The CYP2C9 and CYP2C19 polymorphism are associated with pretreatment drug response prediction, metabolism and disposition. Pakistan consists of a population comprising of various ethnic groups residing in different regions of the country each claiming diverse ethnic origins. The identification of the CYP450 genotypic composition of these populations is therefore necessary to avoid adverse drug reactions in these individuals. The study objective was to investigate the CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17 frequency in nine Pakistani ethnic groups and to check their association with hypertension. DNA was extracted and analyzed by AS-PCR. Four phenotypes were observed and they were: extensive metabolizer (EM), poor metabolizer (PM), intermediate metabolizer (IM) and ultra-rapid metabolizer (UM). Regarding population, over all the percentage of predicted PM allele (CYP2C19*2) was 29.0% compared to (CYP2C19*17) UM allele 23.70%. Among the studied groups, Saraiki and Brahui showed highest percentage of PM allele (40%, 36%) whereas Parsi and Hazara had highest percentage of UM allele (37% and 30% respectively). In case of CYP2C9, CYP2C9*2 showed highest frequency in Saraiki (51%) and Burusho (45%), while in case of CYP2C9*3 Brahui (49%) and Hazara (47%) showed highest frequency. Overall, 75%, 25%; 64.2%, 35.8 % of CYP2C19*2 and 66.6%, 33.4%; 75.6%, 24.4% of CYP2C19*17 wild type and mutant allele frequency was observed in patients and controls (p<0.05). Similarly, 51%, 49%; 76%, 24% of CYP2C9*2 and 46.5%, 53.5%; 46%, 54% of CYP2C9*3 wild type and mutant allele frequency was observed in patients and controls (p<0.05). In conclusion the high prevalance of CYP2C9*2, CYP2C9*3, CYP2C19*2 and *17 in Pakistani population leads to the recommendation of a pre-treatment test to monitor drug response and dosage (personalized medicine) to avoid post-treatment adverse drug reactions.
Both Zainuddin Ibn Nujaim (d. 970HJ) and Herbert Broom (d. 1882CE) are famous for the arrangement, interpretations and for sound applications of juristico-legal maxims and rules respectively in Muslim and western world of law and jurisprudence. The al-Ashbah wa-Al-Nazair of Ibn Nujaim and Broom’s Legal Maxims of Herbert Broom speak of their deep approach to the concerned discipline. This article provides a general analysis of the juristico-legal interpretations regarding the elementary maxim of hardship and injuria remedium (hardship and harm remission) as made by Ibn Nujaim (d.970HJ) and Herbert Broom(d.1882CE) in their aforesaid books.
The aim of present research is to define and analyze some new families of holomorphic mappings related to the conic domain. Different techniques and tools are employed to investigate these families including differential subordination, Bernardi integral operator, Carlson-Shaffer linear operator, hypergeometric mapping, convolution operator, real and the complex orders. These families are extensively explored by studying their coefficient bounds, arc length problems, covering results, integral representations, inclusion results, radius of convexity problems, necessary conditions, growth rate of coefficients, distortion results, subordination results, convolution preserving properties and Fekete-Szegö inequality. Numerous well-known results appear as special cases for the different choices of parameter from our main results. Our investigation also contains a sound relationship between the results presented here with the results which are already available in the literature.