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At least 883 records · Page 49Linked to original sources
PubMed1996

The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation.

The three types of peroxisome proliferator activated receptor (PPAR), alpha, beta (or delta), and gamma, each with a specific tissue distribution, compose a subfamily of the nuclear hormone receptor gene family. Although peroxisome proliferators, including fibrates and fatty acids, activate the transcriptional activity of these receptors, only prostaglandin J2 derivatives have been identified as natural ligands of the PPAR gamma subtype, which also binds thiazolidinedione antidiabetic agents with high affinity. Activated PPARs heterodimerize with RXR and alter the transcription of target genes after binding to specific response elements or PPREs, consisting of a direct repeat of the nuclear receptor hexameric DNA core recognition motif spaced by one nucleotide. The different PPARs can be considered key messengers responsible for the translation of nutritional, pharmacological and metabolic stimuli into changes in the expression of genes, more specifically those genes involved in lipid metabolism. PPAR alpha is involved in stimulating beta-oxidation of fatty acids. In rodents, a PPAR alpha-mediated change in the expression of genes involved in fatty acid metabolism lies at the basis of the phenomenon of peroxisome proliferation, a pleiotropic cellular response, mainly limited to liver and kidney and which can lead to hepatocarcinogenesis. In addition to their role in peroxisome proliferation in rodents, PPAR is also involved in the control of HDL cholesterol levels by fibrates and fatty acids in rodents and humans. This effect is, at least partially, based on a PPAR-mediated transcriptional regulation of the major HDL apolipoproteins, apo A-I and apo A-II. The hypotriglyceridemic action of fibrates and fatty acids also involves PPARs and can be summarized as follows: (1) an increased lipolysis and clearance of remnant particles, due to changes in LPL and apo C-III levels, (2) a stimulation of cellular fatty acid uptake and their conversion to acyl-CoA derivatives by the induction of FAT, FATP and ACS activity, (3) an induction of fatty acid beta-oxidation pathways, (4) a reduction in fatty acid and triglyceride synthesis, and finally (5) a decrease in VLDL production. Hence, both enhanced catabolism of triglyceride-rich particles as well as reduced secretion of VLDL particles are mechanisms that contribute to the hypolipidemic effect of fibrates and FFAs. Whereas for PPAR beta no function so far has been identified, PPAR gamma triggers adipocyte differentiation by inducing the expression of several genes critical for adipogenesis.

Adipocytes↗
PubMed1988

Mouse cerebellar granule neurons arrest the proliferation of human and rodent astrocytoma cells in vitro.

To understand the control of glial tumor cell proliferation, we have examined the effects of neurons on a number of human and rodent glioma lines. These included C6, G26-24, U-251, HTB-16, and A-172 cells of astroglial lineage and G26-20 of bipotential astrocytic and oligodendrocytic lineage. Rapid, specific binding of granule neurons to the human A-172, HTB-16, and U-251 and mouse G26-24 cell lines occurred, after which 3H-thymidine incorporation by these astrocytoma cells dropped 2-5-fold within 12 hr. The number of glial cells remained constant for 5-7 d when the glia were cocultured with granule neurons. Thereafter many neurons detached from the glial cells and glial proliferation commenced again. No effects on glial cell number were seen when PC12 cells were substituted for cerebellar granule neurons. To test the mechanism of neuronal control of glioma cell growth, we added granule neurons or PC12 cells that had been fixed lightly with paraformaldehyde, a plasma membrane fraction of purified granule cells, PC12 cells or astrocytoma cells, or medium conditioned by either granule cells or a mixed population of cerebellar neurons and astroglia. The proliferation of responsive glioma cell lines ceased in the presence of either fixed granule neurons or plasma membranes purified from granule neurons. The addition of fixed PC12 cells or plasma membranes purified from PC12 cells, 3T3 cells, or astrocytoma cells had no effect on glial cell growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Successful plague control in Namibia.

OBJECTIVE: To demonstrate that plague can be successfully controlled. DESIGN: A descriptive study outlining patterns of plague occurrence in relation to variables such as age group, gender, place and time. SETTING: Two northern districts, namely Engela in Ohangwena region and Onandjokwe in Oshikoto region, an area of 2,000 km2. SUBJECTS: All patients who presented to the health facilities with signs and symptoms of plague were considered. Diagnosis was made on the basis of clinical symptomatology and laboratory confirmation. OUTCOME MEASURES: A plague control programme was established involving the following components: management capability at the local level, case recognition and management, dusting programme, rodent trapping programme, health education, establishment of plague laboratory, and plague surveillance system. RESULTS: Following the establishment of the control programme plague cases were reduced from 1,092 to zero within 3 years and deaths from 45 to zero within 2 years. The case fatality rate was reduced from 4.12% to 0% over a 3-year period. No cases have been reported in Namibia for the past 3 years. CONCLUSION: The Namibian experience has demonstrated that plague can be controlled through a combination of strategies taking local conditions into consideration.

Adolescent↗
PubMed2001

Examination of angiotensin II type 1 and type 2 receptor expression in human kidneys by immunohistochemistry.

Recent studies have suggested that both the angiotensin II type 1 (AT1) and type 2 (AT2) receptors may be involved in the control of renal function in rodents. The aim of this study was to examine the distribution of these receptors in normal and diseased human kidneys. Kidney samples were obtained from 21 patients with and without glomerular lesions (3 control kidney samples from patients undergoing nephrectomy, 4 patients with minimal change disease, 6 patients with IgA nephropathy, and 8 patients with membranous glomerulonephritis). AT1 receptor immunohistochemical staining was examined and found to be most prominent in blood vessels, but staining of the tubules and glomeruli was also seen. In the case of the AT2 receptor, mild-moderate immunohistochemical staining was seen in the blood vessels, with weaker staining in the glomeruli. A similar distribution was seen in the patients with glomerulopathy. These results suggest that both AT1 and AT2 receptors are expressed in the normal human kidney, as well as in patients with glomerular disease. The histological distribution of these receptors supports the notion that both receptors may have a physiological role in normal and diseased kidneys in humans.

Female↗
PubMed2004

Autoclave sterilization produces acrylamide in rodent diets: implications for toxicity testing.

Acrylamide (AA) is a neurotoxic and carcinogenic contaminant that is formed during the cooking of starchy foods. Assessment of human risks from toxicants is routinely performed using laboratory rodents, and such testing requires careful control of unintended exposures, particularly through the diet. This study describes an analytical method based on liquid chromatography with electrospray tandem mass spectrometry that was used to measure endogenous AA in rodent diets and to survey a number of commercial products for contamination. Method sensitivity permitted accurate quantification of endogenous levels of AA in raw diets below 20 ppb. Autoclaving a standard rodent diet (NIH-31) increased the AA content 14-fold, from 17 to 240 ppb. A nutritionally equivalent diet that was sterilized by irradiation was found to contain approximately 10 ppb of AA (NIH-31IR). A toxicokinetic study of AA and its epoxide metabolite, glycidamide, was performed by switching mice from NIH-31IR to the autoclaved diet for a 30 min feeding period (average AA dose administered was 4.5 microg/kg of body weight). The concentrations of AA and glycidamide were measured in serum collected at various times. The elimination half-lives and the areas under the respective concentration-time curves were similar for AA and glycidamide. Mice maintained on autoclaved NIH-31 diet, but otherwise untreated, showed elevated steady state levels of a glycidamide-derived DNA adduct in liver relative to mice maintained on the irradiated diet. This study demonstrates that a heat sterilization procedure used in laboratory animal husbandry (i.e., autoclaving) can lead to the formation of significant levels of AA in basal diets used for toxicity testing. AA in rodent diets is bioavailable, is distributed to tissues, and is metabolically activated to a genotoxic metabolite, which produces quantifiable cumulative DNA damage. Although the contribution of endogenous AA to the incidence of tumors in multiple organs of rodents otherwise untreated in chronic carcinogenicity bioassays (i.e., control groups) is not known, the reduction of endogenous AA through the use of a suitable irradiated diet was deemed to be critical for ongoing studies of AA carcinogenicity and neurotoxicity.

Acrylamide↗
PubMed1987

A stabilized moment estimator for the beta-binomial distribution.

The beta-binomial distribution has been proposed as a model for the incorporation of historical control data in the analysis of rodent carcinogenesis bioassays. Low spontaneous tumor incidences along with the small number and sizes of historical control groups combine to make the moment and maximum likelihood estimates of the beta-binomial parameters deficient. We therefore propose a stabilized moment estimator for one of the parameters. The stabilized moment estimator is similar to the ridge regression estimator and introduces a shrinkage parameter. Computer simulations were run to examine the behavior of the stabilized moment estimator. The effect of the stabilized moment estimator on the score test for dose-related trend is considered both on simulated data and on an example from the literature.

Animals↗
PubMed2003

[Small rodents in the forest ecosystem as infectious disease reservoirs].

Due to numerousness of populations and width of ecologic valence, small rodents are important parts of almost any forest ecosystem. The represent an important animal group, which connects primary makers with higher trophic levels. They transmit various infectious diseases dangerous for the health of people and domestic and wild animals (trichinosis, leptospirosis, tick encephalitis, Lyme disease, hemorrhagic fever with renal syndrome, etc.). The following species of small rodents live in forest ecosystems of Croatia: Chletrionomys glareolus Schreib., Arvicola terrestris L, M. subterraneus de Sel., M. arvalis Pall., M. agrestis L, M. multiplex Fat., Apodemus agrarius Pall., A. sylvaticus L. and A. flavicollis Melch. Small rodents transmit causative agents of diseases in active (excretion products) of passive (ectoparasites and endoparasites) ways. Their multiplication potential is quite high. Transmission of certain disease sometimes takes place extremely fast due to the high number of rodents, their high movability and distribution, and the fact that they easily get in touch with men and domestic and wild animals. The number of population of each species is directly influenced by abiotic and biotic factors and changes during one year and in a several year period. In a year when the influence of ecologic factors is favorable, it is presumed that the number of these rodents will significantly increase, by which the danger of their damaging effect also increases. The following factors influence the increase of a small rodent population: number and physiologic condition of the population, meteorologic conditions, habitat, food sources, natural enemies, and diseases. The occurrence of an epidemic is closely connected to the number and infectivity of causative agents. Regular control of the number of rodent population and their infectivity can help in planning preventive epidemiologic and sanitary measures to preclude the occurrence of epidemics and individual cases of disease among animals and humans who come in contact with forest (forest workers, holiday makers, hikers, soldiers, tourists, etc.).

Animals↗
PubMed2005

Hypercholesterolemia impairs reactive hyperemic vasodilation of 2A but not 3A arterioles in mouse cremaster muscle.

Hypercholesterolemia and atherosclerosis have been associated with changes in the microvasculature, in particular with endothelial dysfunction. In the present study, the impact of atherogenic conditions on arteriolar vasomotor control was determined. Arteriolar [second-order (2A) and third-order (3A) arterioles; diameter range: 9-37 microm] responses during reactive hyperemia (RH) were determined in cremaster muscle of anesthetized mice. C57Bl/6 mice on normal rodent chow were used as controls and high-fat/high-cholesterol (HFC)-fed C57Bl/6 and ApoE3-Leiden mice as hypercholesterolemic mice. The HFC diet resulted in time-dependent increases in plasma cholesterol and triglyceride concentrations (P < 0.001), which were more pronounced in ApoE3-Leiden mice (P < 0.001). In control mice, inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine (L-NNA) reduced baseline diameter from 17.9 +/- 1.2 to 15.9 +/- 1.3 microm (P < 0.05) and decreased the duration of RH [time to 50% (t50) of recovery: 23.3 +/- 3.6 vs. 12.5 +/- 1.3 s (P = 0.003)]. t50 was longer in 2A versus 3A arterioles (33 +/- 3 vs. 18 +/- 2 s, P < 0.001) and increased with wall shear rate at the beginning of RH in 2A arterioles only. Compared with control mice, RH duration was reduced in 2A arterioles of HFC mice (t50: 11 +/- 2 s, P < 0.001 vs. control) but not affected in 3A vessels. L-NNA did not affect baseline diameter in HFC mice and reduced t50 only in "slow" responders (t50 > or = 10 s). It is concluded that hypercholesterolemia results in an impairment of NO-mediated vasomotor control in 2A but not 3A arterioles during dynamic changes of perfusion like RH. 2A arterioles likely therefore represent the functional locus of endothelial dysfunction during atherogenic conditions.

Abdomen↗
PubMed2005

Environmental control and adrenergic regulation of pineal activity in the diurnal tropical rodent, Arvicanthis ansorgei.

Like nocturnal rodents, the diurnal tropical rodent Arvicanthis ansorgei shows a daily rhythm in pineal melatonin content. Seasonal and photoperiodic variations in the biosynthetic activity of the pineal gland: arylalkylamine-N-acetyltransferase (AA-NAT), hydroxyindole-O-methyltransferase (HIOMT) activities and melatonin content were measured in male and female A. ansorgei captured near Samaya, Mali, and kept either under artificial laboratory photoperiods [light-dark (LD) cycles: LD 14:10, LD 12:12 or LD 10:14 or caught in the field in Mali and killed at four different times of the year (January, April, June and November). Under artificial photoperiod, the duration of the nocturnal peak of AA-NAT activity and melatonin content increased with the duration of the dark period while the amplitude did not significantly change. In the field, annual variations in the amplitude of the nocturnal melatonin peak were observed with a maximum in April (highest temperature, low humidity and no grass availability, only seeds) and a minimum in November (high humidity, maximum green grass availability). The variations in the amplitude of the melatonin peak were not correlated with changes in AA-NAT HIOMT activities, suggesting that seasonal variations in the amplitude of the melatonin peak are not driven by these enzymes. Daytime injections of the beta-adrenergic agonist, isoproterenol, stimulated melatonin synthesis in January, April and June, but not in November. The annual differences in the amplitude of the melatonin peak as well as the seasonal differences in the response to an adrenergic stimulation suggest that environmental factors other than photoperiod, such as temperature, humidity and consequent food availability, could be important in the regulation of the annual variations in the pineal biosynthetic activity in this species.

Acetylserotonin O-Methyltransferase↗
PubMed1997

Experimental evaluation of rodent exclusion methods to reduce hantavirus transmission to humans in rural housing.

An experimental assessment of methods to reduce rodent infestations in rural housing was conducted in Yosemite National Park, California, Sequoia/Kings Canyon National Parks, California, and Shenandoah National Park, Virginia. During pretreatment surveys, nearly all (63 of 68) selected units had past or ongoing rodent activity inside. Active infestations were found in 58.8% of the units. Peromyscus spp. represented 91.2% of all animals caught inside housing units. Despite little harborage, rodent activity was common near housing (290 animals/2,254 trap nights). The most common species present was Peromyscus maniculatus (43-50% of all captures). This species was especially frequent (49-87% of Peromyscus captures) around the foundations of housing units. Habitat had little effect on captures. There were 1.8 Peromyscus caught per unit along the foundations of housing in modified rural settings with grass lawns compared with 1.2 Peromyscus caught per unit in sites located in mature woodlands. During autumn of 1994, randomly selected housing units were rodent proofed by sealing openings associated with chases, roof eaves, and attics with insulation and wire mesh. Housing was examined and the fauna was resampled in the spring-summer of 1995. Rodent-proofed houses were infested significantly less often (3 of 28) than control houses (13 of 36) (P = 0.02) and the intensity of infestation was lower in experimental houses (6 versus 23 mice/treatment). More than 25% of the mice trapped inside the houses had been marked outside the houses during the three-day surveys, demonstrating movement of mice adjacent to the buildings into not rodent-proofed housing. As in the previous autumn, most of the animals captured in (98.9%) and along the foundations of the houses (77.5%) were Peromyscus spp. These results demonstrate that Peromyscus frequently invade rural housing but rodent-proofing effectively eliminates or substantially reduces rodent activity.

Animals↗
PubMed2006

Early loss of Fhit in the respiratory tract of rodents exposed to environmental cigarette smoke.

The Fhit gene, encompassing the most active common human chromosomal fragile region, FRA3B, has been shown to act as a tumor suppressor. Several studies have shown significant Fhit alterations or Fhit protein loss in lung cancers from smokers compared with lung cancers from nonsmokers. To evaluate the role of Fhit under controlled experimental conditions, we exposed rodents to environmental cigarette smoke (ECS) and evaluated Fhit expression or Fhit protein in the respiratory tract. After 14 days of exposure to ECS, loss of Fhit protein in the bronchial/bronchiolar epithelium affected half of the tested B6-129(F(1)) mice, either wild type or Fhit(+/-). After 28 days, it affected the vast majority of the tested SKH-1 hairless mice and of A/J mice and all (UL53-3 x A/J)F(1) mice, either wild type or P53(+/-). In Sprague-Dawley rats, exposure to ECS for up to 30 days caused a time-dependent loss of Fhit in pulmonary alveolar macrophages. Moreover, ECS down-regulated Fhit expression and significantly decreased Fhit protein in the rat bronchial epithelium. The oral administration of N-acetylcysteine attenuated the ECS-related loss of Fhit, whereas oltipraz, 5,6-benzoflavone, phenethyl isothiocyanate, and indole 3-carbinol, and their combinations had no significant effect. Parallel studies evaluated a variety of molecular, biochemical, and cytogenetic alterations in the respiratory tract of the same animals. In conclusion, there is unequivocal evidence that Fhit is an early, critical target in smoke-related lung carcinogenesis in rodents, and that certain chemopreventive agents can attenuate the occurrence of this gene alteration.

Acetylcysteine↗
PubMed2006

Refractometry for quality control of anesthetic drug mixtures.

Injectable anesthetic drugs used in rodents are often mixed and further diluted to increase the convenience and accuracy of dosing. We evaluated clinical refractometry as a simple and rapid method of quality control and mixing error detection of rodent anesthetic or analgesic mixtures. Dilutions of ketamine, xylazine, acepromazine, and buprenorphine were prepared with reagent-grade water to produce at least 4 concentration levels. The refraction of each concentration then was measured with a clinical refractometer and plotted against the percentage of stock concentration. The resulting graphs were linear and could be used to determine the concentration of single-drug dilutions or to predict the refraction of drug mixtures. We conclude that refractometry can be used to assess the concentration of dilutions of single drugs and can verify the mixing accuracy of drug combinations when the components of the mixture are known and fall within the detection range of the instrument.

Acepromazine↗