Musbah O. Tanira

Genetic variations related to hypertension: a review

Hypertension is a complex multifactorial disorder with genetic, environmental and demographic factors contributing to its prevalence. The genetic element contribution to blood pressure variation ranges from 30 to 50%. Therefore, identifying hypertension susceptibility genes will help understanding the pathophysiology of the disease. In addition to the potential impact of genomic information in selecting antihypertensive drug therapy, it may also help in recognizing those at risk of developing the disease, which may lead to new preventive approaches. Several strategies and methods have been used to identify hypertension susceptibility genes. Currently, genetic analysis of such data produced complex results, which makes it difficult to draw final conclusion on the use of genomic data in management of hypertension. This review attempts to summarize present known genetic variations that may be implicated in the pathogenesis of hypertension and to discuss various research strategies used to identify them. It also highlights some of the opportunities and challenges, which may be encountered in interpreting the value of these genetic variations to improve management of hypertension.

Ontogenic aspects of cisplatin-induced nephrotoxicity in rats

A multi-age rat model was evaluated to identify a potential age-related difference in kidney injury following administration of cisplatin (CP). Different age groups of Wistar rats (aged 3, 7, 11 and 24 weeks) were given CP intraperitoneally (6 mg/kg) and sacrificed 6 days thereafter. CP-induced nephrotoxicity caused significant decreases in body weight, creatinine clearance, urine osmolality, plasma total anti-oxidant status, cortical glutathione (GSH) concentration and superoxide dismutase activity. It increased kidney weight and plasma concentrations of creatinine and urea. It increased urinary N-acetyl-beta-D-glucosaminidase activity and protein concentration. Most of the above actions were more marked as the animals advanced in age, except for the changes in GSH, which were similar in all age groups. CP produced necrosis in renal tubules and epithelial vacuolization, the extent of which was more evident as the rats grew older. Renal CP concentration was increased with the increased age of the animal, and the cortical CP concentration in 3 week-old rats was nearly half that of 24 week-old rats. This study showed that the vulnerability profile of each age group was different, suggesting that a multi-age pediatric/geriatric animal model is appropriate to assess, more completely, age-dependent changes in drug toxicity.

Combined polymorphism analysis of glutathione S-transferase M1/G1 and interleukin-1B (IL-1B)/interleukin 1-receptor antagonist (IL-1RN) and gastric cancer risk in an Omani Arab population.

Background Host genetics have been implicated in gastric cancer carcinogenesis. Polymorphisms of glutathione S-transferase (GST) M1 and G1 and of interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) were shown to increase gastric cancer predisposition in several studies. To our knowledge, this is the first report on the combined analysis of polymorphisms GSTM1/G1 and IL-1B/IL-1RN genes in gastric adenocarcinoma. Methods Genomic DNA was extracted from peripheral blood of 107 control subjects and 107 gastric cancer patients. Analysis for the GSTM1 and GSTT1 gene polymorphisms was performed by multiplex polymerase chain reaction. The DNA samples were analyzed using the TaqMan allelic discrimination test for the polymorphism of IL-1B at positions-31. The variable number of tandem repeats of IL-1RN was genotyped using polymerase chain reaction followed by agarose gel electrophoresis. Results There were no statistically significant associations between the GSTM1/G1 or IL-1B-31 genes and gastric cancer risk. There was a statistical association between the presence of the IL-1RN*2 allele and gastric cancer (odds ratio 2.2, 95% confidence interval=1.2-3.7, P=0.01). Combined analysis showed that a combination of the null GSTM1 genotype and carriers of IL-1RN*2 was associated with a statistically significant correlation with gastric cancer (odds ratio=3.6, 95% confidence interval=1.4-9.4, P=0.008). Conclusions The current study suggests that the individual variation in both the cellular inflammatory modulator IL-1RN and the antioxidative property of GSTM1 may predispose individuals to an increased risk of gastric cancer.

Frequency of CYP2C9 Genotypes among Omani Patients Receiving Warfarin and Its Correlation with Warfarin Dose

Objectives: This study was conducted to determine the frequency of CYP2C9 alleles in Omani patients receiving warfarin and to correlate genotyping data with warfarin dosage. The Omani population has Asian and African ethnicities. Methods: CYP2C9 genotypes were determined by the polymerase chain reaction restriction fragment length polymorphism method. Non-parametric Kruskal-Wallis test was used to compare groups of continuous data for significance differences. Results: Genotyping data showed that 12.7 and 5.8% of the samples were heterozygous for the CYP2C9*2 and CYP2C9*3 alleles, respectively. The CYP2C9*2 allele frequency was 0.074 in our population. It was 0.029 for CYP2C9*3. Conclusion: This is the first report on the presence of CYP2C9*2 allele homozygocity in any Asian or African population.

Phytochemistry, Pharmacology And Toxicity Of Rhazya Stricta Decne: A Review

Phytochemical, pharmacological and toxicological properties of the medicinal plant Rhazya stricta Decne. are reviewed. Several types of alkaloids and a few flavonoids have been isolated and their structures and stereochemistry characterized. However, in most cases the biological activity of these compounds has not been studied. Most of the pharmacological activity of the plant resides in its alkaloidal fractions which cause depression of the central nervous system and hypotension. Extracts of R. stricta appear to have low toxicity, although its use in pregnant women may be inadvisable.

Evaluation of the relaxant activity of some United Arab Emirates plants on intestinal smooth muscle.

Although medicinal plants are used as antispasmodic agents in folk medicine there have been no scientific studies of the phytochemical composition and usefulness of these plants for such treatment. Extracts of 23 plants used in the traditional medicine of the United Arab Emirates were tested for their effects on intestinal smooth muscle activity.

The effect of Rhazya stricta Decne, a traditional medicinal plant, on spontaneous and drug-induced alterations in activity of rats.

The effect of acute and chronic treatment of rats with a lyophilized extract of the leaves of the medicinal plant Rhazya stricta on total and ambulatory activity was studied. Given acutely at single oral doses of 1, 2, 4, and 8 g/kg, the extract produced dose-dependent decreases in total activity and ambulatory activity. Diazepam (20 mg/kg, orally) produced a decrease in rat activity comparable to that produced by a dose of 1 g/kg of the extract. When given daily at an oral dose of 2 g/kg for 21 consecutive days, the extract produced, on the last day of treatment, significant decrease in activity amounting to about 30% of control activity levels. Subcutaneous (SC) treatment of rats with caffeine (7.5, 15, and 30 mg/kg), dose-dependently and significantly increased total activity and ambulatory activity. These effects were dose-dependently attenuated when the extract was given concomitantly with caffeine at oral doses of 1, 2, and 4 mg/kg. Treatment of rats with zoxazolamine alone (10, 20, or 40 mg/kg, SC) or R. Stricta (1 and 4 g/kg orally) alone significantly decreased total and ambulatory activities. Concomitant treatment with zoxazolamine and R. Stricta decreased the rats activity to a greater degree than with either treatment given alone.

Central nervous system activity of Leucas inflata Benth. in mice

The analgesic activity of the methanol and acetone extracts of Leucas inflata L. (family Labiatae) was evaluated in mice using different experimental models. The effect of the two extracts on pentobarbitone-sleeping time, motor activity, sensorimotor coordination, carrageen induced inflammation, and brewers yeast-induced pyrexia has also been investigated. The two crude extracts have been phytochemically analyzed and some constituents isolated and characterized. These included stigmasterols, a chromone and coumarins. Extracts of L. inflata L., given at single oral doses of 0.25, 0.5, 1.0 or 2.0 g/kg, significantly and dose-dependently, reduced formalin-induced pain, acetic acid induced abdominal constrictions and increased the reaction time in the hot-plate test. Both extracts caused significant and dose-related impairment in the sensorimotor control and ambulatory and total motor activity of treated mice. Both extracts exhibited anti-inflammatory action by reducing paw edema of treated mice. The extracts did not significantly affect the rectal temperature of normothermic mice. However, they were effective in preventing Brewers yeast induced pyrexia. It is concluded that the crude methanol and acetone extract of L. inflata has CNS depressant properties, manifested as antinociception and sedation. Both extracts have anti-inflammatory and antipyretic actions.

Some Effects of Cassia italica on the Central Nervous System in Mice

This work examines some effects of the crude ethanolic extract of the medicinal plant Cassia italica, given at single oral doses of 0.25, 0.5 or 1 g kg−1, on the central nervous system in mice. Several models of nociception have been used to examine the analgesic effect of the extract. HPLC fingerprinting of the extract was performed to ensure uniformity of the extract material used.

Effect of Rhazya stricta Decne on monoamine oxidase and cholinesterase activity and brain biogenic amine levels in rats.

The effect of treatment with the medicinal plant Rhazya stricta Decne, on monoamine oxidase (MAO) and cholinesterase activity, and on the concentration of brain biogenic amines was studied in rats.