EFFECT OF AQUATIC VERSUS CONVENTIONAL THERAPY IN TREATMENT OF CHRONIC LOW BACK PAIN

Background: Chronic LBP a frequent sign of back dysfunction. The recent literature recorded that up to 90% of the world’s population complain from LBP which cause disability in people. This study conducted to compare the efficacy of aquatic and conventional therapy on pain level, functional limitation and lumbar ROM in subjects with CLBP. Methods: Forty CLBP were divided into two groups (A) control 20 subjects received conventional therapy. (B) experimental received 20 subjects received aquatic therapy the treatment was given for six weeks. Results: Mixed MANOVA test showed statistically significant enhancement in values of post-treatment in either group compared with pre-treatment in pain enhancement for group A was 54.86% and 57.74% for group B (P=0.0001), functional limitation enhancement for group A was 55.46% and 58.95% for group B (p=0.0001), and lumbar ROM enhancement for group A was 46.63%, 18.79%, for lumbar flexion, and extension, and for group B was 46.96%, 22.85% (p=0.0001). Conclusion: It is concluded that aquatic and conventional therapies have a similar result in reducing pain severity, functional limitation, and enhancing lumbar ROM in CLBP patients

Pharmacokinetic interactions of selective serotonin reuptake inhibitors with other commonly prescribed drugs in the era of pharmacogenomics

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed to treat depression and a broad range of other comorbidities. The increased use of SSRIs in patients with various comorbidities treated with different drugs engenders the risk of pharmacokinetic drug interactions via cytochrome P450 (CYP450) enzymes inhibition. In the present review, we provide an overview of documented clinically significant drug interactions between SSRIs and other drugs co-prescribed in psychiatric patients for the same or other diseases. We further discuss the significance of drug interactions in the era of pharmacogenomics to underline the need for using information on both genotype and drug interactions towards implementing better clinical outcomes through personalized medicine. © 2012 by Walter de Gruyter Berlin Boston 2012

Genotyping of CYP2C9 and VKORC1 in the Arabic Population of Al-Ahsa, Saudi Arabia

Polymorphisms in the genes encoding CYP2C9 enzyme and VKORC1 reductase significantly influence the dose variability of coumarinic oral anticoagulants (COAs). Substantial inter- and intraethnic variability exists in the frequencies of CYP2C9∗2 and ∗3 and VKORC1 –1639A alleles. However, the prevalence of CYP2C9 and VKORC1 genetic variants is less characterized in Arab populations. A total of 131 healthy adult subjects from the Al-Ahsa region of Saudi Arabia were genotyped for the CYP2C9∗2 and ∗3 and VKORC1 –1639G>A polymorphisms by PCR-RFLP method. The frequencies of the CYP2C9∗2 and ∗3 and VKORC1 –1639A alleles were 13.3%, 2.3%, and 42.4%, respectively, with no subjects carrying 2 defective alleles. The frequencies of the CYP2C9∗3 and VKORC1 –1639A alleles were significantly lower than those reported in different Arabian populations. None of the subjects with the VKORC1 –1639AA genotype were carriers of CYP2C9∗1/∗3 genotypes that lead to sensitivity to COAs therapy. The low frequency of the CYP2C9∗3 allele combined with the absence of subjects carrying 2 defective CYP2C9 alleles suggests that, in this specific population, pharmacogenetic COAs dosing may mostly rely upon VKORC1 genotyping

POR∗28 SNP is associated with lipid response to atorvastatin in children and adolescents with familial hypercholesterolemia

Background: In children and adolescents with familial hypercholesterolemia (FH) pharmacotherapy with statins is the cornerstone in the current regimen to reduce low-density lipoprotein cholesterol (LDLc) and premature coronary heart disease risk. There is, however, a great interindividual variation in response to therapy, partially attributed to genetic factors. The polymorphic enzyme POR transfers electrons from NADPH to CYP450 enzymes including CYP3A, which metabolize atorvastatin. POR∗28 polymorphism is associated with increased CYP3A enzyme activity. We analyzed the association of POR∗28 allele with response to atorvastatin. Materials & methods: One hundred and five FH children and adolescents treated with atorvastatin at doses 10-40 mg were included in the study. Total cholesterol (TChol) and LDLc were measured at baseline and after 6 months of treatment. POR∗28 allele was analyzed with TaqMan assay. CYP3A4∗22, CYP3A5∗3 and SLCO1B1 521T>C and 388A>G genotypes were also determined with TaqMan or PCR-RFLP methods. Results: POR∗28 carriers had significantly lower percent mean reduction of TChol (33.1% in ∗1/∗1, 29.8% in ∗1/∗28 and 25.9% in ∗28/∗28 individuals, p = 0.045) and of LDLc (43.9% in ∗1/∗1, 40.9% in ∗1/∗28 and 30.8% in ∗28/∗28 individuals, p = 0.013). In multivariable linear regression adjusted for confounding factors, POR∗28 genotypes, additionally to baseline cholesterol level, accounted for an estimated 8.3% and 7.3% of overall variability in % TChol and LDLc reduction (β: 4.05; 95% CI: 1.73-6.37; p = 0.001 and β: 5.08; 95% CI: 1.62-8.54; p = 0.004, respectively). CYP3A4∗22, CYP3A5∗3 and SLCO1B1 521T>C and 388A>G polymorphisms were not associated with lipid reductions and did not modify the effect of POR∗28 on atorvastatin response. Conclusion: In children with FH, carriage of POR∗28 allele is associated with reduced effect of atorvastatin on TChol and LDLc and therefore identifies FH children that may require higher atorvastatin doses to achieve full therapeutic benefits. Additional studies in different populations are needed to replicate this association. © 2014 Future Medicine Ltd

CYP2C9*2 allele increases risk for hypoglycemia in POR*1/*1 type 2 diabetic patients treated with sulfonylureas

It is previously shown that carriers of the defective allele CYP2C9*3 that leads to impaired sulfonylurea metabolism are at increased sulfonylurea-induced hypoglycemia risk due to diminished drug metabolism, whereas no effect of CYP2C9*2 allele was found. Recently, a polymorphism in P450 oxidoreductase (POR) gene, assigned as POR*28 allele, was associated with increased CYP2C9 activity. The aim of this study was to assess i) the effect of POR*28 allele on sulfonylurea-induced hypoglycemia risk and ii) the association of CYP2C9*2 allele with hypoglycemia risk in non-carriers of POR*28 allele. The study group consisted of 176 patients with diagnosed type 2 diabetes mellitus (T2DM) treated with sulfonylureas, of whom 92 patients had experienced at least one drug-associated hypoglycemic event (cases), while 84 had never experienced a hypoglycemic event (controls). POR*28 allele was detected by use of real-time TaqMan PCR. POR*28 allele was not associated with sulfonyl-induced hypoglycemia. In POR*1/*1 patients, CYP2C9*1/*2 genotype was more common in cases than in controls (32.7 vs. 14.3%, p=0.041). In a model adjusted for age, BMI, duration of T2DM and renal function, and POR*1/*1 entered as a selection variable, CYP2C9*2 allele increased the hypoglycemia risk in response to sulfonylurea (odds ratio: 3.218, p=0.031). In conclusion, our results suggest that POR*28 allele is masking the association of CYP2C9*2 allele with sulfonyl-induced hypoglycemia. Therefore, POR*28 allele is an important source of CYP2C9 activity variability and combined with CYP2C9 gene polyÂmorphisms may explain individual variability in the effect of sulfonylureas. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart New York