The effect of yeast glycans in experimental LPS-induced endotoxicosis

The immunomodulating action of yeast glycans obtained from Rhodotorula rubra (rhonasan) and Sporobolomyces albo-rubescens (heteroglycan Sp-50) was studied under the conditions of experimental endotoxicosis in mice, induced by the injection of the sublethal dose of Escherichia coli lipopolysaccharide (LPS). In endotoxicosis glycans produced a protective effect, depending on the time of injection. The study demonstrated that after the injection of glycans the survival rate of the animals increased and the LPS-inhibited function of peritoneal macrophages and B lymphocytes was completely or partially restored.     

Metabolic basis of endotoxicosis.

Whereas as specific immunological responses are elicited only after a delay of some days, alteration in various biochemical parameters is observed within 1-2 h of endotoxin administration in a number of animal species. Generally the level of several hepatic enzymes (tryptophan pyrrolase, phophoenol pyruvate carboxykinase) metabolites (glycogen, NAD) and intermediates in the energetic homeostasis is lowered by the toxin, increased by the glucocorticoid hormones and maintained at the normal level when the toxic effects of endotoxin are annulled by the counter effects of the protective agent (such as cortisone). Antagonism is also noted on the synthesis of cellular RNA, DNA and protein. However, no unitary process has as yet been singled out to possessing a cause and effect relationship between toxicity and survival. In the intact animal, it is not possible to affirm whether the toxin exerts a direct effect on the organ, the cell or the process in question, especially since endotoxin is phagocytized by the cells of the reticuloendothelial system (RES) in the liver and elsewhere and since the biochemical parameters are a property of the organ specific epithelial cells. Experiments with tissue slices suffer from the problem of permeability and uptake in vitro and are not readily reproducible. Isolated cells in culture are theoretically ideal but exhibit loss of functions and undergo neoplastic type of transformation that renders them unsuitable for relevant biochemical studies. Primary explants of the hepatocytes and the RE cells, as well as hybrids between these two cellular types appear more promising. However, at the moment, isolated liver preparations perfused in vitro offer the best solution by exhibiting intact function, morphology and excellent reproducibility. Collectively, it is tempting to speculate that the extent of subsequent immunological response is a reflection of the preceding biochemical processing, that both sorts of events are in some way mediated by the RE cells, and that the latter may most easily be studied in the intact liver in vitro.     

The influence of hyperbaric oxygen on hemorheological parameters in diabetic rats

The effect of hyperbaric oxygen (HBO2) treatment on hemorheological parameters of diabetic rats was investigated. This study is a placebo-controlled, in vivo animal study. 30 streptozocin-induced diabetic rats were divided into two groups; one group received hyperbaric oxygen treatment while the other did not. Hematological and hemorheological parameters were tested with blood samples collected directly from the heart using surgical procedures. Student t-tests with a type I (alpha) error at 0.05 was used to test any significant difference between means of the hematologic and hemorheological parameters of the control (CON) and the HBO2 groups. Compared with the placebo group, hyperbaric oxygen resulted in significant higher lipid peroxidation stress of the erythrocytes and resistance of erythrocytes to deformation in rats of the HBO2 group. Whole blood viscosities measured at shear rates of 5, 150 and 400 s(-1) were all higher for the rats in the HBO2 group than those for rats in the control group. In addition, the oxygen delivery index was found to be significantly lower in rats of the HBO2 group. Thus, our work demonstrates that hyperbaric oxygen treatment significantly changes the hemorheological parameters in diabetic rats.     

The complex influence of environmental factors on the state of microcirculation

The state of microcirculation system and its regulation in peace and after growing physical activity is analyzed on people living in different ecological regions. There are three main types of microcirculation. The level of regulation mechanisms activity depends on the type of microcirculation, region of residence and the value of physical activity. People living in a relatively clean regions have stable mechanisms of regulation despite of the level of activity. Mesoemic type living in toxic radiation regions have reduced contribution of VLF and LF-fluctuation (p < 0.05); hypoemic type living in toxic regions have VLF and LF-fluctuation (p < 0.05); hyperemic type living in toxic regions have LF-fluctuation (p < 0.05). We can conclude the tension of regulatory machanisms in microcirculation system increases under ecological pressure and borders on failure of adaptation process.     

The influence of carnosinase gene polymorphisms on diabetic nephropathy risk in African-Americans

Four genome wide linkage scans for diabetic nephropathy have mapped susceptibility loci to chromosome 18q22.3-23 in the region of the carnosinase genes, CNDP1 and CNDP2. CNDP1 has been associated with diabetic nephropathy in Europeans and European Americans, but not African-Americans. Individuals homozygous for a five tri-nucleotide repeat allele (5L; D18S880) are protected from diabetic nephropathy. We identified 64 variants after sequencing the exons, promoter, and 3′ UTR of CNDP1 and CNDP2 in African-American and European American DNA samples. After scanning 44 of these variants, extensive genotyping of 12 SNPs and D18S880 was performed in 1,025 African-American cases with type 2 diabetes (DM)-associated end-stage renal disease (ESRD) and 1,064 African-American non-diabetic non-nephropathy controls to assess whether the carnosinase genes influence risk for DM-ESRD in African-Americans. Evidence of association with DM-ESRD was seen with 2 SNPs: rs6566810 and rs4892247; 3 two-marker haplotypes: rs6566810 and rs17089362, rs17089362 and rs890336, and rs890334 and rs12717111 (global empirical P = 0.0034, 0.0275, and 0.0002, respectively) and 3 three-marker haplotypes: rs6566810, rs17089362, and rs890336; rs890335, rs890334, and rs12717111; and rs890334, rs12717111, and D18S880 (global empirical P = 0.0074, 1.5E-05, and 0.0032, respectively). The risk haplotypes (rs6566810, rs17089362 [A,T] and rs6566810, rs17089362, rs890336 [A,T,C]) were most strongly associated with DM-ESRD among African-Americans in the non 5L–5L group. Variants in the carnosinase genes appear to contribute to diabetic nephropathy susceptibility in African-Americans. Protection from diabetic nephropathy afforded by 5L–5L homozygosity in CNDP1 may be masked by the effects of additional risk haplotypes in CNDP1 and CNDP2. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Genetic and environmental influence on diabetic rat embryopathy

We assessed genetic and environmental influence on fetal outcome in diabetic rat pregnancy. Crossing normal (N) and manifestly diabetic (MD) Wistar Furth (W) and Sprague-Dawley (L) females with W or L males yielded four different fetal genotypes (WW, LL, WL, and LW) in N or MD rat pregnancies for studies. We also evaluated fetal outcome in litters with enhanced or diminished severity of maternal MD state, denoted MD(+)WL and MD(-)LW. The MDWW litters had less malformations and resorptions (0 and 19%) than the MDLL litters (17 and 30%). The MDWL litters (0 and 8%) were less maldeveloped than the MDLW litters (9 and 22%), whereas the MD(+)WL (3 and 23%) and MD(-)LW (1 and 17%) litters showed increased and decreased dysmorphogenesis (compared with MDWL and MDLW litters). The pregnant MDW rats had lower serum levels of glucose, fructosamine, and branched-chain amino acids than the pregnant MDL rats, whereas the pregnant MD(+)W and MD(-)L rats had levels comparable with those of the MDL and MDW rats, respectively. The 8-iso-PGF2α levels of the malformed MDLW offspring were increased compared with the nonmalformed MDLW offspring. Diabetes decreased fetal heart Ret and increased Bmp-4 gene expression in the MDLW offspring and caused decreased GDNF and Shh expression in the malformed fetal mandible of the MDLW offspring. We conclude that the fetal genome controls the embryonic dysmorphogenesis in diabetic pregnancy by instigating a threshold level for the teratological insult and that the maternal genome controls the teratogenic insult by (dys)regulating the maternal metabolism.     

The influence of nutritional state on shoal choice in zebrafish, Danio rerio

We investigated the mechanisms and functions of shoal choice in relation to nutritional state in the zebrafish. Single fish that had been well fed or food deprived for 2 days were presented with a choice between two stimulus shoals. Food-deprived test fish showed a significant preference for well-fed stimulus fish over food-deprived ones whereas well-fed test fish did not exhibit any significant preference. Subsequent experiments showed that food-deprived test fish had a significantly higher foraging success in shoals consisting of well-fed individuals than in ones that comprised food-deprived fish. No difference in the locomotory behaviour of food-deprived and well-fed stimulus fish was found with respect to the proportion of time spent swimming (as opposed to being motionless), the proportion of time spent in the upper part of the test tank and the number of sharp turns. However, body weight, stomach width (measured directly behind the pectoral girdle) and ventro-dorsal height significantly decreased over a 48-h food-deprivation period. The potential use of the latter factors for the recognition of food-deprived individuals is discussed. Copyright 1999 The Association for the Study of Animal Behaviour.     

The influence of salt on the aggregation state of spectrin from bovine ertythrocyte membranes

Sedimentation velocity and gel filtration experiments have been performed with bovine spectrin over a wide range of neutral salt concentrations. Increasing salt concentrations tend to increase both the sedimentation coefficient of spectrin and the elution volume of the protein from 4% agarose columns. No conformation change can be detected by means of optical rotation measurements as the salt concentration is raised. The results are incompatible with the hypothesis that salt causes the aggregation of spectrin, but are consistent with the existence of marked charge effects operative at low salt concentrations. In support of the charge effect hypothesis, acidic groups have been detected on the agarose gels, and ion-exclusion behaviour on the column has been observed with other proteins of similar size.     

The influence of naringin on the oxidative state of rats with streptozotocin-induced acute hyperglycaemia

The effect of various doses (0, 10, 20, 40, or 80 mg/kg body weight) of naringin (a citrus flavonone) was studied on streptozotocin (STZ)-induced hyperglycaemic rats to evaluate the possible hypoglycaemic and antioxidant activity of naringin in diabetes. In comparison to the normoglycaemic group the treatment of rats with a single dose of STZ (65 mg/kg body weight) only revealed a significant increase (P < 0.05) in plasma hydrogen peroxide (H2O2) by 230%, increased the thiobarbituric acid reactive substances (TBARS) as index of the lipid peroxidation level by 69%, while total antioxidant activity was decreased by 36%, with a consistent significant decrease (P < 0.05) in the activity of erythrocytes antioxidative enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and paraoxonase (PON). Exogenous administration of individual gradual doses of naringin to hyperglycaemic rats causes a dose-dependent decrease of the glucose level, an increase of the insulin concentration, a decrease of the H2O2 and TBARS levels, as well as the increase of the total antioxidant status with an increase of antioxidant enzyme activities (CAT, SOD, GPx, and PON). From this study, it may be concluded that all doses of naringin provided a significant amelioration of hypoglycaemic and antioxidant activity in STZ-induced diabetic rats, however, the greatest effect of naringin was observed at 80 mg/kg body weight.     

The influence of respiratory state on monoamine oxidase activity in rat liver mitochondria.

Changes in the respiratory state of rat liver mitochondria caused significant changes (up to 10-fold) in the rates of oxidative deamination of tyramine, indicating interactions between the inner coupling membrane and the monoamine oxidase sites in the outer membrane, and suggesting the possibility that monoamine oxidase is regulated by the thermodynamic state of the mitochondria.     

Integrated influence of environmental factors on the state of microcirculation

The microcirculation system and its regulation at rest and after gradually growing physical activity in subjects living in different environmental regions was studied using laser Doppler flowmetry. Three main types of microcirculation were found. The activity of regulation mechanisms depended on the microcirculation type, residence region, and level of physical activity. Subjects living in relatively clean regions displayed stable regulation mechanisms irrespective of the level of activity. Subjects with the mesoemic type of microcirculation from regions with a high toxic contamination, high radiation background, or exposed to combined adverse factors, as well as subjects with the hypoemic type exposed to toxic and combined factors displayed a decreased contribution of VLF and LF oscillations (p < 0.05), and subjects with the hyperemic type from toxically contaminated regions displayed a decreased contribution of LF oscillations (p < 0.05). The results indicate that, under environmental pressure, regulatory mechanisms are exerted to the extent verging on adaptation failure.     

Dysfunction of soluble guanylyl cyclase in aorta and kidney of Goto-Kakizaki rats: influence of age and diabetic state.

Type 2 diabetes mellitus is frequently associated with arterial hypertension. The mechanisms involved in this association are not known in detail, but endothelial dysfunction and a blunted vascular response to endogenous vasodilators are thought to play a role. In the present study we investigated the in vitro activity of vascular and renal soluble guanylyl cyclase in type 2 diabetic Goto-Kakizaki rats aged 5, 15, and 30 weeks, in comparison with age-matched Wistar controls. Blood pressure was monitored by radiotelemetry, and serum glucose and insulin concentrations were measured by standard assays. Goto-Kakizaki rats of all age groups had serum glucose concentrations significantly higher than those of corresponding Wistar controls. Serum insulin was unchanged until 15 weeks of age and was elevated in the 30-week-old diabetic rats. Blood pressure in Goto-Kakizaki rats was significantly higher than that in Wistar controls, and heart rate was significantly lower. Mesenteric arteries of diabetic rats showed a blunted relaxation in response to acetylcholine and sodium nitroprusside. In aortic tissue from Wistar rats an age-dependent increase was found in nitric oxide-stimulated cGMP formation, which was absent in the diabetic animals. Moreover, the maximum activity of soluble guanylyl cyclase was significantly lower in Goto-Kakizaki rats in all age groups studied. In renal tissue no differences were found between diabetic and control rats, except at 30 weeks of age when Goto-Kakizaki rats showed a significant reduction in basal and stimulated guanylyl cyclase activity. In conclusion, the present study shows a persistent reduction in vascular nitric oxide-sensitive guanylyl cyclase in Goto-Kakizaki rats, which occurred shortly after weaning and may contribute to the elevation in blood pressure in this strain of genetically diabetic rats.     

The influence of aphid-produced honeydew on parasitoid fitness and nutritional state: A comparative study

Honeydew is a sugar-rich resource excreted by many hemipteran species and is a key food source for other insect species such as ants and parasitoid wasps. Here, we evaluated the nutritional value of 14 honeydews excreted by 13 aphid species for the generalist aphid parasitoid Lysiphlebus testaceipes to test a series of hypotheses concerning variation in the nutritional value of honeydew. There was a positive correlation between the body sugar content of honeydew-fed parasitoids and their longevity. This information is valuable for biological control researchers because it demonstrates that the nutritional state of honeydew-fed parasitoids in the wild can indicate their fitness, independently of the honeydew source they have fed on.Although the carbohydrate content and longevity of L. testaceipes differed greatly among the different honeydews, we did not find a significant effect of aphid or host plant phylogeny on these traits. This result suggests that honeydew is evolutionarily labile and may be particularly subject to ecological selection pressures. This becomes apparent when considering host aphid suitability: Schizaphis graminum, one of the most suitable and commonly used hosts of L. testaceipes, produced honeydew of the poorest quality for the parasitoid whereas Uroleucon sonchi, one of the few aphids tested that cannot be parasitized by L. testaceipes, excreted the honeydew with the highest nutritional value. These data are consistent with the hypothesis that hemipterans are subject to selection pressure to minimize honeydew quality for the parasitoids that attack them.