Renal synthesis and excretion of ammonia are critical for efficient removal of acids from the body. Besides the rate of ammonia production, the intrarenal distribution of produced ammonia is a crucial step in the renal regulation of acid-base balance. Various acid-base disorders are associated not only with changes in ammonia production but also with its distribution between the urine and the renal veins. The final effect of ammonia production on acid-base balance largely depends on the events that determine the distribution of ammonia produced between urine and blood. Several factors, among which urine pH, urine flow, total ammonia production "per se" and renal blood flow may affect the percent of ammonia excreted into urines in humans with different acid-base disturbances. Among these factors, urine pH is the most important. An additional effect of stimulated ammoniagenesis is kidney hypertrophy. In tubule epithelial cells, the associated increase in ammonia production, rather than the acidosis per se, is responsible for favoring tubular hypertrophy. This effect is related to the inhibition of protein degradation, owing to changes in lysosomal pH and cathepsin activity, without effects on cell cycle. Both changes of PI-3 kinase pathway and the suppression of chaperone-mediated autophagy are candidate mechanism for ammonia-mediated inhibition of protein degradation in tubule cells. Available data in humans indicate that the response of kidney to metabolic acidosis includes both changes in amino acid uptake and suppression of protein degradation. The latter effect is associated with the increase in ammonia excretion and partition into the urine.

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A group of patients with and hyperlipidemia were divided into male and female groups and further subdivided into 3 groups. These groups received, either simvastatin (20 mg daily), Omega3-fatty acid (2g/day), or both. The blood pressure and lipid profile were measured before and after 4 weeks of treatment. Our data showed that treatment with simvastatin did not produce significant effect on blood pressure, however the blood pressure was significantly reduced in patients received omega 3-fatty acid or simvastatin plus omega3-fatty acid. The total cholesterol (TC), triglycerides (TG), and low density lipoprotein (LDL) significantly decreased in all treated groups. The high density lipoprotein (HDL) significantly increased in all treated groups except in the group of males receiving simvastatin.Alanine transaminase (ALT) increased significantly in female and male groups receiving simvastatin, but significantly decreased in same groups receiving omega 3-fatty acid and in the males receiving simvastatin plus omega3-fatty acid. The aspartate transaminase (AST) levels significantly decreased in all treated groups except in the female group given omega3fatty acid. The alkaline phosphatase (ALP) significantly increased only in the groups given simvastatin alone. The levels of urea and creatinine were not affected in all groups. In our prospective study we found that simvastatin decreased TC, TG and LDL, and resulted in elevation of liver transaminases. Omega3-fatty acid alone or in combination with simvastatin has similar effect on lipid profile and it significantly reduces blood pressure without affecting liver or renal function.

Type 2 of diabetes mellitus (DM) is associated with progressive failure of pancreatic B-cells to secrete insulin, decreased insulin action, due to reduced insulin receptors at the target sites. Dyslipidemia is a common risk of DM and is responsible to a large extent for cardiovascular disease-related morbidity and mortality. This study was planned to compare the effects of metformin alone and a combination of metformin and insulin in presence of simvastatin on glycemic and lipid levels in Libyan diabetic patients. This retrospective study was conducted at Benghazi Diabetic Center (Libya) on 100 patients with type 2 DM of 40-60 years old. Patients were selected for follow up on basis of inclusion and exclusion criteria, and were divided into three groups. The first group (n=30), received metformin (1-2 gm/day). The second group (n=40) received metformin (1-2 gm/day) and insulin (mixtard 30/70, 30-60 units/day) and third group (n=30) received metformin (1-2 gm/day), insulin (30-60 units/day) plus simvastatin (40 mg/day). Glucose blood levels (FBG, PPBG and HBA1c), lipid profile (TC, TG, HDL-C, LDL-C and AI), hepatic function (ALT, AST, ALP and Bilirubin) and renal function (creatinine and urea) were measured for each patient. All the patients had a good glycemic control with significant decrease in HbAc1 of metformin plus insulin treated group. No significant differences in lipid profile of metformin treated group and metformin plus insulin treated group were observed. Date revealed both significant increase in HDL-C and decrease in TC, LDL-C and atherogenic index levels but without any change in TG in metformin and insulin treated group as compared with metformin, insulin plus simvastatin treated group. All the findings of hepatic and renal functions were within the normal range except for bilirubin which significantly increased in metformin, insulin plus simvastatin treated group compared with other treated groups. In conclusion, the efficacy of metformin in controlling hyperglycemia was enhanced with insulin without negative effects. Simvastatin was effective in controlling dyslipidemia associated with DM and produced a profound reduction in TC and LDL-C of the patients.