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Skeletal actin mRNA increases in the human heart during ontogenic development and is the major isoform of control and failing adult hearts.

Expression of the two sarcomeric actins, alpha-skeletal and alpha-cardiac, is regulated in the rodent heart in response to developmental, hormonal, and hemodynamic stimuli. Little is known in man, except that both isogenes were found to be coexpressed in three adult ventricles. In this report, we investigated the isoactin mRNA composition in ventricles from 21 control patients (4 fetal, 5 juvenile, 12 adult) and from 15 patients undergoing cardiac transplantation (5 idiopathic dilated cardiomyopathies, 5 ischemic myopathies with myocardial infarcts, 5 diverse etiologies) by two different and complementary techniques: RNA dot blot analysis with specific cDNA probes, and primer extensions with an oligonucleotide common to alpha-cardiac and alpha-skeletal actins. In the case of dot blot analysis, quantification of each isoform was performed by using as standards RNA transcripts obtained from cloned human alpha-actin sequences, and the total amount of sarcomeric actin mRNA was evaluated as a function of total poly(A+)RNA. We found that both isogenes are always coexpressed, and that the isoactin pattern changes during development. In utero and in neonatal hearts, alpha-skeletal actin mRNA represents less than or equal to 20% of sarcomeric actins, it increases to 48 +/- 6% during the first decade after birth and becomes the predominant isoform of adult hearts (60.4 +/- 8.5%). The 15 adult failing hearts exhibited the same isoactin pattern as the control ones (62.84 +/- 11.06%), and there was no difference in expression between patients with dilated cardiomyopathy or ischemic heart disease. These observations demonstrate that cardiac development in man, in contrast to rodent heart, is characterized by an up-regulation of the skeletal actin gene, the expression of which does not change in hypertrophied and failing hearts, and suggest that the actin and myosin heavy chain families are independently regulated in human heart.

Actins↗

Body weight-tumor incidence correlations in long-term rodent carcinogenicity studies.

Associations between body weight and tumor incidence and among the incidences of selected site-specific tumors were examined for more than 4,000 male and female Fischer-344 rats and B6C3F1 mice in the National Toxicology Program historical control database. Incidences of certain site-specific tumors, most notably mammary gland and pituitary gland tumors in rats and liver tumors in mice, were shown to have a strong positive correlation with 52-wk body weight. Using individual animal data, logistic regression models were derived for predicting site-specific tumor incidence as a function of 52-wk body weight, age, and other factors. This association between body weight and tumor incidence can explain many of the decreased tumor incidences observed in National Toxicology Program carcinogenicity studies. Body weight differences between dosed and control groups can also mask carcinogenic effects for those sites sensitive to body weight changes. Thus, when designing long-term rodent carcinogenicity studies, measures should be taken to minimize potential body weight differences between dosed and control groups. There were a number of small but significant negative correlations among tumor incidences, reflecting primarily the lethality of the tumors in question. None of these correlations (nor the 2 small positive correlations found) are likely to have any impact on the interpretation of experimental results. However, the high negative correlation between pituitary gland and testis tumors in male Fischer-344 rats cannot be dismissed so easily, does not reflect tumor lethality, and is currently being studied further.

Animals↗

Resting energy expenditure of rats acclimated to hypergravity.

BACKGROUND: The use of centrifugation at 1 G has been advocated as a control condition during spaceflight and as a countermeasure to compensate for the adverse effects of spaceflight. Rodents are the primary animal model for the study of the effects of spaceflight and will be used in the evaluation of centrifugation as a countermeasure and means of control at 1 G during flight. HYPOTHESIS: The present study was designed to assess whether resting energy expenditure (EER) of male rats was increased in relation to the magnitude of the level of gravity to which the animals were exposed. The influence of body mass and age on resting energy expenditure (EER) of male rats (n = 42, age 40-400 d) was determined following 2 wk of acclimation to 1, 2.3, or 4.1 G. Hypergravity environments were created by centrifugation. Measurements were made at the gravity level to which the animal was acclimated and during the lights-on period. RESULTS: In rats matched for body mass (approximately 400 g), mean O2 consumption and CO2 production were higher (18% and 27%, respectively) in the 2.3- and 4.1 -G groups than controls. Mean respiratory exchange ratio (RER) increased from 0.80 to 0.87. EER was increased from 47 +/- 0.1 kcal x d(-1) at 1 G, to 57 +/- 1.5 and 58 +/- 2.2 kcal x d(-1) at 2.3 and 4.1 G, respectively. There was no difference in EER between the hypergravity groups. When age differences were considered, EER (kcal x kg(-1) x d(-1)) with increased gravity was 40% higher than at 1 G. The increase in EER was not proportional over gravity levels. CONCLUSION: Acclimation of rats to hypergravity increases their EER, dependent on body mass and age, and may alter substrate metabolism. The increase in EER was not related to the level of gravity increase.

Adaptation, Physiological↗

Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin.

OBJECTIVES: To study TRPV1 immunoreactivity in the urothelium of patients with neurogenic detrusor overactivity (NDO) before and after treatment with resiniferatoxin (RTX) and controls. Functional capsaicin TRPV1 receptors have been demonstrated in urothelial cells of rodent urinary bladder, and TRPV1-knockout mice exhibit diminished nitric oxide and stretch-evoked adenosine triphosphate release from urothelial cells. In patients with NDO, TRPV1 suburothelial nerve density is increased, which is reversed by successful treatment with intravesical RTX. However, the role of urothelial TRPV1 in human bladder disorders is unknown. METHODS: Flexible cystoscopic bladder biopsies were obtained from 14 patients with NDO before and after treatment with RTX and from 8 control patients. Using a specific antibody for immunostaining, TRPV1 immunoreactivity in the urothelium was quantified by image analysis. RESULTS: TRPV1 immunoreactivity was observed in basal and apical urothelial cells. Basal cell layer TRPV1 immunoreactivity was significantly increased in NDO compared with control bladders (P = 0.003). In 5 patients who responded clinically to RTX, basal cell layer and total urothelial TRPV1 immunoreactivity decreased significantly after treatment (P = 0.032 and P = 0.016, respectively). The decreases in the basal cell layer TRPV1 immunoreactivity after RTX were comparable to the decreases in suburothelial TRPV1 nerve fibers in the biopsies previously studied from the same patients. CONCLUSIONS: Increased urothelial TRPV1 in patients with NDO may play a role in the pathophysiology, in concert with increased TRPV1 nerve fibers. Although it is not known whether similar pathogenic mechanisms are involved in the increase of urothelial and neuronal TRPV1, both may be targeted by successful RTX therapy.

Administration, Intravesical↗

The use of cyclodialysis to limit exposure to elevated intraocular pressure in rat glaucoma models.

Elevated intraocular pressure (IOP) is the most common risk factor for glaucoma and pressure control is the goal of current clinical glaucoma therapy. Yet, recent clinical studies have documented that, even after therapeutic lowering of IOP, glaucomatous visual field loss can progress in many patients. Experimental elevation of IOP in the rat is commonly used to model human glaucomatous injury. However, there currently is no rodent model for the clinical situation of glaucomatous progression in eyes with apparently controlled IOP. The purpose of this study was to evaluate the ability of surgical cyclodialysis to produce both prolonged, non-injurious reduction of IOP in rat eyes and to stably normalize IOP in eyes with experimental pressure elevation. To perform cyclodialysis, a blunted spatula was fashioned from a hypodermic needle and used to separate a portion of the ciliary body from the sclera, opening a channel into the suprachoroidal space to allow aqueous outflow. Experimental IOP elevation was produced in rats by unilateral injection of hypertonic saline. Cyclodialysis in normal eyes resulted in an average 40 +/- 4% reduction in IOP, without marked hypotony. IOP lowering could be sustained for at least 6 months. The risk of retinal or optic nerve injury following a single cyclodialysis procedure was minimal as evidenced by unaltered levels of four injury-responsive retinal mRNAs and by normal optic nerve morphology. Cyclodialysis in eyes with experimental IOP elevation resulted in IOP normalization that was sustained for durations of 7 and 21 days in 88% and 53% of eyes, respectively. In addition, in eyes with the same cumulative dose of elevated IOP prior to the procedure, successful IOP normalization by cyclodialysis resulted in significantly less optic nerve injury than that seen in eyes in which IOP control was ineffective (p = 0.03). These studies show that cyclodialysis provides a simple, non-injurious method to reduce experimentally elevated IOP in rats that can be used to model the clinical situation of eyes previously damaged by pressure. This tool offers new opportunities for identifying and studying the molecular processes associated with glaucomatous progression and for testing potential neuroprotective therapies in a clinically relevant situation.

Animals↗

Intravenous adenosine alleviates neuropathic pain: a double blind placebo controlled crossover trial using an enriched enrolment design.

Adenosine analogs produce analgesic actions in nociceptive paradigms and alleviate manifestations of neuropathic pain in nerve injury models in rodents. In humans, previous work indicates an analgesic effect for adenosine administered intravenously in postoperative and neuropathic pain. In this double blind placebo controlled crossover trial, we used an enriched enrolment design to determine the effects of intravenous adenosine (50 microg/kg/min over 60min) on neuropathic pain. In Phase 1 of the trial, adenosine was administered in an open label manner, while in Phase 2 adenosine was administered in a double blind placebo controlled manner to 23 adenosine responders who had experienced a 30% or greater response in the open trial. Outcome measures included the McGill pain questionnaire (MPQ), which generates a pain rating index (PRI), and contains a visual analog scale (VAS) of pain intensity, the neuropathy pain scale (NPS), and a VAS for pain relief. Subjects also graded the degree of allodynia and hyperalgesia using a VAS. Adenosine led to a significant reduction in spontaneous pain according to the MPQ-PRI, the MPQ-VAS and the VAS for pain relief. The NPS showed a pattern similar to the MPQ-PRI, with statistically significant reductions in scales 1 (intensity), 3 (hot), 6 (sensitive), 7 (itchy) and 9 (unpleasant). Adenosine also led to a significant reduction in pinprick hyperalgesia, but not in allodynia. Three patients from Phase 1 of the trial experienced long term resolution of their pain following intravenous adenosine (5,16,25 months). The results of this study support previous reports that indicate intravenous adenosine alleviates neuropathic pain and hyperalgesia.

Adenosine↗

Excretion of electrolytes, free cortisol and aldosterone-18-oxo-glucuronide in 24-hr urines of the Mongolian gerbil (Meriones unguiculatus): effect of lysine-vasopressin and adrenocorticotrophin administration, and of changes in sodium balance.

1. Administration of lysine-vasopressin (LVP, 1 IU/animal) strongly reduced electrolyte excretion in 24 hr urines of adult male Mongolian gerbils, but had no effect on free cortisol (C) or aldosterone-18-oxo-glucuronide (Aldo-gluc.) excretion. 2. (1-24) ACTH, given at a dosage of 20 IU/animal, increased C and Aldo-gluc. excretion but did not influence electrolyte excretion. 3. Fluid intake and potassium excretion were decreased in animals offered a control or a sodium-deficient diet; contrasting, excretion of C was stimulated. 4. In contrast to other rodents, Aldo-gluc. excretion showed no changes in Mongolian gerbils offered a sodium-deficient diet, but was diminished in animals either fed a control diet or given saline (154 mmol/l) as drinking water.

Adrenal Cortex↗

Synaptic depolarizing GABA Response in adults is excitatory and proconvulsive when GABAB receptors are blocked.

In the presence of 4-aminopyridine, interneurons fire synchronously, causing giant GABA-mediated postsynaptic potentials (GPSPs; GPSCs in voltage clamp) in CA3 pyramidal cells in hippocampal slices from adult guinea pigs. These triphasic GPSPs are composed of a GABA(A)-mediated hyperpolarizing component, a depolarizing component, and a GABA(B)-mediated hyperpolarizing component. We propose that GABA(B) receptors exert control over the postsynaptic depolarizing GABA response. Microelectrode and cell-attached recordings demonstrated that the mean number of action potentials during the depolarizing component of the GPSP increased dramatically in the presence of the GABA(B) receptor antagonist (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2- hydroxypropyl](phenylmethyl) phosphinic acid (CGP 55845A; P = 0.003 and 0.0005, respectively). Whole cell voltage-clamp recordings showed that the postsynaptic GABA(B) and depolarizing GABA components of the GPSC overlap substantially, allowing the GABA(B)-mediated hyperpolarization to suppress the excitation mediated by the depolarizing GABA component. Further voltage-clamp recordings showed that CGP 55845A increased the duration of the depolarizing GABA component of the GPSC even when the GABA(B) component had already been blocked by internal QX-314, suggesting that CGP 55845A also increased the duration of GABA release. When glutamatergic transmission is intact, GPSPs directly precede epileptiform afterdischarges. We hypothesize that the depolarizing component of the GPSP triggers the epileptiform events and show here that enhancement of the depolarizing component with CGP 55845A increased epileptiform activity. CGP 55845A increased the likelihood of a GPSP triggering an epileptiform event from 32 to 99% (P = 0.0000001), and significantly increased the number of afterdischarges per epileptiform event (P = 0.001). Loss of GABA(B) receptor function is associated with temporal lobe epilepsy in rodents and humans. We show here that GABA(B) receptors exert control over the synaptic depolarizing GABA response and that block of GABA(B) receptors makes the depolarizing GABA response excitatory and proconvulsive.

4-Aminopyridine↗

Androgens regulate vascular endothelial growth factor content in normal and malignant prostatic tissue.

In previous studies, we have demonstrated that androgen ablation-induced growth inhibition of androgen-responsive PC-82 and A-2 human prostate cancer xenografts involves not only direct activation of programmed (apoptotic) death of these cells but also indirect activation of this death process via a decrease in tumor angiogenesis secondary to a reduction in tumor vascular endothelial growth factor (VEGF) levels. To determine whether androgens consistently regulate angiogenesis via control of VEGF levels, an additional human (i.e., LnCaP) and two rodent (i.e., Dunning G and H) androgen-sensitive prostate cancer sublines were tested. Androgen ablation causes a decrease in the subsequent growth rate of each of these three additional prostate cancer sublines, and this growth inhibition is consistently associated with a >60% reduction in tumor VEGF levels. To examine whether androgens regulate VEGF levels not only in malignant but also in normal prostatic tissue, male rats were castrated, and the temporal changes in the VEGF content of ventral prostate tissue were determined. One week after castration, VEGF content decreased to <20% within the ventral prostate. Subsequent replacement with exogenous androgen to long-term castrated rats stimulated an 8-fold rise in ventral prostate VEGF content within 1 week. To evaluate whether androgen regulation of VEGF is due to a direct effect of androgen on prostatic cells, the dose-response ability of androgens to increase VEGF levels in media of LnCaP cells grown in vitro was tested. These studies demonstrate that androgens directly stimulate VEGF secretion in these cells. The presence of 4-5-fold higher levels of VEGF in prostatic fluid versus seminal vesicle fluid obtained from benign prostatic hyperplasia and clinically localized prostate cancer patients suggests that elevated levels of VEGF may contribute to the progression of these prostatic conditions by promoting angiogenesis. In summary, one of the mechanisms for androgen sensitivity for the control of the growth of both normal and malignant prostatic tissue is via its stimulation of VEGF levels.

Androgens↗

An extracellular protein microdomain controls up-regulation of neuronal nicotinic acetylcholine receptors by nicotine.

In smoker's brain, rodent brain, and in cultured cells expressing nicotinic receptors, chronic nicotine treatment induces an increase in the total number of high affinity receptors for acetylcholine and nicotine, a process referred to as up-regulation. Up-regulation induced by 1 mm nicotine reaches 6-fold for alpha3beta2 nicotinic receptors transiently expressed in HEK 293 cells, whereas it is much smaller for alpha3beta4 receptors, offering a rationale to investigate the molecular mechanism underlying up-regulation. In this expression system binding sites are mainly intracellular, as shown by [(3)H]epibatidine binding experiments and competition with the impermeant ligand carbamylcholine. Systematic analysis of beta2/beta4 chimeras demonstrates the following. (i) The extracellular domain critically contributes to up-regulation. (ii) Only residues belonging to two beta2 segments, 74-89 and 106-115, confer up-regulation to beta4, mainly by decreasing the amount of binding sites in the absence of nicotine; on an atomic three-dimensional model of the alpha3beta2 receptor these amino acids form a compact microdomain that mainly contributes to the subunit interface and also faces the acetylcholine binding site. (iii) The beta4 microdomain is sufficient to confer to beta2 a beta4-like up-regulation. (iv) This microdomain makes an equivalent contribution to the up-regulation differences between alpha4beta2 and alpha4beta4. We propose that nicotine, by binding to immature oligomers, elicits a conformational reorganization of the microdomain, strengthening the interaction between adjacent subunits and, thus, facilitating maturation processes toward high affinity receptors. This mechanism may be central to nicotine addiction, since alpha4beta2 is the subtype exhibiting the highest degree of up-regulation in the brain.

Amino Acid Sequence↗

Hantavirus pulmonary syndrome--Panama, 1999-2000.

Hantavirus pulmonary syndrome (HPS) is an acute viral rodentborne zoonosis characterized by severe cardiopulmonary illness with a 40%-60% case-fatality rate. Since its identification in the United States in 1993, the recognized clinical spectrum of illnesses associated with human hantavirus infection has expanded to include mild illness, and case-patients have been identified in Canada and South America. This report describes the first confirmed HPS cases from Central America and summarizes preliminary results of clinical, epidemiologic, and ecologic investigations. Investigators identified 12 suspected cases with typical disease and captured four common species of rodents near case households.

Adult↗

Small intestinal submucosa: utilization as a wound dressing in full-thickness rodent wounds.

Wound dressings are used as a temporary wound covering to promote wound healing, control wound exudate, and decrease wound contamination as well as evaporative water loss. A new material, porcine small intestinal submucosa, has been used successfully as an arterial and venous graft in both canine and primate animal models with graft patency and infection rates equal to autologous vein. Based on these studies, small intestinal submucosa was used as a biological wound dressing in 20 x 20 mm full-thickness wounds made on Sprague-Dawley rats. In the controls (group I, n = 12), an acrylic frame (20 x 20 mm) was sutured to the wound edges, followed by placement of a thin polyurethane film. In the small intestinal submucosa-treated animals (group II, n = 12), the wound was covered with small intestinal submucosa and then with the acrylic frame and polyurethane film. The wounds were examined both visually and histologically at postapplication days 3, 7, 14, 28, 42 and 56. In addition, the wound contraction rate of 6 animals in both groups were recorded at postapplication day 0 and then at 1 week, 1 month, 2 months, and 3 months. Histological analysis (hematoxylin-eosin and periodic acid-Schiff stains) of the small intestinal submucosa-treated wounds revealed no host-versus-graft rejection and a rate of epithelialization equal to that of the control group. The wound contraction rate was statistically significant (higher; p < .05) in the control group compared to the small intestinal submucosa-treated group. Porcine small intestinal submucosa merits further study as both a biological wound dressing and as a substrate for cultured cells.

Animals↗

Peripheral metabolic responses to prolonged weight reduction that promote rapid, efficient regain in obesity-prone rats.

Weight regain after weight loss is the most significant impediment to long-term weight reduction. We have developed a rodent paradigm that models the process of regain after weight loss, and we have employed both prospective and cross-sectional analyses to characterize the compensatory adaptations to weight reduction that may contribute to the propensity to regain lost weight. Obese rats were fed an energy-restricted (50-60% kcal) low-fat diet that reduced body weight by 14%. This reduced weight was maintained for up to 16 wk with limited provisions of the low-fat diet. Intake restriction was then removed, and the rats were followed for 56 days as they relapsed to the obese state. Prolonged weight reduction was accompanied by 1) a persistent energy gap resulting from an increased drive to eat and a reduced expenditure of energy, 2) a higher caloric efficiency of regain that may be linked with suppressed lipid utilization early in the relapse process, 3) preferential lipid accumulation in adipose tissue accompanied by adipocyte hyperplasia, and 4) humoral adiposity signals that underestimate the level of peripheral adiposity and likely influence the neural pathways controlling energy balance. Taken together, long-term weight reduction in this rodent paradigm is accompanied by a number of interrelated compensatory adjustments in the periphery that work together to promote rapid and efficient weight regain. These metabolic adjustments to weight reduction are discussed in the context of a homeostatic feedback system that controls body weight.

Adipose Tissue↗

Transmission of Borrelia burgdorferi s.l. from mammal reservoirs to the primary vector of Lyme borreliosis, Ixodes ricinus (Acari: Ixodidae), in Sweden.

Factors regulating prevalence of Borrelia burgdorferi s.l. Johnson, Schmid, Hyde, Steigerwalt & Brenner in Ixodes ricinus (L.) were examined during 1991-1992 at Bogesund, near Stockholm in south-central Sweden. Nine species of small and medium-sized mammals (Sorex araneus L., S. minutus L., Neomys fodiens Pennant, Clethrionomys glareolus [Schreber], Microtus agrestis [L.], Apodemus sylvaticus [L.], A. flavicollis [Melchior], Lepus europaeus Pallas, L. timidus L.) were found to infect feeding tick larvae with B. burgdorferi s.l., whereas two species of large mammals (Capreolus capreolus L., Alces alces L.) failed to infect feeding tick larvae with this spirochete. The most important mammalian reservoirs at the study locality were S. araneus and rodents, accounting for 91% of all I. ricinus larvae infected. In view of the great number of potentially effective reservoirs for B. burgdorferi s.l. in Sweden, control of Lyme disease by reduction of abundance of reservoir hosts will be difficult to achieve. We also found that infectivity of a rodent species is related to the number of infesting, potentially infective nymphal I. ricinus. Insectivores and rodents were the most important hosts of larval I. ricinus, whereas most nymphal ticks fed on hares and cervids. Adult I. ricinus were frequently found on all species of hares and cervids examined but never on insectivores and rodents. No single species seemed to be of paramount importance as a source of blood for female ticks. Therefore, control of Lyme disease by reduction of abundance of mammal hosts available for female tick engorgement will probably require massive reductions of numbers of both C. capreolus and L. timidus.

Animals↗

Macrofilaricidal activity of albendazole-ivermectin combination: histopathological evaluation of adult Molinema dessetae.

The macrofilaricidal effect of albendazole in association with ivermectin was assessed in the rodent Proechimys oris, infected with Molinema dessetae. The drug combination was given to five rodents 190 days after infection. A similar group was used as control. The doses administered were 10 mg per kg for albendazole and 0.04 mg per kg for ivermectin over five days. The histological examination of intra-peritoneal nodules done six weeks after therapy revealed a clear-cut macrofilaricidal effect. The number of dead worms was significantly higher in the treated group. The histological examination revealed a lesion pattern that was related to the drug exposure. This consisted of nodules, each containing a necrotic worm that had its morphology preserved and was surrounded by a foreign body granuloma. This lesion was only seen in the treated group. A pattern related with the spontaneous death of worms was also observed. The results obtained here show the importance that albendazole-ivermectin combination could have in human filariasis therapy. Further studies in man should be done to confirm the macrofilaricidal effect of this drug combination in human filariasis.

Albendazole↗

Seasonal 4-year investigation into the role of the alpine marmot (Marmota marmota) as a carrier of zoophilic dermatophytes.

Two hundred and six samples of alpine marmot (Mamota marmota) hair (148 from adults and 58 from young subjects), 102 soil samples from the entrances to the burrows of the above individuals and 20 control specimens (obtained from adjoining areas away from the burrow systems where the rodents are not usually present) were examined from May 1994 to September 1997. Seventy-five isolates belonging to six species of dermatophytes were found in 69 of the 206 hair samples examined (33.5%). Two species were zoophilic, Microsporum canis (7.8%) and Trichophyton mentagrophytes (11.2.%), and four geophilic, Microsporum cookei (2%), M. gypseum (5.8%), Trichophyton ajelloi (3.9%) and T. terrestre (5.8%). The prevalence of each species in the hair samples did not change significantly according to year, season (chi-squared test [limit significance: P <0.05] gives no significant values [P>0.05] both in year and in season comparison) or age/sex (adult versus juvenile: P=0.1; male versus female: P=0.8) of the marmot. Twenty-three of the 102 soil samples (22.5%) were positive for dermatophytes found in the hair of marmots from the same burrow systems. Five of the 20 control soil samples (25%) were positive for dermatophytes. One isolate of M. gypseum, three of T. terrestre and one of T. mentagrophytes were obtained. Compared with other free-ranging rodent hosts studied in Europe, this mycoflora is characterized by the presence and relatively high prevalence of M. canis, frequently reported in symptomatic and asymptomatic cats, dogs and fur animals. M. canis has not been isolated in other rodents in the wild. However, it has recently been reported in asymptomatic foxes (Vulpes vulpes) from northern Italy. The close link between V vulpes and M. marmota, with the former representing the most important mammal predator of the latter in the Alps (only a fraction of the predator's attacks result in the death of the rodent) may have favoured the adaptation of M. canis to this rodent host. The stable character of the M. canis/M. marmota relationship (no seasonally or annually related difference in the prevalence of this dermatophyte has been found) suggests the inclusion of the alpine marmot in the reservoir of this zoophilic pathogenic agent. In this situation, hibernation in labyrinthine burrow systems, where temperature and moisture ranges are quite uniform the whole year round, may favour the viability of M. canis arthroconidia, whose survival in mountain habitat might otherwise be compromised. This seems to be confirmed by the fact that the fungus has never been found in the control samples collected at a distance of 300 m from the outer edge of the sampled burrow systems.

Animals↗

Developmental testing of the Advanced Animal Habitat to determine compatibility with rats and mice.

The Research Animal Holding Facility (RAHF) and the Animal Enclosure Module (AEM) have housed rats during Space Shuttle flights since the 1980s, but the operational constraints of the hardware have limited the scientific return from these Shuttle flights. The RAHF provides environmental control and monitoring for 24 rats with in-flight animal access, but it must be flown in the Spacelab. Due to the infrequent availability of Spacelab flights, rodent experiments rely heavily on the AEM. Unfortunately, the AEM supports only six rats, has no environmental control and provides no animal access in flight. The Advanced Animal Habitat (AAH) is being developed to support up to 12 adult rats or 30 adult mice for up to 30 days, provide active temperature control, animal telemetry and on-orbit video, record environmental parameters in the animal cage, and provide in-flight animal access in the Middeck, the Spacelab or the Space Station. To ensure the AAH can meet these requirements, animal testing is being conducted with rats and mice in every step of development. Testing began with the cage configuration.

Animals↗

[Epidemiology and control of rabies].

The epidemiological criteria of the present sylvatic rabies epizootic are shown using the situation in the Federal Republic of Germany and its neighbouring countries as an example. It is demonstrated that the fox plays the leading role in transmitting the disease to other animal species and remains the main vector in the epizootic. Mustelids are of secondary importance. Cervides, rodents and domestic animals are of no concern in the spread of rabies. Rabies control measures have to be aimed at the population reduction of but one species, the fox, since the frequency of rabies among this species is primarily dependent on the population density. Other wild carnivores especially badgers should be spared. Intensified shooting of foxes as a single control measure has proven ineffective. According to the results obtained in Central Europe, the gassing of fox dens, where applicable, has proven to be the best single measure regularly resulting in a decrease of rabies cases. In individual instances this has led to a complete extinction of rabies. The oral immunization of foxes is not yet regarded as acceptable; large-scale success with this method is not to be expected.

Animals↗