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Search Results: 1 - 10 of 232776 matches for " Saeed R. Khan "
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Stability Characterization, Kinetics and Mechanism of Degradation of Dantrolene in Aqueous Solution: Effect of pH and Temperature  [PDF]
Saeed R. Khan, Mobin Tawakkul, Vilayat A. Sayeed, Patrick Faustino, Mansoor A. Khan
Pharmacology & Pharmacy (PP) , 2012, DOI: 10.4236/pp.2012.33037
Abstract: The mechanism of degradation of dantrolene in aqueous buffer solutions was studied at various pH values in the range of pH 1.2-9.5 and at temperatures ranging from 25℃ to 75℃ to determine the optimum pH and temperature requirements for its stability and eventual product performance over the human gastrointestinal pH range. Dantrolene was analyzed by reversed phase ultra-performance liquid chromatographic (UPLC). Chromatographic separation was achieved on a Waters Acquity UPLC system using a Waters BEH C18 analytical column and Waters BEH C18 guard column. The compounds were eluted with a linear acetonitrile gradient (25%-75%) over three minutes with a buffer composition of 2.0 mM of sodium acetate at pH 4.5 for degradation studies. The flow rate was maintained at 0.5 mL/min. Column temperature was maintained at 35℃. Injection volume was 4 μL and the degradation products were detected by a photodiode array (PDA) detector at 375 nm. Degradation products, including compound B and C were analyzed by mass spectroscopy (MS) and nuclear magnetic resonance spectroscopy (NMR) and the degradation pathways were proposed. Degradation of dantrolene followed pseudo first–order kinetics and a V-shaped pH-rate profile over the pH range 1.2-9.5. The maximum stability was observed at pH 7.4 and 37℃. Although the focus of this paper was on the mechanism of hydrolysis of dantrolene, the poor aqueous solubility of dantrolene, the developed understanding can be utilized to improve the quality of the formulation and the risk associated with the extravasation of dantrolene sodium solution in its current form.
A Comparative Evaluation of Polystyrene Divinylbenzene Copolymer HPLC Columns on the Chromatographic Performance of the Compendial Method for Doxycycline Hyclate Capsules: Implications for Method Implementation of a Medical Countermeasure Medication  [PDF]
Firat Yerlikaya, Adil Mohammad, Patrick J. Faustino, Mansoor A. Khan, Saeed R. Khan
Journal of Analytical Sciences, Methods and Instrumentation (JASMI) , 2015, DOI: 10.4236/jasmi.2015.53003
Abstract: The purpose of this study was to evaluate the impact of polystyrene divinylbenzene copolymer HPLC columns on the chromatographic performance of the USP compendial method for doxycycline hyclate. The compendial method was implemented based on the assessment of the chromatographic performance of six USP defined L21 polystyrene divinylbenzene HPLC columns. Modifications to the method were based on USP <621> for chromatography. The method was validated for the determination of doxycycline hyclate and its impurities in commercially available drug products. A number of different polystyrene-divinylbenzene columns were tested and failed to provide selectivity for the resolution of doxycycline and its impurities. Separation was optimally achieved on an Agilent PLPR-S column (250 × 4.6 mm, 8 μm) by using an Agilent 1260 series HPLC system. Doxycycline hyclate and its impurities were eluted isocratically at a flow rate of 1 mL/min with mobile phase and detected at 270 nm. The column temperature was maintained at 60oC. The method was validated according to USP category I requirements for Assay. Validation acceptance criteria were met in all cases. The analytical range for doxycycline hyclate was 50 - 250 μg/mL and the linearity was r2 > 0.999 over three days. The method was determined to be specific. Both accuracy (95.1% - 102.4%) and precision (0.50% - 4.8%) were established across the analytical range for low, intermediate and high QC concentrations. Method applicability was demonstrated by analyzing marketed products of doxycycline hyclate, in which results showed potency meeting USP acceptance criteria. In conclusion, this study described the remarkable differences in selectivity that were encountered during the implementation phase for the compendial methods for doxycycline and its impurities in marketed products and it could be used in the future to assss the product quality of doxycycline hyclate capsules stored in the National stockpiles.
Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L
Saeed Naima,Khan Muhammad R,Shabbir Maria
BMC Complementary and Alternative Medicine , 2012, DOI: 10.1186/1472-6882-12-221
Abstract: Background The aim of this study was to screen various solvent extracts of whole plant of Torilis leptophylla to display potent antioxidant activity in vitro and in vivo, total phenolic and flavonoid contents in order to find possible sources for future novel antioxidants in food and pharmaceutical formulations. Material and methods A detailed study was performed on the antioxidant activity of the methanol extract of whole plant of Torilis leptophylla (TLM) and its derived fractions {n-hexane (TLH), chloroform (TLC) ethyl acetate (TLE) n-butanol (TLB) and residual aqueous fraction (TLA)} by in vitro chemical analyses and carbon tetrachloride (CCl4) induced hepatic injuries (lipid peroxidation and glutathione contents) in male Sprague-Dawley rat. The total yield, total phenolic (TPC) and total flavonoid contents (TFC) of all the fractions were also determined. TLM was also subjected to preliminary phytochemical screening test for various constituents. Results The total phenolic contents (TPC) (121.9±3.1 mg GAE/g extract) of TLM while total flavonoid contents (TFC) of TLE (60.9 ±2.2 mg RTE/g extract) were found significantly higher as compared to other solvent fractions. Phytochemical screening of TLM revealed the presence of alkaloids, anthraquinones, cardiac glycosides, coumarins, flavonoids, saponins, phlobatannins, tannins and terpenoids. The EC50 values based on the DPPH (41.0±1 μg/ml), ABTS (10.0±0.9 μg/ml) and phosphomolybdate (10.7±2 μg/ml) for TLB, hydroxyl radicals (8.0±1 μg/ml) for TLC, superoxide radicals (57.0±0.3 μg/ml) for TLM and hydrogen peroxide radicals (68.0±2 μg/ml) for TLE were generally lower showing potential antioxidant properties. A significant but marginal positive correlation was found between TPC and EC50 values for DPPH, hydroxyl, phosphomolybdate and ABTS, whereas another weak and positive correlation was determined between TFC and EC50 values for superoxide anion and hydroxyl radicals. Results of in vivo experiment revealed that administration of CCl4 caused a significant increase in lipid peroxidation (TBARS) while decrease in GSH contents of liver. In contrast, TLM (200 mg/kg bw) and silymarin (50 mg/kg bw) co-treatment effectively prevented these alterations and maintained the antioxidant status. Conclusion Data from present results revealed that Torilis leptophylla act as an antioxidant agent due to its free radical scavenging and cytoprotective activity.
Antiurolithic activity of Origanum vulgare is mediated through multiple pathways
Aslam Khan, Samra Bashir, Saeed R Khan, Anwar H Gilani
BMC Complementary and Alternative Medicine , 2011, DOI: 10.1186/1472-6882-11-96
Abstract: The crude aqueous-methanolic extract of Origanum vulgare (Ov.Cr) was studied using the in vitro and in vivo methods. In the in vitro experiments, supersaturated solution of calcium and oxalate, kidney epithelial cell lines (MDCK) and urinary bladder of rabbits were used, whereas, in the in vivo studies, rat model of urolithiasis was used for the study of preventive and curative effect.In the in vitro experiments, Ov.Cr exhibited a concentration-dependent (0.25-4 mg/ml) inhibitory effect on the slope of nucleation and aggregation and also decreased the number of calcium oxalate monohydrate crystals (COM) produced in calcium oxalate metastable solutions. It also showed concentration-dependent antioxidant effect against DPPH free radical and lipid peroxidation induced in rat kidney tissue homogenate. Ov.Cr reduced the cell toxicity using MTT assay and LDH release in renal epithelial cells (MDCK) exposed to oxalate (0.5 mM) and COM (66 μg/cm2) crystals. Ov.Cr relaxed high K+ (80 mM) induced contraction in rabbit urinary bladder strips, and shifted the calcium concentration-response curves (CRCs) towards right with suppression of the maximum response similar to that of verapamil, a standard calcium channel blocker. In male Wistar rats receiving lithogenic treatment comprising of 0.75% ethylene glycol in drinking water given for 3 weeks along with ammonium chloride (NH4Cl) for the first 5 days, Ov.Cr treatment (10-30 mg/kg) prevented as well as reversed toxic changes including loss of body weight, polyurea, crystalluria, oxaluria, raised serum urea and creatinine levels and crystal deposition in kidneys compared to their respective controls.These data indicating the antiurolithic activity in Ov.Cr, possibly mediated through inhibition of CaOx crystallization, antioxidant, renal epithelial cell protective and antispasmodic activities, rationalizes its medicinal use in urolithiasis.Urolithiasis, the formation of urinary stones, is one of the oldest known diseases. Archaeolo
Large gain quantum-limited qubit measurement using a two-mode nonlinear cavity
Saeed Khan,R. Vijay,I. Siddiqi,Aashish A. Clerk
Physics , 2014, DOI: 10.1088/1367-2630/16/11/113032
Abstract: We provide a thorough theoretical analysis of qubit state measurement in a setup where a driven, parametrically-coupled cavity system is directly coupled to the qubit, with one of the cavities having a weak Kerr nonlinearity. Such a system could be readily realized using circuit QED architectures. We demonstrate that this setup is capable in the standard linear-response regime of both producing a highly amplified output signal while at the same time achieving near quantum-limited performance: the measurement backaction on the qubit is near the minimal amount required by the uncertainty principle. This setup thus represents a promising route for performing efficient large-gain qubit measurement that is completely on-chip, and that does not rely on the use of circulators or complex non-reciprocal amplifiers.
HIV-1 subtype A infection in a community of intravenous drug users in Pakistan
Saeed Khan, Mohammad A Rai, Mohammad R Khanani, Muhammad N Khan, Syed H Ali
BMC Infectious Diseases , 2006, DOI: 10.1186/1471-2334-6-164
Abstract: Samples were collected from 34 IDUs after their informed consent. In addition, the study subjects were administered a questionnaire regarding their sexual behavior and travel history. For HIV analysis, DNA was extracted from the samples and analyzed for HIV types and subtypes using subtype-specific primers in a nested polymerase chain reaction (PCR). The results from this PCR were further confirmed using the Heteroduplex Mobility Assay (HMA).We found HIV-1 subtype A in all the 34 samples analyzed. A few of the study subjects were found to have a history of travel and stay in the United Arab Emirates. The same subjects also admitted to having contact with commercial sex workers during their stay abroad.Our study therefore shows clade A HIV-1 to be prevalent among the IDUs in Karachi. As the prevalence of HIV in Pakistan continues to rise, more work needs to be done to track the infection, and to analyze the strains of HIV spreading through the country.HIV-1, the globally prevalent type of HIV, is characterized by high genetic variability and is classified into three groups, M, O, and N. Group M strains show the highest worldwide distribution and currently comprise 11 subtypes (A1, A2, B, C, D, F1, F2, G, H, J and K) and almost 30 Circulating Recombinant Forms (CRFs). HIV subtypes that get introduced in a community tend to spread and evolve within that population. Consequently, HIV subtypes show distinct geographic distribution on regional and global levels. Knowledge of HIV-1 subtypes can therefore be used to understand the foci of HIV infection, routes of its spread, as well as the patterns of the virus' genetic divergence [1-3].Globally speaking, Subtype A is the principal HIV-1 subtype found in Central and North African countries; Subtype B is predominant in USA, Europe, Australia, Thailand and Brazil; Subtype C is prevalent in South Africa, Ethiopia and India; CRF01_AE is common in Southeast Asia [4]. Among the Asian countries, although information on HIV subtype
Development and Application of a Validated UHPLC Method for the Determination of Atropine and Its Major Impurities in Antidote Treatment Nerve Agent Auto-Injectors (ATNAA) Stored in the Strategic National Stockpiles  [PDF]
Cheng H. Yen, Adil Mohammad, Miah Schneider, Salwa K. Poole, Bryan Lowry, Brenda W. Mc Curdy, Patrick J. Faustino, Saeed R. Khan
Pharmacology & Pharmacy (PP) , 2017, DOI: 10.4236/pp.2017.81002
Abstract: The development and implementation of advanced analytical technologies is essential for extending the expiry for complex drug products stored in the Strategic National Stockpiles. Consequently, a novel Ultra High-Performance Liquid Chromatographic (UHPLC) method has been developed for the analysis of atropine and its respective impurities to support the analytical research platform for auto-injectors. This study is part of a larger research effort to improve the efficiency and broaden the applicability of advanced analytical methods for medical counter-measure medications. The current HPLC compendial methodology for atropine sulfate injection requires an analysis time of 40 minutes for atropine. In comparison, the novel gradient UHPLC method required only 8 minutes to evaluate both atropine and its major pharmaceutical impurities. Improved separation was achieved on a Waters Acquity UHPLC BEH C18 1.7 μm, 2.1 × 100 mm column employing gradient elution of mobile phase solvent A (0.1% H3PO4) and solvent B (0.1% H3PO4, 90% ACN, and 10% H2O). The method was validated according to USP Category I requirements for assay. The daily standard calibration curves were linear over a concentration range from 50 μg/mL to 250 μg/mL with a correlation coefficient of >0.999. The detection limit (LOD) and quantitation limit (LOQ) were 3.9 μg/ml and 13.1 μg/ml, respectively. Resolution results indicate that atropine and the following impurities, degradants and a preservative can also be separated and analyzed using this proposed method: noratropine, 4,4’-di-hy-droxydiphenyl ether, 2,4’-dihydroxydiphenyl ether, 4-bromophenol, 4-hydro-xyatropine, tropic acid, apoatropine HCl, atropic acid, hydroquinone, nitroethane, phenol and catechol. The UHPLC method demonstrated enhanced selectivity and significantly reduced the analysis time when compared with the traditional USP compendial HPLC method. The method was successfully applied to the evaluation of atropine in ATNAA auto-injectors lots from the Strategic National Stockpiles.
Apocynin-Treatment Reverses Hyperoxaluria Induced Changes in NADPH Oxidase System Expression in Rat Kidneys: A Transcriptional Study
Sunil Joshi, Benjamin T. Saylor, Wei Wang, Ammon B. Peck, Saeed R. Khan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0047738
Abstract: Purpose We have previously shown that production of reactive oxygen species (ROS) is an important contributor to renal injury and inflammation following exposure to oxalate (Ox) or calcium-oxalate (CaOx) crystals. The present study was conducted, utilizing global transcriptome analyses, to determine the effect of Apocynin on changes in the NADPH oxidase system activated in kidneys of rats fed a diet leading to hyperoxaluria and CaOx crystal deposition. Approach Age-, sex- and weight-matched rats were either fed regular rat chow or regular rat chow supplemented with 5% w/w hydroxy-L-proline (HLP). Half of the rats on the HLP diet were also placed on Apocynin-supplemented H2O. After 28 days, each rat was euthanized, their kidneys freshly explanted and dissected to obtain both cortex and medulla tissues. Total RNA was extracted from each tissue and subjected to genomic microarrays to obtain global transcriptome data. KEGG was used to identify gene clusters with differentially expressed genes. Immunohistochemistry was used to confirm protein expressions of selected genes. Results Genes encoding both membrane- and cytosolic-NADPH oxidase complex-associated proteins, together with p21rac and Rap1a, were coordinately up-regulated significantly in both renal medulla and cortex tissues in the HLP-fed rats compared to normal healthy untreated controls. Activation of NADPH oxidase appears to occur via the angiotensin-II/angiotensin-II receptor-2 pathway, although the DAG-PKC pathway of neutrophils may also contribute. Immuno histochemical staining confirmed up-regulated gene expressions. Simultaneously, genes encoding ROS scavenger proteins were down-regulated. HLP-fed rats receiving Apocynin had a complete reversal in the differential-expression of the NADPH oxidase system genes, despite showing similar levels of hyperoxaluria. Conclusions A strong up-regulation of an oxidative/respiratory burst involving the NADPH oxidase system, activated via the angiotensin-II and most likely the DAG-PKC pathways, occurs in kidneys of hyperoxaluric rats. Apocynin treatment reversed this activation without affecting the levels of hyperoxaluria.
R. Salam, A. Aslam. S. A, Khan, K. Saeed1 and G. Saleem
Pakistan Veterinary Journal , 2003,
Abstract: This project was designed to compare two routes (intraocular and drinking water) of vaccination against Newcastle disease in ten11s of protection against velogenic field isolate of Newcastle disease virus (NOV), The immune response and morphological changes in lymphoid organs (Harderian gland, bursa of fabricius and thymus) of broilers were noted. The role of Harderian gland to generate local and humoral immunity in response to eye drop and drinking water vaccination against NOV was also evaluated. This experiment showed that ocular vaccination resulted in significantly high level of circulating antibodies as compared to drinking water vaccination, No histopathological changes were observed in Iymphow organs after Nov challenge in ocularly vaccinated birds. There were significantly (P<0.05) higher number of plasma cells in sections of Harderian gland after eye drop vaccination, It was concluded that ocular vaccination stimulated Harderian gland to produce strong local protective immunity in ocular as well as in oral mucosa
Evidence for a "Founder Effect" among HIV-infected injection drug users (IDUs) in Pakistan
Mohammad A Rai, Vivek R Nerurkar, Suhail Khoja, Saeed Khan, Richard Yanagihara, Arish Rehman, Shahana U Kazmi, Syed H Ali
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-7
Abstract: Phylogenetic analysis was performed of partial gag sequences, generated using PCR, from 26 HIV-positive IDU samples.Our results showed formation of a tight monophyletic group with an intra-sequence identity of < 98% indicating a "founder effect". Our data indicate that the HIV-1 epidemic in this community of IDUs may have been transmitted by an HIV positive overseas contract worker who admitted to having contact with commercial sex workers during stay abroad.Specific measures need to implemented to control transmission of HIV infection in Pakistan through infected migrant workers.The first evidence of Human immunodeficiency virus (HIV) infection in Pakistan was reported in 1987 among patients receiving tainted blood or blood products [1]. Having been relatively safe from any indigenous HIV cases for around two decades, this conservative South-east Asian nation is finally registering isolated HIV outbreaks all over the country.In 2004, in the remote desert town of Larkana, Pakistan experienced its first HIV outbreak [2]. The implicated populace was a community of Injection Drug Users (IDU), who documented an HIV prevalence approaching an outstanding 27%. Earlier, HIV prevalence in IDUs was reported by the National AIDS Control Program as bordering around 0.4% in December, 2003. After the Larkana episode, outbreaks were also recorded in other major cities of Pakistan [3]. The changing trend denotes that the country is transitioning from a low prevalence to a concentrated epidemic stage.Apart from IDUs, other high-risk populations including truck drivers [4], commercial sex workers, including Hijras [5] have also been identified in the Pakistani context. Even though very little serological data are available, various knowledge, attitude and practice studies [3,6-9] have demonstrated an increasingly vulnerable position for a devastatingly spread of HIV in these high-risk groups.Earlier, we have reported an HIV subtype A concentrated epidemic in a community of IDUs in Ka
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