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PubMed2002

Population-based case-control investigation of risk factors for leptospirosis during an urban epidemic.

Between March and October 2000, 157 suspected cases of leptospirosis hospitalized with complications of Weil's syndrome and a mortality of 8% were identified in Salvador, Brazil. We conducted a population-based case-control study to identify risk factors for acquisition of leptospirosis in neighborhoods with high endemicity during the rainy season-associated urban epidemic. Sixty-six (65%) of 101 laboratory-confirmed cases and 125 age and sex-matched healthy neighborhood controls were interviewed. Residence in proximity to an open sewer (matched odds ratio [OR] = 5.15, 95% confidence interval [CI] = 1.80-14.74), peri-domiciliary sighting of rats (OR = 4.49, 95% CI = 1.57-12.83), sighting groups of five or more rats (OR = 3.90, 95% CI = 1.35-11.27), and workplace exposure to contaminated environmental sources (OR = 3.71, 95% CI = 1.35-10.17) were found to be independent risk factors for acquiring disease. Some of these risk factors are amenable to focused interventions, which include provision of closed drainage systems for sewage and reduction of rodent populations in the peri-domicilary environment. Environmental control of transmission may help to greatly reduce the incidence of severe leptospirosis.

Adolescent↗

PubMed2006

Age, intensity of infestation by flea parasites and body mass loss in a rodent host.

Parasitism by the flea Synosternus cleopatrae does not affect the body mass of its principal rodent host, Gerbillus andersoni under natural infestation levels. We hypothesized that the lack of negative effects of flea parasitism on rodent body mass could be related either to the low level of natural infestation or to the differential susceptibility of rodent age cohorts to flea parasitism. We tested these hypotheses by measuring body mass change under flea parasitism in (a) adult rodents infested with fleas above the natural infestation level (the first hypothesis) and (b) juvenile rodents infested with fleas at natural infestation levels (the second hypothesis). Adult individuals parasitized by a number of fleas higher than in nature lost body mass at higher rates than non-parasitized control individuals. Parasitism significantly affected daily body mass change of juvenile gerbils. Juvenile rodents parasitized by fleas at the natural level of infestation lost body mass faster and gained body mass slower than control animals. We suggest that some regulating mechanisms may limit natural flea densities at a point at which the negative effect on hosts is below the accuracy of our measurements. However, natural flea densities are sufficiently high to harm the more susceptible, juvenile cohort.

Age Factors↗

PubMed1981

Effects of sunflower seed supplements on reproduction and growth of RCS rats with hereditary retinal dystrophy.

Both control and dystrophic pink-eyed RCS rats reproduced poorly when they were fed a standard laboratory rodent diet and were housed in conventional animal rooms unshielded from pathogenic influences. More prolific reproduction and improved growth of young were obtained with a commercial unsterilized closed formula pelleted rodent ration, supplemented with 25% sunflower seed kernels. The sunflower kernels contained a high concentration of vitamin E and 47% fat which was mostly unsaturated. Linoleic acid was 75% of the unsaturated fatty acids. The kernels also contained a higher concentration of selenium (0.8 mg/kg) than standard rodent diets. Effective absorption of the high vitamin E of the diet was shown by analyses of blood plasma of 50-day-old dystrophic and control rats, in which the alpha-tocopherol level was three-fold that in animals fed standard laboratory rodent diet. Dams fed the diet had calmer temperaments and improved lactation. Litters of 8-13 pups were produced, and the pups grew rapidly to weaning with 95% survival of the control strains and 75% survival of the dystrophic strain. Progeny fed the diet for 8-10 months after weaning did not manifest cataracts, which occurred in 23% of the pink-eyed dystrophic animals fed standard rodent diets.

Animal Feed↗

PubMed2005

Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study.

RATIONALE: Dehydroepiandrosterone (DHEA) has been reported to enhance cognition in rodents, although there are inconsistent findings in humans. OBJECTIVES: The aim of this study was to investigate the effects of DHEA administration in healthy young men on episodic memory and its neural correlates utilising an event-related potential (ERP) technique. METHODS: Twenty-four healthy young men were treated with a 7-day course of oral DHEA (150 mg b.d.) or placebo in a double blind, random, crossover and balanced order design. Subjective mood and memory were measured using visual analogue scales (VASs). Cortisol concentrations were measured in saliva samples. ERPs were recorded during retrieval in an episodic memory test. Low-resolution brain electromagnetic tomography (LORETA) was used to identify brain regions involved in the cognitive task. RESULTS: DHEA administration led to a reduction in evening cortisol concentrations and improved VAS mood and memory. Recollection accuracy in the episodic memory test was significantly improved following DHEA administration. LORETA revealed significant hippocampal activation associated with successful episodic memory retrieval following placebo. DHEA modified ERPs associated with retrieval and led to a trend towards an early differential activation of the anterior cingulate cortex (ACC). CONCLUSIONS: DHEA treatment improved memory recollection and mood and decreased trough cortisol levels. The effect of DHEA appears to be via neuronal recruitment of the steroid sensitive ACC that may be involved in pre-hippocampal memory processing. These findings are distinctive, being the first to show such beneficial effects of DHEA on memory in healthy young men.

Adolescent↗

PubMed1997

Effects of two histamine-N-methyltransferase inhibitors, SKF 91488 and BW 301 U, in rodent antinociception.

We have previously reported that the histaminergic system is involved in the control of pain perception, and that substances able to enhance histamine brain levels, such as the histamine-N-methyltransferase inhibitor, metoprine, induce antinociception. In the present study, in order to corroborate the idea of inducing antinociception by inhibiting histamine catabolism, the effects of a noncompetitive histamine-N-methyltransferase inhibitor. SKF 91488, were studied in rodents by means of tests inducing three different kinds of noxious stimuli: thermal (mouse hot plate), chemical (mouse abdominal constrictions) and mechanical (rat paw pressure). The ability to react to noxious stimuli was assessed by the rota-rod test. In addition, a competitive inhibitor of the histamine catabolism enzyme, BW 301 U, was studied in the hot plate test. SKF 91488 (30, 50 and 100 micrograms per animal i.c.v.) raised dose-dependently the pain threshold in all three tests. To verify whether SKF 91488-induced antinociception is due to inhibition of histamine-N-methyltransferase, (R)-alpha-methylhistamine, described to block histamine release and synthesis by stimulating the histamine H3-autoreceptor and activating the negative feed-back mechanism, was used. When administered at doses which do not alter the pain threshold per se, 0.5 microgram per rat i.c.v. or 10 mg kg-1 i.p. in mice, (R)-alpha-methylhistamine was able to antagonize significantly the antinociceptive effect induced by 30 micrograms per animal i.c.v. of SKF 91488. BW 301 U (30 and 100 mg kg-1 i.p.) showed a dose-dependent, long-lasting antinociception, which was also antagonized by pretreatment with (R)-alpha-methylhistamine. The present data show that the antinociceptive effect previously described for metoprine is not restricted to this molecule, but is also shared by other histamine-N-methyl-transferase inhibitors. This generalization provides further evidence to the importance of the histaminergic system in pain control mechanisms.

Analgesics↗

PubMed1981

Peripheral markers of thyroid status unaffected by endurance training in rats.

In order to more clearly define the relationship between endurance exercise training and thyroid activity we have measured T4 turnover in exercise-trained and sedentary rats under conditions of controlled food intake and body weight. Rats were run on rodent treadmills at gradually increasing speeds and durations until at the end of 12 weeks they were running 2 h per day at 31 m/min. Sedentary rats were either allowed to eat ad libitum or were food restricted so that they gained weight at the same rate as controls. Relative heart weight and plantaris citrate synthase activity were both significantly increased in trained animals compared to controls. The thyroxine secretion and degradation rates were not affected by the training. In addition, liver mitochondrial alpha-glycerophosphate dehydrogenase and citrate synthase were measured as indicators of the thyroid state at the tissue level. Neither of these enzymes were increased in the trained rats. We conclude that increased thyroid activity is not essential for inducing and maintaining the adaptations in muscle mitochondrial enzymes which occur in response to prolonged endurance exercise training.

Animals↗

PubMed2001

Testosterone depresses innate and acquired resistance to ticks in natural rodent hosts: a force for aggregated distributions of parasites.

The effects of testosterone on acquired resistance to ticks, Ixodes ricinus, in their natural rodent hosts (voles, Clethrionomys glareolus, and wood-mice, Apodemus sylvaticus) were investigated by manipulating testosterone levels and exposing the hosts to repeated tick infestations. Testosterone reduced both innate and acquired resistance to tick feeding. During primary infestations, attachment rates were higher on rodents with high testosterone levels than on oil-implanted controls. Successive infestations on voles were accompanied by a decrease in tick feeding success and survival, but this decrease was significantly greater in ticks fed on control voles than in those fed on voles implanted with testosterone. When reduced feeding success had been induced, either by vaccination with tick salivary gland extract or by 4 successive infestations, implantation with testosterone partially reversed the acquired resistance. These effects of testosterone will generate heterogeneities within the rodent population with respect to tick distribution and microparasite transmission. The lowest innate and acquired resistance to tick feeding occurs in that fraction of the host population, i.e., sexually active males, most actively involved in the transmission of both Babesia microti and Borrelia burgdorferi s.l.

Animals↗

PubMed1979

Influence of controlled dietary restriction on immunologic function and aging.

The underfeeding regimens tested in rodents for life span prolongation and/or immunologic effects result in a complex blend of protein and energy restriction while offering at least adequate amounts of all other essential nutrients. Underfeeding started at weaning and continued throughout life represents the only proved way of slowing the rate of aging in homeotherms. Mounting evidence indicates that underfeeding initiated later in life may also influence life span favorably. Old mice after lifelong restriction, or moderately aged mice (16.5 months) after 4.5 months of restriction, display "younger" immune systems than do age-matched, normally fed controls, as judged by response to mitogens, the mixed lymphocyte reaction, and other determinants. The immunologic effects of underfeeding, when measured quite early in life, are strain-dependent in the mouse. Diets designed to restrict the intake per week of energy (but not protein) produce the same effects on immune response capacity in very young mice as do energy restricted, protein unbalanced regimens. Underfeeding early in life drastically dampens thymic growth and alters the timing of involution. Early restriction also produces a profound lowering of body temperature in young (C57BL/10Sn x C3H/HeDiSn)F1 females. On the other hand, temperature lowering was not observed in males of this hybrid fed normally for the first year of life and restricted for 3 months prior to measurement. The mechanisms behind these various effects of controlled dietary restriction (i.e., undernutrition without malnutrition) are poorly understood at present.

Aging↗

PubMed2005

Regulated lentiviral NGF gene transfer controls rescue of medial septal cholinergic neurons.

Nerve growth factor (NGF) has been shown to promote survival and function of cholinergic neurons in the basal forebrain in various models of neuronal degeneration in rodents and primates. We examined whether a regulatable in vivo expression system can control the survival of cholinergic neurons after injury, using a tetracycline-regulated promoter ("tet-off" system) to modulate lentiviral NGF gene delivery. Two weeks after lesions to cholinergic neurons, significant cell rescue (65+/-8% neuron survival; P<0.005 compared to controls) was observed when NGF expression was activated. Treatment with the tetracycline analog doxycycline to turn gene expression "off" resulted in a significant loss of cholinergic neurons (only 37+/-5% neurons remained, an amount that did not differ from untreated, lesioned controls). Animals treated with a constitutively active and robust nonregulated NGF expression system showed the same degree of neuronal rescue (73+/-8%) as animals treated with activated tet-regulated vectors. ELISA measurements confirmed that oral treatment of animals with doxycycline reduced NGF protein levels to levels in untreated control subjects. These data demonstrate for the first time that NGF delivery by lentiviral gene transfer using tetracycline-regulated promoters can completely regulate neuronal rescue and protein production in the brain.

Animals↗

PubMed1990

Characterization of the interstitial cellular infiltrate in experimental chronic cyclosporine nephropathy.

In a recently described rodent model of chronic cyclosporine nephropathy (CCN) (consisting of irregularly distributed areas of interstitial inflammation, interstitial fibrosis, and tubular atrophy) we have characterized the interstitial inflammatory cells. Using a modified avidin-biotin peroxidase technique, kidney tissue was examined with monoclonal antibodies directed against leukocyte-common antigen (LCA), T lymphocytes, T helper and T nonhelper lymphocytes, Ia (B cell marker), and macrophages. Injured cortex from cyclosporine-treated animals demonstrated increased numbers of T helper and B lymphocytes, macrophages, and cells bearing LCA. Cytotoxic (T nonhelper) cells were scant. Non-injured areas of cortex from CsA-treated animals demonstrated only a modest increase in macrophages when compared with vehicle controls and normal rats. We conclude that CCN in rodents is characterized by an interstitial inflammatory infiltrate of T helper cells, B cells, and macrophages. The role of these cells in the pathogenesis of CCN, however, remains speculative.

Animals↗

PubMed1990

Brain stem auditory-evoked potentials in different strains of rodents.

This study was conducted to evaluate variations in brain stem auditory-evoked potentials (BAEPs) among different strains of rodents. BAEPs were recorded by routine procedures from rodents of different strains or species. These included 22 Long-Evans, 28 Wistar and 28 Sprague-Dawley rats, and six hamsters. Within the first 10 ms, there were five consistent and reproducible positive waves of BAEPs in each rodent, named I, II, III, IV and V in correspondence with the nomenclature of waves I-VII in human BAEPs. These BAEPs were also similar to those observed in other vertebrates and in human controls. However, there were variations in waveforms and peak latencies among rodents, even in the rats of the same strain that came from different laboratory centres. At optimal stimulation intensity, usually around 90 dB, the mean latencies of the waves varied as follows: I, 1.23-1.53 ms; II, 1.88-2.28 ms; III, 2.62-2.94 ms; IV, 3.49-3.97 ms; and V, 4.47-5.14 ms. They were significantly different between species, but not in different strains of rats if they came from the same animal centre. The conduction time in the central portion illustrated by interpeak latencies between I and III, III and V, and I and V was dependent on the species (P less than 0.05). When recorded in a soundproof incubator, the minimal hearing threshold showed a significant species difference. The animal BAEP model can be employed for evaluating the physiological function or the pathological conditions of the brain stem. The confirmation of BAEP variations among different species or strains will be helpful in deciding which kind of rodents will be appropriate to serve as animal models for the various purposes of BAEP studies.

Animals↗

PubMed1998

Controlled reperfusion and pentoxifylline modulate reperfusion injury after single lung transplantation.

OBJECTIVE: Rodent models have suggested that initial low-pressure reperfusion of transplanted lungs reduces injury after ischemia. We investigated this phenomenon and the use of pentoxifylline in a porcine model of left single lung transplantation. METHODS: Donor lungs were preserved with Euro-Collins solution for a mean ischemic time of 18.4 hours. Neutrophil trapping in the graft, pulmonary artery pressure, and gas exchange were assessed over a 12-hour period. Partial occlusion of the contralateral pulmonary artery allowed manipulation of the pulmonary artery pressure in the transplanted lung. Group A (n = 5) was perfused at a mean pulmonary artery pressure of 20 mm Hg, group B was reperfused at a mean pulmonary artery pressure of 45 mm Hg for 10 minutes before reducing the pressure to the same as group A, and group C was reperfused at a mean pressure of 20 mm Hg for 10 minutes, then increased to a mean of 45 mm Hg for the remainder of the experiment. Group D was reperfused as in group A with the addition of intravenous pentoxifylline. RESULTS: Leukocyte sequestration was observed in the first 10 minutes after reperfusion in groups A, B, and C, with maximal sequestration at 2 minutes. Significantly more sequestration was observed in the first 6 minutes in group B than in groups A and C, which were similar. Pentoxifylline significantly reduced leukocyte sequestration. Pulmonary venous oxygen tension in the allograft lung was worst in group B. Groups A and C were similar, but group D was superior to all other groups (p < 0.001). CONCLUSIONS: Low-pressure reperfusion, even when limited to the first 10 minutes, modulates reperfusion injury possibly through a leukocyte-dependent mechanism. The addition of pentoxifylline in the recipient confers significant additional benefit.

Animals↗

PubMed2000

Modulation of estrous cycle and LH, FSH and melatonin levels by pinealectomy and sham-pinealectomy in female rats.

1. The pineal has been shown to have a role in controlling reproduction of polyestrus mammals (like humans and laboratory rodents). It influences the age of sexual maturation; the timing of the ovulatory cycle; and gonadal steroidogenesis. 2. Here the authors report the early and late effects of pinealectomy (Px) and sham-pinealectomy (SPx) on the estrous cycle periodicity, plasma LH, FSH and urinary 6-sulphatoxymelatonin (6-SMT) excretion in female rats. 3. Female Wistar rats (3-4 months of age) were maintained on 12/12 L/D cycle. Orbital venous plexus blood and urine samples were collected from the same rat during the estrus phase before surgery, 4-7 and 55-60 days post surgery. 4. Daily vaginal smears were taken to monitor the estrous cycle and they showed a time dependent increase in the estrus stage duration in Px rats (estrus stage: 1 day in control; 3-4 days after 45 days Px). 5. The decrease of gonadotropins at early post Px was due to surgical stress. 6. 6-SMT levels were significantly lower at 4-7 days post SPx, but at 55-60 d post surgery these levels returned to control values, which indicate pineal gland integrity. The reduction in urinary 6-SMT may be attributed to a possible high level of plasma corticosterone occurring after surgical manipulations. 7. 6-SMT levels in Px rats were extremely lower at 4-7 and 55-60 days post surgery, but not null, confirming the surgical removal of the pineal gland and indicating the synthesis of melatonin in sites other than the pineal gland.

Animals↗

PubMed1981

Control of the corpus luteum: a model system for toxicology research.

The rodent corpus luteum is an ephemeral structure releasing progesterone for only a few hours rather than several days. However, in response to the mating stimulus, sufficient prolactin is released from the pituitary gland in a unique pattern to activate the corpus luteum and maintain it in a secretory state for several days. Progesterone, secreted from the corpus luteum, prolongs the secretion of prolactin, while the uterus may secrete a substance which terminates the functional life of the corpus luteum directly and also acts upon he prolactin secretory apparatus within the hypothalamopituitary axis to terminate prolactin secretion.

Animals↗

PubMed1986

Evolution of a focus of Lyme disease.

Epidemiological investigations were initiated in 1984 when significant Lyme disease activity was observed within a 5-km radius of an area previously used as a non-endemic control site for Lyme disease research in New Jersey. Through 1983, collections of Ixodes dammini from vegetation and feral rodents were infrequent and no human cases were identified within a 16-km radius of the control site. In 1984, 4 human cases and 3 serologically reactive canines (greater than or equal to 1:512) were recognized within the area and adult I. dammini populations were over 3-fold greater than those at our primary study location where Lyme disease has been endemic since 1981. Using darkfield microscopy, 53.4% of adult I. dammini were infected with Borrelia burgdorferi as compared to 50.0% of adults collected during the same period at the known endemic study site. These data indicate that a focus of Lyme disease has recently become established at the previously non-endemic control site and that the establishment of new foci may occur more rapidly than once thought.

Animals↗

PubMed1995

Interaction of hypertension and caloric restriction on cardiac mass and isomyosin expression.

Previous studies show that elevations in blood pressure induce concomitant increases in both cardiac mass and slow beta-myosin heavy chain (MHC) expression in rodents, whereas caloric restriction of 50% (CR) causes an increase in beta-MHC while modestly lowering blood pressure in normotensive rats. The goals of this study were to 1) determine if beta-MHC expression could be independently regulated by CR and hypertension when these two interventions are combined and 2) determine if CR exerts a lowering of blood pressure in two contrasting models of rodent hypertension. Rodents were assigned to the following groups: 1) normal control (NC); 2) abdominal aortic constriction (Abcon), a model that induces hypertension via renin-angiotensin II; 3) nephrectomy-deoxycorticosterone acetate treatment (DOCA), a model that induces hypertension through increased salt retention; 4) CR; 5) Abcon+CR; 6) DOCA+CR. Results show that both Abcon and DOCA induced significant increases in systemic blood pressures, left ventricular (LV) weight/body weight, and the relative content of beta-MHC compared with NC. When applied in combination with either Abcon or DOCA, CR significantly blunted the changes observed in both systemic blood pressures and LV weight/body weight. In contrast, CR in conjunction with DOCA augmented % beta-MHC expression relative to either DOCA or CR alone. These data suggest 1) caloric restriction exerts a powerful impact on reducing experimentally induced hypertension in rodents and 2) the regulation of beta-MHC expression appears to be regulated by at least two processes, one associated with the stimulus of hypertension and the other involving an independent pathway linked to caloric restriction.

Animals↗

PubMed1995

Failure of the estrous cycle and spermatogenesis to respond to day length in a subtropical African rodent, the pouched mouse (Saccostomus campestris).

Little is known about the role of photoperiod in the control of reproduction in mammals from the tropics in general and, in particular, from the Afrotropics. The present study examined the reproductive photosensitivity of the pouched mouse (Saccostomus campestris: Cricetidae), a small, seasonally breeding rodent that occurs from about 12 degrees S to 33 degrees S in Africa. Groups of 10 laboratory-bred male pouched mice were exposed to either long-day (16L:8D) or short-day (8L:16D) conditions for 14 wk, after which they were killed and the spermatogenic activity of the testes was assessed histologically. A group of 10 adult, multiparous females were exposed to long-day conditions for 3 mo, after which the lengths of five consecutive estrous cycles were measured. Thereafter, day length was reduced to 10L:14D, and after 16 days acclimation, the lengths of five estrous cycles were measured. Finally, day length was reduced to 8L:16D, and after 33 days, the lengths of five estrous cycles were measured. Day length had no influence on body size, testis size, or the histology of the testis, and all specimens were actively producing spermatozoa. The length of the estrous cycle (4.0 +/- 0.3 days under long-day conditions) did not change significantly with the decrease in photoperiod. In a third experiment, 14 multiparous and six nulliparous females that had been maintained under short-day conditions for 33 days were mated and successfully reared litters.(ABSTRACT TRUNCATED AT 250 WORDS)

Africa↗

PubMed1990

Evidence against altered expression of GLUT1 or GLUT4 in skeletal muscle of patients with obesity or NIDDM.

Studies of experimental diabetes in rodents induced by the beta-cell toxin streptozocin have shown that the insulin-resistant glucose transport of peripheral tissues (muscle and adipose) in these animals can be ascribed in part to a pretranslational reduction of the major insulin-sensitive glucose transporter (GLUT4) in these tissues. Because a central feature of non-insulin-dependent diabetes mellitus (NIDDM) is an imparied ability of insulin to enhance glucose disposal in skeletal muscle, we examined the hypothesis that reduced expression of GLUT4 is a characteristic finding in the skeletal muscle of subjects with NIDDM. Biopsies of skeletal muscles were obtained from 17 patients with NIDDM and 10 lean and 9 obese nondiabetic subjects. Among the diabetic subjects, 7 were newly diagnosed and untreated. Compared with age-matched and body-weight-matched healthy control subjects, there was no significant alteration in the level of GLUT4 mRNA demonstrated by Northern blot and slot blot or GLUT4 protein determined by immunoblotting muscle membranes. Neither GLUT4 mRNA nor protein concentration correlated with the degree of glycemic control, fasting plasma insulin or glucose, diabetes duration, body mass index, sex, or age. GLUT1 mRNA and protein levels were also not significantly different between diabetic and matched control subjects. Thus, unlike streptozocin-induced diabetes in rodents, there is no evidence that impaired expression of the major insulin-responsive glucose transporter is responsible for insulin-resistant glucose transport in the skeletal muscle of these lean and moderately obese NIDDM patients.

Animals↗