A new model for fetal programming: maternal Ramadan-type fasting programs nephrogenesis.

The effect of maternal Ramadan-type fasting (RTF) on the outcome of pregnancy, kidney development and nephron number in male rat offspring was investigated in current study. Pregnant rats were given food and water ad libitum during pregnancy (control) or restricted for 16 h per day (RTF). Kidney structure was examined during fetal life, at birth, and in early and late adulthood. Maternal body weight, food intake, relative food intake and plasma glucose levels were significantly lower (P<0.001) in the RTF group. Litter and pup weights also were significantly lower (P<0.05) in the RTF group at birth, with no difference in the litter size. The RTF group had a longer gestation, delayed nephrogenesis with less well-differentiated glomeruli, more connective tissue, fewer medullary rays, an increase in the nephrogenic zone/cortical zone ratio, and significant increase (P<0.001) in kidney apoptosis at birth. On the other hand, maternal fasting reduced nephron number (by ~31%) with unchanged kidney and total glomerular volumes. Mean glomerular volume was significantly higher in RTF offspring. Assessment of renal structure revealed mild glomerulosclerosis with enlarged lobulated glomeruli in the renal cortex and high interstitial fibrosis in the medulla of RTF kidneys. Taken together, gestational fasting delays nephrogenesis and reduces nephron number in the kidneys of the offspring, that could be partially owing to increased apoptosis.

ß-Catenin accumulation and S33F mutation of CTNNB1 gene in colorectal cancer in Saudi Arabia.

Several risk factors associated with colorectal cancer (CRC) have been identified including ß-catenin/CTNNB1 hotspot mutations. The levels of ß-catenin within a cell are regulated via phosphorylation of the N terminus of ß-catenin by GSK-3ß. Thus far three serines (S33, 37, 45) and one threonine (T41) are considered to be the substrates for GSK-3ß phosphorylation. In the present investigation an attempt was made to study the role of ß-catenin mutations in exon-3 in 60 colorectal cancer patients from Kingdom of Saudi Arabia (KSA). The hot spot mutation region of ß-catenin exon 3 was evaluated in matched tumor and normal tissues using PCR and direct sequencing. Sequencing of exon 3 of the CTNNB1 gene revealed an activating mutation (S33F) in one of the tumor samples as compared to the normal tissue from the same patient where there was no such mutation found. Immunohistochemical staining showed the accumulation of ß-catenin protein both in cytoplasm and in the nuclei of cancer cells as compared to normal tissue.

Circulating Levels of the Adipokines Monocyte Chemotactic Protein-4 (MCP-4), Macrophage Inflammatory Protein-1ß (MIP-1ß), and Eotaxin-3 in Severe Obesity and Following Bariatric Surgery.

The aim of the study was to investigate the involvement of the adipokines eotaxin-3, MIP-1ß, and MCP-4 in obesity and related comorbidities and the modification of their circulating levels after bariatric surgery. Eighty severely obese subjects and 20 normal-weight controls were included in the study. Circulating levels of MCP-4, MIP-1ß, and eotaxin-3, and the main clinical, biochemical, and instrumental parameters for the evaluation of cardiovascular and metabolic profile were determined in controls and in obese subjects at baseline and 10 months after surgery. Within the obese group at baseline, eotaxin-3 levels were higher in males than females and in smokers than non-smokers and showed a positive correlation with LDL-cholesterol, apolipoprotein B, and leptin. MIP-1ß showed a positive correlation with age and leptin and a negative correlation with adiponectin and was an independent predictor of increased carotid artery intima-media thickness. MCP-4 levels were higher in obese subjects than controls and showed a positive correlation with body mass index, eotaxin-3, and MIP-1ß. Bariatric surgery induced a marked decrease in all the 3 adipokines. MCP-4 is a novel biomarker of severe obesity and could have an indirect role in favoring sub-clinical atherosclerosis in obese patients by influencing the circulating levels of eotaxin-3 and MIP-1ß, which are directly related to the main atherosclerosis markers and risk factors. The reduction of circulating levels of MCP-4, eotaxin-3, and MIP-1ß could be one of the mechanisms by which bariatric surgery contributes to the reduction of cardiovascular risk in these patients.