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Objective:To assess therifampicin resistance in re-treatment cases of pulmonary tuberculosis using gene-xpert.Material and methods:This cross sectional study was conducted at Department of Pulmonology Bahawal Victoria Hospital, Bahawalpur.Total 145 patients who came for re-treatment of TB either male or female having age 20-60 years were selected for this study.Results:Mean age of the patients was 45.79 ± 11.65 years and mean duration of TB was 5.44 ± 2.9 years.Rifampicin resistance was found in 55 (38%) cases by using gene-xpert test. Rifampicin resistance is significantly associated with gender but insignificantly associated with age and duration of TB.Conclusion:In present study very high percentage of rifampicin resistance was found in retreatment cases of TB by using gen-xpert test.Significant association of gender with rifampicin resistance was noted but insignificant association of age and duration of TB with rifampicin resistance was detected.
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ABSTRACT Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Quinazolines/pharmacology , Azepines/pharmacology , Virus Activation/drug effects , HIV Infections/virology , HIV-1/drug effects , Niacinamide/pharmacology , Methyltransferases/antagonists & inhibitors , Piperazines/pharmacology , Leukocytes, Mononuclear/virology , CD4-Positive T-Lymphocytes , Gene Expression Regulation, Viral , Virus Latency , Viral Load/drug effects , Viral Tropism/drug effectsABSTRACT
Currently, the use of natural compounds obtained from plants tremendously increased due to their promising therapeutic properties. The aim of this study was to formulate a stable emulgel formulation loaded with Cinnamomum tamala (CT) extract. The antioxidant activity of plant extract was determined by DPPH inhibition assay. The extract was successfully loaded into an emulgels using different concentrations of carbopol-940, liquid paraffin, emulsifying agents and preservatives. Preliminary stability study was performed of 17 CT emulgel formulations at accelerated temperature of 50 °C for 2-months. Organoleptic evaluation, centrifugation, globule size, pH, electrical conductivity and rheological studies were performed for a period of 90-days at different temperature including 8, 25, 40 and 40 °C ±75% RH. The CT extract showed promising antioxidant activity of about 81%. On the other hand, the CT loaded emulgel formulation displayed high physical stability at all tested conditions of temperature and time. However, slight decrease in pH and minimum increase in conductivity was observed at 40 and 40 °C±75% RH. The rheological examination of CT emulgel indicated the flow index values of all the samples kept at different temperatures were less than 1, demonstrated non-newtonian and pseudo-plastic nature of CT emulgel. Taken together, the CT emulgel formulation has been evinced to be an excellent addition in the field of topical formulations.
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Opioid drugs are the first line of defense in severe pain but the adverse effects associated with opioids are considered as a serious issue worldwide. Acupuncture/electroacupuncture is a type of Chinese medicine therapy which is an effective analgesic therapy, well documented in animals and human studies. Electroacupuncture stimulation could release endogenous opioid peptides causing analgesia in a variety of pain models. It can be used as an alternative therapy to control the opioid crisis.
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The objective of this study was to develop Aceclofenac fast dispersible compacted pellets with improved taste and fast drug release. Pellets were prepared by extrusion-spheronization technique followed by direct compression to make compacted pellets. Formulations were comprised of sucrose, mannitol, ac-di-sol, aspartame, pine apple flavor and magnesium stearate. A mixture of distilled water and isopropyl alcohol [1:1] was used for wet massing. The effect of acdi-sol on the drug release pattern was examined and dissolution profile comparison was established. All formulations followed First order and Weibull models and f2 values indicated dissimilarity with the marketed immediate release product. Taste of compacted pellets was evaluated by a panel of 12 human volunteers. Formulation P5 was found to be an optimized formulation due to satisfactory quality attributes
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Prescriptions comprising multi-drug therapy mostly illustrate the prescribing error. The phenomenon of error is bonded with human inaccuracy. The erroneous practice is observed in under developed countries like Pakistan, Bangladesh and also in developed ones. Consequently drug-drug interaction is one of the most common error associated with potentially serious adverse response even death. Accordingly the present study was conducted to assess the prevalence of prescribing errors and drug-drug interactions in out-patients receiving angiotensin receptor blockers. The study was done with population size one hundred fifty prescriptions obtained from different out-patient settings in Karachi. The prescriptions were screened for prescribing errors and risk factors for drug-drug interactions. Drug-drug interactions were recognized by Micromedex.2.0.Drug-Reax®database. The most common type of error was omission error. These errors were patient's age, weight and diagnosis found in 51.3%, 97.3% and 74% of prescriptions, respectively. The prevalence of drug-drug interaction was 38%. A total of 746 drugs were prescribed with an average of 5 drugs per prescription and 450 medication errors were detected. Majority of the interaction were moderate [19.33%], others were minor [14%] and major [6%] in severity. Patients who prescribed many drugs [more than 5 drugs in a while] had a higher risk of developing drug-drug interactions [OR=4.76; 95% CI=2.30-9.64; p=0.0001*].The study data reports the occurrence of prescribing errors in Karachi and also necessitate the need of clinical pharmacist's services in health care system. The step will help to minimize the risk factors by having the drug prescriptions reviewed by the pharmacists
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A simple, sensitive and rigorous method for estimation of dimenhydrinate in human plasma was searched and its validation was carried out. LLE [Liquid-Liquid extraction] of analyte with mixture of Hexane and ethyl acetate [1:1 v/v] was carried out for the preparation of Plasma Samples, Chromatographic elution of dimenhydrinate was conducted in human plasma and mobile phase with C-18 bonda Pack column [10 micro m; 250 × 4.6], using a mobile phase consisting a solution of ammonium bicarbonate in water and methanol at a flow rate of 0.5ml/minute with UV detection at 229 nm. The resolution of dimenhydrinate was well performed from plasma components. This method was validated and exhibited linearity with concentration range of 6 to 380ng/ml of dimenhydrinate in plasma. The Intraday precision was 89.2 to 96.89% and Inter day precision was 88.6% to 93.26%, the average recovery of dimenhydrinate was 97.02%. The efficacy of extraction was proved by above mentioned results. 2ng/ml and 6ng/ml, were appraised as the LOD and LOQ of dimenhydrinate, stability studies disclosed that dimenhydrinate exhibited stability in Plasma after Freeze and thaw cycles and upon -20 degree C storage, the method was developed well
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Pakistan is categorized to below to middle income countries where two third of the national annual health expenditure is in the form of out of pocket [OOP] cost. A prevalence based study was conducted to determine the OOP cost treatment of hypertension in Karachi by interviewing 350 hypertensive patients aged >30 years through a validated questionnaire. Hypertension [HTN] was classified into stage 1 and stage 2 and was found to be common in females [53.42%] than males [46.57%]. The total costs of stage 1and stage 2 HTN were calculated to be217869.7PKR and17545457.6 PKR respectively. The average treatment cost of stage 1 was observed to be significantly lower [p=0.006] than the cost of stage 2 HTN. Moreover; the cost of antihypertensive drugs, physician fees and laboratory tests were considerably different however; no variation was seen in cost of transport and loss of productivity through absenteeism from work. Overall, the present study indicates that the antihypertensive treatment has imposed a high burden on the pocket of common man and this is a major reason for treatment non-adherence. Consequently, it increases the risks of cardiovascular events, morbidity and mortality. Therefore, effective strategic planning is need of time to reduce OOP cost for better control on hypertension in Pakistan
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In this study cost effective direct compression technique was used for the development and optimization of intermediate release [IntR] ketoprofen tablets using central composite design [CCRD]. Fifteen different formulations [F1-F15] were developed using [X[1]] microcrystalline cellulose [Avicel PH-102] [18-51%], [X[2]] methocel K4M [0.1- 25%] and [X[3]] starch [1.5-18%] as selected variables while responses were % friability and Carr's Index [compressibility index]. Powder blends of all formulations were evaluated using Angle of Repose, Carr's Index and porosity. Results of powder blends comply with USP standards and are classified as Fair Excellent. From F1-F15 only four formulations i.e. F6, F7, F14 and F15 were selected on acceptable weight basis, micromeritic properties and on the concentration of excipients. For the assessment of physico chemical properties of the optimized formulations different tests were performed. All results were found to be adequate range. In vitro assessment of the optimized formulations were also carried out in different dissolution media i.e. pH 1.2, phosphate buffer 4.5, pH 6.8 and pH 7.5. Release behaviour of F6, F7, F14 and F15 were estimated by using one - way ANOVA, model - independent, model dependent methods. Results of f1 and f2 showed that all the test formulations i.e. F6, F7, F14 were found to be similar with the reference formulation i.e. F15 at various dissolution media. Also all the formulations followed Hixson-Crowell kinetic model. The parameter n showed Anomalous transport [non - fickian diffusion]. The mean dissolution time [MDT] was found to be in the range of 2.632-2.922. Results of ANOVA indicated no significant difference within and between formulations at different dissolution media as p values were found to be >0.05. Also all the selected formulations were found to be stable at accelerated conditions
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A Simple, sensitive and accurate high-performance liquid chromatographic [HPLC] method for effective and specific analysis of Loxoprofen [LXP] in the mobile phase and human plasma was developed. Effective chromatographic separation was attained on a Mediterranea Sea C18 column [250×4.6mm, 5um] with mobile phase containing acetonitrile and 0.01 M NaH2PO4 buffer [55: 45] by adjusting pH 6.5 with sodium dihydrogen phosphate buffer at a flow rate of 1ml/ min. Calibration ranges from 0.1ppm to 10 ppm with a coefficient of relation value [R2=0.999] by using a linear regression method and lower limit of quantification was 0.1ppm. The current method showed inter-day and intra-day accuracy and precision within the range of +/- 10%. % RSD was found to be less than 5 %. Analytical recovery was more than 90% which confirmed the reliability of current method. The proposed method was found appropriate for assessment of LXP in pharmacokinetic and bioequivalence study
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Objective To report the indigenous people's uses of plants from a multidimensional perspective in a remote area where strong ethnobotanical cultural practices prevail. Methods An ethnobotanical survey was conducted in the field during 2014–2016. Ethnobotanical data were gathered from 182 informants through oral interviews and semi-structured questionnaires. The distribution of plants was explored using both descriptive and graphical methods. Further, a Multinomial Logit Specification was applied to find out the probability of the occurrence of diverse utilization of plants in multipurpose domains. Results The study identified 202 plant species distributed among 71 families and 156 genera. Ethnobotanical data indicate that there are more medicinal (36.96%) uses of plants as compared to all other use categories. The output from the Multinomial Logit Specifications (MLS) model reveals that perennial and non-woody plants are exploited more for medicinal and food uses than annual and woody plants. In the context of ethnomedicinal uses, aerial plant parts particularly leaves are more extensively used for the preparation of herbal recipes as compared to underground parts. Conclusions The results of the study emphasize the need to create awareness among the local communities about the conservation status of plant species in order to maintain a sustainable resource of plant-derived materials into the future. The novel econometric approach employed in this study adds a new insightful methodology to the existing body of literature in the field of ethnobotany. We strongly recommend conservation measures, alongside phytochemical and pharmacological studies on the useful plant species identified in this study in order to ensure their sustainable and effective utilization.
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OBJECTIVE@#To report the indigenous people's uses of plants from a multidimensional perspective in a remote area where strong ethnobotanical cultural practices prevail.@*METHODS@#An ethnobotanical survey was conducted in the field during 2014-2016. Ethnobotanical data were gathered from 182 informants through oral interviews and semi-structured questionnaires. The distribution of plants was explored using both descriptive and graphical methods. Further, a Multinomial Logit Specification was applied to find out the probability of the occurrence of diverse utilization of plants in multipurpose domains.@*RESULTS@#The study identified 202 plant species distributed among 71 families and 156 genera. Ethnobotanical data indicate that there are more medicinal (36.96%) uses of plants as compared to all other use categories. The output from the Multinomial Logit Specifications (MLS) model reveals that perennial and non-woody plants are exploited more for medicinal and food uses than annual and woody plants. In the context of ethnomedicinal uses, aerial plant parts particularly leaves are more extensively used for the preparation of herbal recipes as compared to underground parts.@*CONCLUSIONS@#The results of the study emphasize the need to create awareness among the local communities about the conservation status of plant species in order to maintain a sustainable resource of plant-derived materials into the future. The novel econometric approach employed in this study adds a new insightful methodology to the existing body of literature in the field of ethnobotany. We strongly recommend conservation measures, alongside phytochemical and pharmacological studies on the useful plant species identified in this study in order to ensure their sustainable and effective utilization.
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Objective: To determine Rapid and End treatment response of patients treated with Sofosbuvir in Chronic Hepatitis C at tertiary care hospital
Methods: It was an observational study conducted at Memon Medical Institute from January 2016 to July 2017. The inclusion criteria for patients was 18 years of age or older, having chronic infection with HCV. Total=201 received sofosbuvir with or without interferon in our OPDs. Patients were categorized into Treatment naive, treatment experienced and decompensated chronic liver disease. Pregnant patients and those not willing to participate were excluded. Initially genotyping and Quantitative HCV RNA test was done
Results: A total of 201 subjects were included in the study with mean age of the patients was 46.22+/- 14.41 years. Of 201 patients, n= 131 [65.2%] chronic hepatitis C, compensated cirrhosis n= 47[23.4%], and with decompensated cirrhosis n=23[11.4%]. Most commonly genotype 3 n= 180 [89.6%] was present followed by genotype 1 n=9 [4.5%], genotype 2 n=1[0.5%], genotype 4 n=1[0.5%]
Of patients with genotype 3, 123 received dual therapy and 57 were given triple therapy. After one month of therapy HCV RNA by PCR, 200[99.5%] achieved RVR, 199[99%] achieved ETR and SVR achieved in 178[88.5%] while remaining 1 patient did not achieved RVR, 2 ETR and 12 patients did not achieved SVR and remaining 11 SVR lost follow up
Conclusion: Sofosbuvir has shown to be very effective and successful with achievement of virological response with little or no resistance in all genotypes mainly genotype 3 treated in our study population. The promising results of our study will aid in better outcomes and therefore help in eradication of the virus
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Humans , Female , Male , Adult , Middle Aged , Aged , Aged, 80 and over , Sofosbuvir/therapeutic use , Tertiary Care Centers , Observational Studies as Topic , Sustained Virologic Response , Genotype , Liver CirrhosisABSTRACT
Objective: The uridine nucleotide analogue sofosbuvir is a selective inhibitor of hepatitis C virus [HCV] NS5B polymerase approved for the treatment of chronic HCV infection with genotypes 1 - 4. The objective of the study was to evaluate the interim results of efficacy and safety of regimens containing Sofosbuvir [Zoval] among Pakistani population with the rapid virologic response [RVR2/4 weeks] with HCV infections
Methods: This is a multicenter open label prospective observational study. Patients suffering from chronic Hepatitis C infection received Sofosbuvir [Zoval] 400 mg plus ribavirin [with or without peg interferon] for 12/24 weeks. The interim results of this study were rapid virological response on week 4. Data was analyzed using SPSS version 21 for descriptive statistics
Results: A total of 573 patients with HCV infection were included in the study. The mean age of patients was 46.07 +/- 11.41 years. Out of 573 patients 535 [93.3%] were treatment naive, 26 [4.5%] were relapser, 7 [1.2%] were non-responders and 5 [1.0%] were partial responders. A rapid virologic response was reported in 563[98.2%] of patients with HCV infection after four weeks of treatment. The treatment was generally well tolerated
Conclusion: Sofosbuvir [Zoval] is effective and well tolerated in combination with ribavirin in HCV infected patients
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A compound herbal formulation [POL[4]] is used traditionally in interior parts [Distt. Badin] of Sindh, Pakistan, for the treatment of metabolic disorders like diabetes and hyperlipidemia. This study is aimed to determine the effectiveness of POL[4] and its ingredients in hyperlipidemia and associated endothelial dysfunction and hypertension. POL[4] is composed of equal proportion of Nigella sativa, Cichorium intybus, Trigonella foenum graecum and Gymnema sylvestre mixed in powdered form. Chronic [6 to 7 weeks] administration of POL[4] and its ingredients mixed in diet caused a notable attenuation in total cholesterol, low density lipoprotein cholesterol, triglycerides, atherogenic index, Creactive protein and glucose, while it has increased high density lipoprotein levels. POL[4] intervention markedly [p<0.01] reduced systolic blood pressure in rats to 127+/-1.92 vs. 145.4+/-1.07 mm of Hg using tail-cuff method and significantly [p<0.05] improved endothelium-dependent relaxation [75+/-2.88 vs. 82.75+/-1.22%] to acetylcholine in isolated aortae of rats in treatment groups using force transducer and PowerLab system. Similar activities were assessed on the part of ingredients of POL[4]. These findings indicate that POL[4] and its ingredients possess antihyperlipidemic, endotheliumdependent modulatory and antihypertensive activities, thus providing an evidence to the vernacular use of POL[4] in hyperlipidemia and hypertension
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In the present work a specific, accurate, precise, and reproducible UV-HPLC method was developed and validated for the analysis of Aceclofenac. This method involved elution of Aceclofenac in a mobile phase which is composed of buffer pH 6.8 [i.e. using 0.01N KH2PO4] and HPLC grade Acetonitrile [60:40]. Separation of the analyte was achieved using HPLC isocratic pump attached to the UV-VIS detectorC18, guard column and C18 column. The injection volume was 20 micro L, detected at 274 nm; flow rate: 1mL/min. Standard calibration curve was measured and found linear from 0.1 to 40 micro g/ml. The validation parameters were measured according to FDA guidelines and successful results were obtained. The presented analytical method could be employed for pharmacokinetic studies
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A swift, precise and simple HPLC bioanalytical technique with UV detection was established and validated for quantitative estimation of valsartan in human plasma. The analyte was separated from plasma by protein precipitation with acetonitrile and chromatographically separated on Zorbax SB-C18 [5 micro m, 4.6mm x 15cm] column. The solvent mixture system consisting of acetonitrile, water and glacial acetic acid [40:59:1 v/v], was pumped using isocratic mode at 1mL/min flow rate. Samples' detection of drug was made spectrophotometrically at a wavelength of 264nm. The analyte response was instituted to be linear from 0.06 to 8 micro g/mL with a regression value of 0.999. The accuracy of the proposed method was ranged between 97.2-100.3% with 5% RSD. The analytical recovery [>95%] was consistently observed and satisfactory sample stability was also found at different environmental conditions. In conclusion the reported bio-analytical method is easy and robust that was successfully utilized in estimation of valsartan in a pharmacokinetic study
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Urinary tract infection [UTI] affects women more than males mainly due to smaller urethra and feminine genital anatomy. Symptoms of UTI includes painful micturaition, flank pain, fever etc while its signs are pyuria, bacteriuria and tenderness in flank. In order to rule out UTI, laboratory tests are primarily performed, most important are urine routine examination, urine culture and sensitivity test. Radiological evaluation of urinary system is also done to determine the underlying causes of infection and the extent of damage caused to the renal system by the infection
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The objective of this study was validation of a reverse phase HPLC method for the estimation of metoclopramide HCl in plasma already validated for determination of metoclopramide HCl in tablets dosage form. A reverse chromatographic method was used for estimation of metoclopramide HCl with the mobile phase of acetonitrile, 20mM potassium dihydrogen phosphate buffer solution [pH 3.0 adjusted with orthophosphoric acid] in the ratio of 40: 60. The column used was Waters C18 3.9x300mm micro Bondapak [RP]. The flow rate of the mobile phase was 2ml/ minute. The detector was set at the wavelength of 275nm. This method validated in plasma and was found to be linear, with correlation coefficient [R[2]], value of 0.9988, in the range of 48 ng/ml-0.25ng/ml. The method modified was accurate, precise, sensitive and showed good stability results. The % RSD of the retention time and peak area of metoclopramide HCl was 0.19% and 1.44% respectively. All the parameters such as specificity, linearity, range, accuracy, precision, system suitability, solution stability, detection and quantification limits were evaluated to validate this method and were found within the acceptance limits. The method can be effectively used for estimation of metoclopramide HCl in plasma
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Humans , Calibration , Metoclopramide/blood , Metoclopramide/pharmacokinetics , Reproducibility of Results , Drug StabilityABSTRACT
The objective of this study was to assess the quality of six different brands of enteric coated Ketoprofen 100 mg tablets, KPB[2] to KPB[6] are available in commercial market of Karachi, Pakistan, while KPB[1] was obtained from international source. We performed different physico-chemical assessments i.e. weight variation, diameter, hardness, friability, thickness, disintegration, content uniformity, assay and dissolution test. Results of all the investigations were found to be in adequate limits. Also pharmaceutical equivalence was determined by selecting different tests and assay assessment. Furthermore, in vitro therapeutic equivalence was also estimated at phosphate buffer pH 6.8 and 7.5. Results were evaluated by one way ANOVA, model independent and model dependent methods. ANOVA results showed that release behaviour were found to be similar as p values >0.05, also KPB[1] - KPB[6] followed Weibull model at different dissolution media. Results indicated that innovator and brands not only passes the pharmaceutical equivalence assessment but also comply with the in vitro therapeutic equivalence