Non-dipping pattern of nocturnal blood pressure in obstructive sleep apnea syndrome: possible role of oxidative stress and endothelin-1 precursor

There is growing evidence suggesting that obstructive sleep apnea OSA is linked to the occurrence of cardiovascular disorders. Lack of normal nocturnal dipping of blood pressure has also been considered a risk factor for the occurrence of cardiovascular disorders. Non-dipping has been described in patients with OSA and is attributed to autonomic dysfunction. However, the search for a causal link between OSA and cardiovascular disease is still underway. To evaluate the occurrence of non-dipping pattern of nocturnal blood pressure, and the possible role of oxidative stress and ET-1 precursor in patients with OSA. Thirty eight patients with OSA and fourteen normal control subjects were enrolled in this study and were subjected to history taking, clinical examination, early morning blood samplings for the measurement of serum malondialdehyde [MDA] and endothelin 1 precursor [ET-1 precursor]. All patients with OSA were subjected to full polysomnographic study and monitoring of nocturnal blood pressure changes. Nocturnal blood pressure measurement of all patients revealed that thirty six patients [94.7%] were non-dippers, 15 patients [39.5%] suffered from ischemic heart disease. Serum endothelin-1 precursor and serum malondialdehyde levels were significantly higher in patients with OSA than in the control group. The systolic blood pressure measured before sleep was also significantly higher in patients than in the control group. The Epworth sleepiness scale and the clinical apnea score were significantly higher in patients than in the control group. The high incidence of non-dipping pattern of nocturnal blood pressure in both normotensive and hypertensive patients with OSA may be considered a warning sign for the occurrence of cardiovascular complications in these patients. Both increased oxidative stress and ET-1 precursor may be among the causative factors responsible for the high prevalence of the non-dipping pattern through increasing sympathetic nervous system activity

Human resistin gene polymorphism: association with serum resistin level and insulin resistance in type 2 diabetes mellitus

Resistin is an adipocyte - secreted cytokine associated with insulin resistance in rodents. In humans, it remains controversial whether circulating resistin levels are associated with insulin resistance, type 2 diabetes, or obesity. The role of resistin gene, referred to RETN, in human type 2 diabetes or obesity is largely unclear in studies of its association with SNPs or serum resistin. Major genetic factors of type 2 diabetes, a probable polygenic disease, remain to be identified. Therefore the aim of our work was to study circulating level of resistin and to correlate this level with resistin gene 3'UTR+62G-A polymorphism and factors related to insulin resistance in type 2 diabetic patients. 40 male patients with type 2 diabetes [group I] and 10 age-matched healthy controls [group II] were included. All patients and controls were subjected to full history taking, clinical examination stressing on waist circumference, BMI and blood pressure. Laboratory investigations included lipid panel [TG, total cholesterol, HDL-C and LDL-C], glycemic parameters [FBS, Hb A1c, fasting insulin, HOMA, IR], serum uric acid, highly sensitive CRP, serum resistin and molecular detection of resistin gene 3'UTR+62G-A polymorphism using PCR-RFLP. Serum resistin levels, highly sensitive CRP, anthropometric measures and metabolic parameters were significantly higher in type 2 diabetic patients [group I] than in healthy controls [group II] [P<0.05]. In type 2 diabetic patients the serum resistin was negatively correlated with HDL-C and positively correlated with BMI, HOMA-IR and highly sensitive CRP [P < 0.05]. In diabetic subjects the genotype distributions of resistin gene 3'UTR polymorphism were as follows: 3 [7.5%] subjects were heterozygous [GA], 1 [2.5%] was homozygous [AA] for the mutant allele and 36 [90%] were homozygous [GG] for the wild allele. Type 2 diabetic subjects had a significantly lower frequency of resistin gene 3'UTR + 62A variant [GG: GA/AA, 90%:10%] than control subjects [GG: GA/AA, 60%:40%; odds ratio, 6.0; 95% confidence interval, 1.17 to 30.7; P = 0.041]. G allele was linked to greater insulin resistance as indicated by higher HOMA-IR index [P = 0.004]. Also diabetic subjects harboring the G allele showed significant higher levels of serum resistin, BMI, highly sensitive CRP as well as a significant decrease in HDL-cholesterol [P = 0.042, 0.007, 0.008, 0.003 respectively]. These findings suggest that resistin gene 3'UTR + 62G-A is associated with serum resistin level and may play a role in the pathogenesis of type 2 diabetes and insulin resistance. The strong correlation of resistin with highly sensitive CRP suggests that resistin may be considered as inflammatory marker associated with type 2 diabetes

Experimental trichinosis: parasitological, electrophysiological and biochemical studies

Trichinosis is a parasitic infection affecting the gut and the muscles causing mild gastrointestinal symptoms followed by periorbital oedema, muscle pains, fever and eosinophilia. The infection evokes functional disturbances in physiological effector systems. Furthermore, several biochemical changes are associated with the infection. Therefore, this work was carried out to study the electrophysiological changes in intestine, striated and cardiac muscles by electromyography [EMG] and to assess the biochemical changes through measurement of serum cholinesterase and intestinal myeloperoxidase activity [MPO] in both light and heavy infected experimental animals by Trichinella spiralis [T. spiralis]. Electrophysiological results showed increased contractility of the smooth muscle layers of the intestine only early in the infection, whereas both striated and cardiac muscles showed increase in the contractility with the progress of infection in both light and heavy infection. Significant myocardial dysfunction in the form of bradycardia, in addition to major histopathological changes in the heart occurred from the beginning of the infection and increased till the end of the study. Biochemical study showed gradual increase in serum cholinesterase, while, the intestinal MPO showed increase only in the early stage of the infection. It was noticed that all changes were more pronounced in the heavily infected group than the lightly infected one

Effect of folic acid and vitamin B[12] supplementation on isoprenaline induced myocardial infarction, endothelial dysfunction and atherothrombosis in experimental hyperhomocysteinemic rats

Elevated total plasma homocysteine [tHcy] concentration is an independent risk factor for ischemic heart disease and other vascular disorders. Treatment with vitamins [folic acid and B12] has shown to reduce plasma homocysteine level but it is not clear to what extent such treatment may reduce clinical vascular events or mortality. The aim of the present study was to evaluate hyperhomocysteinemia as a risk factor of isoprenaline induced myocardial infarction [MI], endothelial dysfunction and hypercoagulable state and to examine the effect of folic acid either alone or in combination with vitamin B[12] on the experimentally induced myocardial infarction and to evaluate the effect of such vitamin treatment on the biomarkers of endothelial dysfunction and hypercoagulable state in post-methionine load hyperhomocysteinemic rats. Hyperhomocysteinemia [Hhcy] was induced in rats by daily intake of methionine [1g/kg b.wt.] in the drinking water for 4 weeks. MI was then induced by subcutaneous injection of isoprenaline in a dose of 85mg/kg b.wt/day for two days. Serum marker enzymes, creatine kinase [CK] and lactate dehydrogenase [LDH] were measured. Lipid peroxidation was measured as malondialdehyde [MDA] and reduced glutathione [GSH] concentrations in heart tissue. Plasma concentrations of von Willebrand factor [vWF] and D-dimer as markers of endothelial dysfunction and prothrombotic state were measured either in the experimental untreated hyperhomocysteinemic rats or in the treated ones. Hhcy resulted in a significant increase in serum CK and LDH levels. Cardiac MDA was significantly increased while GSH was significantly decreased in Hhcy group compared to the normal control group, plasma concentrations of vWF and D-dimer were also significantly increased. Serum marker enzymes and markers of cardiac oxidative stress were greatly exaggerated in Hhcy rats treated with isoprenaline in comparison with isoprenaline group. Administration of folic acid [10mg/kg, b.wt orally via gavage] alone and in combination with vitamin B[12] [500 ug/kg b.wt. i.m], concurrently for 4 weeks during the induction of Hhcy markedly reduced the increase in serum CK and LDH as well as the plasma concentration of vWF and D-dimer. Cardiac MDA content was decreased while cardiac GSH was elevated in the treated group compared to untreated Hhcy rats. These results suggest that Hhcy aggravates MI via oxidative stress mechanisms and that Hhcy may impair endothelial function and increases the biomarkers of prothrombotic state Treatment with either folic acid alone or in combination with vitamin B[12] can ameliorate the detrimental effects of Hhcy, reduce the risk of MI, appears to improve endothelial dysfunction and decrease plasma concentration of biomarkers of hypercoagulability. This provides preliminary evidence that such vitamin supplementation may have beneficial cardiovascular effects. However clinical benefit of vitamin supplementation has not yet been demonstrated and clinical trials are urgently required