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Biomedical subjects

A K Hansen

Publications and source records attributed to A K Hansen.

At least 37 records · Page 2Linked to original sources

Marburg and Ebola virus infections in laboratory non-human primates: a literature review.

BACKGROUND AND PURPOSE: Several non-human primate species are used as laboratory animals for various types of studies. Although importation of monkeys may introduce different diseases, special attention has recently been drawn to Marburg and Ebola viruses. This review presented here discusses the potential risk of these viruses for persons working with non-human primates as laboratory animals by focusing on epidemiology, virology, symptoms, pathogenesis, natural reservoir, transmission, quarantine of non-human primates, therapy, and prevention. CONCLUSION: A total of 23 Marburg and Ebola virus outbreaks causing viral hemorrhagic fever has been reported among humans and monkeys since the first outbreak in Marburg, Germany in 1967. Most of the 1,100 human cases, with nearly 800 deaths, developed in Africa due mainly to direct and intimate contact with infected patients. Few human cases have developed after contact with non-human primates used for various scientific purposes. However, adequate quarantine should be applied to prevent human infections not only due to Marburg and Ebola viruses, but also to other infective agents. By following proper guidelines, the filovirus infection risk for people working with non-human primates during quarantine exists, but is minimal. There seems to be little risk for filovirus infections after an adequate quarantine period. Therefore, non-human primates can be used as laboratory animals, with little risk of filovirus infections, provided adequate precautions are taken.

Animals↗

[Local intra-arterial thrombolysis. Results in arterial thromboses and graft occlusions].

The purpose of this study was to evaluate the efficacy of intraarterial low-dose recombinant tissue plasminogen activator (rt-PA) in patients with acute or subacute thrombosis of the native arterial system or in an arterial artificial or venous by-pass graft. Twenty patients with 22 cases of thrombosis received intraarterial thrombolysis during the period 1.1.1995 to 31.12.1995. Ten patients (50%) achieved complete radiological thrombolysis, and in seven patients (35%) partial thrombolysis was achieved. Half of these patients required a subsequent PTA or an operation. There were only three patients (15%) where no lysis occurred. The results seemed very satisfactory and we conclude that thrombolysis should be considered as the first-choice treatment in this category of patients. The indications may be extended to patients with critical ischaemia with the introduction of the pulse-spray technique as the time to complete lysis is considerably shorter with this technique.

Evaluation Studies as Topic↗

Effects of perindopril and hydrochlorothiazide on the long-term progression of lithium-induced chronic renal failure in rats.

Administration of lithium in the diet to new-born rats induces chronic renal failure associated with hypertension, proteinuria and irreversible tubulo-interstitial morphological changes. In the present study we induced chronic renal failure by administration of lithium for 16 weeks to new-born rats, and examined the spontaneous course of this nephropathy and the effects of antihypertensive treatment with either perindopril (12 mg/kg diet) or hydrochlorothiazide (500-1000 mg/kg diet) during a 24 weeks follow up period without lithium. In the placebo group, progression to terminal uraemia occurred in all rats with severe renal failure (initial Purea > 15 mM) (10 of 18). Rats with mild-moderate renal failure (Purea 9-15 mM) showed no deterioration in renal function despite persistent systolic hypertension and irreversible structural renal changes. Perindopril normalized the blood pressure in all rats but did not prevent the progression to terminal uraemia (8 to 18). Hydrochlorothiazide partially controlled the hypertension and accellerated the progression of uraemia without increasing the mortality (7 of 17). Irrespective of treatments, the predominant quantitative structural changes (e.g. decreased volume of proximal tubular cells) showed significant correlations with the degree of renal dysfunction, but not with systolic blood pressure in the surviving rats. It is concluded that progression of lithium-induced nephropathy to terminal uraemia occurs when the nephrotoxic insult results in a more than 50% reduction of the glomerular filtration rate, judged from Purea levels. The failure of effective antihypertensive treatment with an angiotension-converting enzyme inhibitor to modify the progression suggests that in this model, systemic or glomerular hypertension may not be an important pathophysiological factor. The structural and functional deterioration observed in Li-uraemic rats during treatment with hydrochlorothiazide remains unexplained.

Animals↗

Health status of experimental pigs.

Due to the increase in the use of pigs in research, there seems to be a demand from the scientific community for an improved quality of experimental pigs. Germ-free pigs may be produced by removing fully developed foetuses aseptically from the uterus by hysterectomy and rearing them in isolators, alternatively embryo transfer may be used. Such rederived pigs may be maintained in isolators in the gnotobiotic status or gnotobiotic pigs may be used for the upstart of a breeding colony housed under conditions (i.e. a barrier) protecting them against certain agents, for which a monitoring system is operated. Different categories of barrier-bred pigs, such as, minimal disease, specific pathogen-free and microbiologically defined, are presented and differences between these categories are discussed. Basic principles of health monitoring in pigs, e.g. sample size, testing frequency and methods, are outlined. It is discussed how the lack of positive findings in health monitoring may be due to other factors than freedom from infection, e.g. treatment with antibiotics or a statistically invalid examination. Finally, the risk of infection with certain porcine agents when housing barrier-bred pigs in conventional experimental units is discussed.

Animal Diseases↗

Microbiological monitoring of laboratory pigs.

Purpose-bred minipigs, are often used as the non-rodent species in toxicology. Infections may interfere with animal experiments, and there are no scientific reasons why the non-rodent species should be of a lower microbiological quality than the rodent species. Therefore, a system for health monitoring of pigs was developed in order to raise the quality of laboratory pigs to the level of laboratory rodents. This system, which includes screening for several viruses, bacteria and ecto- and endoparasites, was used for monitoring minipigs from a barrier unit with the same standards applied to rodents units. In these pigs only rotaviruses are found, which was shown by both serological antibody detection and by detection of rotaviral antigen in faeces. In minipigs from another unit with far less hygienic protection rotaviruses were also found along with certain influenza- and coronaviruses, as well as Pasteurella spp. It is concluded, that it is possible to raise pigs of a microbiological quality comparable to the quality of rats and mice, and that advanced microbiological monitoring in pigs will reveal useful information.

Animals↗

A serological indication of the existence of a guineapig poliovirus.

Attempts were made to clarify whether laboratory guineapigs may harbour a poliovirus which, in 1911, was described as the cause of a disease called guineapig lameness. By the use of ELISA for antibodies against the poliovirus, Theiler's murine encephalomyelitis virus (TMEV), it was shown that two pet shop guineapigs suffering from lameness had extremely high titres against poliovirus, while healthy guineapigs from the same pet shop were negative. Clearly positive results were also found in 35 out of 152 laboratory guineapig sera. Positive results were found in only two out of six breeding centres, but in three out of three experimental units, all of which purchased guineapigs from one of the seropositive breeding colonies. The diseased guineapigs recovered fully after treatment with vitamins in the drinking water, a treatment used for guineapig lameness by small animal practitioners. A theory that vitamin C deficient guineapigs are, due to an impaired steroid secretion, predisposed to succumbing to infection and develop demyelinating disease similar to that in TMEV infected mice is discussed briefly. Guineapig sera were also tested serologically for other infections. Antibodies against lymphocytic choriomeningitis virus, Clostridium piliforme and Toxoplasma gondii were not found, but one breeding colony was infected with adenovirus, pneumonia virus of mice, reovirus type 3, Sendai virus, parainfluenza (simian) virus type 5 and Encephalitozoon cuniculi. Two other breeding colonies were infected with both reovirus type 3 and E. cuniculi. In all three experimental units infection with adenovirus was observed, and in two of these Sendai virus and E. cuniculi antibodies were also found. The pet shop guineapigs were infected with adenovirus, reovirus type 3 and E. cuniculi.

Animals↗

Neonatal treatment of BB rats with sulphatide delays development of diabetes but does not change incidence.

Sulphatide is a newly described autoantigen in insulin-dependent diabetes mellitus; it is present in the islets of Langerhans, and anti-sulphatide antibodies are found in diabetic patients and in spontaneously diabetic BB rats. The aim of the study was to treat neonatal BB rats with sulphatide in order to induce tolerance and thereby possibly influence later diabetes development. One hundred and twelve newborn BB rats, divided into three groups, were treated once daily during the first 6 days of life with intrathymic injections of sulphatide, galactosyl-ceramide (which is similar to sulphatide but without sulphate) or phosphate buffer alone. Although the results showed no difference in diabetes incidence among the three groups, there was a delayed onset of diabetes in the sulphatide-treated group, which developed diabetes on average at 77 +/- 1 days of age, compared to 70 +/- 2 days (p < 0.02) for the galactosyl-ceramide-treated group and 70 +/- 1 days (p < 0.01) for the buffer-treated group. The degree of insulitis and the size of islets of Langerhans were studied histologically for the diabetic animals in all three groups; there were no significant differences although the sulphatide-treated group tended to have a more normal histology. The blood glucose levels for the diabetic BB rats were similar in all three groups. Thus, neonatal treatment with the diabetic autoantigen sulphatide at the chosen dosage does not influence the incidence of diabetes, but delays the onset of disease.

Animals↗

Antibiotic treatment of nude rats and its impact on the aerobic bacterial flora.

A colony of nude rats were treated with the antibiotics ampicillin, spiramycin, sulfadoxine/trimethoprim, tetracycline, lincomycin and spectinomycin over a period of 30 weeks. The rats were monitored bacteriologically during the whole treatment period and for a period of 24 weeks after the treatment. Antibiograms of each isolated microorganism were made in vitro. The primary target, Pasteurella pneumotropica, was suppressed by the treatment, but reappeared after ending the medication. Klebsiella pneumoniae subsp. pneumoniae, never observed before the use of antibiotics in the colony, became one of the most common organisms in the colony. Furthermore, this bacterium was resistant to all antibiotics tested in vitro. Also other Enterobacteriaceae and some Streptococcaceae were propagated. Only Staphylococcus aureus seemed to have been eradicated by the treatment. It is concluded, that such antibiotic treatment does not necessarily improve the microbiological quality of the rats, and that it imposes a high risk of propagating resistant bacteria.

Animals↗

Effect of cell growth rate on expression of the anaerobic respiratory pathway operons frdABCD, dmsABC, and narGHJI of Escherichia coli.

The fumarate reductase (frdABCD), dimethyl sulfoxide (DMSO)-trimethylamine-N-oxide (TMAO) reductase (dmsABC), and nitrate reductase (narGHJI) operons in Escherichia coli encode enzymes involved in anaerobic respiration to the electron acceptors fumarate, DMSO or TMAO, and nitrate, respectively. They are regulated in response to anaerobiosis and nitrate availability. To determine how each operon is regulated in response to changes in cell growth rate and in oxygen availability, expression of frdA-lacZ, dmsA-lacZ, and narG-lacZ fusion genes was examined during continuous culture. After a change in the cell growth rate, each anaerobic electron transport pathway operon fusion responded somewhat differently. Whereas frdA-lacZ expression increased by fivefold as the growth rate decreased from 0.60 to 0.12/hour during aerobic growth, little change was seen under anaerobic conditions. In contrast, growth rate-dependent expression of narG-lacZ expression occurred under anaerobic conditions but not under aerobic conditions. Finally, dmsA-lacZ expression did not vary greatly for any of the growth rates tested. When cells were shifted from aerobic to anaerobic growth conditions, expression of each fusion increased at a moderate rate and peaked or "overshot" before reaching a new equilibrium value. This "overshoot" phenomenon was independent of the fnr gene product, which functions as a transcriptional activator of each respiratory operon during anaerobic conditions. In contrast to the moderate rate of anaerobic induction seen for narG-lacZ expression, the addition of nitrate caused a rapid induction response. The cell appears to have many ways to adjust cell respiration in response to changes in cell growth conditions.

Aerobiosis↗

Studies on the diagnosis of Tyzzer's disease in laboratory rat colonies with antibodies against Bacillus piliformis (Clostridium piliforme).

To develop a system to be used for confirming diagnosis of Tyzzer's disease in seropositive rat colonies, 38 Mol:SPRD, BB/Wor/Mol-BB, and Stroke-Prone rats suffering from megaloileitis were examined. All affected rats had been found by a systematic examination of 5-week-old male rats from barrier-protected colonies, sero-positive to Bacillus piliformis, the agent of Tyzzer's disease. The rats were evaluated by serologic testing, histologic examination of the ileum, liver, and heart (hematoxylin and eosin and Warthin-Starry staining), and immunofluorescence staining of tissue smears of the ileum and liver. The presence of B. piliformis was verified in 24 of the rats. All animals that had the agent in the liver or heart also had it in the ileum. The sensitivity of immunofluorescence staining for identification of the agent was higher than that for Warthin-Starry staining. Thirty-seven rats had histologic changes indicative of Tyzzer's disease in the liver, and 23 had histologic changes in the myocardium. All rats had a high titer of antibodies against B. piliformis. Having verified the presence of the agent, germ-free sentinels were placed in one of the colonies. These also became infected, as did germ-free sentinels caged with the infected rats outside the barrier unit. The number of sentinels infected increased with the age of the sentinels at introduction. To prove the absence of Tyzzer's disease in a seropositive colony, it is considered necessary to examine approximately 3,000 5-week-old rats for abdominal distension and demonstrate negative staining of the ileum for B. piliformis.

Animals↗

Neonatal stimulation of beta-cells reduces the incidence and delays the onset of diabetes in a barrier-protected breeding colony of BB rats.

The off-spring in a barrier maintained colony of spontaneously type 1 diabetic BB/Wor/Mol-BB rats was treated with a daily injection of either saline, forskolin, arginine, glucose or both glucose and arginine for the first six days after birth. The incidence was reduced from 88% to 72% by the neonatal stimulation with arginine and glucose in combination, which also delayed the onset time from 76.0 +/- 2.2 days to 88.1 +/- 2.3 days. No such effect was observed after stimulation with either one of the compounds. Neonatal stimulation with forskolin also delayed the onset to 87.9 +/- 3.8 days, however without reducing the incidence. A higher incidence of diabetes was observed in the barrier-protected rats taking part in this study than in an earlier study using BB rats of the same origin, but kept under conventional conditions.

Animals↗

Rederivation of rat colonies seropositive for Bacillus piliformis and the subsequent screening for antibodies.

Latent infection of rats in a breeding colony with Bacillus piliformis detectable by antibodies to the agent in an immunofluorescence assay was eliminated by a combination of traditional rederivation techniques, using animal units not previously used for rat breeding, and the use of specific disinfection procedures. The success rate was apparently correlated with the use of peracetic acid instead of aldehyde products to decontaminate the animal unit.

Animal Husbandry↗

Correlation between megaloileitis and antibodies to Bacillus piliformis in laboratory rat colonies.

Rat colonies in which antibodies to Bacillus piliformis were detected in animals examined at the age of 8 to 15 weeks were compared with rat colonies where no such antibodies were present. The seropositive colonies had a low incidence of megaloileitis in 5-week-old rats of Sprague-Dawley stock and some few inbred strains. In seronegative colonies, no megaloileitis was detected. In rats with megaloileitis, significantly high titers to B. piliformis were noted and the agents could be identified in the ileal mucosa by immunofluorescence technique.

Animals↗

Comparative evaluation of the immune status of congenitally athymic and euthymic rat strains bred and maintained at different institutes: 1. Euthymic rats.

We performed a comparative evaluation of the immune status, focused on the T-cell system, of euthymic rat strains in which the nude mutation had been introduced. From 10 institutes, we sampled 12 groups of euthymic rats at ages of 1 1/2-2 months and 1/2 year. We analyzed weight of body, spleen and thymus; antibody response and delayed-type hypersensitivity response to ovalbumin immunization; and (immuno)histopathology of spleen, lymph nodes, and lymphoid tissue along the gastrointestinal tract. In the spleen morphometric analysis was done of the periarteriolar lymphocyte sheath (using the antibody R73 recognizing the alpha beta-T-cell receptor) and of the red pulp (using the antibody ED2 recognizing red pulp macrophages). For almost all parameters tested, statistically significant differences between the groups (origin of the animals) were observed. A cluster analysis on the basis of body weight, spleen weight, and morphometric data of spleen did not yield clusters with a different composition among animals from individual groups. Based on the antibody response to ovalbumin, clustering revealed groups of "fast-and-high", "slow-and-low", and "intermediate" responders. The various groups differed in location within these clusters, i.e. the speed and extent of the immune response depends on the background euthymic strain. Considering the microbiological status assessed by serology, a variation was found both in post-infection state at entrance in the study, and in primo-infection associated with a rise in antibody concentrations during the study. These states showed no negative effect on anti-ovalbumin reactivity. Rather, the response in primo-infection to Rat Corona Virus, Sendai Virus, and Pneumonia Virus of Mice was the highest in animals clustered as "fast-and high" responders to ovalbumin.

Animals↗

Comparative evaluation of the immune status of congenitally athymic and euthymic rat strains bred and maintained at different institutes: 2. Athymic rats.

We performed a comparative evaluation of the immune status, focused on the T-cell system, in congenitally athymic rat strains. From 11 institutes around the world, we sampled 15 groups of animals at ages of 1 1/2-2 months and 1/2 year. The analysis included weight of body and spleen; antibody response and delayed-type hypersensitivity response after immunization with ovalbumin; and (immuno)histology of spleen, lymph nodes and lymphoid tissue along the gastrointestinal tract. Morphometric analysis was done for alpha beta-T-cell receptor-bearing cells in spleen tissue as a measure of the periarteriolar lymphocyte sheath; it was also done for splenic red pulp using the antibody ED2 recognizing red pulp macrophages. For almost all variables analyzed, statistically significant differences between the groups were observed. The extent of alpha beta-T-cell receptor-bearing cells in the spleen increased with age. The functioning of these cells in immunological responses can be questioned, because an immune response to ovalbumin was invariably absent. But secondary follicles with germinal centers, reflecting T-cell-dependent B-cell reactivity, were observed in lymph nodes and Peyer's patches (up to 40% and 75%, respectively, depending on the group), with a higher prevalence in older animals. A cluster analysis on the basis of body and spleen weight and composition of spleen compartments did not yield clusters with a different profile in regard to the animals' group of origin. The data presented are useful when comparing studies performed with various athymic rat strains at different institutes.

Animals↗

Postoperative hypophosphataemia and muscle function.

Muscle function tests of the triceps brachii muscle were performed before operation and on the third postoperative day in ten patients undergoing elective cholecystectomy. Electromyograms (EMGs) were recorded by surface electrodes during sustained isotonic and isometric muscle contraction with a constant force of 20 per cent of the preoperative maximal voluntary contraction. Root-mean-square of the EMG was calculated together with the neuromuscular efficiency and measures of the fatiguability. These parameters were compared with changes in the simultaneously measured serum phosphate concentrations. Mean (s.e.m.) neuromuscular efficiency measured after 32-40 s of muscle contraction decreased 14(5) per cent after operation (P less than 0.01), whereas the mean fatiguability of the muscle was unchanged. Mean serum phosphate concentration was 0.87(0.06) mmol/l before operation and 0.79(0.06) mmol/l 3 days after the operation (P greater than 0.05). Two patients developed severe postoperative hypophosphataemia (serum phosphate concentration less than 0.50 mmol/l). Postoperative muscle function deterioration was not associated with changes in the serum phosphate level (P greater than 0.10; r = 0.03). We conclude that patients undergoing cholecystectomy develop postoperative deterioration in skeletal muscle function, which is not associated with serum phosphate concentration.

Adult↗