Usefulness of stochastic analysis of body weight as a tool in experimental aging research

The statistical characteristics of body weight in a number of longitudinally studied mouse populations were examined. Frequency distribution of body weights appears to be rather “fluid” (though within a strict range), changing from symmetric to positively skewed to symmetric and finally to negatively skewed as the mice pass through the stages of early maturity, middle age, and senescence. Because body weight is a highly integrated physiological variable, it is postulated that various diets which affect survivorship would affect body weight frequency distribution similarly. The data from studies with an antioxidant diet and two toxic diets support this hypothesis. In general, the effects on body weight can be assessed in a relatively short time (6–9 months) after initiation of the experiment and 4–6 months before the effect of the experimental diet is manifested in the population's survivorship, thus offering an analytical tool for considerable shortening of the duration of such studies.     

Analysis of cDNA sequences of feline SAAs

Feline amyloidosis is an uncommon disorder caused by deposits of amyloid in a variety of organs. Most frequently encountered types are amyloid derived of pancreatic islet amyloid polypeptide (AIAPP) in older cats and of the apolipoprotein, apo-serum amyloid A (AA) in Abyssinian/Somali (Aby) and Siamese/Oriental (Siam) cats occurring at a relatively young age. For the AA protein of the Aby, Siam and domestic shorthair cat (DSH) breed different amino acid sequences have been described. It is not yet clear, however, whether the tendency to develop AA amyloidosis in Aby and Siam is associated with specific apoSAA protein sequences and whether this is breed specific. In this study, DNA from one Siam and two DSH cats revealed on Southern blot three bands suggesting at least three genes or gene clusters. The SAA cDNAs of hepatic mRNA from three Abys, five Siams and five DSHs were amplified by RT-PCR, cloned and sequenced. Siams and Abys had limited SAA sequence variability. All five Siams, three of which were positive for amyloid, had the amyloidogenic Siam SAA and the amyloidogenic Aby SAA sequence. Two of the Abys, both with amyloid, had the amyloidogenic Aby SAA sequence. The third Aby, without amyloid, missed its amyloidogenic sequence. The SAA sequences of the DSHs found in the present preliminary survey, suggested a possible tendency for more variability, whereas the amyloidogenic Siam as well as the amyloidogenic Aby sequence were found once. Up to five different sequences were found in a single animal. All five DSHs, moreover, had a specific sequence lacking in the Siams and Abys. The present results, especially those of the Siams, favor that in addition to the occurrence of amyloid associated SAA genes other factors such as infections and inflammatory processes are involved in the development of phenotypical amyloidosis.     

Dietary Phosphorus Excess: A Risk Factor in Chronic Bone,Kidney, and Cardiovascular Disease?

There is growing evidence in the nephrology literature supporting the deleterious health effect of excess dietary phosphorus intake. This issue has largely escaped the attention of nutrition experts until this symposium, which raised the question of whether the same health concerns should be extended to the general population. The potential hazard of a high phosphorus intake in the healthy population is illustrated by findings from acute and epidemiologic studies. Acute studies in healthy young adults demonstrate that phosphorus intakes in excess of nutrient needs may significantly disrupt the hormonal regulation of phosphorus contributing to disordered mineral metabolism, vascular calcification, bone loss, and impaired kidney function. One of the hormonal factors acutely affected by dietary phosphorus loading is fibroblast growth factor-23, which may be a key factor responsible for many of the cardiovascular disease (CVD) complications of high phosphorus intake. Increasingly, large epidemiological studies suggest that mild elevations of serum phosphorus within the normal range are associated with CVD risk in healthy populations. Few population studies link high dietary phosphorus intake to mild changes in serum phosphorus due to study design issues specific to phosphorus and inaccurate nutrient composition databases. The increasing phosphorus intake due to the use of phosphorus-containing ingredients in processed food and the growing consumption of processed convenience and fast foods is an important factor that needs to be emphasized.     

Analysis of polymorphisms and haplotypes in genes associated with vascular tone,hypertension and oxidative stress in Mexican-Mestizo women with severe preeclampsia

ObjectiveSeveral studies have reported the association of genes related to vascular tone, hypertension, oxidative stress and preeclampsia. We investigated the possible association among three polymorphisms in eNOS (as well their haplotypes): one of MTHFR, one of GSTP1 and one of AGT, with severe preeclampsia in Mexican-Mestizo women.MethodsTwo hundred thirty women with severe preeclampsia and 350 control subjects were genotyped; for rs2070744 and rs1799983 of eNOS, rs1801133 of MTHFR, rs1695 of GSTP1 and rs699 of AGT we used real-time PCR allelic discrimination and for VNTR of eNOS, PCR. Allele frequency differences were assessed by χ². Logistic regression was used to test for associations and for haplotype frequencies using Haploview 4.2.ResultsGenotypic and allelic distribution of the polymorphisms was similar between cases and controls; likewise, haplotype frequencies of the three polymorphisms of eNOS did not differ significantly.ConclusionsTo our knowledge, this is the first time that these polymorphisms have been analyzed together and exclusively in women with severe preeclampsia. However, we did not find an association between polymorphisms of eNOS, MTHFR, GSTP1 and AGT with severe preeclampsia in our population. Additionally, we observed differences in the distribution of the alleles and genotypes of these polymorphisms in our population in comparison to those described in other ethnic groups.