The lipid-lowering efficacy of rosuvastatin is associated with variations in SLCO1B1: a 12-month prospective cohort study.

OBJECTIVE: Statins' efficacy and safety are subject to wide inter-individual variability, partly due to genetic predisposition. Studies have shown that the genetic variations in the common solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene polymorphisms affect the transport of statins' transport into hepatocytes, their plasma concentration, and circulation time. The ultimate result is variable and personalized statins response and statin-associated muscular symptoms (SAMS). Here we report an update on the differential response to rosuvastatin therapy in the Pakistani population. PATIENTS AND METHODS: A total of 166 hyperlipidemic patients on rosuvastatin were prospectively followed for 24 weeks. Muscle symptoms were recorded after 6-8 weeks of therapy, and assessment was done according to the SAMS-clinical index tool. Patients were genotyped for SLCO1B1 c.521T>C and c.388A>G polymorphisms, for association with lipid-lowering response and statin-associated muscle symptoms. The plasma level of rosuvastatin was determined through Liquid chromatography-mass spectrometry (LCMS) for possible correlation with adverse effects and lipid-lowering efficacy. RESULTS: Mean reduction in low-density lipoprotein cholesterol (LDL-C) was 42.34 mg/dl (p<0.001), 35.66 mg/dl (p<0.001), and 24.47 mg/dl (p=0.202) in reference, heterozygous and mutant homozygous groups of SLCO1B1 c.521T>C, respectively. A 15.70% and 42.14% diminished LDL-C reduction was observed in c.521TC and c.521CC, respectively, compared to the reference c.521TT genotype. Similarly, for SLCO1B1 c.388A>G, 20.50% and 29.40% less LDL-C lowering effect was observed in heterozygous and mutant homozygous carriers, respectively. SAMS were observed in 37% and 33% of heterozygous and minor homozygous, respectively, (p=0.059). The rosuvastatin plasma level was 1.89-fold higher in the c.521CC genotype than in the reference homozygous type. CONCLUSIONS: Differential lipid-lowering response and muscular symptoms due to rosuvastatin are associated with the SLCO1B1 common polymorphisms. Further studies are needed to validate dose adjustment and rationalization.

Genetic variability of NaCl tolerance in tomato.

Cultivation of crops in soils with high salt (NaCl) content can affect plant development. We examined the morphological and physiological mechanisms of salt tolerance in tomato. The responses of 72 accessions of tomato (Solanum lycopersicum) to salinity were compared by measuring shoot and root lengths, and fresh shoot and root weights relative to those of controls (plants grown in normal salt levels). All traits were reduced at the seedling stage when salinity levels were increased. The accession x salinity interaction was significant for all traits. Root length had higher heritability than other traits and was used as a selection criterion to identify salt-tolerant and -non-tolerant accessions. On the basis of root length, accessions LA2661, CLN2498A, CLN1621L, BL1176, 6233, and 17870 were considered to be more tolerant than accessions 17902, LO2875 and LO4360. The degree of salt tolerance was checked by analyzing K+ and Na+ concentrations and K+/Na+ ratio in tissues of plants treated with 10 and 15 dS/m salinity levels. Tolerance of these accessions to salinity was most associated with low accumulation of Na+ and higher K+/Na+ ratios.

Phylogenetic relationships among Saccharum clones in Pakistan revealed by RAPD markers.

Forty sugarcane genotypes (clones), including elite lines, commercial cultivars of Saccharum officinarum and S. barberi clones, were fingerprinted with 30 RAPD markers, using a PCR-based marker assay. The genetic distance for RAPD data was determined according to Nei, and relationships between accessions were graphed in a dendrogram. Genetic distance values ranging from 16.2 to 86.3% were observed among the 40 sugarcane accessions. The lowest genetic distance was found between genotypes US-406 and US-186. These two genotypes differed from each other in only 25 bands with 15 different primers. Genotypes Col-54 and CP-72-2086 were the second most similar group, with a genetic distance of 19.46%. The most dissimilar of all the accessions were CP-77-400 and US-133, with a genetic distance of 86.3%. RAPD fingerprints help sugarcane breeders clarify the genetic pedigree of commercial sugarcane varieties and can be used to evaluate the efficiency of conventional breeding methods.

Splenectomized versus non-splenectomized patients with thalassemia major. Echocardiographic comparison.

OBJECTIVE: To study the effect of splenectomy in patients with thalassemia major on the cardiovascular system through echocardiographic study. METHODS: A prospective, cross sectional study was carried out from December 2006 to December 2007. Patients from the Thalassemia Center in the Maternity and Children's Hospital, Madina, Kingdom of Saudi Arabia, were screened by means of history, physical examination, laboratory studies, and echocardiography. RESULTS: Fifty-seven patients were studied: 36 were non-splenectomized, while 21 were surgically splenectomized. The 2 study groups were well matched for age, gender, height, and weight. The total amount of blood given during the previous year (6577.1+/-206.9 ml versus 5390.5+/-220.2 ml, p=0.0005), and the annual transfusion index (200.9+/-11.3 versus 134.1+/-7.3, p=0.0001) were significantly lower in the splenectomized group. There was no significant difference between the 2 groups regarding laboratory studies. Left ventricular systolic function shows no difference regarding fraction shortening between the 2 groups. The mitral valve E/A ratio was significantly higher in the splenectomized group (1.6+/-0.2 versus 1.4+/-0.2, p=0.02). The pulmonary artery pressure was higher in the splenectomized group (34.2+/-9.1 versus 20.8+/-9.2 mm Hg, p=0.0001). There was a significantly higher number of patients with pulmonary hypertension in the splenectomized group (14 [66.7%] versus 6 [16.7%], p=0.0004). CONCLUSION: Splenectomized patients with thalassemia major are at high risk of having impaired diastolic left ventricular function and pulmonary hypertension.

Efficacy of concomitant use of PUVA and methotrexate in disease clearance time in plaque type psoriasis.

OBJECTIVE: To document the efficacy of concomitant use of PUVA and methotrexate in disease clearance time in plaque type psoriasis. METHOD: Sixty male patients between 18 to 50 years of age suffering from plaque type of psoriasis with PASI score more than 10 were enrolled in the study between March 2001 to November 2001. They were divided into three groups of 20 patients each. Group A received only PUVA, Group B received only Methotrexate and group C received both PUVA and Methotrexate concomitantly. PUVA was given four times a week according to11011 schedule. The end point for clearance of psoriasis was taken as 75% reduction in PASI score from the baseline. RESULTS: Group A: The minimum number of PUVA sessions needed for clearance was 20 and the maximum number was 25 (mean - 22.5). The mean clearance time was 5.5 weeks. The cumulative dose of UVA radiation ranged from 150-250 J/cm2 (mean -200 J/cm2). Group B: The time required for clearance was 7 weeks at the minimum and 9 weeks at the maximum (mean - 8 weeks). Group C: The minimum number of PUVA sessions needed for clearance was 8 and maximum was 12 (mean 10). The mean time for clearance was 2.5 weeks. The cumulative dose of UVA radiation ranged from 56-108 J/cm2 (mean-82 J/cm2). No significant side effects were seen in the three treatment groups. CONCLUSION: The results suggest that combination of PUVA and methotrexate is an effective and safe modality for clearance of psoriasis.