Initial maternal meiotic I error leading to the formation of a maternal i(2q) and a paternal i(2p) in a healthy male

We report on the investigation of the parental origin and mode of formation of the two isochromosomes, i(2p) and i(2q), detected in a healthy adult male. Conventional cytogenetic analysis revealed the proband’s lack of structurally normal chromosomes 2, these being replaced by an i(2p) and an i(2q). Investigation of the parental origin of the isochromosomes revealed a paternal origin of the i(2p) chromosome and a maternal origin of the i(2q) chromosome. Thus, the formation of both isochromosomes, or at least of the paternal i(2p), appears to have occurred postzygotically. Interestingly, whilst a paternal isodisomy was observed for the entire 2p, maternal heterodisomy was detected for two segments of 2q, separated by a segment showing isodisomy. The results are indicative of an initial error (non-disjunction or i(2q) formation) concerning the maternal chromosomes 2 during meiosis I, which likely favored the subsequent mitotic recombination event resulting in the presence of two isochromosomes. To the best of our knowledge this is the first case of an initial meiotic error, followed by postzygotic trisomy rescue through the formation of isochromosomes, resulting in a normal phenotype. A prenatal detection, by cytogenetic and molecular analysis, of such chromosome abnormality would have led to the incorrect conclusion of a most likely poor prognosis for the fetus

Mutations in RAD21 disrupt regulation of apob in patients with chronic intestinal pseudo-obstruction

Background Aims Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimics a mechanical subocclusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and to identify potential biomarkers. Methods We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of messenger RNA (mRNA) and proteins were analyzed by quantitative reverse-transcription polymerase chain reaction, immunoblot, and mobility shift assays. Complementary DNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a). Gut tissues were collected and analyzed. Results We identified a homozygous mutation (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p.622 allele. rad21a Morpholino zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in the regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 also is overexpressed in sporadic CIPO in sera and gut biopsy specimens. Conclusions Some patients with CIPO carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB. Reduced expression of rad21 in zebrafish, and dysregulation of these target genes, disrupts intestinal transit and the development of enteric neurons. © 2015 by the AGA Institute

Effect of exercise therapy on lipid profile and oxidative stress indicators in patients with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Yoga has been shown to be a simple and economical therapeutic modality that may be considered as a beneficial adjuvant for type 2 diabetes mellitus. This study investigated the impact of Hatha yoga and conventional physical training (PT) exercise regimens on biochemical, oxidative stress indicators and oxidant status in patients with type 2 diabetes.</p> <p>Methods</p> <p>This prospective randomized study consisted of 77 type 2 diabetic patients in the Hatha yoga exercise group that were matched with a similar number of type 2 diabetic patients in the conventional PT exercise and control groups. Biochemical parameters such as fasting blood glucose (FBG), serum total cholesterol (TC), triglycerides, low-density lipoprotein (LDL), very low-density lipoproteins (VLDL) and high-density lipoprotein (HDL) were determined at baseline and at two consecutive three monthly intervals. The oxidative stress indicators (malondialdehyde – MDA, protein oxidation – POX, phospholipase A2 – PLA2 activity) and oxidative status [superoxide dismutase (SOD) and catalase activities] were measured.</p> <p>Results</p> <p>The concentrations of FBG in the Hatha yoga and conventional PT exercise groups after six months decreased by 29.48% and 27.43% respectively (P < 0.0001) and there was a significant reduction in serum TC in both groups (P < 0.0001). The concentrations of VLDL in the managed groups after six months differed significantly from baseline values (P = 0.036). Lipid peroxidation as indicated by MDA significantly decreased by 19.9% and 18.1% in the Hatha yoga and conventional PT exercise groups respectively (P < 0.0001); whilst the activity of SOD significantly increased by 24.08% and 20.18% respectively (P = 0.031). There was no significant difference in the baseline and 6 months activities of PLA2 and catalase after six months although the latter increased by 13.68% and 13.19% in the Hatha yoga and conventional PT exercise groups respectively (P = 0.144).</p> <p>Conclusion</p> <p>The study demonstrate the efficacy of Hatha yoga exercise on fasting blood glucose, lipid profile, oxidative stress markers and antioxidant status in patients with type 2 diabetes and suggest that Hatha yoga exercise and conventional PT exercise may have therapeutic preventative and protective effects on diabetes mellitus by decreasing oxidative stress and improving antioxidant status.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12608000217303</p

Rheological properties of blood in patients with chronic liver disease

We analyzed rheologic parameters, including erythrocyte rigidity (ER), whole blood and plasma viscosity, erythrocyte and platelet count, hemoglobin, hematocrit, mean corpuscular volume (MCV), fibrinogen, erythrocyte sedimentation rate (ESR), cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low density lipoprotein (VLDL), and gamma globulin levels in 18 patients with chronic liver disease and 20 healthy volunteers. Fifteen patients had cryptogenic cirrhosis while 3 had chronic active hepatitis. ER and MCV was significantly higher in the patient group than the control group while whole blood and plasma viscosities were significantly lower. There were significant correlations between ER and blood and plasma viscosity, ER and MCV, plasma and blood viscosity, HDL and plasma viscosity and a negative correlation between ER and ESR. Our results demonstrate that erythrocytes become more rigid in chronic liver disease. We suggest that erythrocytes with increased rigidity can impair hepatic microvascular circulation and thus contribute to liver dysfunction

Vitamin E and ATPases: Protection of ATPase activities by vitamin E supplementation in various tissues of hypercholesterolemic rats

It has been shown that the lipid composition of plasma membrane can be modified in vivo by dietary fat. It has also been observed that an increase in the cholesterol content of plasma membranes results in decreased activities of ATPases. In the present study, we evaluated the changes in the activities of ATPases from erythrocytes, hepatocytes, and kidney cortex caused by cholesterol-rich diet in rats and subsequently examined the role of vitamin E administration on the cholesterol-induced effects in these tissues. Administration of hypercholesterolemic diet to the rats for 4.5 months, significantly decreased membrane Na+-K+-ATPase and Ca+2-ATPase activities in comparison to the controls in all tissues studied, Vitamin E supplementation to the hypercholesterolemic rats led to a recovery in membrane ATPase activities

Effect of chronic smoking on the rheological behaviour and lipid composition of erythrocytes

The rheological properties of blood have important effects on blood circulation. Chronic cigarette smoke is a generally accepted major cardiovascular risk factor, but the mechanisms by which it promotes ischaemic vascular diseases are not fully understood. The changes might contribute to an explanation of how chronic smoking alters the rheological behaviour of red blood cells and increases both plasma and blood viscosity in ischaemic vascular disease. We have now assessed 25 healthy controls and 25 chronic smokers for their erythrocyte deformability, plasma and blood viscosity and Htc, and also determined erythrocyte cholesterol, total and cholinated phospholipids. When we compared healthy controls with chronic smokers, erythrocyte deformability, plasma and blood viscosity and Htc were significantly different (P < 0.01, P < 0.001 respectively). Cigarette smoking caused significant changes in the erythrocyte cholesterol, total and cholinated phospholipid levels (P < 0.001). These results suggest that chronic smoking may increase the risk of ischaemic vascular disease by changing the rheological behaviour and composition of phospholipids in the erythrocytes. Med Sci Res 27:825-826 (C) 1999 Lippincott Williams & Wilkins

Oxidant and antioxidant systems in NIDDM patients: Influence of vitamin E supplementation

Free radical-mediated oxidative stress has been implicated in adverse tissue changes in a number of diseases. In view of the role of oxidative processes in non-insulin dependent diabetes mellitus (NIDDM), in this study, we investigated the oxidant and antioxidant status of plasma in patients with NIDDM and the effect of vitamin E (800 IU/day) supplementation on oxidative stress, antioxidant defense system, fructosamine levels and insulin action. Thirty controls and 40 NIDDM patients were studied. In controls and patients, plasma lipids, vitamin E, lipid peroxide, total thiols (t-SH), superoxide peroxidase (SOD) and glutathione peroxidase (GPx) were measured in the basal state and after vitamin E (800 IU/d) supplementation for a month. All lipids and lipid fractions in plasma were significantly decreased, whereas the HDL-C level was changed in diabetic patients supplemented with vitamin E when compared with baseline values. Vitamin E administration also significantly reduced fasting glucose and fructosamine levels, whereas increased significantly reduced fasting glucose and fructosamine levels, whereas increased significantly plasma C-peptide and insulin levels (p < 0.01, p < 0.001, respectively). Following vitamin E supplementation, TBARs levels were found to be significantly lower (p < 0.001) than the baseline value NIDDM patients are. On the other hand, activities of GPx and SOD were significantly higher (p < 0.001) than baseline values. A similar trend was observed for total thiols contents, but in this case, the increase was not significant. In conclusion, this study demonstrates that vitamin E improved beta-cell function and increased plasma insulin and C-peptide levels, possibly by inducing the antioxidant capacity of the organism and/or reducing the peripheral resistance in NIDDM. Long-term studies are needed to demonstrate the beneficial effects of vitamin E on treatment/prevention of NIDDM