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PubMed1985

Delayed developmental sequences in rodent diabetic embryopathy.

Diabetes induced by alloxan at day 6 of gestation in Wistar rats produced decreased fetal growth, delayed skeletal ossification, decreased fetal kidney beta-glucuronidase, and an increased frequency of fetal birth defects which correlated with the degree of diabetic control. Offspring of severely diabetic mothers (mean blood glucose greater than 501 mg/dl) sacrificed at 20 days had a mean weight of 2.12 +/- 0.16 g, a mean of 1.8 +/- 0.46 caudal ossification centers, and a 28% incidence of birth defects as compared to 3.70 +/- 0.22 g, 5.9 +/- 0.42 caudal centers, and 1.1% defects for controls. Offspring of severely diabetic mothers sacrificed at 21 days had mean numbers of caudal and sternal ossification centers which did not significantly differ from controls, indicating that decreased ossification observed at 20 days of gestation is a delayed developmental sequence which is mostly corrected by 21 days. Offspring of moderately diabetic (mean blood glucose 300-500 mg/dl) and insulin-treated dams (mean blood glucose 152-168 mg/dl) had intermediate degrees of growth or ossification delay and birth defect frequency at both the 20- and 21-day sacrifices. Maternal diabetes also retards the developmental increase in fetal kidney beta-glucuronidase such than 20-day offspring of severely diabetic mothers had a mean specific activity of 1.1 nmol/min/mg compared to 3.0 nmol/min/mg for controls. The results support prior studies in rodents suggesting a progression of early growth delay, altered developmental sequences, and birth defects in diabetic pregnancy. This progression is suggested as a common teratogenic mechanism which has implications for evaluating analogous pregnancies in man.

Animals↗

PubMed2006

Habitat-specific impacts of multiple consumers on plant population dynamics.

Multiple consumers often attack seeds, seedlings, and adult plants, but their population-level consequences remain uncertain. We examined how insect and small mammal consumers influenced the demography and abundance of the perennial shrub, bush lupine (Lupinus arboreus). In grassland and dune habitats we established replicate experimental lupine populations in 81-m2 plots that were either protected from, or exposed to, herbivorous voles and granivorous mice (via fencing) and/or root feeding insects (via insecticide treatment). Populations were initiated with transplanted seedlings in 1999 and 2000. We followed the demography of these cohorts, subsequent generations, and the seed bank for 5.5 years. Voles and insects killed many seedlings in dune (1999 only) and grassland (1999 and 2000) habitats. After 2000, insects and voles had minimal effects on seedling or adult survival. Seed predation by granivorous mice, however, greatly depressed seedling recruitment, resulting in lower adult lupine abundance in control plots vs. those protected from rodents. In grasslands, initial effects of voles and insects on seedling survival produced large differences among treatments in adult plant density and the cumulative number of seeds produced throughout the experiment. Differences among grassland populations in seed rain, however, had little influence on the magnitude of seedling recruitment into this habitat. Instead, recruitment out of a preexisting seed bank compensated for the lack of seed production in populations exposed to consumers. Shading by dense adults in plots protected from consumers limited seedling establishment within these populations. Although differences among populations in cumulative seed rain did not influence adult establishment, populations protected from consumers accumulated substantially larger seed banks than controls. These results illustrate how density dependence, habitat-specific seed dynamics, and particular demographic impacts of consumers interact to shape plant population responses to consumers.

Analysis of Variance↗

PubMed1993

Host feeding preference of Phlebotomus guggisbergi, a vector of Leishmania tropica in Kenya.

Recently the sandfly Phlebotomus guggisbergi was found to be a vector of Leishmania tropica causing cutaneous leishmaniasis in the Laikipia focus, Kenya, but extensive searches have shed no light on the identity of the rural reservoir host(s). In order to discover more about the biology of the vector, a host feeding preference study was conducted on wild sandflies in their natural cave environment over a 6-month period. Solid state Army miniature (SSAM) traps, without light bulb, were suspended over cages with potential hosts or an empty cage control. The animals tested included sheep, goat, dog, cat, hamster, rabbit, giant rat (Cricetomys gambianus), crested rat (Lophiomys imhausi) and rock hyrax (Procavia capensis), all of which (except hamsters) are normally found in the vicinity of the study site. Sandfly collections from traps baited with goat, sheep, cat, dog, rabbit, or wild rodent species were significantly higher than the control, whereas trap collections with hamster and rock hyrax were not significantly different from the control. Numbers of sandflies collected from the goat, sheep and cat were significantly greater than from the rabbit and rodents. The sex ratio also varied between collections: larger animals attracted a higher proportion of female P. guggisbergi than did the smaller animals (P > 0.05). Therefore greater emphasis should be placed on surveying larger animals to assess their status as reservoir hosts for L. tropica in Kenya.

Animals↗

PubMed1994

Purkinje cell density in cerebella of alcoholized and non-alcoholized male rat offspring.

The effect of alcohol intake by male rats was evaluated on Purkinje cell morphology and number in their offspring. Forty five male Wistar rats, 45 days old, were used and divided into three groups of 15 rats each: control group (CG), fed with conventional Purina rodent feed (CPRF) and water ad libitum; experimental group (EG), fed with CPRF ad libitum and a mixture of water/ethanol, which represented 36% of kilocalories in food; and an equienergetic intake control group (ECG), which was given CPRF (in grams) and sugar in their drinking water, in order to substitute the energetic value provided by alcohol. Five subgroups (n = 3) were created to be used for different treatment periods: 60, 90, 120, 150 and 180 days; all groups started treatment when they were 70 days old. At the end of each treatment period, male rats were mated with nulliparous females not having undergone treatment. Offspring were obtained and studied at 14 and 21 days of age. The Purkinje cells of the cerebella of 14- and 21-day-old offspring belonging to the CG and ECG showed no morphological changes. On the other hand, in 14-day-old offspring belonging to the experimental group of parents alcoholized during 90, 120, and 180 days, a large number of hyperchromatic Purkinje cells were seen, forming zones of cells undergoing a degenerative process. No significant differences in cellular density were determined between the CG and the ECG. When comparing the CG vs. EG and the ECG vs. EG, significant differences were found in the 14-day-old offspring as well as in the 21-day-old ones with a p < 0.05 of rats belonging to parents alcoholized for 90, 120, and 180 days. The results may indicate that there are changes in the germinal plasma of males due to alcohol consumption; therefore, reflecting this effect on a decrease of Purkinje cells and probably on other cell populations.

Alcoholism↗

PubMed2000

Two-dimensional electrophoresis of liver proteins: characterization of a drug-induced hepatomegaly in rats.

Two-dimensional electrophoresis (2-DE) of liver proteins was applied to further characterize an unusual drug-induced increase in hepatocellular rough endoplasmic reticulum (RER) in Sprague-Dawley rats given a substituted pyrimidine derivative. Absolute liver weights of drug-treated rats (9.9 +/- 0.4 g) increased above vehicle-treated controls (7.2 +/- 0.2 g) by 37%. Light microscopy revealed diffuse granular basophilia of the hepatocellular cytoplasm, uncharacteristic of hepatocytes and suggested cells rich in ribosomes, which was confirmed by electron microscopy. Immunostaining for cell proliferation, viz., 5-bromo-2'-deoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA), indicated marked hepatocellular proliferative activity. 2-DE of solubilized liver using an ISO-DALT gel system indicated significant (p<0.001) quantitative changes in at least 17 liver proteins (12 increased, 5 decreased) compared to controls. The protein with the largest increase was homologous to acute-phase reactant, contrapsin-like protein inhibitor-6. Other markedly upregulated proteins were methionine adenosyltransferase, a catalyst in methionine/ATP metabolism and mitochondrial HMG-CoA synthase, involved in cholesterol synthesis. The complementary strategies of 2-DE coupled either with database spot mapping or protein isolation and amino acid sequencing successfully identified a subset of proteins from xenobiotic-damaged rodent livers, the expression of which differed from controls. However, the current bioinformatics platform for rodent hepatic proteins and limited knowledge of specific protein functionality restricted application of this proteomics profile to further define a mechanistic basis for this unusual hepatotoxicity.

Animals↗

PubMed2002

Visual pigment coexpression in all cones of two rodents, the Siberian hamster, and the pouched mouse.

PURPOSE: To decide whether the identical topography of short- and middle-wavelength cone photoreceptors in two species of rodents reflects the presence of both opsins in all cone cells. METHODS: Double-label immunocytochemistry using antibodies directed against short-wavelength (S)-and middle- to long-wavelength (M/L)-sensitive opsin were used to determine the presence of visual pigments in cones of two species of rodents, the Siberian hamster (Phodopus sungorus) and the pouched mouse (Saccostomus campestris) from South Africa. Topographical distribution was determined from retinal whole-mounts, and the colocalization of visual pigments was examined using confocal laser scanning microscopy. Opsin colocalization was also confirmed in consecutive semithin tangential sections. RESULTS: The immunocytochemical results demonstrate that in both the Siberian hamster and the pouched mouse all retinal cones contain two visual pigments. No dorsoventral gradient in the differential expression of the two opsins is observed. CONCLUSIONS: The retina of the Siberian hamster and the pouched mouse is the first example to show a uniform coexpression of M and S cone opsins in all cones, without any topographical gradient in opsin expression. This finding makes these two species good models for the study of molecular control mechanisms in opsin coexpression in rodents, and renders them suitable as sources of dual cones for future investigations on the role and neural connections of this cone type.

Animals↗

PubMed2006

Standard morphologic evaluation of the heart in the laboratory dog and monkey.

The nonrodent species most commonly utilized in preclinical safety studies are the purpose-bred beagle dog and cynomolgus macaque (Macaca fascicularis). Potential effects of a new chemical entity (NCE) on the heart pose serious concerns; consequently in vivo testing is focused on detection of functional alterations as well as morphological changes. Macroscopic and microscopic evaluation of the heart is based on a standard survey of key structures to properly assess presence of spontaneous and potential drug-induced lesions. Evaluation of historical controls to determine type and frequency of background change is valuable, as studies with non-rodent species generally have a small sample size. Archived control dog and monkey data were retrospectively reviewed, including terminal body weight (BW), heart weight (HW), and archival glass slides of heart. Control dogs had minimal background changes that included myxomatous or cartilagenous change in the cardiac skeleton and a variable degree of vacuolation in Purkinje fibers. Control monkey hearts commonly contained inflammatory cell infiltrates, myocyte anisokaryosis, and handling artifacts, while myocyte degeneration, squamous plaques, pigment, and intimal plaques were occasionally observed. These findings highlight the utility of consistently recorded and readily accessible archived control data when attempting to discern background spontaneous changes and artifacts from test-article induced changes.

Animals↗

PubMed2007

Chicken ovalbumin upstream promoter transcription factor II regulates uncoupling protein 3 gene transcription in Phodopus sungorus.

BACKGROUND: Ucp3 is an integral protein of the inner mitochondrial membrane with a role in lipid metabolism preventing deleterious effects of fatty acids in states of high lipid oxidation. Ucp3 is expressed in brown adipose tissue and skeletal muscle and controlled by a transcription factor complex including PPARalpha, MyoD and the histone acetyltransferase p300. Several studies have demonstrated interaction of these factors with chicken ovalbumin upstream promoter transcription factor II (Coup-TFII). This nuclear receptor is involved in organogenesis and other developmental processes including skeletal muscle development, but also co-regulates a number of metabolic genes. In this study we in silico analyzed the upstream region of Ucp3 of the Djungarian hamster Phodopus sungorus and identified several putative response elements for Coup-TFII. We therefore investigated whether Coup-TFII is a further player in the transcriptional control of the Ucp3 gene in rodents. RESULTS: By quantitative PCR we demonstrated a positive correlation of Coup-TFII and Ucp3 mRNA expression in skeletal muscle and brown adipose tissue in response to food deprivation and cold exposure, respectively. In reporter gene assays Coup-TFII enhanced transactivation of the Ucp3 promoter conveyed by MyoD, PPARalpha, RXRalpha and/or p300. Using deletions and mutated constructs, we identified a Coup-TFII enhancer element 816-840 bp upstream of the transcriptional start site. Binding of Coup-TFII to this upstream enhancer was confirmed in electrophoretic mobility shift and supershift assays. CONCLUSION: Transcriptional regulation of the Coup-TFII gene in response to starvation and cold exposure seems to be the regulatory mechanism of Ucp3 mRNA expression in brown adipose and skeletal muscle tissue determining the final appropriate rate of transcript synthesis. These findings add a crucial component to the complex transcriptional machinery controlling expression of Ucp3. Given the substantial evidence for a function of Ucp3 in lipid metabolism, Coup-TFII may not only be a negative regulator of glucose responsive genes but also transactivate genes involved in lipid metabolism.

Animals↗

PubMed2002

Lithium modulates expression of TRH receptors and TRH-related peptides in rat brain.

Lithium is an established mood stabilizer and neuroprotective agent frequently used in the treatment of bipolar disorder and as an adjuvant in drug-resistant unipolar depression. The mechanisms underlying both the therapeutic efficacy of lithium and the exacerbation of symptoms following rapid withdrawal are not understood. From previous studies showing antidepressant and neuroprotective activities of thyrotropin releasing hormone (TRH) and TRH-related neuropeptides we hypothesized that lithium may have substantial effects on the expression and secretion of these peptides and/or their receptors in various rat brain regions involved in the regulation of mood. Chronic lithium effect on TRH receptor binding studies: The effect of 1 and 2 weeks of dietary lithium on [(3)H]3-Me-His-TRH binding to plasma membranes of nucleus accumbens, amygdala and pituitary of young adult male Wistar and the endogenously 'depressed' Wistar Kyoto (WKY) rats was measured by the method of Burt and Taylor [Burt, D.R., Taylor, R.L., Endocrinology 106 (1980) 1416-1423]. Acute, chronic and withdrawal effect of lithium on TRH and TRH-like peptide levels in young, adult male Sprague-Dawley rats: Rats were divided into four lithium treatment groups. Control animals received a standard laboratory rodent chow. The acute group received a single i.p. injection of 1.5 milli-equivalents of LiCl 2 h prior to killing. The chronic and withdrawal groups received standard rodent chow containing 1.7 g/kg LiCl for 2 weeks. Withdrawal rats were returned to standard chow 48 h prior to killing while the chronic animals continued on the LiCl diet. TRH, TRH-Gly (pGlu-His-Pro-Gly, a TRH precursor), EEP (pGlu-Glu-Pro-NH(2), a TRH-like peptide with antidepressant activity) and Ps4 (a prepro-TRH-derived TRH-enhancing decapeptide) immunoreactivity (IR) were measured in 13 brain regions. The remaining samples were pooled and fractionated by high-pressure liquid chromatography followed by EEP radioimmunoassay. Chronic lithium treatment increased [(3)H]3Me-TRH binding in the nucleus accumbens and amygdala about two-fold in both Wistar and WKY rats but no change was observed in pituitary binding. The most widespread changes in TRH and TRH-related peptide levels were observed in the withdrawal group compared to the controls. The direction of change for the total IR was consistent for all TRH-IR and TRH-related peptide-IR within a given tissue. For example, withdrawal increased all peptide levels in the pyriform cortex and striatum but decreased these levels in the anterior cingulate and lateral cerebellum. Both acute injection and chronic treatment with LiCl decreased TRH and TRH-related peptide levels in the entorhinal cortex. Acute injection and withdrawal both increased EEP-IR in striatum by more than two-fold. The acute effects are most likely due to changes in the release of these peptides since 2 h is not sufficient time for alterations in peptide biosynthesis. Chronic treatment increased levels of pGlu-Phe-Pro-NH(2) levels in hippocampus, pGlu-Leu-Pro-NH(2), and peak '2' in septum by more than four-fold. The present results are consistent with a component role for TRH and related peptides in the mood-altering effects of lithium administration and withdrawal frequently observed during treatment for depression and bipolar disorder.

Acute Disease↗

PubMed2005

Just the two of us: melatonin and adenosine in rodent pituitary function.

The function of the pituitary gland is tightly controlled by neuronal and hormonal afferents of the brain. In this review, the role of the neurohormone melatonin and the neuromodulator adenosine for rodent pituitary function will be elucidated. Adenosine is known as an important paracrine modulator for pituitary endocrine and folliculostellate cells, with availability regulated by local metabolic cellular activity. In general, adenosine inhibits the cyclic adenosine monophosphate (AMP) pathway in pituitary cells by binding to A1-, and A3-adenosinergic receptors, and activates it via A2-adenosinergic receptors. The neurohormone melatonin integrates time-of-day and time-of-year into pituitary function via binding to MT1-melatonin receptors. Melatonin impacts at the hypothalamic level neurons that synthesize releasing and release-inhibiting hormones, and at the pituitary level only cells of the hypophyseal pars tuberalis (PT). Thereby, the daily changes in the duration of the nocturnal melatonin surge are decoded and subsequently relayed to the pars distalis to adapt gonadotropin and prolactin release, respectively, to season. An exciting integration of time within the regulation of pituitary function was deciphered by analysing transmembrane signalling events in cells of the hypophyseal PT: a consecutive daily impact of initially the neurohormone melatonin and later the neuromodulator adenosine on rodent PT cells leads to a circadian rhythm in the transcription of cyclic-AMP-sensitive genes.

Adenosine↗

PubMed2005

Mycotoxins in laboratory rodent feed.

Twenty-one batches of fixed-formula rodent diets from three feed manufacturers were tested for the presence of five mycotoxins: deoxynivalenol (DON), nivalenol (NIV), HT-2 toxin, T-2 toxin and ochratoxin A (OTA). Five batches were also tested for the presence of zearalenone (ZEN) and six batches for aflatoxins. Detectable levels of DON (up to 298 microg/kg), NIV (up to 118 microg/kg), OTA (up to 3.1 microg/kg) or ZEN (up to 26.7 microg/kg) were found in samples from all manufacturers. Three batches contained two (DON or NIV and OTA or ZEN) and one batch contained three (DON, OTA and ZEN) different mycotoxins. Aflatoxins, T-2 and HT-2 were not detected in any of the batches. The concentrations of mycotoxins detected in the feed were low, but indicated that feed ingredients, probably the cereal ingredients, were contaminated by mycotoxins. Since mycotoxins are known to have toxic and/or immunosuppressive effects, non-contaminated ingredients should be used for production of laboratory animal feed. The results imply that an improved quality control of ingredients used for laboratory rodent feed should be implemented.

Animal Feed↗

PubMed1999

Lineage selection and the evolution of multistage carcinogenesis.

A wide array of proto-oncogenes and tumour suppressor genes are involved in the prevention of cancer. Each form of cancer requires mutations in a characteristic group of genes, but no single group controls all cancers. This lack of generality shows that the control of cancer is not an ancient, fixed property of cells. By contrast, it supports a dynamic evolutionary model, whereby genetic controls over unregulated cell growth are recruited independently through evolutionary time in different tissues within different taxa. The complexity of this genetic control can be predicted from a population genetic model of lineage selection driven by the detrimental fitness effects of cancer. Cancer occurs because the genetic control of cell growth is vulnerable to somatic mutations (or 'hits'), particularly in large, continuously dividing tissues. Thus, compared to small rodents, humans must have evolved more complex genetic controls over cell growth in at least some of their tissues because of their greater size and longevity; an expectation relevant to the application of mouse data to humans. Similarly, the 'two-hit' model so successfully applied to retinoblastoma, which originates in a small embryonic tissue, is unlikely to be generally applicable to other human cancers; instead, more complex scenarios are expected to dominate, with complexity depending upon a tissue's size and its pattern of proliferation.

Animals↗

PubMed1998

Epidemiology of rodent bites and prediction of rat infestation in New York City.

The authors examined the epidemiology of rodent bites occurring in New York City from 1986 through 1994 to identify factors contributing to increased probability of rodent bite and rat infestation. City blocks on which a rodent bite case had been reported (n=415) and three control blocks per bite block, matched by borough and randomly selected, were compared according to demographic characteristics obtained from US Census data. Environmental variables were defined using a geographic information system to extract distances to areas potentially providing food or refuge for rats, such as parks. Borough-specific models of bite risk were generated by logistic regression using data collected from 1991 to 1994; risk values were then generated for all city blocks. Field surveys for signs of rat infestation conducted on 31 randomly selected blocks indicated a significant association between degree of infestation and predicted risk. Spatial analyses comparing neighboring blocks showed that blocks with bite cases were significantly clustered. The models based on data from previous years correctly predicted 72 percent of 53 block addresses of rodent bite cases from 1995 as being locations of high or intermediate risk. A combination of geographic and epidemiologic analyses could help investigators identify the spatial occurrence of rat infestation over a large area and might help to focus control activities.

Adolescent↗

PubMed1984

Two cell-surface markers for human chromosome 1 in interspecies hybrids.

Monoclonal antibodies AbAJ9 and AbT87 define two distinct human cell-surface antigen systems (1, 2). Both antibodies react with a wide variety of cultured human cell types but not with rodent cell lines. AbAJ9 identifies a glycoprotein of 140,000 mol wt and AbT87 identifies a glycoprotein of 60,000 mol wt. The genetic control of antigen expression was studied in rodent-human somatic cell hybrids containing different subsets of the entire human chromosome complement, using an immune rosetting assay for serological analysis and hybrid selection. The presence of human chromosome 1 was found to be both necessary and sufficient for expression of antigens AJ9 and T87 in hybrid cells. Two independent gene loci on chromosome 1, designated MSK -1 for AJ9 and MSK -2 for T87 , control the expression of these antigens. We have assigned MSK -1 to region 1 cen-p22 and MSK -2 to region 1q32 -qter, using hybrids containing only fragments of human chromosome 1.

Animals↗

PubMed1991

Effectiveness of host-targeted permethrin in the control of Ixodes dammini (Acari: Ixodidae)

Tubes of commercially available permethrin-treated cotton balls were distributed twice each year in 1989 and 1990 at five sites in a Lyme disease endemic area in Connecticut. Five additional sites were not treated. At each application, 48 tubes, sufficient to treat 0.4 ha, were dispersed at 10-m intervals through woodlands, around ornamental plantings, and along rockwalls. The cotton was collected by white-footed mice (Peromyscus leucopus) from the majority of the tubes, which resulted in a decrease (37.2% in 1989 and 91.5% in 1990) in the number of subadult Ixodes dammini Spielman, Clifford, Piesman, and Corwin on the mice in the treated areas. There were no significant decreases in the number of host-seeking nymphs or adults of I. dammini in 1989 or 1990 between the treated and untreated sites. The rates of infection in the host-seeking nymphs with Borrelia burgdorferi, the etiological agent of Lyme disease, at the treated sites (13.0 and 14.6% for 1989 and 1990, respectively) were comparable to those at the untreated sites (16.9 and 13.2% for 1989 and 1990, respectively). The distribution of permethrin-treated cotton around individual residences significantly reduced the number of ticks on P. leucopus but was not sufficient to reduce the risk of exposure to infected host-seeking nymphs and adults of I. dammini after two seasons of treatment.

Animals↗

PubMed1999

A case-control study after a hantavirus infection outbreak in the south of Belgium: who is at risk?

Puumala is the most common hantavirus serotype in Europe and is spread mainly by the red bank vole. Between 1 July 1992 and 31 January 1994, an outbreak of Puumala virus-induced nephropathia epidemica (NE) occurred in the Belgian Ardennes. Serologically confirmed cases (n = 41) were compared with two groups of asymptomatic seronegative controls. Risks identified included sighting of living rodents, exposure to rodent droppings, and trapping rodents during the 4 weeks preceding onset of symptoms. Activities during this 4-week period that presented the greatest risk were woodcutting, reopening of a nonaerated room, and strenuous physical effort. This is the first case-control study on risk factors for NE in Europe. In comparison with the American form of hantavirus pulmonary syndrome, which is spread by deer mice, professional activity appears to be a more important risk factor for acquisition of hantavirus in Europe.

Adolescent↗

PubMed1982

Rodent islet cell antigens recognized by antibodies in sera from diabetic patients.

Rat islets, rat insulinoma cells and islets from three different mouse strains were labelled with 35S-cysteine and/or 35S-methionine. Detergent lysates of the cells were subjected to immunoprecipitation with sera from 5 newly diagnosed diabetic children and 5 control sera. The immunoprecipitates were analysed by sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis followed by autoradiography. One of the sera immunoprecipitated a protein of Mr 64K from lysates of rat islets, rat insulinoma cells, A. TH and NMRI but not CBA/H mouse islets. This protein was not consistently immunoprecipitated by the other diabetic sera, however, it was never found with control sera nor was it detected in rodent lymphocytes. Some proteins of lower molecular weight (59K, 57K, 40K, 29K) were specifically immunoprecipitated by one or more diabetic sera from some of the rodent islet cell preparations. It is concluded that rodent islet cells contain a protein of Mr 64K which may be antigenically related to a 64K protein previously detected in immunoprecipitates of human islet cells with the same diabetic sera. The variable results with rat and mouse islet cell material suggest that the level of cross-reactivity is low. Further studies are needed to clarify whether the lower molecular components detected in some immunoprecipitates represent other antigenic determinants or degradation products of the 64K protein.

Adolescent↗

PubMed2003

Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies.

Dietary supplements containing conjugated linoleic acid (CLA) are widely promoted as weight loss agents available over the counter and via the Internet. In this review, we evaluate the efficacy and safety of CLA supplementation based on peer-reviewed published results from randomized, placebo-controlled, human intervention trials lasting more than 4 weeks. We also review findings from experimental studies in animals and studies performed in vitro. CLA appears to produce loss of fat mass and increase of lean tissue mass in rodents, but the results from 13 randomized, controlled, short-term (<6 months) trials in humans find little evidence to support that CLA reduces body weight or promotes repartitioning of body fat and fat-free mass in man. However, there is increasing evidence from mice and human studies that the CLA isomer trans-10, cis-12 may produce liver hypertrophy and insulin resistance via a redistribution of fat deposition that resembles lipodystrophy. CLA also decreases the fat content of both human and bovine milk. In conclusion, although CLA appears to attenuate increases in body weight and body fat in several animal models, CLA isomers sold as dietary supplements are not effective as weight loss agents in humans and may actually have adverse effects on human health.

Animals↗