systemically administered lidocaine is acting through the same mechanisms as cholinergic agonists and affects the intraspinal release of acetylcholine. Microdialysis probes were placed in anesthetized rats for sampling of acetylcholine. Ten and 30 mg/kg lidocaine injected intravenously significantly increased the intraspinal release of acetylcholine. The effect of lidocaine could be reduced by pretreatment with intraspinally administered atropine or mecamylamine. Our results suggest that the antinociceptive effect produced by systemically administered lidocaine is mediated through an action on muscarinic and nicotinic receptors.

  • 5.
    Abelson, Klas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Höglund, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Intravenously administered oxotremorine and atropine, in doses known to affect pain threshold, affect the intraspinal release of acetylcholine in rats2002In: Pharmacology and Toxicology, ISSN 0901-9928, E-ISSN 1600-0773, Vol. 90, no 4, p. 187-192Article in journal (Refereed)
    Abstract [en]

    Abstract:Both systemically and intrathecally administered cholinergic agonists produce antinociception while cholinergic antagonists decrease pain threshold. The mechanism and the site of action of these substances are not known. In the present study it was hypothesized that systemically administered muscarinic agonists and antagonists modify nociceptive threshold by affecting intraspinal release of acetylcholine (ACh). Catheters were inserted into the femoral vein in rats maintained on isoflurane anaesthesia for administration of oxotremorine (10–300 μg/kg) and atropine (0.1, 10, 5000 μg/kg). Spinal microdialysis probes were placed intraspinally at approximately the C2–C5 spinal level for sampling of acetylcholine and dialysis delivery of atropine (0.1, 1, 10 nM). Additionally, the tail-flick behaviour was tested on conscious rats injected intraperitoneally with saline, atropine (10, 100 and 5000 μg/kg), or subcutaneously with oxotremorine (30, 100, 300 μg/kg). Subcutaneous administration of oxotremorine (30, 100, 300 μg/kg) significantly increased the tail-flick latency. These doses of oxotremorine dose-dependently increased the intraspinal release of acetylcholine. Intravenously administered atropine, in a dose that produced hyperalgesia (5000 μg/kg) in the tail-flick test, significantly decreased the intraspinal release of acetylcholine. Our results suggest an association between pain threshold and acetylcholine release in spinal cord. It is also suggested that an approximately 30% increase in basal ACh release produces antinociception and that a 30% decrease in basal release produces hyperalgesia.

  • 6.
    Abelson, Klas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Höglund, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    The effects of the alpha2-adrenergic receptor agonists clonidine and rilmenidine, and antagonists yohimbine and efaroxan, on the spinal cholinergic receptor system in the rat2004In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 94, no 4, p. 153-60Article in journal (Refereed)
    Abstract [en]

    Cholinergic agonists produce spinal antinociception via mechanisms involving an increased release of intraspinalacetylcholine. The cholinergic receptor system interacts with several other receptor types, such as a2-adrenergic receptors.To fully understand these interactions, the effects of various receptor ligands on the cholinergic system must be investigatedin detail. This study was initiated to investigate the effects of the a2-adrenergic receptor agonists clonidine and rilmenidineand the a2-adrenergic receptor antagonists yohimbine and efaroxan on spinal cholinergic receptors in the rat. Spinalmicrodialysis was used to measure in vivo changes of acetylcholine after administration of the ligands, with or withoutnicotinic receptor blockade. In addition, in vitro binding properties of the ligands on muscarinic and nicotinic receptorswere investigated. It was found that clonidine and rilmenidine increased, while yohimbine decreased spinal acetylcholinerelease. Efaroxan affected acetylcholine release differently depending on concentration. Nicotinic receptor blockade atten-uated the effect of all ligands. All ligands showed poor binding affinity for muscarinic receptors. On the other hand, allligands possessed affinity for nicotinic receptors. Clonidine and yohimbine binding was best fit to a one site binding curveand rilmenidine and efaroxan to a two site binding curve. The present study demonstrates that the tested a2-adrenergicreceptor ligands affect intraspinal acetylcholine release in the rat evoked by nicotinic receptor mechanisms in vivo, andthat they possess binding affinity to nicotinic receptors in vitro. The binding of a2-adrenergic receptor ligands to nicotinicreceptors might affect the intraspinal release of acetylcholine.

  • 7.
    Abelson, Klas
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Kommalage, Mahinda
    Höglund, Urban
    Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats2004In: Neuroscience Letters, ISSN 0304-3940, Vol. 368, no 1, p. 116-120Article in journal (Refereed)
  • 8.
    Abelson, Klas S. P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Fard, Shahrzad Shirazi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Nyman, Julia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Goldkuhl, Renée
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Distribution of [3H]-corticosterone in urine, feces and blood of male Sprague-Dawley rats after tail vein and jugular vein injections2009In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 23, no 3, p. 381-386Article in journal (Refereed)
    Abstract [en]

    The present study aimed to investigate the time-course and distribution of [(3)H]-corticosterone in urine, feces and blood of male Sprague-Dawley rats after intravenous administration of a low dose (1 microCi), and to investigate whether different intravenous routes of administration may affect the dynamics of excreted [(3)H]-corticosterone in the feces. One microCi [(3)H]-corticosterone was injected intravenously either through the tail vein in manually restrained rats or through a jugular vein catheter three days after surgical implantation. Urine and feces were collected at different time points over 78 h from the rats injected in the tail vein, and blood and feces were collected over 48 h from rats injected in the jugular vein. In the blood, radioactivity peaked immediately and decreased rapidly within 90 minutes. The radioactivity was excreted in urine within six h and in feces after at least 12 h. Sixty percent of the radioactivity was detected in the urine and 40% in feces during the study period of 78 h. The detected amount of radioactivity in feces was higher and displayed a more pronounced peak 12 h after injection when the substance was administered through a jugular vein catheter compared to tail vein injection. The data obtained in the present study may serve as an important benchmark when choosing time points for fecal collection for quantification of corticosterone or corticosterone metabolites as a non-invasive measure of preceding HPA-axis activation.

  • 9. Abelson, Klas S. P.
    et al.
    Jacobsen, Kirsten R.
    Sundbom, Renée
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Kalliokoski, Otto
    Hau, Jann
    Voluntary ingestion of nut paste for administration of buprenorphine in rats and mice2012In: Laboratory Animals. Journal of the Laboratory Animal Science Association, ISSN 0023-6772, E-ISSN 1758-1117, Vol. 46, no 4, p. 349-351Article in journal (Refereed)
    Abstract [en]

    An adequate analgesic strategy is important to improve the postoperative recovery and welfare of laboratory rats and mice. It is desirable that the method for administering the drug is non-invasive and stress-free. We have previously validated a method for administering buprenorphine in a nut paste for voluntary ingestion. This method has many advantages over parenteral administration. To use the method in a successful way, however, it is important to prepare and administer the mix correctly. The present paper describes in detail how to implement the method, by means of habituation, presentation, adequate concentrations and amounts of buprenorphine/nut paste, and dosage of buprenorphine to rats and mice.

  • 10.
    Carlsson, Hans-Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Lyberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Royo, Felix
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Quantification of stress sensitive markers in single fecal samples do not accurately predict excretion of these in the pig2007In: Research in Veterinary Science, ISSN 0034-5288, E-ISSN 1532-2661, Vol. 82, no 3, p. 423-428Article in journal (Refereed)
    Abstract [en]

    All feces produced during 24 h were collected from five pigs and cortisol and immunoreactive cortisol metabolites (CICM), and IgA were quantified. Within pigs, the concentrations of CICM and IgA varied extensively between random samples obtained from a single fecal dropping, and deviated in most cases significantly from the true concentration measured in total fecal output (CV 6.7-130%). The CICM and IgA contents varied considerably (CV 8.1-114%) within and between individual fecal droppings from the same pig compared to the total fecal excretion. In conclusion, single random samples could not be used to reliably quantify the total fecal concentration or excretion of CICM or IgA in pigs. Analyses of all feces collected during shorter periods than 24 h did not provide an accurate estimate of the daily excretion of CICM. Thus, the concentration of stress sensitive molecules in random single fecal samples as an indicator of animal welfare should be interpreted with prudence.

  • 11.
    Carlsson, Hans-Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Royo, Felix
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Faheem, Shaik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Tufvesson, Måns
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Separation of pair housed roosters is associated with transient increased fecal corticosterone excretion2009In: Research in Veterinary Science, ISSN 0034-5288, E-ISSN 1532-2661, Vol. 86, no 1, p. 183-187Article in journal (Refereed)
    Abstract [en]

    Immunoreactive corticosterone and corticosterone metabolites (ICCM) were quantified in excreta of permanently single housed (n=10) and permanently pair housed (n=20) roosters. The pair housed roosters were separated and single housed, and ICCM were quantified in the droppings before and during 15 days after separation. There was no statistically significant difference in ICCM excretion in the droppings between the permanently single or pair housed roosters. After separation, however, the previously pair housed roosters showed a significantly transient elevated excretion of ICCM in droppings the second day after separation indicating that the separation and relocation is associated with an activation of the hypothalamic-pituitary-adrenal axis. The excretion of ICCM in droppings was not correlated to the concentration of ICCM in droppings. It is thus important that excretion of ICCM be expressed as amount excreted per time unit since the total excretion is dependant on both concentration of ICCM and amount of droppings produced.

  • 12.
    Dahlin, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Kanui, Titus I.
    Department of Veterinary Anatomy and Physiology, University of Nairobi, Nairobi, Kenya.
    Wambugu, Stanley N.
    Department of Veterinary Anatomy and Physiology, University of Nairobi, Nairobi, Kenya.
    Abelson, Klas S. P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine. Department of Experimental Medicine, University of Copenhagen and National University Hospital, Copenhagen, Denmark.
    The Suspended Formalin Test: A Method Designed for Studying Formalin-Induced Behaviour in the Speke's Hingeback Tortoise (Kinixys spekii)2012In: Scandinavian Journal of Laboratory Animal Science, ISSN 0901-3393, Vol. 39, no 1, p. 11-15Article in journal (Refereed)
    Abstract [en]

    The present study aimed to develop a method for testing pain-related behaviour induced by formalin in theSpeke’s hingeback tortoise (Kinixys spekii). These animals retract their head and limbs into their shell whenapproached, making behavioural testing almost impossible. It was found that suspending the animals in theair, facing away from the observer, made the animals keep their limbs out of the shell. Subcutaneous injectionof formalin induced easily identifiable and quantifiable behaviours that lasted for 20 minutes. Contraryto the biphasic effect of formalin observed in rats and mice, the response in tortoises was monophasic. Thesuspended formalin test may be useful for studying nociceptive mechanisms in tortoises, which in turn willbe important for a further understanding of the nociceptive system in reptiles as well as in mammals.

  • 13.
    Dahlin, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Lam, Jenn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Astuti, Pudji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Siswanto, Harry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Abelson, Klas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Body weight and faecal corticosterone metabolite excretion in male Sprague-Dawley rats following short transportation and transfer from group-housing to single-housing2009In: Scandinavian Journal of Laboratory Animal Science, ISSN 0901-3393, Vol. 36, no 2, p. 205-213Article in journal (Refereed)
    Abstract [en]

    Body weight and faecal excretion of corticosterone metabolites (CM)   were recorded daily in 18 young male Sprague-Dawley rats from the day   they arrived at the animal facility from the breeder. The animals were   group-housed (n=3) and divided in two groups after 7 days. One group   (n=9 animals in 3 cages) was moved to another room in the facility and   the other group remained in the original holding room. After an   additional 7 days the animals which had been moved were separated and   single housed for an additional 7 days. The body weights developed   normally in all rats during the three-week period. Faecal CM excretion   appeared high immediately after the rats arrived from the breeder, and   decreased to reach significantly lower levels 6 days after arrival.   This was likely related to natural fluctuations in faecal CM output   rather than substantial stress. None of the husbandry procedures   performed during the study had any effect on faecal corticosterone   metabolite secretion compared to control. The results suggest that   neither transportation from the breeder, moving within the facility,   nor being transferred from group housing to single housing are events   stressful enough to be reflected by the parameters analysed in the   present study. However, the faecal CM excretions clearly fluctuate over   several days, which must be considered when using faecal samples for   non-invasive stress assessment.

  • 14.
    Fernström, Anna-Linnea
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Sutian, Wawan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Royo, Felix
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Westlund, Karolina
    Nilsson, T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Carlsson, Hans Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Stress in cynomolgus monkeys (Macaca fascicularis) subjected to long-distance transport and simulated transport housing conditions2008In: Stress, ISSN 1025-3890, E-ISSN 1607-8888, Vol. 11, no 6, p. 467-476Article in journal (Refereed)
    Abstract [en]

    The stress associated with transportation of non-human primates used in scientific research is an important but almost unexplored part of laboratory animal husbandry. The procedures and routines concerning transport are not only important for the animals' physical health but also for their mental health as well. The transport stress in cynomolgus monkeys (Macaca fascicularis) was studied in two experiments. In Experiment 1, 25 adult female cynomolgus monkeys were divided into five groups of five animals each that received different diets during the transport phase of the experiment. All animals were transported in conventional single animal transport cages with no visual or tactile contact with conspecifics. The animals were transported by lorry for 24 h at ambient temperatures ranging between 20 degrees C and 35 degrees C. Urine produced before, during and after transport was collected and analysed for cortisol by enzyme-linked immunosorbent assay (ELISA). All monkeys exhibited a significant increase in cortisol excretion per time unit during the transport and on the first day following transport.Although anecdotal reports concerning diet during transport, including the provision of fruits and/or a tranquiliser, was thought likely to influence stress responses, these were not corrobated by the present study. In Experiment 2, behavioural data were collected from 18 cynomolgus macaques before and after transfer from group cages to either single or pair housing, and also before and after a simulated transport, in which the animals were housed in transport cages. The single housed monkeys were confined to single transport cages and the pair housed monkeys were kept in their pairs in double size cages. Both pair housed and singly housed monkeys showed clear behavioural signs of stress soon after their transfer out of their group cages.However, stress-associated behaviours were more prevalent in singly housed animals than in pair housed animals, and these behaviours persisted for a longer time after the simulated transport housing event than in the pair housed monkeys. Our data confirm that the transport of cynomolgus monkeys is stressful and suggest that it would be beneficial for the cynomolgus monkeys to be housed and transported in compatible pairs from the time they leave their group cages at the source country breeding facility until they arrive at their final laboratory destination in the country of use.

  • 15. Gicheru, Michael
    et al.
    Jeneby, Maamun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Macharia, J.C.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Suleman, Mbaruk
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Prevalence of antibodies and cell mediated immune responce against Leishmania major in feral non-human primates from Kenya2009In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 109, no 2, p. 136-140Article in journal (Refereed)
    Abstract [en]

    In Kenya, Leishmania major is responsible for human cutaneous leishmaniasis (CL). Natural infection with L. major of a vervet monkey and experimental susceptibility of some nonhuman primates (NHPs) from Kenya has been established. However, there has been no comprehensive study of the prevalence of zoonotic CL in Kenya. And also, no investigation has been done to assess whether NHPs could be potential reservoir hosts of L. major even when the involvement of reservoir animals is obligatory in transmission of this parasite. To achieve this, wild caught Chlorocebus aethiops (Vervet monkeys n=213), Papio cynocephalus anubis (olive baboons n=101) and Cercopithecus mitis (Syke's monkeys n=64) from five geographical locations in Kenya were screened for antibodies against L. major using enzyme linked immunosorbent assay (ELISA) and Western blot (WB) analysis. From the population of C. aethiops (n=213) captured, 57 were used in lymphocyte proliferation assay. ELISA revealed a high prevalence of leishmaniasis sero conversion in olive baboons 78/101 (77.2%), vervet monkeys 129/213 (60.6%) and Sykes' monkeys 43/64 (67.2%). WB detected anti-L. major antibodies in 48.5% (49/101) of the baboons, 48% (102/213) of vervet monkeys and 37.5% (24/64) of Sykes' monkey sera. Specific proliferation of peripheral blood mononuclear cells to L. major antigen was demonstrated in 17 of the 57 (29.8%) vervet monkeys. In conclusion, the results of serological assays provide strong circumstantial evidence that CL is prevalent in five Provinces of Kenya and that Kenyan NHPs could be could be a potential reservoir hosts of L. major.

  • 16.
    Goldkuhl, Renee
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Abelson, Klas S. P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Effects of Voluntarily-ingested Buprenorphine on Plasma Corticosterone Levels, Body Weight, Water Intake, and Behaviour in Permanently Catheterised Rats2010In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 24, no 2, p. 131-135Article in journal (Refereed)
    Abstract [en]

    This study investigated the peri- and postoperative effect of pre-emptive analgesia through voluntary ingestion of buprenorphine in Nutella (R), in male Sprague-Dawley rats. An arterial catheter was inserted and the rats were connected to an automated blood sampling device (AccuSampler (R)). Blood samples were drawn up to 18 h after surgery and the plasma concentrations of corticosterone were quantified. Postoperative changes in water intake and body weight were recorded, and the behaviour of the rats was analysed during two 30-min periods. Pre-emptive oral buprenorphine treatment reduced the plasma corticosterone levels in the postoperative period, compared to controls treated with local anaesthetics. Buprenorphine-treated rats consumed more water and maintained body weight better. Behavioural observations indicated that buprenorphine changed the behaviour in non-operated rats but there was no difference in the operated rats. The present study strengthens the hypothesis that pre-emptive oral buprenorphine in Nutella is suitable for treatment of postoperative pain in rats.

  • 17.
    Goldkuhl, Renée
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Abelson, Klas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Effect of subcutaneous injection and oral voluntary ingestion of buprenorphine on post-operative serum corticosterone levels in male rats2008In: European Surgical Research, ISSN 0014-312X, E-ISSN 1421-9921, Vol. 41, no 3, p. 272-278Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adequate peri-operative analgesia may reduce post-operative stress response and improve recovery in laboratory animals. We have established a method involving repeated automated blood sampling, allowing quantification of serum corticosterone levels in rats for stress assessment without stress-inducing handling or restraint. In the present study, the effects of the commonly used route of buprenorphine administration (0.05 mg/kg injected subcutaneously) were compared with oral administration (0.4 mg/kg mixed with Nutella and orally administered by voluntary ingestion) in male Sprague-Dawley rats. METHODS: A catheter was placed in the jugular vein and attached to an Accusampler for automated blood sampling. During 96 h after surgery, blood was collected at specified time points. Pre- and post-operative body weights and water consumption were registered. RESULTS: Buprenorphine significantly suppressed levels of circulating corticosterone after the oral but not after the subcutaneous treatment. Both buprenorphine treatments had a positive impact on maintenance of body weight and water consumption, compared to the control group that received no buprenorphine. CONCLUSION: The present investigation suggests that oral voluntary ingestion ad libitum is an efficacious, convenient and non-invasive way of administering peri-operative buprenorphine to rats, as judged by corticosteroid response and effects on body weight and water consumption.

  • 18.
    Goldkuhl, Renée
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Jacobsen, Kirsten R.
    Kalliokoski, Otto
    Hau, Jann
    Abelson, Klas S. P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Plasma concentrations of corticosterone and buprenorphine in rats subjected to jugular vein catheterization2010In: Laboratory Animals. Journal of the Laboratory Animal Science Association, ISSN 0023-6772, E-ISSN 1758-1117, Vol. 44, no 4, p. 337-343Article in journal (Refereed)
    Abstract [en]

    The present study investigated the postoperative plasma concentrations of corticosterone and buprenorphine in male Wistar and Sprague-Dawley rats, treated with buprenorphine administered either through subcutaneous (SC) injection or through voluntary ingestion (VI). The animals were treated with buprenorphine for pre-emptive analgesia prior to surgical placement of a jugular catheter, followed by automated blood sampling during 96 h. Buprenorphine was administered on a regular basis throughout the experiment, and blood was collected on selected time points. Body weight was measured before and 96 h after surgery. It was found that the two rat stocks responded in a similar manner to both buprenorphine treatments, with the exception of body weight change in Wistar rats, in which body weight was reduced after SC treatment. The plasma concentration of corticosterone was significantly higher in the SC-treated animals than in the VI-treated animals during the first 18 h of the study, while plasma buprenorphine concentration was at least as high and more even over time after VI treatment. The present study shows that buprenorphine administration through VI is suitable for both Wistar and Sprague-Dawley rats, with lower stress response and higher plasma concentrations of buprenorphine than after the traditional SC route of administration.

  • 19. Jacobsen, K. R.
    et al.
    Kalliokoski, O.
    Hau, J.
    Abelson, Klas S. P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Voluntary ingestion of buprenorphine in mice2011In: Animal Welfare, ISSN 0962-7286, Vol. 20, no 4, p. 591-596Article in journal (Refereed)
    Abstract [en]

    Buprenorphine is a widely used analgesic for laboratory rodents. Administration of the drug in a desirable food item for voluntary ingestion is an attractive way to administer the drug non-invasively. However, it is vital that the animals ingest the buprenorphine-food-item mix as desired. The present study investigated how readily female and male mice (Mus musculus) of two different strains consumed buprenorphine mixed in a commercially available nut paste (Nutellac (R)), and whether variation between genders and strains would affect the subsequent serum concentrations of buprenorphine. Buprenorphine at different concentrations mixed in Nutella (R) was given to male and female C57BL/6 and BALB/c mice in a complete cross-over study. Pure Nutella or buprenorphine (1.0-3.0 mg kg(-1) bodyweight [bw]) mixed in 10 g kg(-1) bw Nutella (R) were given to the mice at 1500h. The mice were video recorded until the next morning, when blood was collected by submandibular venipuncture. The concentration of buprenorphine in the Nutella (R) mix did not affect the duration of ingestion in any of the groups. However, female mice consumed the Nutella (R) significantly faster than males. Repeated exposure significantly reduced the start time of voluntary ingestion, but not the duration of eating the mixture. These differences did not however affect the serum concentration of buprenorphine measured 17 h post administration.

  • 20.
    Jeneby, Maamun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Haemoprotozoan Parasites of Non-Human Primates in Kenya: Studies on Prevalence and Characterization of Haemoprotozoan Parasites of Wild-Caught Baboons, African Green Monkeys and Syke's Monkeys2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis reports on cross-sectional surveys aimed at detecting and characterizing haemoprotozoan parasites infecting wild free-ranging non human primates (NHPs) in Kenya, East Africa. Blood samples from olive baboons (Papio cynocephalus anubis), vervet monkeys or African green monkeys (AGMs, Chlorocebus aethiops) and Syke's monkeys (Cercopithecus mitis) from five provinces of Kenya were analyzed. The haemoprotozoan parasites survey was performed with microscopic evaluation of blood smears, serological techniques and molecular tools.

    Blood specimens and serum samples from 121 NHPs were tested for the presence of Trypanosoma brucei (Study I). Indirect antibody enzyme-linked immunosorbent assay (Ab-ELISA) detected titers of anti-T. brucei antibodies in 19% (23/121) of the sera sampled. Subsequent field-oriented latex agglutination test (LAT) detected presence of T. brucei antigens in 16% (19/121) of the sera. However, there were no active infections detected on fixed blood smears, or wet blood films. Of the 378 NHPs sera samples tested for Leishmania major exposure using Ab-ELISA, 66% had detectable anti-L. major antibodies (study II). Western blot (WB) assay detected anti-L. major antibodies in sera from 46% (175/378) of the NHPs samples. Specific proliferation of peripheral blood mononuclear cells to L. major antigen was demonstrated in 23% (17/57) of AGMs samples. Haemoprotozoan parasites, Entopolypoides macaci and Hepatocystis kochi were detected by microscopic evaluation of Giemsa-stained blood smears from 179 NHPs (study III). The prevalence rate of E. macaci was 43% in African green monkeys, 35% in Syke’s monkeys and 33% in baboons. H. kochi infection rate was 18% in African green monkeys, 23% in baboons and 25% in Syke’s monkeys. Subsequent indirect immunofluorescent antibody test (IFAT) supported the morphologic appearance of E. macaci observed by microscopy. Molecular tools were used to detect and identify haemoprotozoan parasites in wild free-ranging NHPs (study IV). Nested polymerase chain reaction (PCR) targeting Babesia β-tubulin gene detected a 22% (27/125) B. microti infections in free-ranging NHPs in Kenya. PCR also detected 22% mixed infections by Hepatocystis and Entopolypoides, 12% Hepatocystis and Babesia and 7% Entopolypoides and Babesia (study V). Phylogenetic analysis inferred from mitochondrial cytochrome b (Cyt-b) gene confirmed the presence of Hepatocystis kochi whereas analysis of 18SS rRNA gene confirmed presence of two piroplasms, Babesia sp. and Entopolypoides macaci.

    In conclusion, epidemiological results from sero-prevalence studies provide strong circumstantial evidence that some species of Kenyan NHPs are naturally exposed to L. major and T. brucei infections and could be potential reservoir hosts for these haemoparasites. Molecular diagnosis revealed the occurrence of mixed parasite infections and confirmed the circulation of Babesia and Entopolypoides species in the same populations of Kenyan NHPs.

    List of papers
    1. Sero-epizootiologic survey of Trypanosoma brucei in Kenyan nonhuman primates
    Open this publication in new window or tab >>Sero-epizootiologic survey of Trypanosoma brucei in Kenyan nonhuman primates
    2002 (English)In: Journal of zoo and wildlife medicine, ISSN 1042-7260, ISSN ISSN 1042-7260, Vol. 33, no 4, p. 337-341Article in journal (Refereed) Published
    Keywords
    nonhuman primates, Trypanosoma brucei, Kenya
    National Category
    Microbiology in the medical area
    Research subject
    Comparative Medicine
    Identifiers
    urn:nbn:se:uu:diva-150264 (URN)
    Available from: 2011-03-28 Created: 2011-03-28 Last updated: 2018-01-12
    2. Prevalence of antibodies and cell mediated immune responce against Leishmania major in feral non-human primates from Kenya
    Open this publication in new window or tab >>Prevalence of antibodies and cell mediated immune responce against Leishmania major in feral non-human primates from Kenya
    Show others...
    2009 (English)In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 109, no 2, p. 136-140Article in journal (Refereed) Published
    Abstract [en]

    In Kenya, Leishmania major is responsible for human cutaneous leishmaniasis (CL). Natural infection with L. major of a vervet monkey and experimental susceptibility of some nonhuman primates (NHPs) from Kenya has been established. However, there has been no comprehensive study of the prevalence of zoonotic CL in Kenya. And also, no investigation has been done to assess whether NHPs could be potential reservoir hosts of L. major even when the involvement of reservoir animals is obligatory in transmission of this parasite. To achieve this, wild caught Chlorocebus aethiops (Vervet monkeys n=213), Papio cynocephalus anubis (olive baboons n=101) and Cercopithecus mitis (Syke's monkeys n=64) from five geographical locations in Kenya were screened for antibodies against L. major using enzyme linked immunosorbent assay (ELISA) and Western blot (WB) analysis. From the population of C. aethiops (n=213) captured, 57 were used in lymphocyte proliferation assay. ELISA revealed a high prevalence of leishmaniasis sero conversion in olive baboons 78/101 (77.2%), vervet monkeys 129/213 (60.6%) and Sykes' monkeys 43/64 (67.2%). WB detected anti-L. major antibodies in 48.5% (49/101) of the baboons, 48% (102/213) of vervet monkeys and 37.5% (24/64) of Sykes' monkey sera. Specific proliferation of peripheral blood mononuclear cells to L. major antigen was demonstrated in 17 of the 57 (29.8%) vervet monkeys. In conclusion, the results of serological assays provide strong circumstantial evidence that CL is prevalent in five Provinces of Kenya and that Kenyan NHPs could be could be a potential reservoir hosts of L. major.

    Keywords
    Nonhuman primates, Leishmaniasis, seroprevalence, Kenya
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-105020 (URN)10.1016/j.actatropica.2008.09.020 (DOI)000262737200008 ()18983806 (PubMedID)
    Available from: 2009-05-31 Created: 2009-05-31 Last updated: 2017-12-13Bibliographically approved
    3. Enzootic simian piroplasm(Entopolypoides macaci) in wild-caught Kenyan non-human primates.
    Open this publication in new window or tab >>Enzootic simian piroplasm(Entopolypoides macaci) in wild-caught Kenyan non-human primates.
    Show others...
    2008 (English)In: Journal of medical primatology, ISSN 0047-2565, E-ISSN 1600-0684, Vol. 37, no 6, p. 329-336Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND

    Three species of non-human primates comprising African green monkeys (AGMs), (Cercopithecus aethiops, n = 89), Syke's monkeys (Cercopithecus mitis, n = 60) and olive baboons (Papio cynocephalus anubis, n = 30), were screened for Entopolypoides macaci.

    METHODS

    Observation of blood smears prepared from these animals revealed E. macaci infection rate of 42.7% in AGMs, 35% in Syke's monkeys and 33.3% in baboons.

    RESULTS

    Gender infection rate was 38.2% in females and 29% in males. Statistically, there was no significant difference in infection rates between the monkey species and sexes (P > 0.05). Subsequent indirect immuno fluorescent antibody test supported the morphological appearance of E. macaci observed by microscopy. Sera from infected animals reacted positively (1:625) with E. macaci antigen, but not to Babesia bigemina or B. bovis antigen at 1:125 titer.

    CONCLUSION

    This study has revealed high prevalence of E. macaci infection in all three widely distributed Kenyan non-human primates. With the continued use of these animals as models for human parasitic diseases, the presence of this highly enzootic parasite should be noted.

    Keywords
    C. mitis, Cercopithecus aethiops, Entopolypoides macaci, Kenya, Papio cynocephalus anubis, prevalence
    Identifiers
    urn:nbn:se:uu:diva-105008 (URN)10.1111/j.1600-0684.2008.00294.x (DOI)18507704 (PubMedID)
    Available from: 2009-05-31 Created: 2009-05-31 Last updated: 2017-12-13Bibliographically approved
    4. Prevalence of Babesia microti in free-ranging Baboons and African Green Monkeys
    Open this publication in new window or tab >>Prevalence of Babesia microti in free-ranging Baboons and African Green Monkeys
    Show others...
    2011 (English)In: Journal of Parasitology, ISSN 0022-3395, E-ISSN 1937-2345, Vol. 97, no 1, p. 63-67Article in journal (Refereed) Published
    Abstract [en]

    Babesia microti-like parasites have been reported to infect captive non-human primates (NHPs). However, studies on the prevalence of Babesia spp. in free-ranging NHPs are lacking. This investigation aimed at determining the prevalence of B. microti in wild-caught Kenyan NHPs. In total, 125 animals were studied, including 65 olive baboons (Papio cynocephalus anubis) and 60 African green monkeys ([AGMs] Chlorocebus aethiops). Nested polymerase chain reaction targeting Babesia β-tubulin genes was used to diagnose infection prevalence. Results indicated a prevalence of 22% (27/125) B. microti infection in free-ranging NHPs in Kenya. There was no statistically significant difference in B. microti infection prevalence between baboons and AGMs or male and female animals. This is the first report of the presence and prevalence of B. microti in free-ranging Kenyan NHPs.

    Keywords
    Babesia microti
    National Category
    Microbiology in the medical area
    Research subject
    Comparative Medicine
    Identifiers
    urn:nbn:se:uu:diva-150261 (URN)10.1645/GE-2391.1 (DOI)21348608 (PubMedID)
    Available from: 2011-03-28 Created: 2011-03-28 Last updated: 2018-01-12Bibliographically approved
    5. Detection and molecular characterization of haemoprotozoan parasites of wild-caught nonhuman primates in Kenya
    Open this publication in new window or tab >>Detection and molecular characterization of haemoprotozoan parasites of wild-caught nonhuman primates in Kenya
    (English)Manuscript (preprint) (Other academic)
    Keywords
    haemoprotozoan parasites, nonhuman primates, PCR, Kenya
    National Category
    Microbiology in the medical area
    Research subject
    Comparative Medicine
    Identifiers
    urn:nbn:se:uu:diva-150441 (URN)
    Available from: 2011-03-30 Created: 2011-03-30 Last updated: 2018-01-12Bibliographically approved
  • 21.
    Jeneby, Maamun
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Ngeiywa, M.
    Yole, Dorcas S.
    Mwenda, Jason M.
    Suleman, Mbaruk
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Enzootic simian piroplasm(Entopolypoides macaci) in wild-caught Kenyan non-human primates.2008In: Journal of medical primatology, ISSN 0047-2565, E-ISSN 1600-0684, Vol. 37, no 6, p. 329-336Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Three species of non-human primates comprising African green monkeys (AGMs), (Cercopithecus aethiops, n = 89), Syke's monkeys (Cercopithecus mitis, n = 60) and olive baboons (Papio cynocephalus anubis, n = 30), were screened for Entopolypoides macaci.

    METHODS

    Observation of blood smears prepared from these animals revealed E. macaci infection rate of 42.7% in AGMs, 35% in Syke's monkeys and 33.3% in baboons.

    RESULTS

    Gender infection rate was 38.2% in females and 29% in males. Statistically, there was no significant difference in infection rates between the monkey species and sexes (P > 0.05). Subsequent indirect immuno fluorescent antibody test supported the morphological appearance of E. macaci observed by microscopy. Sera from infected animals reacted positively (1:625) with E. macaci antigen, but not to Babesia bigemina or B. bovis antigen at 1:125 titer.

    CONCLUSION

    This study has revealed high prevalence of E. macaci infection in all three widely distributed Kenyan non-human primates. With the continued use of these animals as models for human parasitic diseases, the presence of this highly enzootic parasite should be noted.

  • 22.
    Jeneby, Maamun
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Suleman, Mbaruk
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Ozwara, Hastings
    Institute of Primate Research.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Detection and molecular characterization of haemoprotozoan parasites of wild-caught nonhuman primates in KenyaManuscript (preprint) (Other academic)
  • 23. Kalliokoski, Otto
    et al.
    Abelson, Klas S. P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Koch, Janne
    Boschian, Anna
    Thormose, Sarah F.
    Fauerby, Natasha
    Rasmussen, Rune S.
    Johansen, Flemming F.
    Hau, Jann
    The Effect of Voluntarily Ingested Buprenorphine on Rats Subjected to Surgically Induced Global Cerebral Ischaemia2010In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 24, no 5, p. 641-646Article in journal (Refereed)
    Abstract [en]

    The effect of perioperatively administered buprenorphine analgesia on rats subjected to surgically induced global ischaemia was assessed. Rats supplied with buprenorphine, mixed in nut paste for voluntary ingestion, displayed significant reductions in postoperative excretions of faecal corticosterone, in both magnitude and variance. This is indicative of lowered stress levels and less inter-animal metabolic variation. Although corticosterone has been reported to modulate the extent of cerebral damage, histology of coronal sections exhibited no differences in the extent of the ischaemia in buprenorphine-treated and untreated animals. A part from a slightly higher hyperthermia immediately after surgery and typical opiate-associated behaviour, the buprenorphine treatment had no apparent adverse effects on the experimental model. In contrast, the analgesic treatment improved the model by minimizing stress-associated confounding variables in the experimental animals.

  • 24. Kalliokoski, Otto
    et al.
    Jacobsen, Kirsten R.
    Hau, Jann
    Abelson, Klas S. P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Serum concentrations of buprenorphine after oral and parenteral administration in male mice2011In: The Veterinary Journal, ISSN 0007-1935, E-ISSN 1879-3606, Vol. 187, no 2, p. 251-254Article in journal (Refereed)
    Abstract [en]

    Buprenorphine is the most commonly used drug for peri-operative pain relief in laboratory rodents. The systemic concentrations of buprenorphine were measured in mice following administration intravenously (IV), subcutaneously (SC), orally by gavage and by voluntary ingestion, to determine the post-administration serum concentration of buprenorphine. Voluntarily ingested buprenorphine resulted in long-lasting high serum concentrations, as did oral gavage administration (24h serum concentration: 110ngh/mL for both routes of administration). In contrast, buprenorphine administered parenterally remained in the circulation for a substantially shorter time (24h serum concentration for IV and SC were 40ngh/mL and 30ngh/mL, respectively). This marked difference was probably due to the higher dose used for oral administration, which is regarded necessary for sufficient analgesic effect, and to the slower absorption of the oral boli, as well as saturation of the hepatic buprenorphine metabolising pathways. Voluntary ingestion of buprenorphine was found to constitute a practical way to provide laboratory mice with efficient pain relief.

  • 25.
    Kanaykina, Nadya
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuroanatomy.
    Abelson, Klas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    King, Dale
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuroanatomy.
    Liakhovitskaia, Anna
    Schreiner, Silke
    Wegner, Michael
    Kozlova, Elena N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuroanatomy.
    In vitro and in vivo effects on neural crest stem celldifferentiation by conditional activation of Runx1 short isoform and its effecton neuropathic pain behavior2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 1, p. 56-64Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Runx1, a Runt domain transcription factor, controls thedifferentiation of nociceptors that express the neurotrophin receptor Ret,regulates the expression of many ion channels and receptors, and controls thelamina-specific innervation pattern of nociceptive afferents in the spinal cord. Moreover, mice lacking Runx1 exhibit specific defects in thermal and neuropathic pain. We investigated whether conditional activation of Runx1 short isoform(Runx1a), which lacks a transcription activation domain, influencesdifferentiation of neural crest stem cells (NCSCs) in vitro and in vivo duringdevelopment and whether postnatal Runx1a activation affects the sensitivity toneuropathic pain. METHODS: We activated ectopic expression of Runx1a in cultured NCSCs using the Tet-ON gene regulatory system during the formation ofneurospheres and analyzed the proportion of neurons and glial cells originatingfrom NCSCs. In in vivo experiments we applied doxycycline (DOX) to pregnant mice (days 8-11), i.e. when NCSCs actively migrate, and examined the phenotype ofoffsprings. We also examined whether DOX-induced activation of Runx1a in adultmice affects their sensitivity to mechanical stimulation following a constrictioninjury of the sciatic nerve. RESULTS: Ectopic Runx1a expression in cultured NCSCsresulted in predominantly glial differentiation. Offsprings in which Runx1a hadbeen activated showed retarded growth and displayed megacolon, pigment defects,and dystrophic dorsal root ganglia. In the neuropathic pain model, the threshold for mechanical sensitivity was markedly increased following activation of Runx1a.CONCLUSION: These data suggest that Runx1a has a specific role in NCSCdevelopment and that modulation of Runx1a activity may reduce mechanicalhypersensitivity associated with neuropathic pain.

  • 26.
    Langoi, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Mwethera, P G
    Abelson, Klas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Farah, I O
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Reversal of ketamine/xylazine combination anesthesia by atipamezole in olive baboons (Papio anubis)2009In: Journal of medical primatology, ISSN 0047-2565, E-ISSN 1600-0684, Vol. 38, no 6, p. 404-410Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The potential of Atipamezole (ATI) to reverse Ketamine/Xylazine (KET/XYL) anesthesia in the Olive baboon (Papio anubis) was studied. METHODS: Anesthesia was induced with 10 mg/kg KET and 0.5 mg/kg XYL intramuscularly. Mean arousal time (MAT), heart rate (HR), systolic arterial blood pressure (SAP), rectal temperature, respiratory rate (RR), and hemoglobin oxygen saturation (SpO(2)) were monitored. Baboons were treated with: KET/XYL only, KET/XYL followed by 100 microg/kg ATI or by 200 microg/kg ATI administered 25 minutes after KET/XYL. RESULTS: Atipamezole rapidly reversed depressed HR and SAP (10 +/- 5.2 minutes), RR (5 +/- 2 minutes) and SpO(2) (3 +/- 6 minutes) and significantly decreased MAT (13 +/- 2.2 minutes) vs. KET/XYL alone (35 +/- 5 minutes). Emesis was absent and salivation was observed after administration of 200 microg/kg ATI only. CONCLUSIONS: Atipamezole at 100 microg/kg is sufficient for rapid and smooth reversal of KET/XYL anesthesia in the Olive baboon with minimal side effects.

  • 27.
    Maamun, Jeneby
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Suleman, Mbaruk
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Akinyi, Mercy
    Institute of Primate Reseach National Museums of Kenya.
    Ozwara, Hastings
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Kariuki, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Prevalence of Babesia microti in free-ranging Baboons and African Green Monkeys2011In: Journal of Parasitology, ISSN 0022-3395, E-ISSN 1937-2345, Vol. 97, no 1, p. 63-67Article in journal (Refereed)
    Abstract [en]

    Babesia microti-like parasites have been reported to infect captive non-human primates (NHPs). However, studies on the prevalence of Babesia spp. in free-ranging NHPs are lacking. This investigation aimed at determining the prevalence of B. microti in wild-caught Kenyan NHPs. In total, 125 animals were studied, including 65 olive baboons (Papio cynocephalus anubis) and 60 African green monkeys ([AGMs] Chlorocebus aethiops). Nested polymerase chain reaction targeting Babesia β-tubulin genes was used to diagnose infection prevalence. Results indicated a prevalence of 22% (27/125) B. microti infection in free-ranging NHPs in Kenya. There was no statistically significant difference in B. microti infection prevalence between baboons and AGMs or male and female animals. This is the first report of the presence and prevalence of B. microti in free-ranging Kenyan NHPs.

  • 28.
    Mayo, Susan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Zagon, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Royo, Felix
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Enhancement of anamnestic immunospecific antibody response in orally immunised chickens2009In: Journal of Immunological Methods, ISSN 0022-1759, Vol. 342, no 1-2, p. 58-63Article in journal (Refereed)
    Abstract [en]

    Production of immunospecific egg yolk antibodies (IgY antibodies) in egg laying hens through oral immunization is an attractive alternative to conventional antibody production in mammals for economic reasons as well as for animal welfare reasons. oral immunization results in a systemic humoral response, but oral booster immunizations lack efficiency. The aim of the present study was to develop immunization schemes in which the concentration of immunospecific IgY would increase following oral booster immunizations. Two groups of egg laying hens (5 in each group) were immunized orally (each immunization event consisted of dosing on three consecutive days) with Bovine Serum Albumin (BSA) in combination with RhinoVax (R) (RV) using different immunization schemes. A 3rd group served as a reference and received BSA emulsified in Freund's Incomplete Adjuvant (FIA) by subcutaneous injection three times and one oral dose with BSA+RV. The eggs of the chickens in this group had a significantly higher immunospecific anti BSA IgY-concentration than did any of the eggs from the orally immunized chickens. One of the immunization regimes (immunizations in weeks 1, 7 and 18) clearly included a booster effect of the immunization in week 18, demonstrating the presence of memory cells following the two initial oral immunizations. Considering that oral immunization results in approximately ten times lower concentrations of immunospecific antibodies in the egg yolk, compared to traditional subcutaneous immunization schemes, the oral immunization routines have to be further refined to compete with parenteral immunization protocols.

  • 29.
    Mayo, Susan L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Non-invasive Antibody Production in the Chicken2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The production of antibodies for analytical purposes using invasive procedures on small mammals is common practice in biomedical research. The aim of this study was to develop an efficient method for non-invasive antibody production in the chicken. This thesis presents an alternative method that eliminates the discomfort, pain and distress invoked by traditional immunization procedures on mammals by instead harvesting antibodies (IgY) from the yolk of eggs laid by orally immunized hens.

    An efficient oral immunization regime was developed by first trying out a suitable non-aggressive oral adjuvant with Bovine Serum Albumine (BSA) as the model antigen. It was found that the pegylated mono/diglyceride RhinoVax® (Softigen®) at a concentration of 20% (v/v) produced a good humoral antibody response in chickens as well as development of IgY antibodies in the egg yolk. The age of the chicken is important in order to have a proper humoral immune response. We found that chicken older than 22 days produced circulating immunospecific anti BSA-antibodies of of IgG, IgM and IgA class when orally immunized with BSA alone, whereas chickens 15 days old only produced IgM and IgA antibodies.

    This is the first report of oral immunizations with a high dose (250–300mg) of BSA in 20% RhinoVax® consisting of 3 or 5 consecutive daily doses resulting in high concentrations of immunospecific IgY antibodies in the yolk. Using this technique of three consecutive daily doses repeated after 7 weeks and after 18 weeks, a booster effect was induced after the third immunization. This is the first demonstration of a clear anamnestic immune response in orally immunized chickens. The results suggest that it may be possible to further increase the concentration of immunospecific IgY antibodies by modifying the immunization regime. It seems plausible to develop a procedure where the immunogen can be fed to the chickens as in an ordinary egg producing farm thus making antibody production not classified as an animal experiment.

    List of papers
    1. Immunospecific antibody concentration in egg yolk of chickens orally immunised with varying doses of bovine serum albumin and the mucosal adjuvant RhinoVax using different immunisation regimes
    Open this publication in new window or tab >>Immunospecific antibody concentration in egg yolk of chickens orally immunised with varying doses of bovine serum albumin and the mucosal adjuvant RhinoVax using different immunisation regimes
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    2006 (English)In: Scandinavian Journal of Laboratory Animal Science, ISSN 0901-3393, Vol. 33, no 3, p. 163-169Article in journal (Refereed) Published
    Abstract [en]

    Antibody harvested from eggs of immunised chickens, IgY, has proven to be a non-invasive alternative to antibodies purified from serum of mammals. Taking the non-invasive concept further, the development of oral immunization techniques combined with IgY harvest from chicken eggs may subsequently eliminate all regulated procedures from polyclonal antibody production. In the present study, we report the effects of varying the temporal administration mode of the antigen (immumogen) comparing dosing on three consecutive days with dosing on five consecutive days, and of incorporating a mucosal adjuvant. Two antigen doses were compared: 30 mg bovine serum albumin (BSA) and 300 mg BSA, with and without the mucosal adjuvant, RhinoVax (R), administered to laying chickens. The egg yolk of chickens dosed with BSA in combination with 20% RhinoVax (R), contained significantly higher concentrations of immunospecific IgY than did egg yolks of chickens fed with BSA without adjuvant. The most efficient dose in the RhinoVax (R)-treated groups was 300 mg BSA regardless of whether the chickens were initially immunised daily for three or five days. A 3-day dosing regime with BSA alone also induced immiumospecific IgY production. This study confirms that RhinoVax (R) is an efficient oral adjuvant. It also demonstrates the efficacy of daily immunizations on three or five consecutive days on immunospecific IgY production. The chickens received oral booster immunizations one and two months after the initial immunization. No real effect could be recorded after the second and third immunization, although the study did provide some evidence of memory based on an optimum IgY concentration recorded after the 2(nd) immunization.

    National Category
    Biomedical Laboratory Science/Technology
    Research subject
    Comparative Medicine
    Identifiers
    urn:nbn:se:uu:diva-101414 (URN)000241584200004 ()
    Available from: 2009-04-26 Created: 2009-04-26 Last updated: 2017-12-13Bibliographically approved
    2. Enhancement of anamnestic immunospecific antibody response in orally immunised chickens
    Open this publication in new window or tab >>Enhancement of anamnestic immunospecific antibody response in orally immunised chickens
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    2009 (English)In: Journal of Immunological Methods, ISSN 0022-1759, Vol. 342, no 1-2, p. 58-63Article in journal (Refereed) Published
    Abstract [en]

    Production of immunospecific egg yolk antibodies (IgY antibodies) in egg laying hens through oral immunization is an attractive alternative to conventional antibody production in mammals for economic reasons as well as for animal welfare reasons. oral immunization results in a systemic humoral response, but oral booster immunizations lack efficiency. The aim of the present study was to develop immunization schemes in which the concentration of immunospecific IgY would increase following oral booster immunizations. Two groups of egg laying hens (5 in each group) were immunized orally (each immunization event consisted of dosing on three consecutive days) with Bovine Serum Albumin (BSA) in combination with RhinoVax (R) (RV) using different immunization schemes. A 3rd group served as a reference and received BSA emulsified in Freund's Incomplete Adjuvant (FIA) by subcutaneous injection three times and one oral dose with BSA+RV. The eggs of the chickens in this group had a significantly higher immunospecific anti BSA IgY-concentration than did any of the eggs from the orally immunized chickens. One of the immunization regimes (immunizations in weeks 1, 7 and 18) clearly included a booster effect of the immunization in week 18, demonstrating the presence of memory cells following the two initial oral immunizations. Considering that oral immunization results in approximately ten times lower concentrations of immunospecific antibodies in the egg yolk, compared to traditional subcutaneous immunization schemes, the oral immunization routines have to be further refined to compete with parenteral immunization protocols.

    Keywords
    IgY antibodies, Oral immunization, Immunological memory, Animal welfare
    National Category
    Medical and Health Sciences
    Research subject
    Comparative Medicine
    Identifiers
    urn:nbn:se:uu:diva-101415 (URN)10.1016/j.jim.2008.11.017 (DOI)000264685300006 ()
    Available from: 2009-04-26 Created: 2009-04-26 Last updated: 2010-08-11Bibliographically approved
    3. Systemic immune response of young chickens orally immunized with bovine serum albumin
    Open this publication in new window or tab >>Systemic immune response of young chickens orally immunized with bovine serum albumin
    2003 (English)In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 17, no 3, p. 261-268Article in journal (Refereed) Published
    Abstract [en]

    The efficacy of oral immunization, with and without commercial adjuvants, to mount a systemic immune response in young chickens was studied. Bovine serum albumin (BSA) mixed with a pegylated C8/C10 mono/di-glyceride, (Softigen(R)), or Cholera toxin B-subunit (CTB), administered orally by gavage to 15-day-old chickens resulted in circulating immunospecific anti-BSA IgG, IgM and IgA antibodies. Continuous 5-day oral administration of BSA without adjuvant also resulted in immunospecific IgM and 1&A antibodies in the circulation of chickens first immunized at 15 days of age; and immunospecific antibodies of all three classes in chickens first immunized when they were 22 days old. IgG and IgM serum concentrations were more than 4 to 10 times higher, respectively, in CTB- and Softigen-treated chickens as compared to chickens immunized without adjuvants. The IgA response in the orally immunized chickens seemed unaffected by CTB and Softigen. The antibody concentrations in chickens immunized subcutaneously with BSA emulsified in Freund's Incomplete Adjuvant (FIA) were approximately 10 times higher than those of the chickens orally immunized using CTB and Softigen.

    Keywords
    oral immunization, cholera toxin B-subunit, pegylated C8/C10 mono/diglyce ride, softigen, IgG, IgA, IgM, bovine serum albumin, chickens, gallus domesticus, Freund's adjuvant
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-102071 (URN)000184551000011 ()12929578 (PubMedID)
    Available from: 2009-04-30 Created: 2009-04-30 Last updated: 2017-12-13Bibliographically approved
    4. Correlation between adjuvanticity and imnunogenicity of cholera toxin B subunit in orally immunised young chickens - Brief report
    Open this publication in new window or tab >>Correlation between adjuvanticity and imnunogenicity of cholera toxin B subunit in orally immunised young chickens - Brief report
    2005 (English)In: APMIS, Vol. 113, no 4, p. 284-287Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-73752 (URN)
    Available from: 2006-03-20 Created: 2006-03-20 Last updated: 2011-01-11
    5. Rhino Vax is an efficient adjuvant in oral immunization of young chickens and cholera toxin B is an effective oral primer in traditional subcutaneous immunization with Freund's incomplete adjuvant
    Open this publication in new window or tab >>Rhino Vax is an efficient adjuvant in oral immunization of young chickens and cholera toxin B is an effective oral primer in traditional subcutaneous immunization with Freund's incomplete adjuvant
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    2005 (English)In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 19, p. 375-382Article in journal (Refereed) Published
    Abstract [en]

    Forty-five approximately 50% in-bred 14-day-old White Leghorn female chickens (Gallus domesticus) originating from 11 hens were distributed into 5 treatment groups containing one sister in each treatment group. Phase 1 involved oral administration of an antigen, Bovine Serum Albumin (BSA), in combination with various adjuvant preparations, either Cholera Toxin B-subunit (CTB) and/or RhinoVax® (RV). A positive control group received BSA emulsified in Freund's Incomplete Adjuvant (FIA) by subcutaneous injection. All chickens responded with immunospecific IgA, IgM and IgG antibodies in their circulation. Classical parenteral immunisation with FIA was generally the most potent mode of antigen administration. The highest immunospecific IgG concentrations recorded in the orally-immunised chickens were in the group immunised with 20% RV as the adjuvant. The concentration in this group was approximately 5 times lower than that recorded in the FIA group. For practical egg yolk polyclonal antibody production purposes, the oral regime using 20% RV as adjuvant seems an attractive alternative to the more invasive technique of injecting the antigen in FIA emulsions. In Phase 2 all chickens were subjected to traditional subcutaneous immunisation with a new antigen, human IgG emulsified in FIA. The two groups of chickens that had received CTB orally during Phase 1 responded with significantly higher immunospecific antibody concentrations than did the other chickens, indicating that oral administration of CTB prior to traditional parenteral immunisation may have a priming effect on the humoral immune system. The immunospecific antibody response varied between the 11 families of chickens. There was no correlation between familial responsiveness to oral and subcutaneous immunisations. Families that were high responders to oral immunisation were not high responders to parenteral immunisation and vice versa.

    Keywords
    adjuvant, animal welfare, chicken, cholera toxin B, Freund's incomplete adjuvan, oral immunisation, RhinoVax®
    Identifiers
    urn:nbn:se:uu:diva-79155 (URN)15796200 (PubMedID)
    Available from: 2006-04-04 Created: 2006-04-04 Last updated: 2017-12-14Bibliographically approved
  • 30.
    Mayo, Susan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Persdotter Hedlund, Gabriella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Tufvesson, Måns
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Systemic immune response of young chickens orally immunized with bovine serum albumin2003In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 17, no 3, p. 261-268Article in journal (Refereed)
    Abstract [en]

    The efficacy of oral immunization, with and without commercial adjuvants, to mount a systemic immune response in young chickens was studied. Bovine serum albumin (BSA) mixed with a pegylated C8/C10 mono/di-glyceride, (Softigen(R)), or Cholera toxin B-subunit (CTB), administered orally by gavage to 15-day-old chickens resulted in circulating immunospecific anti-BSA IgG, IgM and IgA antibodies. Continuous 5-day oral administration of BSA without adjuvant also resulted in immunospecific IgM and 1&A antibodies in the circulation of chickens first immunized at 15 days of age; and immunospecific antibodies of all three classes in chickens first immunized when they were 22 days old. IgG and IgM serum concentrations were more than 4 to 10 times higher, respectively, in CTB- and Softigen-treated chickens as compared to chickens immunized without adjuvants. The IgA response in the orally immunized chickens seemed unaffected by CTB and Softigen. The antibody concentrations in chickens immunized subcutaneously with BSA emulsified in Freund's Incomplete Adjuvant (FIA) were approximately 10 times higher than those of the chickens orally immunized using CTB and Softigen.

  • 31.
    Mayo, Susan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Royo, Felix
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Tufvesson, Måns
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Immunospecific antibody concentration in egg yolk of chickens orally immunised with varying doses of bovine serum albumin and the mucosal adjuvant RhinoVax using different immunisation regimes2006In: Scandinavian Journal of Laboratory Animal Science, ISSN 0901-3393, Vol. 33, no 3, p. 163-169Article in journal (Refereed)
    Abstract [en]

    Antibody harvested from eggs of immunised chickens, IgY, has proven to be a non-invasive alternative to antibodies purified from serum of mammals. Taking the non-invasive concept further, the development of oral immunization techniques combined with IgY harvest from chicken eggs may subsequently eliminate all regulated procedures from polyclonal antibody production. In the present study, we report the effects of varying the temporal administration mode of the antigen (immumogen) comparing dosing on three consecutive days with dosing on five consecutive days, and of incorporating a mucosal adjuvant. Two antigen doses were compared: 30 mg bovine serum albumin (BSA) and 300 mg BSA, with and without the mucosal adjuvant, RhinoVax (R), administered to laying chickens. The egg yolk of chickens dosed with BSA in combination with 20% RhinoVax (R), contained significantly higher concentrations of immunospecific IgY than did egg yolks of chickens fed with BSA without adjuvant. The most efficient dose in the RhinoVax (R)-treated groups was 300 mg BSA regardless of whether the chickens were initially immunised daily for three or five days. A 3-day dosing regime with BSA alone also induced immiumospecific IgY production. This study confirms that RhinoVax (R) is an efficient oral adjuvant. It also demonstrates the efficacy of daily immunizations on three or five consecutive days on immunospecific IgY production. The chickens received oral booster immunizations one and two months after the initial immunization. No real effect could be recorded after the second and third immunization, although the study did provide some evidence of memory based on an optimum IgY concentration recorded after the 2(nd) immunization.

  • 32.
    Ngotho, Maina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Maina, Naomi
    Kagira, John
    Royo, Felix
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Farah, Idle O.
    Hau, Jann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    IL-10 is up regulated in early and transitional stages in vervet monkeys experimentally infected with Trypanosoma brueei rhodesiense2006In: Parasitology international, ISSN 1383-5769, E-ISSN 1873-0329, Vol. 55, no 4, p. 243-248Article in journal (Refereed)
    Abstract [en]

    IL-10 has been suggested as a possible parameter for human African trypanosomiasis stage determination. However, conclusive experimental studies have not been carried out to evaluate this, which is a prerequisite before a potential test can be validated in humans for diagnostic purposes. We used the vervet monkey model of trypanosomiasis to scrutinize IL-10 in blood and cerebrospinal fluid (CSF). Five adult males were experimentally infected with T.b. rhodesiense. The infected animals became anemic and exhibited weight loss. Parasitemia was patent after 3 days and fluctuated around 3.7 x 10(7) trypanosomes/ml throughout the experimental period. The total CSF white cell counts increased from pre-infection means around 3 cells/mu l to a peak of 30 cells/mu l, 42 days post-infection (DPI). IL-10 was not detectable (< 2 pg/ml) in serum prior to infection. IL-10 serum concentrations increased to 273 pg/ml 10 DPI coinciding with the first peak of parasitemia. Thereafter the levels declined to a mean value of 77 pg/ml 34 DPI followed by a significant rise to a second peak of 304 pg/ml (p < 0.008) 42 DPI. There was no detectable IL-10 in CSF. IL-10 synthesis is thus stimulated both in the early and transitional stages of experimental trypanosomiasis. That IL-10 is produced in early stage disease is an interesting finding unlikely to be detected in humans where it is difficult to determine the exact time of infection. The IL-10 peak observed on day 42 of infection might indicate onset of parasite neuroinvasion coinciding with a peak in white blood cell counts in the blood and CSF.

  • 33.
    Paramastri, Yasmina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Royo, Felix
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Eberova, Jitka
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Sajuthi, Dondin
    Fernström, Anna-Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Pamungkas, Joko
    Hau, Jann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Urinary and fecal immunoglobulin A, cortisol and 11-17 dioxoandrostanes, and serum cortisol in metabolic cage housed female cynomolgus monkeys (Macaca fascicularis)2007In: Journal of medical primatology, ISSN 0047-2565, E-ISSN 1600-0684, Vol. 36, no 6, p. 355-364Article in journal (Refereed)
    Abstract [en]

    Background and methods: Quantitative enzyme-immunoassays of urinary and fecal immunoglobulin A (IgA), cortisol and 11-17-dioxoandrostanes (11,17-DOA), and serum cortisol in eight metabolic-cage-housed female cynomolgus monkeys were performed. The monkeys were divided into two groups, B and NB. Group B animals were blood sampled every 6 hours, whereas Group NB animals were not handled/blood sampled. Results: