Journal of Biology Agriculture and Healthcare, 2014
Genus Amanita is among the most commonly found and most familiar genera belonging to phyllum Basi... more Genus Amanita is among the most commonly found and most familiar genera belonging to phyllum Basidiomycota known for its toxic species. Members of these genera are known to have a universal veil and a prominent volva at the base of their stipe which indicate their angiocarpic mode of germination. Universal veil is aimed at the protection of gills and the immature hymenium which is exposed for the spore dispersal at the time of maturity. Some members of this group are deadly poisonous although they also have much medicinal importance. Escalating human activities, environmental alterations, impact of biotic components and the distribution pattern of species has introduced some new species in the region. Ayubia National Park always remains a fascinating place for mushroom hunters and number of species of plants and fungi have already been reported. The present survey was aimed at an addition to the previous study of Genus Amanita and also to check the certain features of the genus Amanita. A new species Amanita banningiana was reprted from the site and observed morphologically as well as anatomically with the aid of eminent literature and scientists.
... The stem barks of UD were collected from Mt. Phal-gong, Kyungbuk Province, Korea in May 2002 ... more ... The stem barks of UD were collected from Mt. Phal-gong, Kyungbuk Province, Korea in May 2002 and identified by KS Kim, College of Oriental Medicine, Dongguk University, Korea. ... Western blotting analysis was performed by the method described previously (Kim et al., 2005). ...
Rationale : Fatty acid nitroalkenes are endogenously generated electrophilic byproducts of nitric... more Rationale : Fatty acid nitroalkenes are endogenously generated electrophilic byproducts of nitric oxide and nitrite-dependent oxidative inflammatory reactions. Existing evidence indicates nitroalkenes support posttranslational protein modifications and transcriptional activation that promote the resolution of inflammation. Objective : The aim of this study was to assess whether in vivo administration of a synthetic nitroalkene could elicit antiinflammatory actions in vivo using a murine model of vascular injury. Methods and Results : The in vivo administration (21 days) of nitro-oleic acid (OA-NO 2 ) inhibited neointimal hyperplasia after wire injury of the femoral artery in a murine model (OA-NO 2 treatment resulted in reduced intimal area and intima to media ratio versus vehicle- or oleic acid (OA)-treated animals, P <0.0001). Increased heme oxygenase (HO)-1 expression accounted for much of the vascular protection induced by OA-NO 2 in both cultured aortic smooth muscle cells a...
The purpose of the present study is the preparation and characterization of collagen/antitumor dr... more The purpose of the present study is the preparation and characterization of collagen/antitumor drug hybrids as drug delivery systems. Materials used for obtaining collagen-based drug delivery systems were collagen type I (Coll) as matrix and irinotecan (I) as hydrophilic active substances. After incorporation of I into Coll in differing ratios, the obtained hybrid materials (Coll/I) could be used according to our results as potential drug delivery systems in medicine for the topical (local) treatment of cancerous tissues or bone. The released amount of I varies with amount of Coll from hybrid materials: the higher, the slower the release amount of irinotecan transferred is in the first 6 hours. The in vitro citotoxicity demonstrates an antitumoral activity of the obtained hybrid materials and their potential use for biomedical applications as drug delivery systems in tumoral treatments.
Small intracranial aneurysms pose significant challenges to endovascular therapy. Surgical clippi... more Small intracranial aneurysms pose significant challenges to endovascular therapy. Surgical clipping is considered by many to be the preferred treatment for these lesions. We present the results of the first study comparing the 2 treatment modalities in small ruptured aneurysms. Between 2004 and 2011, 151 patients with small ruptured aneurysms (≤3 mm) were treated in our institution: 91 (60.3%) with endovascular therapy and 60 (39.7%) with surgical clipping. The surgical and endovascular groups were generally comparable with regard to baseline demographics, with the exception of larger mean aneurysm size in the endovascular group versus the surgical group (2.8 versus 2.5 mm, respectively;…
Journal of Cerebral Blood Flow & Metabolism, 2012
Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intens... more Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intense investigation, our understanding of the mechanisms leading to aneurysm development, progression and rupture remain incompletely defined. An accumulating body of evidence implicates inflammation as a critical contributor to aneurysm pathogenesis. Intracranial aneurysm formation and progression appear to result from endothelial dysfunction, a mounting inflammatory response, and vascular smooth muscle cell phenotypic modulation producing a pro-inflammatory phenotype. A later final common pathway appears to involve apoptosis of cellular constituents of the vessel wall. These changes result in degradation of the integrity of the vascular wall leading to aneurysmal dilation, progression and eventual rupture in certain aneurysms. Various aspects of the inflammatory response have been investigated as contributors to IA pathogenesis including leukocytes, complement, immunoglobulins, cytokines, ...
The world's population is aging, with the number of older adults projected to increase dramatical... more The world's population is aging, with the number of older adults projected to increase dramatically over the next two decades. This trend poses major challenges to health care systems, reflecting the greater healthcare utilization by and more comorbid conditions among elderly adults. Chronic kidney disease (CKD) is a substantial concern in the elderly, with both an increasing incidence of treated kidney failure with dialysis as well as a high prevalence of earlier stages of CKD. Given the high burden of risk factors for CKD, the high prevalence of CKD in the elderly is not surprising, with the rise in obesity, diabetes and hypertension in middle-aged adults likely foreshadowing further increases in CKD prevalence among the elderly. It is now commonly agreed that the presence of CKD identifies a higher risk state in the elderly, with increased risk for multiple adverse outcomes, including kidney failure, cardiovascular disease, cognitive impairment, and death. Accordingly, CKD in older adults is worthy of attention by both health care providers and patients, with the presence of a reduced GFR or albuminuria in the elderly potentially informing therapeutic and diagnostic decisions for these individuals.
The efforts made in the last decade regarding the molecular landscape of acute myeloid leukemia (... more The efforts made in the last decade regarding the molecular landscape of acute myeloid leukemia (AML) have created the possibility of obtaining patients’ personalized treatment. Indeed, the improvement of accurate diagnosis and precise assessment of minimal residual disease (MRD) increased the number of new markers suitable for novel and targeted therapies. This progress was obtained thanks to the development of molecular techniques starting with real-time quantitative PCR (Rt-qPCR) passing through digital droplet PCR (ddPCR) and next-generation sequencing (NGS) up to the new attractive metabolomic approach. The objective of this surge in technological advances is a better delineation of AML clonal heterogeneity, monitoring patients without disease-specific mutation and designing customized post-remission strategies based on MRD assessment. In this context, metabolomics, which pertains to overall small molecules profiling, emerged as relevant access for risk stratification and targe...
Cisplatin is amongst the most potent chemotherapeutic drugs with applications in more than 50% of... more Cisplatin is amongst the most potent chemotherapeutic drugs with applications in more than 50% of cancer treatments, but dose-dependent side effects limit its usefulness. Berberis vulgaris L. (B. vulgaris) has a proven role in several therapeutic applications in the traditional medicinal system. High-performance liquid chromatography was used to quantify berberine, a potent alkaloid in the methanolic root extract of B. vulgaris (BvRE). Berberine chloride in BvRE was found to be 10.29% w/w. To assess the prophylactic and curative protective effects of BvRE on cisplatin-induced nephrotoxicity, hepatotoxicity, and hyperlipidemia, in vivo toxicity trials were carried out on 25 healthy male albino Wistar rats (130–180 g). Both prophylactic and curative trials included a single dose of cisplatin (4 mg/kg, i.p.) and nine doses of BvRE (500 mg/kg/day, orally). An array of marked toxicity effects appeared in response to cisplatin dosage evident by morphological condition, biochemical analysi...
Tissue diagnosis of peripheral pulmonary lesions (PPLs) can be challenging. In the past, flexible... more Tissue diagnosis of peripheral pulmonary lesions (PPLs) can be challenging. In the past, flexible bronchoscopy was commonly performed for this purpose but its diagnostic yield is suboptimal. This has led to the development of new bronchoscopic modalities such as radial endobronchial ultrasound (R-EBUS), electromagnetic navigation bronchoscopy (ENB) and virtual bronchoscopy (VB). We performed this meta-analysis using data from previously published R-EBUS studies, to determine its diagnostic yield and other performance characteristics. Ovid MEDLINE and PubMed databases were searched for R-EBUS studies in September 2016. Diagnostic yield was calculated by dividing the number of successful diagnoses by the total number of lesions. Meta-analysis was performed using MedCalc (Version 16.8). Inverse variance weighting was used to aggregate diagnostic yield proportions across studies. Publication bias was assessed using funnel plot and Duval and Tweedie's test. 57 studies with a total of...
Platelet function is intricately linked to the pathophysiology of critical Illness, and some stud... more Platelet function is intricately linked to the pathophysiology of critical Illness, and some studies have shown that antiplatelet therapy (APT) may decrease mortality and incidence of acute respiratory distress syndrome (ARDS) in these patients. Our objective was to understand the efficacy of APT by conducting a meta-analysis. We conducted a meta-analysis using PubMed, Central, Embase, The Cochrane Central Register, the ClinicalTrials.gov Website, and Google Scholar. Studies were included if they investigated critically ill patients receiving antiplatelet therapy and mentioned the outcomes being studied (mortality, duration of hospitalization, ARDS, and need for mechanical ventilation). We found that there was a significant reduction in all-cause mortality in patients on APT compared to control (odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.70-0.97). Both the incidence of acute lung injury/ARDS (OR: 0.67; 95% CI: 0.57-0.78) and need for mechanical ventilation (OR: 0.74; 95%...
To investigate the role of cigarette smoke exposure (CSE) in the regulation of cerebral smooth mu... more To investigate the role of cigarette smoke exposure (CSE) in the regulation of cerebral smooth muscle cell (SMC) phenotypic modulation in a NAPDH (NOX)-dependent manner and its effect on cerebral aneurysm (CA) formation and rupture. Cultured rat cerebral vascular SMCs and mice following cerebral aneurysm induction surgery underwent CSE during both in vitro and in vivo experiments. In cultured cerebral vascular SMCs, CSE increased expression of NOX-1 and reactive oxygen species (ROS) as early as 4 hours after treatment, with maximal upregulation of proinflammatory/matrix remodeling genes (MCP-1, MMPs, TNF-α, IL-1β, NF-κB, KLF4) at 24 hours. SMC contractile genes (SM-a-actin, SM-22a, SM-MHC) and myocardin were maximally decreased at 24 hours. Inhibition with superoxide dismutase and viral Ad/AS-NOX1 decreased CSE-induced upregulation of NOX-1 and inflammatory genes and downregulation of SMC contractile genes and myocardin. NOX p47phox-/- mice and those pretreated with apocynin had sig...
Bronchiolitis obliterans syndrome (BOS) is a devastating complication after allogeneic stem cell ... more Bronchiolitis obliterans syndrome (BOS) is a devastating complication after allogeneic stem cell transplantation (allo-SCT). Early identification of high-risk patients is pivotal for success. Lung proteins, KL-6, CCSP, SPA , and SP-D, measured in the serum may identify high-risk patients for BOS earlier than pulmonary function tests (PFTs) can identify changes or clinical symptoms. Lung proteins were measured in patients' serum at baseline and at 1, 3, 6, 9, 12, 18, and 24 months after transplantation along with history, clinical examination, and PFTs. Serum levels of lung proteins were also measured in healthy control subjects. The primary endpoint was the development of BOS confirmed by pathological biopsy or National Institutes of Health criteria. Between September 2009 and September 2011, 39 patients were enrolled. Six children developed BOS at a median time of 200 days (range, 94 to 282). KL-6 levels were low in control subjects, at a median of .1 U/mL (range, .1 to 1.5). Pre-SCT and 1-month KL-6 levels were significantly higher in surviving patients who developed BOS (n ¼ 6) versus those who did not (n ¼ 18
Rapid response teams have been adopted across hospitals to reduce the rate of inpatient cardiopul... more Rapid response teams have been adopted across hospitals to reduce the rate of inpatient cardiopulmonary arrest. Yet, data are not uniform on their effectiveness across university and community settings. The objective of our study was to determine the impact of rapid response teams on patient outcomes in a community teaching hospital with 24/7 resident coverage. Our retrospective chart review of preintervention-postintervention data included all patients admitted between January 2004 and April 2006. Rapid response teams were initiated in March 2005. The outcomes of interest were inpatient mortality, unexpected transfer to the intensive care unit, code blue (cardiac or pulmonary arrest) per 1000 discharges, and length of stay in the intensive care unit. Rapid response teams were activated 213 times during the intervention period. There was no statistically significant difference in inpatient mortality (3.13% preintervention versus 2.91% postintervention), code blue calls (3.09 versus ...
Inflammation plays a key role in formation and rupture of intracranial aneurysms. Because hepatoc... more Inflammation plays a key role in formation and rupture of intracranial aneurysms. Because hepatocyte growth factor (HGF) protects against vascular inflammation, we sought to assess the role of endogenous HGF in the pathogenesis of intracranial aneurysms. Circulating HGF concentrations in blood samples drawn from the lumen of human intracranial aneurysms or femoral arteries were compared in 16 patients. Tissue from superficial temporal arteries and ruptured or unruptured intracranial aneurysms collected from patients undergoing clipping (n=10) were immunostained with antibodies to HGF and its receptor c-Met. Intracranial aneurysms were induced in mice treated with PF-04217903 (a c-Met antagonist) or vehicle. Expression of inflammatory molecules was also measured in cultured human endothelial, smooth muscle cells and monocytes treated with lipopolysaccharides in presence or absence of HGF and PF-04217903. We found that HGF concentrations were significantly higher in blood collected fr...
Purpose. To investigate the sensitivity of mesenteric angiography, technical success of hemostasi... more Purpose. To investigate the sensitivity of mesenteric angiography, technical success of hemostasis, clinical success rate, and complications of transcatheter embolization for the treatment of acute nonvariceal gastrointestinal hemorrhage.Material and Methods. A retrospective review of 200 consecutive patients who underwent mesenteric arteriography for acute nonvariceal gastrointestinal hemorrhage between February 2004 and February 2011 was done.Results. Of 200 angiographic studies, 114 correctly revealed the bleeding site with mesenteric angiography. 47 (41%) patients had upper gastrointestinal hemorrhage and 67 (59%) patients had lower gastrointestinal hemorrhage. Out of these 114, in 112 patients (98%) technical success was achieved with immediate cessation of bleeding. 81 patients could be followed for one month. Clinical success was achieved in 72 out of these 81 patients (89%). Seven patients rebled. 2 patients developed bowel ischemia. Four patients underwent surgery for bowel...
Background Pakistan is a highly endemic area for hepatitis E virus (HEV) infection. The aim of th... more Background Pakistan is a highly endemic area for hepatitis E virus (HEV) infection. The aim of the current study was to isolate and characterize strains of HEV in two mini outbreaks. Results RNA was extracted and reverse transcribed to cDNA. Nested PCR was done for the detection of HEV RNA. The positive bands were eluted, cloned in TA vector and sequenced in both directions using genetic Analyzer (Applied Biosystem Inc, USA). Phylogenetic analysis was done using MEGA4 software. We isolated two new HEV genotype-1 strains from Lahore, Pakistan, based on cloning and sequencing of ORF2 region. Conclusions Our study suggest that both the human HEV strains were closely related to the Sar-55 but different from the Abb-2B and 87-Pakistan-B HEV isolates sharing 88-91% sequence identity to Pakistani isolate Sar-55. These results indicated that Sar-55 is the main endemic HEV strain in various areas of the country.
Background: Cancer associated with smoking and drinking remains a serious health problem worldwid... more Background: Cancer associated with smoking and drinking remains a serious health problem worldwide. The survival of patients is very poor due to the lack of effective early biomarkers. FOXM1 overexpression is linked to the majority of human cancers but its mechanism remains unclear in head and neck squamous cell carcinoma (HNSCC). Methodology/Principal Findings: FOXM1 mRNA and protein expressions were investigated in four independent cohorts (total 75 patients) consisting of normal, premalignant and HNSCC tissues and cells using quantitative PCR (qPCR), expression microarray, immunohistochemistry and immunocytochemistry. Effect of putative oral carcinogens on FOXM1 transcriptional activity was dose-dependently assayed and confirmed using a FOXM1-specific luciferase reporter system, qPCR, immunoblotting and short-hairpin RNA interference. Genome-wide single nucleotide polymorphism (SNP) array was used to 'trace' the genomic instability signature pattern in 8 clonal lines of FOXM1-induced malignant human oral keratinocytes. Furthermore, acute FOXM1 upregulation in primary oral keratinocytes directly induced genomic instability. We have shown for the first time that overexpression of FOXM1 precedes HNSCC malignancy. Screening putative carcinogens in human oral keratinocytes surprisingly showed that nicotine, which is not perceived to be a human carcinogen, directly induced FOXM1 mRNA, protein stabilisation and transcriptional activity at concentrations relevant to tobacco chewers. Importantly, nicotine also augmented FOXM1-induced transformation of human oral keratinocytes. A centrosomal protein CEP55 and a DNA helicase/putative stem cell marker HELLS, both located within a consensus loci (10q23), were found to be novel targets of FOXM1 and their expression correlated tightly with HNSCC progression. Conclusions/Significance: This study cautions the potential co-carcinogenic effect of nicotine in tobacco replacement therapies. We hypothesise that aberrant upregulation of FOXM1 may be inducing genomic instability through a program of malignant transformation involving the activation of CEP55 and HELLS which may facilitate aberrant mitosis and epigenetic modifications. Our finding that FOXM1 is upregulated early during oral cancer progression renders FOXM1 an attractive diagnostic biomarker for early cancer detection and its candidate mechanistic targets, CEP55 and HELLS, as indicators of malignant conversion and progression.
Journal of Biology Agriculture and Healthcare, 2014
Genus Amanita is among the most commonly found and most familiar genera belonging to phyllum Basi... more Genus Amanita is among the most commonly found and most familiar genera belonging to phyllum Basidiomycota known for its toxic species. Members of these genera are known to have a universal veil and a prominent volva at the base of their stipe which indicate their angiocarpic mode of germination. Universal veil is aimed at the protection of gills and the immature hymenium which is exposed for the spore dispersal at the time of maturity. Some members of this group are deadly poisonous although they also have much medicinal importance. Escalating human activities, environmental alterations, impact of biotic components and the distribution pattern of species has introduced some new species in the region. Ayubia National Park always remains a fascinating place for mushroom hunters and number of species of plants and fungi have already been reported. The present survey was aimed at an addition to the previous study of Genus Amanita and also to check the certain features of the genus Amanita. A new species Amanita banningiana was reprted from the site and observed morphologically as well as anatomically with the aid of eminent literature and scientists.
... The stem barks of UD were collected from Mt. Phal-gong, Kyungbuk Province, Korea in May 2002 ... more ... The stem barks of UD were collected from Mt. Phal-gong, Kyungbuk Province, Korea in May 2002 and identified by KS Kim, College of Oriental Medicine, Dongguk University, Korea. ... Western blotting analysis was performed by the method described previously (Kim et al., 2005). ...
Rationale : Fatty acid nitroalkenes are endogenously generated electrophilic byproducts of nitric... more Rationale : Fatty acid nitroalkenes are endogenously generated electrophilic byproducts of nitric oxide and nitrite-dependent oxidative inflammatory reactions. Existing evidence indicates nitroalkenes support posttranslational protein modifications and transcriptional activation that promote the resolution of inflammation. Objective : The aim of this study was to assess whether in vivo administration of a synthetic nitroalkene could elicit antiinflammatory actions in vivo using a murine model of vascular injury. Methods and Results : The in vivo administration (21 days) of nitro-oleic acid (OA-NO 2 ) inhibited neointimal hyperplasia after wire injury of the femoral artery in a murine model (OA-NO 2 treatment resulted in reduced intimal area and intima to media ratio versus vehicle- or oleic acid (OA)-treated animals, P <0.0001). Increased heme oxygenase (HO)-1 expression accounted for much of the vascular protection induced by OA-NO 2 in both cultured aortic smooth muscle cells a...
The purpose of the present study is the preparation and characterization of collagen/antitumor dr... more The purpose of the present study is the preparation and characterization of collagen/antitumor drug hybrids as drug delivery systems. Materials used for obtaining collagen-based drug delivery systems were collagen type I (Coll) as matrix and irinotecan (I) as hydrophilic active substances. After incorporation of I into Coll in differing ratios, the obtained hybrid materials (Coll/I) could be used according to our results as potential drug delivery systems in medicine for the topical (local) treatment of cancerous tissues or bone. The released amount of I varies with amount of Coll from hybrid materials: the higher, the slower the release amount of irinotecan transferred is in the first 6 hours. The in vitro citotoxicity demonstrates an antitumoral activity of the obtained hybrid materials and their potential use for biomedical applications as drug delivery systems in tumoral treatments.
Small intracranial aneurysms pose significant challenges to endovascular therapy. Surgical clippi... more Small intracranial aneurysms pose significant challenges to endovascular therapy. Surgical clipping is considered by many to be the preferred treatment for these lesions. We present the results of the first study comparing the 2 treatment modalities in small ruptured aneurysms. Between 2004 and 2011, 151 patients with small ruptured aneurysms (≤3 mm) were treated in our institution: 91 (60.3%) with endovascular therapy and 60 (39.7%) with surgical clipping. The surgical and endovascular groups were generally comparable with regard to baseline demographics, with the exception of larger mean aneurysm size in the endovascular group versus the surgical group (2.8 versus 2.5 mm, respectively;…
Journal of Cerebral Blood Flow & Metabolism, 2012
Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intens... more Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intense investigation, our understanding of the mechanisms leading to aneurysm development, progression and rupture remain incompletely defined. An accumulating body of evidence implicates inflammation as a critical contributor to aneurysm pathogenesis. Intracranial aneurysm formation and progression appear to result from endothelial dysfunction, a mounting inflammatory response, and vascular smooth muscle cell phenotypic modulation producing a pro-inflammatory phenotype. A later final common pathway appears to involve apoptosis of cellular constituents of the vessel wall. These changes result in degradation of the integrity of the vascular wall leading to aneurysmal dilation, progression and eventual rupture in certain aneurysms. Various aspects of the inflammatory response have been investigated as contributors to IA pathogenesis including leukocytes, complement, immunoglobulins, cytokines, ...
The world's population is aging, with the number of older adults projected to increase dramatical... more The world's population is aging, with the number of older adults projected to increase dramatically over the next two decades. This trend poses major challenges to health care systems, reflecting the greater healthcare utilization by and more comorbid conditions among elderly adults. Chronic kidney disease (CKD) is a substantial concern in the elderly, with both an increasing incidence of treated kidney failure with dialysis as well as a high prevalence of earlier stages of CKD. Given the high burden of risk factors for CKD, the high prevalence of CKD in the elderly is not surprising, with the rise in obesity, diabetes and hypertension in middle-aged adults likely foreshadowing further increases in CKD prevalence among the elderly. It is now commonly agreed that the presence of CKD identifies a higher risk state in the elderly, with increased risk for multiple adverse outcomes, including kidney failure, cardiovascular disease, cognitive impairment, and death. Accordingly, CKD in older adults is worthy of attention by both health care providers and patients, with the presence of a reduced GFR or albuminuria in the elderly potentially informing therapeutic and diagnostic decisions for these individuals.
The efforts made in the last decade regarding the molecular landscape of acute myeloid leukemia (... more The efforts made in the last decade regarding the molecular landscape of acute myeloid leukemia (AML) have created the possibility of obtaining patients’ personalized treatment. Indeed, the improvement of accurate diagnosis and precise assessment of minimal residual disease (MRD) increased the number of new markers suitable for novel and targeted therapies. This progress was obtained thanks to the development of molecular techniques starting with real-time quantitative PCR (Rt-qPCR) passing through digital droplet PCR (ddPCR) and next-generation sequencing (NGS) up to the new attractive metabolomic approach. The objective of this surge in technological advances is a better delineation of AML clonal heterogeneity, monitoring patients without disease-specific mutation and designing customized post-remission strategies based on MRD assessment. In this context, metabolomics, which pertains to overall small molecules profiling, emerged as relevant access for risk stratification and targe...
Cisplatin is amongst the most potent chemotherapeutic drugs with applications in more than 50% of... more Cisplatin is amongst the most potent chemotherapeutic drugs with applications in more than 50% of cancer treatments, but dose-dependent side effects limit its usefulness. Berberis vulgaris L. (B. vulgaris) has a proven role in several therapeutic applications in the traditional medicinal system. High-performance liquid chromatography was used to quantify berberine, a potent alkaloid in the methanolic root extract of B. vulgaris (BvRE). Berberine chloride in BvRE was found to be 10.29% w/w. To assess the prophylactic and curative protective effects of BvRE on cisplatin-induced nephrotoxicity, hepatotoxicity, and hyperlipidemia, in vivo toxicity trials were carried out on 25 healthy male albino Wistar rats (130–180 g). Both prophylactic and curative trials included a single dose of cisplatin (4 mg/kg, i.p.) and nine doses of BvRE (500 mg/kg/day, orally). An array of marked toxicity effects appeared in response to cisplatin dosage evident by morphological condition, biochemical analysi...
Tissue diagnosis of peripheral pulmonary lesions (PPLs) can be challenging. In the past, flexible... more Tissue diagnosis of peripheral pulmonary lesions (PPLs) can be challenging. In the past, flexible bronchoscopy was commonly performed for this purpose but its diagnostic yield is suboptimal. This has led to the development of new bronchoscopic modalities such as radial endobronchial ultrasound (R-EBUS), electromagnetic navigation bronchoscopy (ENB) and virtual bronchoscopy (VB). We performed this meta-analysis using data from previously published R-EBUS studies, to determine its diagnostic yield and other performance characteristics. Ovid MEDLINE and PubMed databases were searched for R-EBUS studies in September 2016. Diagnostic yield was calculated by dividing the number of successful diagnoses by the total number of lesions. Meta-analysis was performed using MedCalc (Version 16.8). Inverse variance weighting was used to aggregate diagnostic yield proportions across studies. Publication bias was assessed using funnel plot and Duval and Tweedie's test. 57 studies with a total of...
Platelet function is intricately linked to the pathophysiology of critical Illness, and some stud... more Platelet function is intricately linked to the pathophysiology of critical Illness, and some studies have shown that antiplatelet therapy (APT) may decrease mortality and incidence of acute respiratory distress syndrome (ARDS) in these patients. Our objective was to understand the efficacy of APT by conducting a meta-analysis. We conducted a meta-analysis using PubMed, Central, Embase, The Cochrane Central Register, the ClinicalTrials.gov Website, and Google Scholar. Studies were included if they investigated critically ill patients receiving antiplatelet therapy and mentioned the outcomes being studied (mortality, duration of hospitalization, ARDS, and need for mechanical ventilation). We found that there was a significant reduction in all-cause mortality in patients on APT compared to control (odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.70-0.97). Both the incidence of acute lung injury/ARDS (OR: 0.67; 95% CI: 0.57-0.78) and need for mechanical ventilation (OR: 0.74; 95%...
To investigate the role of cigarette smoke exposure (CSE) in the regulation of cerebral smooth mu... more To investigate the role of cigarette smoke exposure (CSE) in the regulation of cerebral smooth muscle cell (SMC) phenotypic modulation in a NAPDH (NOX)-dependent manner and its effect on cerebral aneurysm (CA) formation and rupture. Cultured rat cerebral vascular SMCs and mice following cerebral aneurysm induction surgery underwent CSE during both in vitro and in vivo experiments. In cultured cerebral vascular SMCs, CSE increased expression of NOX-1 and reactive oxygen species (ROS) as early as 4 hours after treatment, with maximal upregulation of proinflammatory/matrix remodeling genes (MCP-1, MMPs, TNF-α, IL-1β, NF-κB, KLF4) at 24 hours. SMC contractile genes (SM-a-actin, SM-22a, SM-MHC) and myocardin were maximally decreased at 24 hours. Inhibition with superoxide dismutase and viral Ad/AS-NOX1 decreased CSE-induced upregulation of NOX-1 and inflammatory genes and downregulation of SMC contractile genes and myocardin. NOX p47phox-/- mice and those pretreated with apocynin had sig...
Bronchiolitis obliterans syndrome (BOS) is a devastating complication after allogeneic stem cell ... more Bronchiolitis obliterans syndrome (BOS) is a devastating complication after allogeneic stem cell transplantation (allo-SCT). Early identification of high-risk patients is pivotal for success. Lung proteins, KL-6, CCSP, SPA , and SP-D, measured in the serum may identify high-risk patients for BOS earlier than pulmonary function tests (PFTs) can identify changes or clinical symptoms. Lung proteins were measured in patients' serum at baseline and at 1, 3, 6, 9, 12, 18, and 24 months after transplantation along with history, clinical examination, and PFTs. Serum levels of lung proteins were also measured in healthy control subjects. The primary endpoint was the development of BOS confirmed by pathological biopsy or National Institutes of Health criteria. Between September 2009 and September 2011, 39 patients were enrolled. Six children developed BOS at a median time of 200 days (range, 94 to 282). KL-6 levels were low in control subjects, at a median of .1 U/mL (range, .1 to 1.5). Pre-SCT and 1-month KL-6 levels were significantly higher in surviving patients who developed BOS (n ¼ 6) versus those who did not (n ¼ 18
Rapid response teams have been adopted across hospitals to reduce the rate of inpatient cardiopul... more Rapid response teams have been adopted across hospitals to reduce the rate of inpatient cardiopulmonary arrest. Yet, data are not uniform on their effectiveness across university and community settings. The objective of our study was to determine the impact of rapid response teams on patient outcomes in a community teaching hospital with 24/7 resident coverage. Our retrospective chart review of preintervention-postintervention data included all patients admitted between January 2004 and April 2006. Rapid response teams were initiated in March 2005. The outcomes of interest were inpatient mortality, unexpected transfer to the intensive care unit, code blue (cardiac or pulmonary arrest) per 1000 discharges, and length of stay in the intensive care unit. Rapid response teams were activated 213 times during the intervention period. There was no statistically significant difference in inpatient mortality (3.13% preintervention versus 2.91% postintervention), code blue calls (3.09 versus ...
Inflammation plays a key role in formation and rupture of intracranial aneurysms. Because hepatoc... more Inflammation plays a key role in formation and rupture of intracranial aneurysms. Because hepatocyte growth factor (HGF) protects against vascular inflammation, we sought to assess the role of endogenous HGF in the pathogenesis of intracranial aneurysms. Circulating HGF concentrations in blood samples drawn from the lumen of human intracranial aneurysms or femoral arteries were compared in 16 patients. Tissue from superficial temporal arteries and ruptured or unruptured intracranial aneurysms collected from patients undergoing clipping (n=10) were immunostained with antibodies to HGF and its receptor c-Met. Intracranial aneurysms were induced in mice treated with PF-04217903 (a c-Met antagonist) or vehicle. Expression of inflammatory molecules was also measured in cultured human endothelial, smooth muscle cells and monocytes treated with lipopolysaccharides in presence or absence of HGF and PF-04217903. We found that HGF concentrations were significantly higher in blood collected fr...
Purpose. To investigate the sensitivity of mesenteric angiography, technical success of hemostasi... more Purpose. To investigate the sensitivity of mesenteric angiography, technical success of hemostasis, clinical success rate, and complications of transcatheter embolization for the treatment of acute nonvariceal gastrointestinal hemorrhage.Material and Methods. A retrospective review of 200 consecutive patients who underwent mesenteric arteriography for acute nonvariceal gastrointestinal hemorrhage between February 2004 and February 2011 was done.Results. Of 200 angiographic studies, 114 correctly revealed the bleeding site with mesenteric angiography. 47 (41%) patients had upper gastrointestinal hemorrhage and 67 (59%) patients had lower gastrointestinal hemorrhage. Out of these 114, in 112 patients (98%) technical success was achieved with immediate cessation of bleeding. 81 patients could be followed for one month. Clinical success was achieved in 72 out of these 81 patients (89%). Seven patients rebled. 2 patients developed bowel ischemia. Four patients underwent surgery for bowel...
Background Pakistan is a highly endemic area for hepatitis E virus (HEV) infection. The aim of th... more Background Pakistan is a highly endemic area for hepatitis E virus (HEV) infection. The aim of the current study was to isolate and characterize strains of HEV in two mini outbreaks. Results RNA was extracted and reverse transcribed to cDNA. Nested PCR was done for the detection of HEV RNA. The positive bands were eluted, cloned in TA vector and sequenced in both directions using genetic Analyzer (Applied Biosystem Inc, USA). Phylogenetic analysis was done using MEGA4 software. We isolated two new HEV genotype-1 strains from Lahore, Pakistan, based on cloning and sequencing of ORF2 region. Conclusions Our study suggest that both the human HEV strains were closely related to the Sar-55 but different from the Abb-2B and 87-Pakistan-B HEV isolates sharing 88-91% sequence identity to Pakistani isolate Sar-55. These results indicated that Sar-55 is the main endemic HEV strain in various areas of the country.
Background: Cancer associated with smoking and drinking remains a serious health problem worldwid... more Background: Cancer associated with smoking and drinking remains a serious health problem worldwide. The survival of patients is very poor due to the lack of effective early biomarkers. FOXM1 overexpression is linked to the majority of human cancers but its mechanism remains unclear in head and neck squamous cell carcinoma (HNSCC). Methodology/Principal Findings: FOXM1 mRNA and protein expressions were investigated in four independent cohorts (total 75 patients) consisting of normal, premalignant and HNSCC tissues and cells using quantitative PCR (qPCR), expression microarray, immunohistochemistry and immunocytochemistry. Effect of putative oral carcinogens on FOXM1 transcriptional activity was dose-dependently assayed and confirmed using a FOXM1-specific luciferase reporter system, qPCR, immunoblotting and short-hairpin RNA interference. Genome-wide single nucleotide polymorphism (SNP) array was used to 'trace' the genomic instability signature pattern in 8 clonal lines of FOXM1-induced malignant human oral keratinocytes. Furthermore, acute FOXM1 upregulation in primary oral keratinocytes directly induced genomic instability. We have shown for the first time that overexpression of FOXM1 precedes HNSCC malignancy. Screening putative carcinogens in human oral keratinocytes surprisingly showed that nicotine, which is not perceived to be a human carcinogen, directly induced FOXM1 mRNA, protein stabilisation and transcriptional activity at concentrations relevant to tobacco chewers. Importantly, nicotine also augmented FOXM1-induced transformation of human oral keratinocytes. A centrosomal protein CEP55 and a DNA helicase/putative stem cell marker HELLS, both located within a consensus loci (10q23), were found to be novel targets of FOXM1 and their expression correlated tightly with HNSCC progression. Conclusions/Significance: This study cautions the potential co-carcinogenic effect of nicotine in tobacco replacement therapies. We hypothesise that aberrant upregulation of FOXM1 may be inducing genomic instability through a program of malignant transformation involving the activation of CEP55 and HELLS which may facilitate aberrant mitosis and epigenetic modifications. Our finding that FOXM1 is upregulated early during oral cancer progression renders FOXM1 an attractive diagnostic biomarker for early cancer detection and its candidate mechanistic targets, CEP55 and HELLS, as indicators of malignant conversion and progression.
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Papers by SHAFIN ALI