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At least 739 records · Page 41Linked to original sources

PubMed1988

Site-specific inhibition of receptivity by intracranial anisomycin in hamsters.

The ventromedial nucleus of the hypothalamus (VMH) has been implicated in the mediation of the hormonal control of female rodent sexual behavior. However, in hamsters, progesterone (P) has been found to have effects on sexual receptivity in other diencephalic and mesencephalic sites as well. Progesterone is thought to exert its behavioral effects by altering protein synthesis in CNS target neurons. We tested the effects of 30 gauge implants of the protein synthesis inhibitor anisomycin in the preoptic area (POA), VMH, and ventral mesencephalon (VMES) 30 minutes before 500 micrograms P SC, on the facilitation of lordosis in ovariectomized estrogen-primed female hamsters. The same animals were tested one week later with estrogen and progesterone treatment but without anisomycin. Anisomycin reduced sexual receptivity (lordosis) when placed in the VMH or VMES, but not when delivered to the POA. The results confirm the importance of the VMH in the mediation of progesterone facilitation of female sexual behavior, but also provide evidence that ventral midbrain structures may play a role in female sexual receptivity in hamsters. These two structures may be important for different aspects of lordosis. Progesterone effects in both sites appear to be protein synthesis dependent.

Animals↗

PubMed1995

Non-genotoxic mechanisms of carcinogenesis: studies of cell transformation and gap junctional intercellular communication.

It is widely accepted that a series of genetic changes accumulate during carcinogenesis. In addition, it is likely that various non-genotoxic mechanisms also operate at different stages of carcinogenesis. It is even possible that non-genotoxic mechanisms indirectly generate genetic changes, e.g., through induction of cell proliferation, active oxygen species or cytosine methylation. This may partially explain why many carcinogens are devoid of activity when tested in the usual genetic toxicology assays. In vitro cell transformation mimics certain stages of in vivo carcinogenesis. It has therefore been proposed that both genotoxic and non-genotoxic aspects of carcinogenesis can be studied in cell transformation systems, with tumor formation by transformed cells in syngenic animals or nude mice as the endpoint. Many genotoxic as well as non-genotoxic carcinogens induce transformation of Syrian hamster embryo, murine Balb/c 3T3 and murine C3H10T1/2 cells; interaction of genotoxic and non-genotoxic mechanisms can be clearly seen in 2-stage cell transformation studies in which a genotoxic initiating agent and a non-genotoxic promoting agent act synergistically to induce transformation of rodent cells. Aberrant control of gap junctional intercellular communication (GJIC) in cell transformation and carcinogenesis is well documented. Possible genotoxic as well as non-genotoxic mechanisms involved in abnormal gap junction communication control in multistage carcinogenesis are discussed.

Animals↗

PubMed2006

Efficient testing strategies for evaluation of xenobiotics with neuroendocrine activity.

Maturation of neuroendocrine regulations is an extremely complex process made up of several stages, that can be permanently affected by any exogenous substances able to interfere with the hormonal signalling at various levels. The Endocrine Disrupting Chemicals (EDCs) are a heterogeneous group of xenobiotics with potential endocrine activities which have been identified as priority risk factors in toxicological research. The present review is aimed at suggesting a number of endocrine and behavioural endpoints to be used in experimental studies to: (i) characterize more thoroughly the functional effects of developmental exposure to agents known to act as endocrine disruptors and (ii) unmask possible interferences with the maturation of the hypothalamus-hypophysis-gonad/thyroid (HHG/Th) axis by different class of xenobiotics not considered as EDCs. A combined testing strategy, considering both markers of endocrine/hormonal maturation and behavioural endpoints under hormonal control in laboratory rodents, may evidence even subtle perturbations of the neuroendocrine homeostasis, that often go undetected.

Animals↗

PubMed2004

Background concentrations of dioxins, furans, and PCBs in Sprague-Dawley rats and juvenile swine.

In preparation for a study of the relative oral bioavailability of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in soils (typically containing less than 1 ppb 2,3,7,8-tetrachlo-rodibenzo-p-dioxin [TCDD] toxic equivalents [TEQ]), the background concentrations of PCDD/Fs and selected polychlorinated biphenyls (PCBs) were measured in liver and adipose tissue from female Sprague-Dawley rats and juvenile swine after 30 d of ingesting laboratory chow. The measured concentrations of TCDD and other PCDD/Fs in rat livers were severalfold less than previously reported in the literature for control (unexposed) laboratory rodents. The concentrations of PCDD/Fs and selected PCBs in livers of swine were three- to fourfold lower than those reported for rats. The lower concentrations found in this study compared to previous findings may be due to inadvertent laboratory contamination in previous studies or to declining levels of PCDD/Fs in laboratory feed, which parallel the declines in emissions, general environmental levels, and human food and tissue levels of PCDD/Fs.

Adipose Tissue↗

PubMedDate not supplied

Bilateral enucleation and captivity influence the reproductive cycle of male Viscacha (Lagostomus maximus maximus).

The viscacha (Lagostomus maximus maximus) is a seasonal rodent living in the Southern Hemisphere. The adult males exhibit an annual reproductive cycle characterized by a gonadal regression period during winter. In this study, we investigated the effects of bilateral enucleation and captivity on their annual reproductive cycle. Testicular volume relative to body weight was recorded monthly in intact and bilaterally enucleated animals placed under natural photoperiod, water, and food ad lib. and constant temperature. Testes and accessory organs were evaluated by qualitative and quantitative light microscopic studies. The intact animals showed an annual reproductive cycle with complete gonadal atrophy in the first year. In the second year, testicular regression was observed but attenuated in regard to that recorded in the first winter period, indicating that adaptive changes might be involved. Bilateral enucleation in the viscacha dampened and extended the period of its annual reproductive cycle. The results suggest that both conditions, constant captivity and enucleation, produced stimulatory effects on the reproductive system of this rodent. Furthermore, local control mechanisms might be responsible for the morphological differences observed in testes, epididymis, and seminal vesicles from both groups, which exhibited similar levels of serum testosterone. Finally, an intact retinohypothalamic-pineal axis and/or photoperiodic input would be necessary to maintain the reproductive cycle amplitude and timing in viscacha.

Animals↗

PubMed2005

Strategies for testing long-term transcutaneous amperometric glucose sensors.

OBJECTIVES: Transcutaneous and embedded devices were developed for use in characterizing the in vivo performance of subcutaneously implanted glucose sensors. The devices were used as a portal for accessing electrochemical glucose sensors from the exterior. They were designed to prevent the sensors from being pulled out of the animals and the sensor leads from breaking. Development of the devices took into consideration rodent mobility, infection control, and animal welfare balanced with sensor durability, accessibility, and functionality. METHODS: Our approach was developed over five animal protocols spanning a period of 6 months. A total of 68 sensors were implanted with 60 associated devices in 22 Sprague-Dawley outbred rats. RESULTS: The average sensor lifetime was 11.2 +/- 3.1 days with a maximum of 56 days. All-cause sensor failure averaged one sensor per day. As implantation devices were modified, failure attributable to the device was decreased by 40%. The resulting devices showed good durability and allowed for easy sensor access and testing. CONCLUSIONS: These data represent baseline sensor function against which future sensor improvements may be measured. The new devices and techniques described should be a valuable tool in the development of continuous glucose sensors.

Animals↗

PubMed1996

Treatment of experimental brain injury with moderate hypothermia and 21-aminosteroids.

Studies of experimental traumatic brain injury have found that histologic injury is significantly reduced and behavioral outcome improved in animals treated with moderate hypothermia (32-33 degrees C) or a 21-aminosteroid. Because these treatments are thought to work through different neurochemical mechanisms, their combined use might be expected to be more efficacious than either treatment alone. To test this hypothesis, we studied each treatment separately and in combination in a rodent model of controlled cortical contusion. Treatment with moderate hypothermia (32 degrees C for 4 h), a 21-aminosteroid (U-74389G, Upjohn, 10 mg/kg intravenously, repeated 3 h after the first dose), or both, was initiated 10, 25, or 40 min after injury. The brains were perfused 24 h after injury, and sagittal sections were stained for the 68-kDa "core" neurofilament subunit, a marker of axonal injury. The total number of positively stained axons in the ipsilateral internal capsule were counted under light microscopy. Compared with the control group (injury but no treatment), treatment with each therapy alone or combined, initiated 10 min after injury, caused significant reductions in the number of stained axons (21-aminosteroid alone-35% reduction; hypothermia alone-55% reduction; combination-48% reduction). The number of positively stained axons was significantly reduced in the aminosteroid and combination therapy groups at all three postinjury times (p = 0.01) and in the hypothermia groups treated at 10 or 25 min (p = 0.01) but not at 40 min after injury. We concluded that combination therapy with hypothermia and 21-aminosteroids was no more efficacious than either therapy alone, and that 21-aminosteroid therapy was more efficacious than hypothermia when treatment was initiated 40 min after injury.

Animals↗

PubMed1983

Effect of indomethacin on reproduction under laboratory and field conditions in deermice (Peromyscus maniculatus).

The purpose of this investigation was to determine the long-term effect of enterically administered indomethacin (a prostaglandin synthetase inhibitor) on reproduction in Peromyscus maniculatus (deermice) under both laboratory and field conditions. Indomethacin-coated wheat (1 mg/kg wheat) was provided to the experimental animals in the laboratory and under field conditions ad libitum. Rat chow was also provided to the animals in the laboratory. The laboratory data indicate that the number and size of the litters from the control breeding pairs were larger (number of litters=22; average number of pups/litter=4.9) than the experimental breeding pairs (number of litters=2; average number of pups/litter=2.5) over a 100-day experimental period. Field data indicate that the number of pregnant animals, the total number of animals, and mean juvenile males and females live-trapped decreased in the experimental group with respect to the control group during the experiment. The data suggest that deermice will consume indomethacin under both laboratory and field conditions, and that it effectively inhibits reproduction on a long-term basis. It is, therefore, possible that prostaglandin synthetase inhibitors may be used to control populations of rodent pests. Additionally, the data raise questions about the effect of long-term use of nonsteroidal analgesic compounds similar to indomethacin on human reproduction.

Animals↗

PubMed1997

Antibody responses and infertility in mice following oral immunization with attenuated Salmonella typhimurium expressing recombinant murine ZP3.

Ovarian ZP3, the primary sperm receptor, is a major glycoprotein of mouse zona pellucida (ZP). Because antibodies raised against ZP3 block sperm-egg interaction, ZP3 has been considered a candidate immunogen in the development of a contraceptive vaccine. This study explored the possibility of using an attenuated Salmonella typhimurium vaccine strain expressing recombinant ZP3 to elicit an antibody response and infertility in mice. A cDNA sequence generated by the polymerase chain reaction encoding 342 amino acid residues (23-364) of the mouse (m)ZP3 was cloned into an Asd+ vector. An avirulent Salmonella vaccine strain stably expressed the ZP3 polypeptide and colonized the internal organs of mice after oral inoculation. Oral immunization of female BALB/c mice with the recombinant Salmonella vaccine strain expressing mZP3 induced significant levels of anti-native ZP IgG antibodies in serum and IgA antibodies in vaginal secretions. The IgG antibodies thus induced also bound to ZP in vivo. When mated with males, 3 of 6 females immunized with the recombinant Salmonella were infertile. In contrast, none of the mice that received Salmonella containing the vector plasmid produced antibodies to ZP and all were fertile. No ovarian inflammation was observed in the immunized mice at autopsy. The results suggest a potential oral contraceptive vaccine to control populations of rodent vectors of disease and to induce reversible infertility in humans.

Animals↗

PubMed2006

Rats subjected to extended L-tryptophan restriction during early postnatal stage exhibit anxious-depressive features and structural changes.

Serotonin transmission dysfunction has been suggested to play an important role in depression and anxiety. This study reports the results of a series of experiments in which rats were subjected to extended maize-based tortilla diets during early postnatal stages. This diet contains only approximately 20% of the L-tryptophan in normal diets of laboratory rodents. Compared with controls, experimental rats displayed a significant increase of immobility counts in the forced swimming test and exhibited anxiety-like behavior in the elevated plus maze test after 1 month of diet treatment. Low levels of serotonin contents were found in prefrontal cortex, striatum, hippocampus, and brainstem using high-performance liquid chromatography. Immunocytochemical reactions against 5-Bromo-2'-deoxyuridine revealed a significant decrease in the proliferation rate for the subgranular zone of dentate gyrus. c-Fos expression after the forced swimming test was found reduced in prefrontal cortex, dentate gyrus, CA1, and hilus of hippocampus and amygdala. Moreover, dendrite arbor atrophy and decreased spine density were evident in Golgi-Cox-impregnated CA1 pyramidal neurons. Abnormal dendrite swelling in dentate gyrus granule cells was also observed. These findings indicate an involvement of hyposerotoninergia in emotional disturbance produced by L-tryptophan restriction during critical developmental stages and suggest that neuroplasticity changes might underlie these changes.

Age Factors↗

PubMed2004

Increased susceptibility to liver injury after hemorrhagic shock in rats chronically fed ethanol: role of nuclear factor-kappa B, interleukin-6, and granulocyte colony-stimulating factor.

Chronic ethanol use preceding severe trauma and hemorrhagic shock (HS) is associated with an increased incidence of multiorgan failure (MOF) and death; however, the molecular basis for this increased susceptibility is unknown. We previously demonstrated that production of interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF), mediated by nuclear factor-kappa B (NF-kappa B), each make essential contributions to organ injury and inflammation in a rodent model of controlled HS, and we proposed in this study to examine the hypothesis that the increased susceptibility to MOF after shock/trauma in the setting of chronic ethanol use is due to an exaggerated activation of NF-kappa B and production of these proinflammatory cytokines. We observed increased HS-induced liver injury 4 h after resuscitation in rats fed the ethanol-containing Lieber-DeCarli liquid diet for 8 weeks compared with rats fed the control liquid diet (3-fold increase in serum alanine aminotransferase [ALT], P = 0.008, and 2-fold increase in focal liver necrosis, P = 0.005). The increased liver injury in the ethanol-fed HS rats was accompanied by a 70% increase in liver NF-kappa B activation (P < 0.05), a 3- to 5-fold increase in hepatocyte and Kupffer cell production of IL-6 and G-CSF (P < 0.05 for each), and a 2-fold increase in neutrophil infiltration (P < 0.005) compared with the control diet-fed HS rats. Thus, increased susceptibility to HS-induced liver injury in the setting of chronic ethanol use may be mediated, at least in part, by increased NF-kappa B activation resulting in increased local production of IL-6 and G-CSF and increased infiltration of neutrophils, which can damage liver cells directly and contribute to impaired sinusoidal blood flow.

Animals↗

PubMed2004

Interleukin-6 infusion blunts proinflammatory cytokine production without causing systematic toxicity in a swine model of uncontrolled hemorrhagic shock.

BACKGROUND: Serum elevations of interleukin-6 (IL-6) correlate with multiple organ dysfunction syndrome and mortality in critically injured trauma patients. Data from rodent models of controlled hemorrhage suggest that recombinant IL-6 (rIL-6) infusion protects tissue at risk for ischemia-reperfusion injury. Exogenous rIL-6 administered during shock appears to abrogate inflammation, providing a protective rather than a deleterious influence. In an examination of this paradox, the current study aimed to determine whether rIL-6 decreases inflammation in a clinically relevant large animal model of uncontrolled hemorrhagic shock, (UHS), and to investigate the mechanism of protection. METHODS: Swine were randomized to four groups (8 animals in each): (1) sacrifice, (2) sham (splenectomy followed by hemodilution and cooling to 33 degrees C), (3) rIL-6 infusion (sham plus UHS using grade 5 liver injury with packing and resuscitation plus blinded infusion of rIL-6 [10 mcg/kg]), and (4) placebo (UHS plus blinded vehicle). After 4 hours, blood was sampled, estimated blood loss determined, animals sacrificed, and lung harvested for RNA isolation. Quantitative reverse transcriptase-polymerase chain reaction was used to assess granulocyte colony-stimulating factor (G-CSF), IL-6, and tumor necrosis factor-alpha (TNFalpha) messenger ribonucleic acid (mRNA) levels. Serum levels of IL-6 and TNFalpha were measured by enzyme-linked immunoassay (ELISA). RESULTS: As compared with placebo, IL-6 infusion in UHS did not increase estimated blood loss or white blood cell counts, nor decrease hematocrit or platelet levels. As compared with the sham condition, lung G-CSF mRNA production in UHS plus placebo increased eightfold (*p < 0.05). In contrast, rIL-6 infusion plus UHS blunted G-CSF mRNA levels, which were not significantly higher than sham levels (p = 0.1). Infusion of rIL-6 did not significantly affect endogenous production of either lung IL-6 or mRNA. As determined by ELISA, rIL-6 infusion did not increase final serum levels of IL-6 or TNFalpha over those of sham and placebo conditions. CONCLUSIONS: Exogenous rIL-6 blunts lung mRNA levels of the proinflammatory cytokine G-CSF. The administration of rIL-6 does not increase the local expression of IL-6 nor TNFalpha mRNA in the lung. Additionally, rIL-6 infusion does not appear to cause systemic toxicity.

Animals↗

PubMed1993

The ABA-1 allergen of the nematode Ascaris suum: epitope stability, mass spectrometry, and N-terminal sequence comparison with its homologue in Toxocara canis.

ABA-1 is a major allergen of nematode parasites of the genus Ascaris which includes the large roundworms of humans and pigs, A. lumbricoides and A. suum, respectively. The allergen was purified from A. suum by immunoaffinity chromatography for immunochemical examination. The IgE antibody repertoire is under MHC control in infected rodents and the IgE-binding epitopes were robust to treatment with heat or periodate, and electroblotting on nitrocellulose. This implies that the IgE epitopes comprise primary peptide sequence or an unusually stable secondary or tertiary structure. The molecular mass of ABA-1 is controversial, but mass spectrometry analysis indicated that there were five components of similar size, with the major species being 14,643.2 +/- 1.4 D. Finally, N-terminal sequence analysis of ABA-1 and TBA-1 (the homologue in the canine nematode infective to humans, Toxocara canis) revealed a high degree of similarity, and we have previous evidence that ABA-1 homologues are widespread amongst ascaridid parasites of humans. ABA-1 and its homologues might, therefore, be important to the immunopathology of many infections with nematode parasites, upon which the genetic constitution of the hosts will also have a bearing.

Allergens↗

PubMed1989

Is greater female longevity a general finding among animals?

(A) There are data showing beyond question a gender gap, with women living longer than men, especially in economically developed societies. There is greater male vulnerability to the major causes of human death. (B) In lower animals there are data suggesting a female survival advantage to adult life in many species, but the observations do not consider longevity or survival to an advanced age. (C) In laboratory rodents kept under controlled conditions the relationship of sex to longevity is variable, with males sometimes showing greater longevity than females and with life span being dependent on factors like breeding and diet. (D) Similar genetic and hormonal processes operate in humans and in non-human mammals including the genetic mechanism of sex determination, the hormonal consequences of sex determination, and the effects of hormones on processes which affect longevity such as cholesterol levels and immune functions. (E) Causes of death in humans and animals are different, and it seems unlikely, therefore, that the same mechanisms could be determinants of longevity in all mammalian species. (F) Human male and female longevity continue to change, and it is likely that the gender gap will narrow, with societal and medical changes in post-industrial societies reducing the male disadvantages in behaviour and in the handling of cholesterol. (G) It remains an important question whether part of the gender gap seen in humans is based on other differences in the basic biology of males and females.

Animal Population Groups↗

PubMed2005

Quantitative risk assessment for multivariate continuous outcomes with application to neurotoxicology: the bivariate case.

The neurotoxic effects of chemical agents are often investigated in controlled studies on rodents, with multiple binary and continuous endpoints routinely collected. One goal is to conduct quantitative risk assessment to determine safe dose levels. Such studies face two major challenges for continuous outcomes. First, characterizing risk and defining a benchmark dose are difficult. Usually associated with an adverse binary event, risk is clearly definable in quantal settings as presence or absence of an event; finding a similar probability scale for continuous outcomes is less clear. Often, an adverse event is defined for continuous outcomes as any value below a specified cutoff level in a distribution assumed normal or log normal. Second, while continuous outcomes are traditionally analyzed separately for such studies, recent literature advocates also using multiple outcomes to assess risk. We propose a method for modeling and quantitative risk assessment for bivariate continuous outcomes that address both difficulties by extending existing percentile regression methods. The model is likelihood based; it allows separate dose-response models for each outcome while accounting for the bivariate correlation and overall characterization of risk. The approach to estimation of a benchmark dose is analogous to that for quantal data without the need to specify arbitrary cutoff values. We illustrate our methods with data from a neurotoxicity study of triethyl tin exposure in rats.

Animals↗

PubMed1989

Haemophilus infection in a colony of laboratory rats.

During routine quality control of laboratory rodents, short gram-negative rods with satellite growth adjacent to a Staphylococcus strain were isolated from rats. They proved to be members of the family Pasteurellaceae. On the basis of their dependence on V factor they were classified as Haemophilus sp. Systematic investigations in our laboratory rat colony revealed a high prevalence of these bacteria. They were isolated from 75 of 446 rats (16.8%) which were monitored by culture during a 2-year investigation. Most strains were isolated from the lungs and the trachea; some were cultured from the nasal cavity and the female genital tract. Antibodies to these bacteria were detected in sera from 385 of 829 rats (46.5%) by using an indirect immunofluorescence test. The majority of culturally and serologically positive animals came from three separate holding areas; they all came from the same breeder. Investigation of rats immediately on receipt from the breeder showed that they were culturally and serologically positive for Haemophilus sp. Histological examination of rats which were monoinfected with Haemophilus sp. showed a mild inflammatory cell infiltration in the lungs and a light diffuse hyperemia. In the physiological and biochemical investigations of 53 isolates, all strains had an identical biochemical profile. On the basis of the 35 criteria examined, a definite classification is not possible. These Haemophilus bacteria are probably members of a hitherto unknown species.

Animals↗

PubMed2001

Exercise and lactation: are they compatible?

Lactation is an energy-demanding physiological process for the maternal organism and life-giving for the offspring. Likewise, exercise is an energy-demanding process. This review addresses the compatibility of exercise during lactation. Human studies suggest no detrimental effect of exercise during lactation on milk composition and volume, infant growth and development, or maternal health. Studies also demonstrate improved cardiovascular fitness in lactating, exercising women and suggest a quicker return to pre-pregnancy body weight and a more positive sense of well-being, compared to sedentary controls. Findings from rodent studies, although of questionable value for humans, have generally shown no detrimental influence of exercise during pregnancy and lactation on pup growth and development. To date, findings suggest that exercise and lactation are compatible activities.

Animals↗

PubMed1990

Measurement of dietary and dentifrice effects upon calculus accumulation rates in the domestic ferret.

Most animal models for the study of calculus accumulation and control currently use rodents or dogs. In an effort to overcome limitations inherent in the use of these species, we investigated calculus formation in domestic ferrets, a species used by King et al. in the 1940's and 1950's. Ferrets are much smaller than dogs, and, unlike rodents, can be scored while alive. In this study, we examined the kinetics of calculus formation in female ferrets fed with moist canned cat food--either plain or supplemented with sucrose--and two combinations of mineral salts. An additional group given supplemented cat food was treated twice daily with regular Crest toothpaste. Animals were sedated with a 1:1 mixture of ketamine and xylazine solutions and given a mechanical prophylaxis prior to the trial period, then scored for area and extent of calculus accumulation at two, four, six, and eight weeks thereafter. The data showed that the mineral-supplemented groups accumulated calculus at a significantly faster rate than the unsupplemented or dentifrice-treated groups, but the differences were no longer significant at eight weeks. This demonstrated that the ferret is a suitable model for the study of calculus, that dietary mineral content influenced calculogenesis, and that the application of regular dentifrice initially slowed, but did not prevent, calculus accumulation.

Analysis of Variance↗