Muhammad Islam

Mesenchymal stem cells (MSCs) as skeletal therapeutics–an update

Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repair/regeneration. In this context, both, autologous and allogeneic cell transfer options have been utilized. Studies suggest that MSCs are transplanted either alone by mixing with autogenous plasma/serum or by loading onto repair/induction supportive resorb-able scaffolds. Thus, this review is aimed at highlighting a wide range of pertinent clinical therapeutic options of MSCs in the treatment of skeletal diseases and skeletal tissue regeneration. Additionally, in skeletal disease and regenerative sections, only the early and more recent preclinical evidences are discussed followed by all the pertinent clinical studies. Moreover, germane post transplant therapeutic mechanisms afforded by MSCs have also been conversed. Nonetheless, assertive use of MSCs in the clinic for skeletal disorders and repair is far from a mature therapeutic option, therefore, posed challenges and future directions are also discussed. Importantly, for uniformity at all instances, term MSCs is used throughout the review.

Genderwise clinical response of antipsychotics among schizophrenic patients: a prospective observational study from Lahore, Pakistan

Abstract Objective: The study was aimed to evaluate the gender specific response to adherence and occurrence of side effects among schizophrenic patients in Lahore, Pakistan. Methods: A prospective study was performed for a period of 1 year among 180 newly diagnosed schizophrenics, aged 20–60 years to observe the symptoms, medication adherence and side effects. Morisky–Green–Levine Scale was used to evaluate medication adherence, LUNSER for side effects and PANSS to measure positive and negative symptoms. Data were analyzed using SPSS. Results: Positive symptoms (Male: Baseline 36.14 vs. endpoint 23.58, Female: 35.29 vs. 23.74) and negative symptoms (Males 27.9 vs. 20.05, Females 28.41 vs. 20.2) of schizophrenia were equally reduced after a follow up of 1 year in both the genders. Male population suffered more accumulative side effects (11.4 in males vs. 6.40 in females), extrapyramidal symptoms such as tardive dyskinesia and tremors (1.21 in males vs. 0.57 in females) and other side effects as compared to women (p ≤ .005). Males were found poorly adherent to antipsychotic treatment than females (93.3% in males vs. 6.7% in females (p ≤ .005). Conclusions: Prescribing practices should not overlook sex specific factors like hormonal changes, altered brain morphology and socioeconomic factors that may be responsible for the difference in the response to the course of schizophrenia.

Prevalence and management of anemia in pre-dialysis Malaysian patients: A hospital-based study

Objective: Anemia, a common complication of chronic kidney diseases (CKD), is involved in significant cardiovascular morbidity. Therefore, the objective of our study was to investigate the prevalence and severity of anemia in pre-dialysis patients, as well as to determine the predictors of anti-anemic therapy. Method: A retrospective, observational study was conducted on adult pre-dialysis patients receiving treatment at the Hospital Universiti Sains Malaysia from January 2009 to December 2013. Results: A total of 615 eligible cases were included. The mean age of patients was 64.1±12.0 years. The prevalence of anemia was 75.8%, and the severity of anemia was mild in 47.7% of the patients, moderate in 32.2%, and severe in 20%. Based on morphological classification of anemia, 76.9% of our patients had normochromic-normocytic anemia whereas 21.8 and 1.3% had hypochromic-microcytic anemia and macrocytic anemia, respectively. Oral iron supplements were prescribed to 38.0% of the patients and none of the patients was given erythropoietin stabilizing agents (ESA) or intravenous iron preparations. In logistic regression, significant predictors of anti-anemic preparation use were decreased hemoglobin and hematocrit, and advanced stages of CKD. Conclusion: The results of the present study suggest that the prevalence of anemia in pre-dialysis patients is higher than currently accepted and it is found to be correlated with renal function; prevalence increases with declined renal function. An earlier identification as well as appropriate management of anemia will not only have a positive impact on quality of life but also reduce hospitalizations of CKD patients due to cardiovascular events.

Method Development and Stress Degradation Profile of 5-Benzyl-1,3,4-Oxadiazole-2-Thiol Studied by UV Spectroscopy

Considering the pharmacological activities of 5-benzyl-1,3,4-oxadiazole-2-thiol (OXPA), the present study aimed to develop and validate a UV-spectroscopic method according to the ICH guidelines to be used to study degradation profile of the compound. The method was developed at 263 nm, the wavelength giving maximum absorbance. Linearity of the method was evaluated by analyzing a series of standard solutions. Then, recovery, accuracy and sensitivity were determined. The compound was subjected to a number of stress conditions to determine it in the presence of degradants (specificity). The proposed method showed linearity in a concentration range (0.33 - 40.0 μg/mL) with correlation coefficient (R2) = 0.998. The recovery was within 100.63 – 102.46%, intraday and inter-day accuracy were found to be 99.10 – 102.46% with relative standard deviation less than 2%, and the LOD and LOQ were found to be 0.099 and 0.330 μg/mL, respectively. The OXPA was degraded with the passage of time under acidic conditions and oxidized completely in 35% H2O2, whereas the degradation was 58.47% in 3% H2O2. Dry heat (80°C) exposure for 48 h resulted in 1.09% degradation, whereas UV exposure resulted in complete loss of the compound. These results indicate that the method is simple, sensitive, accurate and specific, hence may be used to carry out quantitative work on OXPA.

Reverse-Phase Chromatographic Determination and Intrinsic Stability Behavior of 5-[(4-Chlorophenoxy)Methyl]-1,3,4-Oxadiazole-2-Thiol

Abstract The study describes the development and preliminary validation of a simple reverse-phase chromatographic method for determination of a novel drug candidate, 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM), in bulk and stressed solution, in order to find out the intrinsic stability behavior of the compound. Isocratic elution was carried out at a flow rate of 1.0 mL min-1 through a Promosil C18 column maintained at 25 °C, using the mobile phase comprising acetonitrile and aqueous o-H3PO4 (pH 2.67) (1:1, V/V). Detection was performed at 258 nm. The response of the detector was linear in a concentration range of 1.25-50.00 μg mL-1 with the correlation coefficient of 0.9996 ± 0.0001. Cumulative intra-day, inter-day and inter-instrument accuracy (99.5 ± 1.0, 100.2 ± 1.0 and 100.3 ± 0.4 %, resp.) with RSD less than 5 % indicated that the method was accurate and precise. The resolution and selectivity factor (>2 and >1, resp.), particularly in copper metal- and dry-heat-stress solutions, depicted the selectivity of the method. OXCPM remained stable under hydrolytic (acidic and neutral pH, ≤ 37 °C), photolytic and moist heat stress conditions. Under alkaline conditions (hydrolytic and photolytic), polar products were formed that eluted very fast through the column (tR < 3.75 min). At room temperature, the compound was susceptible to oxidation by hydrogen peroxide and transition metals. The ionogram of most of the stress solutions indicated the presence of a product having m/z 256, which might be a result of N- or Smethylation or -SH oxidation. The results of the study indicate that the method is selective, sensitive and suitable to be used for determination of OXCPM in bulk and under stress conditions.

Impact of duration of therapy on side effect profile of anti-HCV protocol: A retrospective cohort study from two tertiary health facilities in Pakistan

Purpose: To evaluate the plausible risks and adverse effects related to the duration of therapy in hepatitis C (HCV) patients in Lahore, Pakistan. Method: A retrospective observational study involving 250 HCV patients who received combination therapy with ribavirin and interferon was conducted. The patients were segregated into two groups on the basis of duration of therapy (≤ 6 months and > 6 months). Adverse effect profiles of patients under treatment were collected using a pre-validated questionnaire and compared using Pearson’s Chi- Square Test/Chi-Square Goodness-of-Fit tests and unpaired t-test. Results: Patients who underwent treatment for ≤ 6 months frequently encountered side-effects such as GIT disturbance (23.77 %) and joint pains (29.63 %). Additionally, diabetes mellitus (27.86 %) and frequent injections (74.59 %) were the most commonly observed co-morbid condition and disease risk, respectively. On the other hand, in patients who underwent therapy for > 6 months, skin disorders (30.46 %) and gastric acidity (10.15 %) were the most frequently observed side-effects with less frequent reporting on co-morbid conditions and disease risk factors. Moreover, there was a significant reduction in body weight (p = 0.03), serum bilirubin (p = 0.0005), albumin (p = 0.003) and triglycerides (p = 0.006) levels due to longer duration of treatment. Conclusion: The data suggest that treatment-related risks are higher among HCV patients on shorter treatment duration whereas adverse events subside in patients on longer duration of therapy (>6 months). Changes in biochemical profile were also more evident in those receiving treatment for periods >6 months. Keywords: Interferon, Ribavirin, Side effects, Duration of therapy, Outcomes of therapy

Glutathione sulfotransferase inhibition activity of a self-fermented beverage, Kanji

Abstract Context: Kanji, a liquid preparation of roots of Daucus carota L. ssp. sativus (Hoffm.) Arcang. var. vavilovii Mazk. (Apiaceae), may inhibit glutathione sulfotransferase (GST) activity due to ferulic acid content. Objectives: GST inhibition activity and characterization of Kanji and methanol extract of D. carota roots, and oral absorption pattern of ferulic acid from Kanji in rats. Materials and methods: GST inhibition activity of Kanji and methanol extract of D. carota roots in concentration range 0.001–100.00 mg/mL was determined using Sprague Dawley rat liver cytosolic fraction. Methanol extract upon column chromatography gave ferulic acid, which was used to characterize Kanji and determine its oral absorption pattern in Wistar rats. Results: The GST inhibition activity of Kanji (100.00 μg/mL), methanol extract of D. carota roots (100.00 μg/mL) and tannic acid (10.00 μg/mL, positive control) was found to be 0.162 ± 0.016, 0.106 ± 0.013 and 0.073 ± 0.004 μM/min/mg, respectively. Different Kanji samples and methanol extract contained ferulic acid (0.222–0.316 mg/g) and 0.77 mg/g, respectively. Ferulic acid did not appear in plasma after oral administration of Kanji. Discussion: Kanji having solid contents 80.0 μg/mL, equivalent to 0.0025 μg/mL ferulic acid, does not inhibit the activity of GST. The oral administration of Kanji, in human equivalent dose (528 mg/kg, 16.67 μg ferulic acid), to rats indicated poor absorption of ferulic acid. Conclusion: Kanji having solid contents 14–36 mg/mL does not inhibit GST activity, hence may not interfere with drugs that are the substrates of GST, if taken concomitantly.