Mohammad Ismail

Anti-inflammatory activities of Taxusabietane A isolated from Taxus wallichiana Zucc.

Current study was conducted to identify constituents of Taxus wallichiana Zucc. that might be responsible for its folk use in anti-inflammatory conditions. Taxusabietane A was isolated from the bark extract of Taxus wallichiana Zucc. Taxusabietane A was analyzed for in-vitro and in-vivo anti-inflammatory activities using Lipoxygenase (LOX) inhibition assay and carrageenan-induced paw edema model. Taxusabietane A revealed considerable LOX inhibitory activity with the IC(50) value being 57 ± 0.31. Standard compound Baicalein showed the IC(50) value being 22.1 ± 0.03 μM. Taxusabietane A also showed significant (5 and 10 mg/kg) anti-inflammatory activity induced by carrageenan. However, this study highlighted the potential of Taxusabietane A to be further explored as a new lead compound for management of conditions associated with inflammation.

Capsule endoscopy: a review.

Capsule endoscopy (CE) is a novel technology that allows direct noninvasive visualization of the entire small intestine. CE permits a detailed examination in the ambulatory setting, allowing identification of clinically relevant lesions, and it is appealing to both patients and providers. There are two types of capsules that are currently commercially available: one specifically designed to view the small bowel and the other for the esophagus. Common indications for small bowel CE include obscure gastrointestinal bleeding, initial diagnosis of suspected Crohns disease, and other small bowel pathology. The esophageal capsule is currently used to evaluate Barrett esophagus and esophageal varices. It is a well-tolerated procedure with relatively few complications. Although CE performance may be superior to existing technologies, its impact on clinical decision-making and patient outcomes are of even greater importance. Herein lies a review of the latest information on CE, its indications, complications, future utilities, and developing technology.

Application of SeDeM Expert system in formulation development of effervescent tablets by direct compression

The SeDeM expert system is a pre formulation tool applied for the prediction of the suitability of a material for direct compression. This innovative tool provides an index of good compressibility of the material indicating its aptitude to be compressed by direct compression. In the study the SeDeM expert system has been applied for the prediction of the behavior of the material to be used in the formulation of effervescent tablets by direct compression. Different formulations were developed on the basis of the results of the SeDeM expert system. Various parameters for the material as per the SeDeM expert system were determined according to their official and reported methods. Powder blend for different formulations was evaluated for their rheological properties while tablets were evaluated for various official and unofficial tests. Suitability of the material for direct compression was successfully predicted using the SeDeM expert system. Domperidone was found unsuitable for direct compression. During formulation all excipients responded as they were predicted as per the SeDeM expert system. Tablets produced using the resultant formulations were having sufficient mechanical strength, free of premature effervescence and were capable to be scaled up for commercial manufacturing.

Genetic Susceptibility to Oral Cancer due to Combined Effects of GSTT1, GSTM1 and CYP1A1 Gene Variants in Tobacco Addicted Patients of Pashtun Ethnicity of Khyber Pakhtunkhwa Province of Pakistan

Associations of GSTT1, GSTM1 and CYP1A1 gene variants with risk of developing oral cancer were evaluated in this study. A case-control study was conducted in Pashtun population of Khyber Pakhtunkhwa province of Pakistan in which 200 hospital based oral cancer cases and 151 population based healthy controls exposed to similar environmental conditions were included. Sociodemographic data were obtained and blood samples were collected with informed consent for analysis. GSTM1 and GSTT1 were analysed through conventional PCR method while specific RT-PCR method was used to detect CYP1A1 polymorphisms. Results were analyzed for conditional logistic regression model by SPSS version 20. The study shows that patients with either GSTM1 or GSTT1 null genotypes have significantly higher risk of oral cancer (adjusted odds (OR): (3.019 (1.861-4.898) and 3.011(1.865-4.862), respectively), which further increased when either one or both null genes were present in combination (adjusted odds (OR): (3.627 (1.981-6.642 and 9.261 (4.495-19.079), respectively). CYP1A1 rs4646903 gene variants individually showed weak association OR: 1.121 (0.717-1.752); however, in the presence of GSTM1 and/or GSTT1 null genotypes further increasing the association (adjusted odds (ORs): 4.576 (2.038-10.273), 5.593 (2.530-12.362) and 16.10 (3.854-67.260 for GSTM/GSTT null and CYP1A1 wild type, GSTM/GSTT either null and CYP1A1 variant alleles, and all 3 gene polymorphisms combinations, respectively). Our findings suggest that presence of GSTM1 and/or GSTT1 null genotypes along with variant alleles of CYP1A1 may be the risk alleles for oral cancer susceptibility in Pashtun population.

High prevalence of the risk factors for QT interval prolongation and associated drug–drug interactions in coronary care units

ABSTRACT Objectives: Patients admitted in coronary care units are susceptible to QT interval prolongation due to numerous risk factors. The purpose of this study was to identify the prevalence of risk factors for QT interval prolongation; QT prolonging medications; drug–drug interactions; their predictors; and torsades de pointes risks of drugs. Methods: After obtaining approval, this cross-sectional study was carried out during one-year period in coronary care units of two major tertiary care hospitals of Khyber Pakhtunkhwa, Pakistan. The Arizona Center for Education and Research on Therapeutics QT drugs lists and Micromedex DrugReax® were used to identify the QT prolonging medications and QT prolonging drug–drug interactions. Results: Total 649 patients were included in this study. The most frequent QT prolonging risk factors included use of ≥ 1 QT prolonging drugs (74.9%) and myocardial infarction (61.3%). Total 181 patients were presented with 361 QT prolonging drug–drug interactions. There was significant association of the occurrence of QT prolonging drug–drug interactions with female gender (p = 0.01), 9–10 prescribed medications (p = 0.001), and > 10 prescribed medications (p < 0.001). Conclusions: The majority of patients presented with multiple risk factors for QT prolongation in coronary care units which may precipitate lethal outcomes.

Moxifloxacin-induced QT interval prolongation and torsades de pointes: a narrative review

ABSTRACT Introduction: Moxifloxacin is widely used for the treatment of a number of infectious diseases because of its favorable pharmacological profile and high clinical success rate. However, it is often criticized for its higher risk of QTc interval prolongation (QTIP) and torsades de pointes (TdP). Areas covered: A review of published literature on moxifloxacin-related QTIP and TdP. Readers will be provided with a comprehensive overview of the prevalence, cellular mechanism, risk factors, and magnitude of QTIP of moxifloxacin. Expert commentary: In healthy subjects, moxifloxacin prolongs the QTc interval by 11.5–19.5 ms, it binds at the Tyr652 residue in the S6 pore domain of the human ether a-go-go gene related potassium channel. Considerable QTIP (30–60 ms) have also been reported in some patients, for instance the incidence of QTIP (30–60 ms) in elderly pneumonia patients was 15.5%. Moxifloxacin-induced QTIP may be of little clinical importance in healthy individuals. However, marked QTIP (>60 ms) and TdP have been reported in high-risk patients (patients who have multiple QT prolonging risk factors). Patients must be thoroughly assessed prior to the use of moxifloxacin and high-risk patients must be identified using risk assessment tools to ensure safe use of moxifloxacin and to safeguard patients’ health.

Potential drug-drug interactions in outpatient department of a tertiary care hospital in Pakistan: a cross-sectional study

BackgroundPotential drug–drug interactions (pDDIs) are one of the preventable drug related problems having the risk of serious adverse events or therapeutic failure. In developing countries like Pakistan, this issue remains poorly addressed. The objective of this study was to explore prevalence of pDDIs in the Outpatient Department (OPD) of a tertiary care hospital in Pakistan. The secondary aim was to describe the levels of reported pDDIs and develop a list of widespread clinically relevant interactions.MethodsPrescriptions of 2400 OPD patients were analyzed for pDDIs through Micromedex Drug-Reax®. Prevalence, severity- and documentation-levels and widespread clinically relevant interactions were reported.ResultsOf total 2400 prescriptions, pDDIs were present in 22.3%. Whereas, moderate- and major-pDDIs were found in 377 (15.7%) and 225 (9.4%), respectively. PDDIs were more prevalent in Medicine (9.2%) and Cardiology (2.6%) as compared with other OPD specialties. Total 942 pDDIs were identified, of which, the majority were either moderate- (61.9%) or major-pDDIs (32.1%). Some of the most common interactions were ibuprofen + levofloxacin (n = 50), ciprofloxacin + diclofenac (32), aspirin + atenolol (24), and diclofenac + levofloxacin (19). The potential adverse outcomes of widespread interactions were seizures, bleeding, QT-interval prolongation, arrhythmias, tendon rupture, hypoglycemia/hyperglycemia, serotonin syndrome, drug toxicity, and decreased therapeutic response.ConclusionsOPD patients were at risk to pDDIs, particularly to major- and moderate-pDDIs. Screening of prescriptions for pDDIs and monitoring of pharmacotherapy in terms of response and associated adverse drug events will contribute to patient safety.

Potential drug-drug interactions in pediatric patients admitted to intensive care unit of Khyber Teaching Hospital, Peshawar, Pakistan: A cross-sectional study

Purpose To investigate frequencies, levels, clinical relevance and predictors of potential drug‐drug interactions (pDDIs) in pediatric intensive care unit (PICU). Methods Case notes of 411 patients were reviewed for pDDIs through Micromedex. Frequencies, levels and clinical relevance of pDDIs were reported. Logistic regression was applied to calculate the odds‐ratios for predictors of pDDIs. Results We recorded pDDIs in 59.4% patients. Major‐pDDIs were found in 34.5% patients. Total 990 pDDIs were identified, of which, 37.8% were of moderate‐severity and 30.6% of major‐severity. Patients case notes of top‐ten pDDIs showed presence of signs/symptoms such as fever, jaundice, vomiting, anorexia, tachycardia, drowsiness, & lethargy; and abnormalities in labs such as total leukocytes count, blood urea nitrogen, alanine aminotransferase, & potassium‐level. Odds of exposure to major‐pDDIs were significantly higher in patients aged 6–12 years (p = 0.008); hospital stay of ≥ 7 days (p = 0.05); and ≥ 11 prescribed medicines (p < 0.001). Conclusion Substantial numbers of patients in PICU are exposed to pDDIs. Major‐pDDIs are of particular concern. Timely identification of pDDIs, preferably with computerized source, is crucial point for their management. Monitoring of clinically relevant parameters and identification of various predictors are needed to minimize or prevent the associated negative consequences of pDDIs. HighlightsConsiderable number of pediatric patients in ICU presents with pDDIs. Major‐pDDIs are of particular concern.Use of computerized DDIs screening system in pediatric ICU are very useful to identify pDDIs.Rational prescribing can be promoted by giving proper consideration to the identified contraindicated and major‐pDDIs.Patients’ monitoring‐plan should include monitoring parameters for pDDIs as well.

Research Data Supporting "Synthesis, Application and Carbonation Behaviour of Ca2Fe2O5 for Chemical Looping H2 Production"

Chemical looping hydrogen production uses the oxidation and reduction of metal oxides, typically iron, to produce hydrogen. This work focuses on the modification of iron oxide with calcium oxide to form an oxygen carrier containing di-calcium ferrite (Ca2Fe2O5), which presents favourable thermodynamics for achieving higher conversions of steam to hydrogen compared to chemically unmodified iron oxide. Different methods of synthesis, viz. mechanochemical synthesis and co-precipitation, were used to produce Ca2Fe2O5, and their resulting performances were compared. Consistent with thermodynamic predictions, it was found that CO2, or steam, was sufficient to fully regenerate the reduced carriers to Ca2Fe2O5. The cyclic stability of the oxygen carriers were studied in fluidised bed reactors and by thermogravimetric analysis (TGA). Good stability of the materials was observed for up to 50 cycles, with no evidence of agglomeration even up to 950 oC. The rate of deactivation was found to correlate with the purity of Ca2Fe2O5 and the presence of impurity phases such as CaFe2O4, which tended to segregate into its constituent elemental oxides. Carbonation of the oxygen carriers was examined by TGA, and was found to occur appreciably only for the reduced carrier (a mixture of CaO and Fe) between temperatures of 500 – 700 oC and 0.1 – 0.5 atm of CO2, whereas the oxidised carrier (viz. Ca2Fe2O5) did not carbonate. Fresh and cycled materials were characterised by XRD, SEM and BET analysis. Ca2Fe2O5 is a potentially viable material as an oxygen carrier for hydrogen production, but owing to thermodynamic limitations cannot be used for complete fuel oxidation.

868 Liver Transplantation for Hepatic Sarcoidosis: Long Term Follow-up and Recurrence After Liver Transplantation, a Single Center Experience

0.002, 95% CI 1.9 17), MELD score ≥ 15 (OR 2.1, p = 0.006, 95% CI 1.24 3.58), and HDL cholesterol < 30mg/dL (OR 2.98, p = 0.001, 95% CI 1.52 5.84). The age, sex, etiology of liver cirrhosis, type of decompensation, serum sodium < 130mEq/L and total cholesterol < 100mg/dL were poor predictors of infection. Mortality rates: First admission 14.3% (43/ 301), at 1 year 39.8% (100/251) and at 3 years 58.1% (91/217). Kaplan Meier survival analysis showed decreased long term survival in patients with infections at first admission for decompensated liver cirrhosis (p <0.001). Conclusions:Community and nosocomial infections have a high incidence at first episode of decompensation of liver cirrhosis and are independent predictors of mortality at hospital admission, at 1 and 3 years. These patients may benefit from intensive treatment and early referral for liver transplantation.