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Background and Aim: Platelets play a role in the microvascular as well as macrovascular complications of diabetic patients with serious implications in the pathogenesis of vascular disease in patients with type 2 diabetes. Hyperglycemia changes platelet functions by impairing calcium homeostasis. So, it is important to study the effect of nifedipine on platelet functions and cardiovascular complications associated with diabetes. Methods: There were 3 groups, i.e. healthy non diabetics (control), type 2 diabetics, and type 2 diabetics with nifedipine therapy (20 in each). For all, the following measurements were done: the cytoplasmic free Ca 2+ concentration, platelet aggregation, lipid profiles, arterial blood pressure and heart rate. Results: Using nifedipine significantly reduced resting and thrombin (0.5 u ⁄ml) phase 2 platelet cytosolic free calcium in the presence of (1 mM) external calcium compared with the diabetic group. Nifedipine showed no significant change in thrombin induced phase 2 platelet cytosolic free calcium in absence of external calcium compared with the diabetic group. There were no significant differences of peak platelet cytosolic free calcium (thrombin 0.5 u⁄ml) induced in the presence of 1 mM external calcium and in the absence of external calcium between all three groups. There was a significant reduction of lipid profiles except HDL in the diabetic group after nifedipine therapy compared with the diabetic group. HDL cholesterol showed significant increase after nifedipine therapy compared with the diabetic group. Conclusion: Nifedipine therapy is useful for patients with diabetes mellitus type 2 from its effects on platelet aggregation, lipid metabolism and cardiovascular functions. J ou rna l o f D ia be tes & M e ta bolism

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In positive feedback mechanisms, the response to a stimulus does not stop or reverse it but instead keeps the sequence of events going up. At first glance, this would appear to be a counter to the principle of homeostasis, since a positive feedback loop has no obvious means of stopping. Not surprisingly, therefore, the positive feedback is less common in nature than the negative one. A positive feedback mechanism can be harmful, as in case of fever that causes metabolic changes pushing it to be higher. However, in some instances, the body uses this mechanism for its advantage. A good example of significant positive feedback is the childbirth. Ovulation, coagulation, platelet aggregation, inflammation and shock are other instances in which the positive feedback plays a valuable role.

Aquaporins (AQPs) form pores in the membranes of cells and selectively conduct water molecules through the membrane, while preventing the passage of ions such as sodium and potassium and other small molecules. The water movement through AQPs is considered to be facilitated simply dependent on the osmotic gradient. There are subtypes of AQPs; classical aquaporins or orthodox AQPs (AQP0, AQP1, AQP2, AQP4, AQP5) permeable only to water molecules ; aquaglyceroporins (AQP3, 7, 9 and 10) permeable to uncharged solutes, such as glycerol, CO2, ammonia and urea in addition to water and unorthodox AQPs, (AQP6, AQP8, AQP11 and AQP12) with unknown functions. The specific distribution of AQP in certain cell types of an organ often reflects a precise function. AQP0 is present in the eye lens for maintaining its transparency. AQP1 is widely distributed water channel in the body. It is mostly expressed in kidneys, lungs, red blood cells, liver, skin, intervertebral disc peripheral and central nervous system. It is involved in angiogenesis, cell migration, cell growth and countercurrent concentration. Its defect shows a protective action against edema in the lungs. AQP2 is expressed in kidney collecting duct and inner ear for water transport in presence of vasopressin; its mutations in kidney can cause nephrogenic diabetes insipidus and its mutation in inner ear provokes Menieres disease. AQP3 is the most abundant skin aquaglyceroporin, where AQP3 facilitated water and glycerol transport plays an important role in hydration of mammalian skin epidermis and proliferation and differentiation of keratinocytes. It is also found in kidney collecting duct, conjunctiva of the eye, oesophagus, colon, spleen, stomach, small intestine, intervertebral disc and respiratory tract airway epithelium. AQP4 is found in astroglial cells at blood-brain barrier and spinal cord, kidney collecting duct, glandular epithelia, airways, skeletal muscle, stomach and retina. AQP4 null mice showed altered cerebral water balance with protection from brain edema. AQP5 helps glandular water secretion so, it expressed in glandular epithelia, corneal epithelium, alveolar epithelium and gastrointestinal tract. AQP6 is expressed in kidney collecting duct intercalated cells, retina, parotid gland acinar cells, inner ear, and brain synaptic vesicles. It is involved in chloride, urea and nitrate permeability. AQP6 may functionally interact with H+-ATPase in the vesicles to regulate intra -vesicle pH and acid -base balance.

IntroductionThe epidemic of metabolic syndrome is increasing worldwide and correlates with elevation in serum uric acid and marked increase in total fructose intake. Fructose raises uric acid and the latter inhibits nitric oxide bioavailability. We hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome and treatment of hyperuricemia or increased nitric oxide may improve it.Material and methodsTwo experiments were performed. Male Sprague-Dawley rats were fed a control diet or a high-fructose diet to induce metabolic syndrome. The latter received either sodium nitrate or allopurinol for 10 weeks starting with the 1st day of fructose to evaluate the preventive role of the drugs or after 4 weeks to evaluate their therapeutic role.ResultsA high-fructose diet was associated with significant (p < 0.05) hyperuricemia (5.9 ±0.5 mg/dl), hypertension (125.2 ±7.8 mm Hg), dyslipidemia and significant decrease in tissue nitrite (27.4 ±2.01 mmol/l). Insulin resistance, as manifested by HOMAIR (20.6 ±2.2) and QUICKI (0.23 ±0.01) indices, as well as adiposity index (12.9 ±1.1) was also significantly increased (p < 0.1). Sodium nitrate or allopurinol was able to reverse these features significantly (p < 0.05) in the preventive study better than the therapeutic study.ConclusionsFructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid. Either sodium nitrate or allopurinol can prevent this pathological condition by different mechanisms of action.

Introduction. Under physiological conditions, maintenance of skeletal mass is the result of a tightly coupled process of bone formation and bone resorption. Disease states, osteoporosis included, arise when this delicate balance is disrupted such as in menopause.The aim of the present work was to study the effect of leptin supplementation on bone metabolism in ovariectomized adult female rats, by measuring indices of bone biomarkers.Material and methods. Forty adult female albino rats were chosen as an animal model for this study and divided into the four equal groups (n=10/group): Group I (control SHAM-operated group), Group II (ovariectomy group). Group III (alendronate group): Ovariectomized rats that received alendronate 0.1 mg/kg body weight i.p. daily for eight weeks. Group IV (leptin group): Ovariectomized rats that received leptin (10µg/kg body weight) i.p. daily for eight weeks. The obtained serum is required for determination of: Serum osteocalcin, alkaline phosphatase, calcium and phosphorus levels.Results. The obtained data revealed that: Treatment with alendronate or leptin caused significant decrease of serum osteocalcin, specific bone alkaline phosphatase and urinary deoxypyridinoline levels compared to ovariectomy group.Conclusions. The results obtained in the present study provide evidence that daily administration of leptin contributes significantly to improve the bone biomarkers of ovariectomy in rats. Leptin prevents ovariectomy induced increases in bone turnover in rats.

Background: Sleep deprivation (SD) is a growing hazard through its effects on metabolism.Orexin is involved in regulation of both sleep and metabolism. Work on orexin receptors may explainthe mechanisms of some hazardous effects of SD. Aim:To test the role of orexin-1 receptor (OX1R)blocker, SB-334867 in changes of triglycerides and cholesterol metabolisminduced by SD. Method: 72 adult albino rats arranged in 4 equal groups: control, SD, SD-OX1R blocked &SD-DMSO groups. The 3 SD groups are subjected to 8 days of paradoxical SD using the modified multiple platform method. The OX1R blocked group was injected intraperitoneallydaily with single dose (3 mg/kg/day) of SB-334867 dissolved in 2 ml DMSOand diluted 1:1000. The SD-DMSO group was injected by 2 ml of DMSO diluted 1:1000. Triglycerides and cholesterol levels weremeasured. Results: Blood triglyceride levels dropped in all groups subjected to SD after the 1 st day while the blood cholesterol level dropped in all groups subjected to SD at the 7 th or 8 th day. In SD-OX1R blocked group showed less drop in blood triglyceridesthan the other SD groups but statistically non-significant change in cholesterol level. Conclusion: SDleads to earlier and more dropin blood triglyceridesthan the drop in cholesterol levels. This can be explained by high metabolism during SD with dependence on triglyceride more than cholesterol. OX1R blocker partially reduces the drop of triglyceride not cholesterol level indicating that orexinmay be involved in control of triglyceride metabolism but not cholesterol.