Phenotypes of Alpha 1 Antitrypsin in Karachi, Pakistan

Objective: To determine serum level of the protease inhibitor, to identify phenotypes and determine their frequencies. Study Design: A prospective study. Setting: PMRC Research Centre, JPMC and the Aga Khan University Hospital Karachi. Subjects: Healthy aduIts without history ol peptic ulcer disease and a normal endoscopy. Methodology: Quantitive measurement of serum alpha 1 AT was carried out by radial immunodiffusion. phenotyping by iso-electric focusing and confirmation of phenotypes by immunofixation and DNA analysis technique. Results:Serum alpha I AT was low in 13.4% of the subjects. Ni MM phenotype predominated followed by SZ SS, MZ and ZZ. DNA diagnosis accurately resolved the phenotypes as S and Z. Conclusion: Frequency by phenotype associated with total and intermediate deficiency is less in the populatio

Synthesis, spectral analysis and pharmacological study of N'- substituted-2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazides

A series of molecules bearing multiple functional groups were synthesized to study their antibiotic effect against Gram-positive and Gram-negative bacteria and lipoxygenase activity as well. 2,4-Dimethylcarbolic acid (1) was refluxed with ethyl 2-bromoacetate to synthesize ethyl 2-(2,4-dimethylphenoxy)acetate (2). Compound 2 was converted to the corresponding hydrazide 3, again on refluxing with hydrazine. The compound 5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-thiol (4) was synthesized by the reaction of 3 and CS2 in the presence of KOH. Compound 4 was further converted to the corresponding ester 5 and then 2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazide (6). The final molecules N'-substituted-2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazide, 8a-m, bearing ether, 1,3,4-oxadiazole, thioether, hydrazone and azomethine functional groups were synthesized by stirring the aryl carboxaldehydes 7a-m with 6 in methanol at room temperature. The depicted structures of all synthesized molecules were corroborated by IR, 1H-NMR and EIMS spectral data analysis. 8m and 8i showed substantial antibacterial activity and lipoxygenase inhibitory activity, respectively

Genetic Variants of Serum Alpha 1 Antitrypsin

Complete absence of data on alpha 1 antitrypsin in this country prompted us to determine serum levels using radial immunodiffusion (RID) and phenotypes by isoelectric focusing (IEF) in 100 healthy adults (52 males and 48 females). Mean serum alpha 1 antitrypsin concentration in healthy subjects was 2.47±0.08 g/l and the main phenotypes MM (70%), M1 M2 (28%) and FM 3(2%) are infrequent in our population (JPMA 45:245,1995)

Teacher Training in Pakistan: Overview of Challenges and their Suggested Solutions

Education is a key component of progress in the present-day world. But this progress cannot be made without efforts of teachers. Therefore, teacher education, in particular teacher training becomes extremely important. In this regard, several trainings programs are initiated and executed across Pakistan but the desired outcomes have not been achieved so far. Hence, this study was conducted to explore the challenges in teacher training in Pakistan and the ways through which these issues can be resolved. The sources for the data of the study were the published studies in the field in the context of Pakistan, national education policy, and other relevant literature. Based on secondary data, the study concludes that the issues with teacher training in Pakistan are administrative as well as faculty related. The findings reveal that the challenges related to policy and planning, poor induction of teachers, lack of resources in teacher training institutions, demotivation among teachers, and unequal distribution of skilled and productive teachers, dual training system and infrequent trainings. These issues can be fixed by fostering encouraging environment, ensuring accountability and merit, providing necessary resources, systematizing professional training programs and their continuation. The findings of this study will, therefore, positively guide policymakers to develop the right and effective policy to improve the standard of teacher education in the country

Epilepsy in pakistan: national guidelines for clinicians

Epilepsy is one of the most common chronic neurological disorders requiring prolonged treatments and drugs. According to The World Health Organization (WHO), epilepsy is one of those serious brain disorders that affect not only the individual but has a deep impact on the family and society in general. Approximately 50 million people are affected with epilepsy around the world36, though proper epidemiological studies do not exist for Pakistan it is estimated that the prevalence of epilepsy is 9.99/1000. Highest prevalence is seen in people younger than 30 years of age, i.e. about 2 million people and 1/10th of the world burden of epilepsy is in Pakistan! The guidelines available in developed countries are gauged in a setting where epilepsy care is provided by epileptologists/neurologists. In Pakistan the scenario is different, there is only one neurologist for 1.4 million (14lac) population contrast to US where one neurologist for 26 thousand people 29. So there is a desperate need to adapt to alternate guidelines with strategies to provide epilepsy management at a primary care level and to standardize epilepsy care on a National level

Determination of Alpha-i Antitrypsin Genetic Deficiency in Duodenal Ulcer by Polymerase Chain Reaction

Objective: To confirm alpha-I-AT deficiency status in duodenal ulcer using a combination of PCR and restricted enzyme digestion. Methods: Fifty patients with endoscopically proven duodenal ulcer and hundred controls with no signs of the disease were included. Alpha-i-AT phenotypes were confirmed by polymerase chain reaction followed by restriction enzyme digestion. Results:Alpha-I-AT concentration in duodenal ulcer patients showed a mean value of 2.12 ± 0.11g/1 (range: 0.52-3.95 g/1, p Conclusion: Alpha-1 AT deficiency was found in 10% of duodenal ulcer patients. DNA analysis more accurately resolved the phenotypes as S and Z mutations (JPMA 52:545; 2002)

Serum Alpha 1 Antitrypsin and Pulmonary Emphysema

Using isoelectric focusing (lEE) and radial immunodiffusion (RID) techniques, serum samples from 100 normal healthy adults and 21 patients with pulmonary emphysema were analysed to identify varioud alpha 1 antitrypsin phenotypes and the Seru m concentrations,Ten percent of the patients had low serum values. The normal or most common genetic form, MM, is the predominant phenotype in both controls and patients (JPMA 46:102, 1996)

Genetic Markers and Duodenal Ulcer

Serum pepsinogen, ui-antitrypsin (ui-AT) and blood groups were studied as genetic markets in 32 patients with endoscopically proven duodenal ulcer and 44 control subjects with no family history of ulcer disease. Serum pepsinogen was detennined by the modified method of Edward et al7, a1-AT by single radial hnmunodiffusion8 (RID) and phenotyping was carried out by isoelectric focusing (IEF)9. Duodenal ulcer patients with hyper- pepsinogenemia (28%) and low serum ui-AT (35%) had a dominant blood group 0, lower mean age, an early onset of disease, a higher frequency of gastrointestinal (CI) bleeding and ulcer perforation. These parameters were found considerably different in patients with normal serum pepsi­nogen and ui-AT. Phenotype analysis of a1-AT revealed that four duodenal ulcer patients had partial deficiency of the protease inhibitor and none of the normal exhibited the deficiency pattern. The etiology of the disease appears to be genetic anomaly in 28% of patients while the rest (72%) had ulcers as a result of neuroendocrinological or environmental factors (JPMA 47:135,1997)