Khyber Medical University is a public sector medical university in Peshawar, Khyber Pakhtunkhwa, Pakistan. It was established in January 2007 with jurisdiction on the entire province including the Federally Administered Tribal Areas. Degrees awarded are MBBS and BDS . Wikipedia.
Ullah I.,Gyeongsang National University |
Ullah N.,Gyeongsang National University |
Ullah N.,Khyber Medical University |
Naseer M.I.,Gyeongsang National University |
And 3 more authors.
BMC Neuroscience | Year: 2012
Background: Exposure to ethanol during early development triggers severe neuronal death by activating multiple stress pathways and causes neurological disorders, such as fetal alcohol effects or fetal alcohol syndrome. This study investigated the effect of ethanol on intracellular events that predispose developing neurons for apoptosis via calcium-mediated signaling. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in ethanol neurotoxicity. The present study was designed to evaluate the neuroprotective mechanisms of metformin (Met) and thymoquinone (TQ) during ethanol toxicity in rat prenatal cortical neurons at gestational day (GD) 17.5.Results: We found that Met and TQ, separately and synergistically, increased cell viability after ethanol (100 mM) exposure for 12 hours and attenuated the elevation of cytosolic free calcium [Ca 2+] c. Furthermore, Met and TQ maintained normal physiological mitochondrial transmembrane potential (Δψ M), which is typically lowered by ethanol exposure. Increased cytosolic free [Ca 2+] cand lowered mitochondrial transmembrane potential after ethanol exposure significantly decreased the expression of a key anti-apoptotic protein (Bcl-2), increased expression of Bax, and stimulated the release of cytochrome-c from mitochondria. Met and TQ treatment inhibited the apoptotic cascade by increasing Bcl-2 expression. These compounds also repressed the activation of caspase-9 and caspase-3 and reduced the cleavage of PARP-1. Morphological conformation of cell death was assessed by TUNEL, Fluoro-Jade-B, and PI staining. These staining methods demonstrated more cell death after ethanol treatment, while Met, TQ or Met plus TQ prevented ethanol-induced apoptotic cell death.Conclusion: These findings suggested that Met and TQ are strong protective agents against ethanol-induced neuronal apoptosis in primary rat cortical neurons. The collective data demonstrated that Met and TQ have the potential to ameliorate ethanol neurotoxicity and revealed a possible protective target mechanism for the damaging effects of ethanol during early brain development. © 2012 Ullah et al; licensee BioMed Central Ltd.
Guo C.,Xi'an Jiaotong University |
Liang F.,Xi'an Jiaotong University |
Shah Masood W.,Khyber Medical University |
Yan X.,Xi'an Jiaotong University
European Journal of Pharmacology | Year: 2014
Hydrogen sulfide (H2S) has been proposed as a novel gas-transmittter, which plays multiple physiological and pathological functions in various body systems, including gastrointestinal tract. The present study was undertaken to investigate the effects and mechanisms of H2S pharmacological preconditioning on gastric epithelial cells ischemia-reperfusion (I/R) injury. We report here that sodium hydrosulfide (NaHS), an H2S donor, concentration-dependently suppressed I/R-induced cellular injury and apoptotic cell death. This protection effect was also confirmed by endogenous over-producing H2S. Furthermore, NaHS also prevented I/R-induced oxidative stress and inflammatory responses, evidenced by increases in GSH level, decreases in MDA contents, reactive oxygen species generation and secretions of NO, IL-6 and TNF-α. NaHS also prevented I/R-induced p38- and c-Jun NH2-terminal kinase (JNK)-mitogen-activated protein kinase (MAPK) phosphorylation and NF-κB activation. H2S also induced Keap1 s-sulfhydration, and further Keap1/Nrf2 disassociation and Nrf2 activation. H2S exerted its protective effect through reactive oxygen species clearance, inhibition of p38 and JNK dependent cell apoptosis and NF-κB dependent inflammation pathway. Our results provide evidence that H2S may have potential therapeutic value in acute gastric mucosal lesion, which is often caused by ischemia/reperfusion. © 2014 Elsevier B.V.
Shoaib M.,University of Malakand |
Shah I.,University of Malakand |
Ali N.,Khyber Medical University |
Shah S.W.A.,University of Malakand
Bangladesh Journal of Pharmacology | Year: 2015
In this study we screened the essential oil of Artemisia macrocephala for acetylcholinesterase (AChe) and butyrylcholinesterase (BChE) inhibitory potentials. Ellman's assay method was used to investigate the enzyme inhibitory potential of the essential oil. The oil sample showed 87.7 ± 1.2, 77.9 ± 0.6, 74.5 ± 1.9 and 62.5 ± 0.3 percent AChE inhibition at 1000, 500, 250 and 125 μg/mL concentrations respectively with IC50 value of 40 μg/mL. Similarly it showed 81.8 ± 0.6, 75.6 ± 1.2, 70.0 ± 0.6 and 64.2 ± 1.4 percent BChE inhibition in 1000, 500, 250 and 125 μg/mL concentrations respectively with IC50 value of 30 μg/mL. The results of this study confirm the beneficial applications of the oil sample in the treatment of various neurodegenerative disorders including Alzeimer, s disease, Parkinson's disease, ataxia and all other forms of dementia. © 2015, Bangladesh Pharmacological Society. All rights reserved.
Ullah F.,Gyeongsang National University |
Ali T.,Gyeongsang National University |
Ullah N.,Khyber Medical University |
Kim M.O.,Gyeongsang National University
Neurochemistry International | Year: 2015
d-galactose has been considered a senescent model for age-related neurodegenerative disease. It induces oxidative stress which triggers memory impairment, neuroinflammation and neurodegeneration. Caffeine act as anti-oxidant and has been used in various model of neurodegenerative disease. Nevertheless, the effect of caffeine against d-galactose aging murine model of age-related neurodegenerative disease elucidated. Here, we investigated the neuroprotective effect of caffeine against d-galactose. We observed that chronic treatment of caffeine (3 mg/kg/day intraperitoneally (i.p) for 60 days) improved memory impairment and synaptic markers (Synaptophysin and PSD95) in the d-galactose treated rats. Chronic caffeine treatment reduced the oxidative stress via the reduction of 8-oxoguanine through immunofluorescence in the d-galactose-treated rats. Consequently caffeine treatment suppressed stress kinases p-JNK. Additionally, caffeine treatment significantly reduced the d-galactose-induced neuroinflammation through alleviation of COX-2, NOS-2, TNFα and IL-1β. Furthermore we also analyzed that caffeine reduced cytochrome C, Bax/Bcl2 ratio, caspase-9, caspase-3 and PARP-1 level. Moreover by evaluating the immunohistochemical results of Nissl and Fluro-Jade B staining showed that caffeine prevented the neurodegeneration in the d-galactose-treated rats. Our results showed that caffeine prevents the d-galactose-induced oxidative stress and consequently alleviated neuroinflammation and neurodegeneration; and synaptic dysfunction and memory impairment. Therefore, we could suggest that caffeine might be a dietary anti-oxidant agent and a good candidate for the age-related neurodegenerative disorders. © 2015 Elsevier Ltd. All rights reserved.
Ramzan F.,Gomal University |
Khan M.A.,Gomal University |
Ramzan M.H.,Khyber Medical University
Endocrine | Year: 2014
The discovery that kisspeptin was critical for normal fertility in all mammalian species including humans, ushered in a new chapter in our understanding of the control of GnRH secretion. Kisspeptin, the product of the KISS1 gene, plays an essential role in the regulation of spermatogenesis acting primarily at the hypothalamic level of the gonadotropic axis. Among the many identified substances in human semen, fructose is becoming increasingly significant. Fructose is synthesized and secreted by the seminal vesicles. Its synthesis is regulated by androgens and it is correlated directly with the levels of testosterone. Dose dependent degeneration of seminal vesicle has been described following intraperitoneal kisspeptin treatment; however, effects of kisspeptin administration on the levels of seminal fructose remain elusive till date. The present study, therefore, addresses the effects of 12-day administration of kisspeptin on seminal fructose levels in male mice. Kisspeptin-10 was administered intraperitoneally at different dosage concentrations (1 μg, 1 ng, and 10 ρg) to adult male mice, twice daily for 12 days. Seminal fructose levels were studied photometrically after 12 days of treatment. At the end of the treatment, seminal fructose levels decreased significantly after all tested doses. Chronic intermittent kisspeptin-10 administration negatively regulates seminal fructose levels in adult male mice. © 2013 Springer Science+Business Media New York.
Yasinzai M.,Quaid-i-Azam University |
Khan M.,Quaid-i-Azam University |
Khan M.,Khyber Medical University |
Nadhman A.,Quaid-i-Azam University |
Shahnaz G.,Quaid-i-Azam University
Future Medicinal Chemistry | Year: 2013
Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The arvailable therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy. Mechanisms of classical drug resistance are often related with the lower drug uptake, increased efflux, the faster drug metabolism, drug target modifications and over-expression of drug transporters. The high prevalence of leishmaniasis and the appearance of resistance to classical drugs reveal the demand to develop and explore novel, less toxic, low cost and more promising therapeutic modalities. The review describes the mechanisms of classical drug resistance and potential drug targets in Leishmania infection. Moreover, current drug-delivery systems and future perspectives towards Leishmaniasis treatment are also covered. © 2013 Future Science Ltd.
Wahab F.,Quaid-i-Azam University |
Wahab F.,Khyber Medical University |
Atika B.,Quaid-i-Azam University |
Shahab M.,Quaid-i-Azam University
Metabolism: Clinical and Experimental | Year: 2013
Changes in metabolic status gate reproductive activity by still incompletely deciphered mechanisms. Many neuropeptides have been shown to be involved in restraining hypothalamic gonadotropin releasing hormone (GnRH) release under conditions of negative energy balance. Broadly, on the basis of their effect on feeding, these can be grouped as orexigenic and anorexigenic neuropeptides. Reciprocally correlated, in response to changes in systemic concentrations of metabolic hormones, the secretion of orexigenic neuropeptides increases while that of anorexigenic neuropeptides decreases during conditions of food restriction. Recently, kisspeptin signaling in hypothalamus has appeared as a pivotal regulator of the GnRH pulse generator. Kisspeptin apparently does not affect feeding, but in light of accumulating data, it has emerged as one of the major conduits in relaying body metabolic status information to GnRH neurons. The present review examines such data obtained from rodent and primate models, which suggest kisspeptin-Kiss1r signaling as a possible pathway providing a link between metabolism and reproduction. © 2013 Elsevier Inc. All rights reserved.
Ul-Haq Z.,University of Glasgow |
Ul-Haq Z.,Khyber Medical University |
Mackay D.F.,University of Glasgow |
Fenwick E.,University of Glasgow |
Pell J.P.,University of Glasgow
Obesity | Year: 2013
Objective: Obesity is associated with impaired overall health-related quality of life but individual studies suggest the relationship may differ for mental and physical quality of life. A systematic review using Medline, Embase, PsycINFO and ISI Web of Knowledge, and random effects meta-analysis was undertaken. Design and Methods: Studies were included in the meta-analysis if they were conducted on adults (defined as age >16 years), reported an overall physical and mental component score of the SF-36, and, or both. Heterogeneity was assessed using I2 statistics and publication and small study biases using funnel plots and Egger's test. Between-study heterogeneity was explored using meta-regression. Results: Eight eligible studies provided 42 estimates of effect size, based on 43,086 study participants. Adults with higher than normal body mass index had significantly reduced physical quality of life with a clear dose-response relationship across all categories. Among class III obese adults, the score was reduced by 9.72 points (95% Confidence Interval 7.24, 12.20, P < 0.001). Mental quality of life was also significantly reduced among class III obese (-1.75, 95% confidence interval -3.33, -0.16, P = 0.031), but was not significantly different among obese (class I and class II) individuals, and was significantly increased among overweight adults (0.42, 95% confidence interval 0.17, 0.67, P = 0.001), compared to normal weight individuals. Heterogeneity was high in some categories, but there was no significant publication or small study bias. Conclusions: Different patterns were observed for physical and mental HRQoL, but both were impaired in obese individuals. This meta-analysis provides further evidence on the impact of obesity on both aspects of health-related quality of life. Copyright © 2013 The Obesity Society.
Ali N.,Khyber Medical University
BMC Complementary and Alternative Medicine | Year: 2013
Background: We have previously reported that aerial parts of Tylophora hirsuta have antispasmodic profile. The current work is an attempt for isolation of pharmacologically active compound(s) that contribute for its antispasmodic activity.Methods: Preliminary phytochemical screening for crude methanol extract of Tylophora hirsuta (Th.Cr) is performed. Brine shrimp cytotoxicity of crude methanol extract is performed. Column chromatography was used for isolation of compounds. Mass spectroscopy, H1 NMR and C13 NMR were used for structural determination of compounds. α-amyrin acetate was tried for possible spasmolytic activity in rabbit's jejunal preparations and KCl-induced contractions.Results: Th.Cr tested positive for saponins, alkaloids, flavonoids and terpenoids. Compound 1 was isolated as α-amyrin acetate. Compound 2 was heptaeicosanol. Crude methanol extract tested positive for brine shrimp cytotoxicity with LC50 492.33± 8.08 mg/ml. Compound 1 tested positive for antispasmodic activity on spontaneous rabbits' jejunum preparations with EC50 (60 ± 2) × 10-5M. The compound also tested positive on KCl induced contractions with EC50 (72 ± 3) × 10-5M.Conclusions: The present work confirms that α-amyrin acetate is has antispasmodic profile and the relaxant effect may be attributed to α-amyrin acetate which is a major compound. © 2013 Ali; licensee BioMed Central Ltd.
Ali A.,Khyber Medical University
Applied Immunohistochemistry and Molecular Morphology | Year: 2016
BACKGROUND:: Clinical translation of immunohistochemistry (IHC) biomarkers requires reliable and reproducible cutoffs or thresholds for interpretation of immunostaining. Most IHC biomarker research focuses on the clinical relevance (diagnostic, prognostic, or predictive utility) of cutoffs, with less emphasis on observer agreement using these cutoffs. From the literature, we identified 3 commonly used cutoffs of 10% positive epithelial cells, 20% positive epithelial cells, and moderate to strong staining intensity (+2/+3 hereafter) to use for investigating observer agreement. MATERIALS AND METHODS:: A series of 36 images of microarray cores stained for 4 different IHC biomarkers, with variable staining intensity and percentage of positive cells, was used for investigating interobserver and intraobserver agreement. Seven pathologists scored the immunostaining in each image using the 3 cutoffs for positive and negative staining. Kappa (κ) statistic was used to assess the strength of agreement for each cutoff. RESULTS:: The interobserver agreement between all 7 pathologists using the 3 cutoffs was reasonably good, with mean κ scores of 0.64, 0.59, and 0.62, respectively, for 10%, 20%, and +2/+3 cutoffs. A good agreement was observed for experienced pathologists using the 10% cutoff, and their agreement was statistically higher than for junior pathologists (P=0.02). In addition, the mean intraobserver agreement for all 7 pathologists using the 3 cutoffs was reasonably good, with mean κ scores of 0.71, 0.60, and 0.73, respectively, for 10%, 20%, and +2/+3 cutoffs. For all 3 cutoffs, a positive correlation was observed with perceived ease of interpretation (P<0.003). Finally, cytoplasmic-only staining achieved higher agreement using all 3 cutoffs than mixed staining patterns. CONCLUSIONS:: All 3 cutoffs investigated achieve reasonable strength of agreement, modestly decreasing interobserver and intraobserver variability in IHC interpretation. These cutoffs have previously been used in cancer pathology, and this study provides evidence that these cutoffs can be reproducible between practicing pathologists. Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.