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author:("Khan, imrad")
1.  Epidemiological Factors in Gall Bladder Cancer in Eastern India-A Single Centre Study 
India has high incidence of Gallbladder carcinoma with regional variation in incidence possibly due to environmental factors. Prospective study of all the gall bladder cancer in our hospital over 18 months analysing how the epidemiological factors are influencing the disease. Incidence-Four cases per 100,000 populations per year. The peak incidence was in 41 to 50 years group (49.20 %). Male to female ratio was 1:3.8. Majority (69.84 %) were in lower socio-economic group. 61 out of 63 patients (96.62 %) were non-vegetarians. 60.34 % and 19.04 % patients weighed between 50 and 55 kg and 55and 60 kg respectively (p = 0.003). Male smokers had significantly higher risk (p = 0.000 1). Gall stones were present in 45 out of 63 cases(71.42 %).45 out of 63 patients were typhoid carriers (p < 0.05). Pain abdomen was the commonest complaint (87.30 %), followed by pallor, lump in right upper quadrant, nausea & vomiting and jaundice in 71.42 %, 69.84 %, 66.66 %, 31.74 % patients respectively. This data highlights high prevalence of gall bladder carcinoma in Eastern India. Better hygiene and water supply to prevent typhoid carriers, prevention of malnutrition, early intervention for cholelithiasis, importance of balanced diet, increase in awareness about risk of tobacco and alcohol consumption-all are highlighted as significant modifiable factors.
doi:10.1007/s13193-012-0203-x
PMCID: PMC3578539  PMID: 24426702
Gallbladder carcinoma; Epidemiology; Cholelithiasis
2.  Insulin Receptor Substrate-1 (IRS-1) Gly927Arg: Correlation with Gestational Diabetes Mellitus in Saudi Women 
BioMed Research International  2014;2014:146495.
Pregnant women with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) share a common pathophysiology associated with similar risk factors. Genetic variants used to determine the risk of developing T2DM might also be associated with the prevalence of GDM. The aim of the present study was to scrutinize the relationship between the G972R polymorphism of the insulin receptor substrate-1 (IRS-1) gene with GDM in the Saudi female population. This is a case-control study that monitored 500 Saudi women. Subjects with GDM (n = 200) were compared with non-GDM (n = 300) controls. We opted to evaluate rs1801278 polymorphism in the IRS1 gene, which plays a critical role in the insulin-signaling pathway. Genotyping was performed with the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The frequency of the rs1801278 polymorphism was significantly higher in women with GDM than in women with non-GDM (for TT + CT versus CC: P = 0.02). Additionally, there was a significant increase in the frequency of the Arg-encoding mutant allele from GDM to non-GDM (for T versus C: P = 0.01). Our results suggest that the rs1801278 polymorphism in the IRS-1 gene is involved in the occurrence of GDM in the Saudi population.
doi:10.1155/2014/146495
PMCID: PMC3948357
3.  Exploratory Study on Plasma Immunomodulator and Antibody Profiles in Tuberculosis Patients 
Host immune responses to Mycobacterium tuberculosis are generally able to contain infection and maintain a delicate balance between protection and immunopathology. A shift in this balance appears to underlie active disease observed in about 10% of infected individuals. Effects of local inflammation, combined with anti-M. tuberculosis systemic immune responses, are directly detectable in peripheral circulation, without ex vivo stimulation of blood cells or biopsy of the affected organs. We studied plasma immunomodulator and antibody biomarkers in patients with active pulmonary tuberculosis (TB) by a combination of multiplex microbead immunoassays and computational tools for data analysis. Plasma profiles of 10 immunomodulators and antibodies against eight M. tuberculosis antigens (previously reported by us) were examined in active pulmonary TB patients in a country where TB is endemic, Pakistan. Multiplex analyses were performed on samples from apparently healthy individuals without active TB from the same community as the TB patients to establish the assay baselines for all analytes. Over 3,000 data points were collected from patients (n = 135) and controls (n = 37). The data were analyzed by multivariate and computer-assisted cluster analyses to reveal patterns of plasma immunomodulators and antibodies. This study shows plasma profiles that in most patients represented either strong antibody or strong immunomodulator biomarkers. Profiling of a combination of both immunomodulators and antibodies described here may be valuable for the analysis of host immune responses in active TB in countries where the disease is endemic.
doi:10.1128/CVI.00213-13
PMCID: PMC3754529  PMID: 23761664
4.  Comparison between short- and long-acting erythropoiesis-stimulating agents in hemodialysis patients: target hemoglobin, variability, and outcome 
Purpose
Maintaining target hemoglobin (Hb) with minimal variability is a challenge in hemodialysis (HD) patients. The aim of this study is to compare the long- and short-acting erythropoietin-stimulating agents such as Aranesp and Eprex in achieving these targets.
Methods
Randomized, prospective, open-labeled study of 24 weeks includes stable patients on HD >3 months, age >18 years, and on Eprex for >3 months. Patients were randomized into two groups: A-(Aranesp group):HD patients on Eprex Q TIW or BIW were converted to Aranesp Q weekly, by using the conversion factor of 200:1 and those on Eprex Q weekly to Aranesp Q 2 weeks; B-(Eprex group):patients continued on Eprex treatment. Hemoglobin target was set at (105–125 g/l). Primary end points were percentage of patients achieving target Hb, hemoglobin variability, and number of dose changes in each group.
Results
This study consisted of 139 HD patients: 72 in the Aranesp and 67 in the Eprex—mean (SD) age 54 (16.2) years, 77 (55 %) males. About 46 % were diabetic. Target Hb achieved in 64.8 % of the Aranesp and 59.7 % in the Eprex (p = 0.006). Hb variability was less frequent in the Aranesp group (p = 0.2). Mean number of dose changes was 1.3 (0.87) in the Aranesp and 1.9 (1.2) in the Eprex (p < 0.001). There was 1 vascular access thrombosis in the Aranesp and 8 in the Eprex (p < 0.001). There was no difference in hospitalization and death number between the 2 groups.
Conclusions
Aranesp Q weekly or every 2 weeks is more efficient in achieving target Hb, with less dose changes and minor vascular access complications.
doi:10.1007/s11255-013-0640-7
PMCID: PMC3932161  PMID: 24448756
Short; Long-acting ESAs; Target hemoglobin; Hemoglobin variability; Hemodialysis
5.  Generation of Functional Thymic Epithelium from Human Embryonic Stem Cells that Supports Host T Cell Development 
Cell stem cell  2013;13(2):10.1016/j.stem.2013.04.004.
SUMMARY
Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T cell development represents a promising approach to reach this goal; however, progress toward generating functional TECs has been limited. Here, we describe a robust in vitro method to direct differentiation of human embryonic stem cells (hESCs) into thymic epithelial progenitors (TEPs) by precise regulation of TGFβ, BMP4, RA, Wnt, Shh, and FGF signaling. The hESC-derived TEPs further mature into functional TECs that support T cell development upon transplantation into thymus-deficient mice. Importantly, the engrafted TEPs produce T cells capable of in vitro proliferation as well as in vivo immune responses. Thus, hESC-derived TEP grafts may have broad applications for enhancing engraftment in cell-based therapies as well as restoring age-and stress-related thymic decline.
doi:10.1016/j.stem.2013.04.004
PMCID: PMC3869399  PMID: 23684540
6.  EASER: Ensembl Easy Sequence Retriever 
The rapid advances in genome sequencing technologies have increased the pace at which biological sequence databases are becoming available to the broad scientific community. Thus, obtaining and preparing an appropriate sequence dataset is a crucial first step for all types of genomic analyses. Here, we present a script that can widely facilitate the easy, fast, and effortless downloading and preparation of a proper biological sequence dataset for various genomics studies. This script retrieves Ensembl defined genomic features, associated with a given Ensembl identifier. Coding (CDS) and genomic sequences can be easily retrieved based on a selected relationship from a set of relationship types, either considering all available organisms or a user specified subset of organisms. The script is very user-friendly and by default starts with an interactive mode if no command-line options are specified.
doi:10.4137/EBO.S11335
PMCID: PMC3855309  PMID: 24324324
sequence analysis; bioinformatics; molecular evolution; genomics; data curation; databases
7.  Mechanism of action of chromogranin A on catecholamine release: molecular modeling of the catestatin region reveals a β-strand/loop/β-strand structure secured by hydrophobic interactions and predictive of activity 
Regulatory peptides  1998;77(0):43-53.
A novel fragment of chromogranin A, known as ‘catestatin’ (bovine chromogranin A344–364), inhibits catecholamine release from chromaffin cells and noradrenergic neurons by acting as a non-competitive nicotinic cholinergic antagonist, and may therefore constitute an endogenous autocrine feedback regulator of sympathoadrenal activity. To characterize how this activity depends on the peptide’s structure, we searched for common 3-dimensional motifs for this primary structure or its homologs. Catestatin’s primary structure bore significant (29–35.5% identity, general alignment score 44–57) sequence homology to fragment sequences within three homologs of known 3-dimensional structures, based on solved X-ray crystals: 8FAB, 1PKM, and 2IG2. Each of these sequences exists in nature as a β-strand/loop/β-strand structure, stabilized by hydrophobic interactions between the β-strands. The catestatin structure was stable during molecular dynamics simulations. The catestatin loop contains three Arg residues, whose electropositive side chains form the terminus of the structure, and give rise to substantial uncompensated charge asymmetry in the molecule. A hydrophobic moment plot revealed that catestatin is the only segment of chromogranin A predicted to contain amphiphilic β-strand. Circular dichroism in the far ultraviolet showed substantial (63%) β-sheet structure, especially in a hydrophobic environment. Alanine-substitution mutants of catestatin established a crucial role for the three central arginine residues in the loop (Arg351, Arg353, and Arg358), though not for two arginine residues in the strand region toward the amino-terminus. [125I]Catestatin bound to Torpedo membranes at a site other than the nicotinic agonist binding site. When the catestatin structure was ‘docked’ with the extracellular domain of the Torpedo nicotinic cholinergic receptor, it interacted principally with the β and δ subunits, in a relatively hydrophobic region of the cation pore extracellular orifice, and the complex of ligand and receptor largely occluded the cation pore, providing a structural basis for the non-competitive nicotinic cholinergic antagonist properties of the peptide. We conclude that a homology model of catestatin correctly predicts actual features of the peptide, both physical and biological. The model suggests particular spatial and charge features of the peptide which may serve as starting points in the development of non-peptide mimetics of this endogenous nicotinic cholinergic antagonist.
PMCID: PMC3676947  PMID: 9809795
Adrenal medulla; Chromaffin; Chromogranin A; Catestatin; Nicotinic cholinergic receptor; Mutagenesis; Homology modeling; Molecular dynamics; Alanine scan; Catecholamine; Synthetic peptide; Circular dichroism
8.  The use of individually wrapped presterilized small orthopaedic implants increase operating time: a prospective experimental study 
JRSM Short Reports  2013;4(6):34.
Objective
There have been concerns about the potential increases in operating time associated with the use of individually wrapped presterilized small orthopaedic implants compared with our traditional method of screw banks. We set out to quantify this theory.
Design
Prospective experimental study.
Setting
Theatre.
Participants
Orthopaedic Surgical Trainees and Theatre Scrub team.
Main outcome measure
The time taken to complete the operation.
Results
The use of prepacked and sterilized implants added 2 min 56 s to the use of a bank with a full complement of normal screws that required tapping and 3 min 58 s if self-tapping screws were used (P < 0.001).
Conclusion
Using individually wrapped presterilized small orthopaedic implants increases operating time.
doi:10.1177/2042533313476413
PMCID: PMC3697854  PMID: 23885288
9.  Association of Human Papilloma Virus Infection and Oral Squamous Cell Carcinoma in Bangladesh 
Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell carcinoma were included in the study. Extracted DNA from the cancerous tissues was checked for PCR reaction to detect the subtypes of human papilloma virus. Data of the present study suggest that oral squamous cell carcinoma are almost absent in Bangladeshi patients with human papilloma virus, particularly HPV 16 and 18.
PMCID: PMC3702360  PMID: 23617206
Human papilloma virus (HPV); HPV type 16; HPV type 18; Oral cancer; Polymerase chain reaction; Bangladesh
10.  A Recombinant Attenuated Mycobacterium tuberculosis Vaccine Strain Is Safe in Immunosuppressed Simian Immunodeficiency Virus-Infected Infant Macaques 
Many resource-poor countries are faced with concurrent epidemics of AIDS and tuberculosis (TB) caused by human immunodeficiency virus (HIV) and Mycobacterium tuberculosis, respectively. Dual infections with HIV and M. tuberculosis are especially severe in infants. There is, however, no effective HIV vaccine, and the only licensed TB vaccine, the Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine, can cause disseminated mycobacterial disease in HIV-infected children. Thus, a pediatric vaccine to prevent HIV and M. tuberculosis infections is urgently needed. We hypothesized that a highly attenuated M. tuberculosis strain containing HIV antigens could be safely administered at birth and induce mucosal and systemic immune responses to protect against HIV and TB infections, and we rationalized that vaccine safety could be most rigorously assessed in immunocompromised hosts. Of three vaccine candidates tested, the recombinant attenuated M. tuberculosis strain mc26435 carrying a simian immunodeficiency virus (SIV) Gag expression plasmid and harboring attenuations of genes critical for replication (panCD and leuCD) and immune evasion (secA2), was found to be safe for oral or intradermal administration to non-SIV-infected and SIV-infected infant macaques. Safety was defined as the absence of clinical symptoms, a lack of histopathological changes indicative of M. tuberculosis infection, and a lack of mycobacterial dissemination. These data represent an important step in the development of novel TB vaccines and suggest that a combination recombinant attenuated M. tuberculosis-HIV vaccine could be a safe alternative to BCG for the pediatric population as a whole and, more importantly, for the extreme at-risk group of HIV-infected infants.
doi:10.1128/CVI.00184-12
PMCID: PMC3416096  PMID: 22695156
11.  Insertion/Deletion polymorphisms do play any role in G6PD deficiency individuals in the Kingdom of the Saudi Arabia 
Bioinformation  2013;9(1):49-53.
Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway (PPP) that plays an important role in protecting cells from oxidative damage by producing NADPH and reduced glutathione. G6PD deficiency is considered one of the most common genetic disorders present in the X chromosome and is the most common of enzymopathic red blood cell disorder. Angiotensin converting enzyme (ACE) plays an essential role in two physiological systems, one leading to the production of angiotensin II and the other to the degradation of bradykinin. Most studies focused on an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene as a marker for a functional polymorphism. The α2B-adrenergic receptor gene (α2BAR) is a three-amino acid deletion (12Glu9) polymorphism is located on chromosome 2. (Glu9/Glu9) of this polymorphism has been first time studies in G6PD individuals. We have selected 39 G6PD deficiency male individuals and PCR was carried out with the I/D polymorphisms. ACE I/D polymorphism study was carried out in G6PD individuals and showed strong association with DD genotypes and D alleles OR=39.38, p<0.0001 (95% CI=8.80-176.1) and OR=38.58, p<0.0001 (95% CI=13.21-112.6). Another gene of α2BAR I/D polymorphism study cannot show any association in DD genotype OR-0.6882,p=0.9388 (95% CI=0.2035-2.327) and with D allele OR-0.9614,p=0.9388 (95% CI=0.3482-2.653). Our study shows that G6PD deficiency is showing strong association in DD genotype and D allele of ACE gene and α2BAR gene have not shown any important role and one of the reason could be the low sample size.
doi:10.6026/97320630009049
PMCID: PMC3563416  PMID: 23390344
G6PD; ACE; α2BAR; Insertion/ Deletion; PCR and Saudi Arabia
12.  Activation of TGF-β Pathway by Areca Nut Constituents: A Possible Cause of Oral Submucous Fibrosis 
PLoS ONE  2012;7(12):e51806.
Oral submucous fibrosis (OSF) is a chronic inflammatory disease characterized by the accumulation of excess collagen, and areca nut chewing has been proposed as an important etiological factor for disease manifestation. Activation of transforming growth factor-β signaling has been postulated as the main causative event for increased collagen production in OSF. Oral epithelium plays important roles in OSF, and arecoline has been shown to induce TGF-β in epithelial cells. In an attempt to understand the role of areca nut constituents in the manifestation of OSF, we studied the global gene expression profile in epithelial cells (HaCaT) following treatment with areca nut water extract or TGF-β. Interestingly, 64% of the differentially regulated genes by areca nut water extract matches with the TGF-β induced gene expression profile. Out of these, expression of 57% of genes was compromised in the presence of ALK5 (TβRI) inhibitor and 7% were independently induced by areca nut, highlighting the importance of TGF-β in areca nut actions. Areca nut water extract treatment induced p-SMAD2 and TGF-β downstream targets in HaCaT cells but not in human gingival fibroblast cells (hGF), suggesting epithelial cells could be the source of TGF-β in promoting OSF. Water extract of areca nut consists of polyphenols and alkaloids. Both polyphenol and alkaloid fractions of areca nut were able to induce TGF-β signaling and its downstream targets. Also, SMAD-2 was phosphorylated following treatment of HaCaT cells by Catechin, Tannin and alkaloids namely Arecoline, Arecaidine and Guvacine. Moreover, both polyphenols and alkaloids induced TGF-β2 and THBS1 (activator of latent TGF-β) in HaCaT cells suggesting areca nut mediated activation of p-SMAD2 involves up-regulation and activation of TGF-β. These data suggest a major causative role for TGF-β that is induced by areca nut in OSF progression.
doi:10.1371/journal.pone.0051806
PMCID: PMC3526649  PMID: 23284772
13.  N-(2,5-Dimeth­oxy­phen­yl)-6-nitro­quinazolin-4-amine 
In the title mol­ecule, C16H14N4O4, the quinazoline ring is substanti­ally planar (r.m.s. deviation = 0.0129 Å) and forms a dihedral angle of 2.73 (8)° with the benzene ring. The conformation of the mol­ecule is stabilized by an intra­molecular C—H⋯N hydrogen bond. In the crystal, mol­ecules are linked into chains running parallel to the b axis by C—H⋯O hydrogen bonds. In addition, π–π stacking is observed between dimethoxy-substituted and nitro-substituted benzene rings, with centroid–centroid distances in the range 3.6438 (10)–3.7148 (10) Å.
doi:10.1107/S1600536812048878
PMCID: PMC3588306  PMID: 23476461
14.  Controllable fabrication of PS/Ag core-shell-shaped nanostructures 
Nanoscale Research Letters  2012;7(1):580.
In this paper, based on the previous steps, a facile in situ reduction method was developed to controllably prepare polystyrene/Ag (PS/Ag) core-shell-shaped nanostructures. The crucial procedure includes surface treatment of polystyrene core particles by cationic polyelectrolyte polyethyleneimine, in situ formation of Ag nanoparticles, and immobilization of the Ag nanoparticles onto the surface of the polystyrene colloids via functional group NH from the polyethyleneimine. The experimental parameters, such as the reaction temperature, the reaction time, and the silver precursors were optimized for improvement of dispersion and Ag coat coverage of the core-shell-shaped nanostructures. Ultimately, the optimum parameters were obtained through a series of experiments, and well-dispersed, uniformly coated PS/Ag core-shell-shaped nanostructures were successfully fabricated. The formation mechanism of the PS/Ag core-shell-shaped nanostructures was also explained.
doi:10.1186/1556-276X-7-580
PMCID: PMC3497707  PMID: 23092195
PS/Ag core-shell-shaped nanostructures; Surface modification; In situ reduction
15.  Inadvertent suprapubic gastrostomy: Report of a unique complication of blind percutaneous suprapubic trocar cystostomy 
Emergency percutaneous trocar suprapubic cystostomy is a common surgical procedure for acute urinary retention. Although uncommon it can be associated with a few complications. The most dangerous complication is iatrogenic bowel injury. Literature shows reported cases of small and large bowel injuries. We report a case of inadvertent placement of suprapubic catheter into a dilated and ptotic stomach. This is the first reported case of this complication of suprapubic cystostomy.
doi:10.4103/0970-1591.105771
PMCID: PMC3579130  PMID: 23450184
Inadvertent bowel injury; iatrogenic bowel injury; suprapubic cystostomy
16.  Plastic surgical trauma: A single-centre experience 
Objectives:
To analyse the demographics, mechanism, nature, anatomical distribution, management and complications in trauma patients presenting to the plastic surgery unit.
Study Design:
Descriptive cross-sectional study.
Setting:
This study was conducted in the Plastic and Reconstructive Surgery Unit, Hayatabad Medical Complex, Peshawar, from 1st January 2009 to 30th April 2012.
Materials and Methods:
All trauma patients referred from emergency department and other departments irrespective of age and gender were enrolled in the study, excluding acute burns and trauma sequelae patients. The details were obtained from the data sheets of the patients. All the data were analysed and projected in the form of tables and figures.
Results:
A total of 1034 patients including 855 (82.7%) males and 179 (17.3%) females presented with plastic surgical trauma, with age ranging from 1 to 86 years, with a mean age of 20.84 ± 15.469 SD. The upper limb was affected in 492 (47.6%) patients, followed by head and neck in 273 (26.4%) cases. Road traffic accidents (RTAs) were the main cause of trauma, affecting 340 (32.9%) patients. Wound excision and closure was performed in 473 (45.7%) patients, followed by skin grafting and flap coverage in 232 (22.4%) and 132 (13.2%) patients, respectively. Postoperative complications were observed in 45 (4.35%) patients.
Conclusion:
Males in their young age mainly presented with plastic surgical trauma with RTA as the main mechanism and laceration as the most common type of these injuries. The upper limb was the most commonly affected region. The frequency of different types of surgical procedures and postoperative complications observed are comparable with international literature except for the microvascular surgery which is not performed in our centre. Regular audit of the plastic surgical trauma should be conducted in all plastic surgical units to both improve trauma care and reaffirm the role of Plastic Surgery in the new age trauma.
doi:10.4103/0970-0358.105970
PMCID: PMC3580356  PMID: 23450198
Plastic surgery; skin grafting; trauma
17.  Aqueous Humor Suppression of Dendritic Cell Function Helps Maintain Immune Regulation in the Eye during Human Uveitis 
This study of DC function in human uveitis suggests that the ocular microenvironment continues to regulate DC function during uveitis, despite IFNγ-driven upregulation of MHC expression, supporting the hypothesis that immune regulation within the eye is maintained during inflammation.
Purpose.
Noninfectious uveitis is characterized by a dysregulated inflammatory or immune response in the eye. It is unclear whether this represents a failure of immune privilege or an overwhelming inflammatory drive that has exceeded the capacity of regulatory mechanisms that are still functioning. The authors investigated immune regulation in the human eye during intraocular inflammation (uveitis) and its impact on dendritic cell (DC) function and subsequent T-cell responses.
Methods.
Myeloid DCs were isolated from the aqueous humor (AqH) and peripheral blood of patients with active uveitis and characterized by flow cytometry. The effect of uveitis AqH was interrogated in an in vitro model of peripheral blood monocyte-derived DCs from healthy controls.
Results.
Myeloid DCs isolated from uveitic AqH were characterized by elevated major histocompatibility complex classes I and II (MHC I/II), but reduced CD86 compared with matched peripheral blood DCs. Exposure of peripheral blood monocyte-derived DCs from healthy controls to the inflammatory AqH supernatant recapitulated this phenotype. Despite interferon gamma (IFNγ)–dependent upregulation of MHC I, inflammatory AqH was overall suppressive to DC function, with reduced CD86 expression and diminished T-cell responses. This suppressive effect was equal to or greater than that induced by noninflammatory AqH, but was glucocorticoid independent (in contrast to noninflammatory AqH).
Conclusions.
These data indicate that the ocular microenvironment continues to regulate DC function during uveitis, despite IFNγ-driven upregulation of MHC expression, supporting the hypothesis that immune regulation within the eye is maintained during inflammation.
doi:10.1167/iovs.11-8802
PMCID: PMC3317427  PMID: 22247464
18.  Plasma Antibody Profiles as Diagnostic Biomarkers for Tuberculosis▿ 
Clinical and Vaccine Immunology : CVI  2011;18(12):2148-2153.
Two billion people are infected with Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), worldwide. Ten million to 20 million of the infected individuals develop disease per year. TB is a treatable disease, provided that it is diagnosed in a timely manner. The current TB diagnostic methods are subjective, inefficient, or not cost-effective. Antibody-based blood tests can be used efficiently and cost-effectively for TB diagnosis. A major challenge is that different TB patients generate antibodies against different antigens. Therefore, a multiplex immunoassay approach is needed. We have developed a multiplex panel of 28 M. tuberculosis antigen-coated microbeads. Plasma samples were obtained from over 300 pulmonary TB patients and healthy controls in a country where TB is endemic, Pakistan. Multiplex data were analyzed using computational tools by multivariate statistics, classification algorithms, and cluster analysis. The results of antibody profile-based detection, using 16 selected antigens, closely correlated with those of the sputum-based diagnostic methods (smear microscopy and culture) practiced in countries where TB is endemic. Multiplex microbead immunoassay had a sensitivity and specificity of approximately 90% and 80%, respectively. These antibody profiles could potentially be useful for the diagnosis of nonpulmonary TB, which accounts for approximately 20% of cases of disease. Since an automated, high-throughput version of this multiplex microbead immunoassay could analyze thousands of samples per day, it may be useful for the diagnosis of TB in millions of patients worldwide.
doi:10.1128/CVI.05304-11
PMCID: PMC3232686  PMID: 21976221
19.  N-Methyl­pyrrolidine-1-carbothio­amide 
There are two independent mol­ecules in the asymmetric unit of the title compound, C6H12N2S, in which the N-methyl­thio­formamide unit and the pyrrolidine ring mean plane are oriented at dihedral angles of 5.9 (5) and 5.9 (4)°. In the crystal, zigzag C(4) chains extending along the a axis are formed due to N—H⋯S hydrogen bonds between alternate arrangements of mol­ecules. The chains are inter­linked by C—H⋯S hydrogen bonds.
doi:10.1107/S1600536812020971
PMCID: PMC3379299  PMID: 22719497
20.  Gene Expression Signature of DMBA-Induced Hamster Buccal Pouch Carcinomas: Modulation by Chlorophyllin and Ellagic Acid 
PLoS ONE  2012;7(4):e34628.
Chlorophyllin (CHL), a water-soluble, semi-synthetic derivative of chlorophyll and ellagic acid (EA), a naturally occurring polyphenolic compound in berries, grapes, and nuts have been reported to exert anticancer effects in various human cancer cell lines and in animal tumour models. The present study was undertaken to examine the mechanism underlying chemoprevention and changes in gene expression pattern induced by dietary supplementation of chlorophyllin and ellagic acid in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model by whole genome profiling using pangenomic microarrays. In hamsters painted with DMBA, the expression of 1,700 genes was found to be altered significantly relative to control. Dietary supplementation of chlorophyllin and ellagic acid modulated the expression profiles of 104 and 37 genes respectively. Microarray analysis also revealed changes in the expression of TGFβ receptors, NF-κB, cyclin D1, and matrix metalloproteinases (MMPs) that may play a crucial role in the transformation of the normal buccal pouch to a malignant phenotype. This gene expression signature was altered on treatment with chlorophyllin and ellagic acid. Our study has also revealed patterns of gene expression signature specific for chlorophyllin and ellagic acid exposure. Thus dietary chlorophyllin and ellagic acid that can reverse gene expression signature associated with carcinogenesis are novel candidates for cancer prevention and therapy.
doi:10.1371/journal.pone.0034628
PMCID: PMC3317635  PMID: 22485181
21.  Anthelmintic and relaxant activities of Verbascum Thapsus Mullein 
Background
Verbascum thapsus is used in tribal medicine as an antispasmodic, anti-tubercular agent and wormicide. In this study, we investigated the antispasmodic and anthelmintic activities of crude aqueous methanolic extract of the plant.
Methods
V. thapsus extracts were tested against roundworms (Ascaridia galli) and tapeworms (Raillietina spiralis). Each species of worm was placed into a negative control group, an albendazole treatment group, or a V. thapsus treatment group, and the time taken for paralysis and death was determined. In addition, relaxation activity tests were performed on sections of rabbit's jejunum. Plant extracts were tested on KCl-induced contractions and the relaxation activities were quantified against atropine. V. thapsus calcium chloride curves were constructed to investigate the mode of action of the plant extracts.
Results
We detected flavonoids, saponins, tannins, terpenoids, glycosides, carbohydrates, proteins, fats and fixed oils in V. thapsus. For both species of worm, paralysis occurred fastest at the highest concentration of extract. The relative index values for paralysis in A. galli were 4.58, 3.41 and 2.08, at concentrations of 10, 20 and 40 mg/ml of plant extract, respectively. The relative index for death in A. galli suggested that V. thapsus extract is wormicidal at high concentration. Similarly, the relative indexes for paralysis and death in R. spiralis suggested that the extract is a more potent wormicidal agent than albendazole. The mean EC50 relaxation activity values for spontaneous and KCl induced contractions were 7.5 ± 1.4 mg/ml (6.57-8.01, n = 6) and 7.9 ± 0.41 mg/ml (7.44-8.46, n = 6), respectively. The relaxation activity of the extract was 11.42 ± 2, 17.0 ± 3, 28.5 ± 4, and 128.0 ± 7% of the maximum observed for atropine at corresponding concentrations. The calcium chloride curves showed that V. thapsus extracts (3 mg/ml), had a mean EC50 (log molar [calcium]) value of -1.9 ± 0.06 (-1.87 - -1.98, n = 6) vs. control EC50 = -2.5 ± 0.12 (-2.37 - -2.56, n = 6), whereas the verapamil (0.1 μM) EC50 was -1.7 ± 0.1 (-1.6 - -1.8, n = 6) vs. control EC50 = -2.4 ± 0.09 (-2.3 - -2.47, n = 5).
Conclusions
Our results suggest that V. thapsus, which is currently used by some tribes in the Malakand region of Pakistan, has anthelmintic and antispasmodic value.
doi:10.1186/1472-6882-12-29
PMCID: PMC3350428  PMID: 22463730
22.  1,3-Bis(1-phenyl­eth­yl)imidazolidine-2-thione 
The complete molecule of the title compound, C19H22N2S, is generated by crystallographic twofold symmetry with the C=S group lying on the rotation axis. The imidazolidine ring adopts a flattened twist conformation. The dihedral angle between the asymmetric part of the imidazolidine-2-thione fragment and the benzene ring is 89.49 (17)°.
doi:10.1107/S160053681201224X
PMCID: PMC3344125  PMID: 22606128
23.  Alcohol and marijuana use while driving--an unexpected crash risk in Pakistani commercial drivers: a cross-sectional survey 
BMC Public Health  2012;12:145.
Background
A significant proportion of road traffic crashes are attributable to alcohol and marijuana use while driving globally. Sale and use of both substances is illegal in Pakistan and is not considered a threat for road traffic injuries. However literature hints that this may not be the case. We did this study to assess usage of alcohol and marijuana in Pakistani commercial drivers.
Methods
A sample of 857 commercial bus and truck drivers was interviewed in October 2008 at the largest commercial vehicle station in Rawalpindi and Islamabad, Pakistan. Time location cluster sampling was used to select the subjects and a structured questionnaire was used to assess the basic demographic profile, substance abuse habits of the drivers while on the road, and reasons for usage of illicit substances while driving were recorded. Self reported information was collected after obtaining informed consent. Chi square and fisher exact tests were used to assess differences between groups and logistic regression was used to identify significant associations between driver characteristics and alcohol and marijuana use.
Results
Almost 10% of truck drivers use alcohol while driving on Pakistani roads. Marijuana use is almost 30% in some groups. Statistically different patterns of usage are seen between population subgroups based on age, ethnicity, education, and marital status. Regression analysis shows association of alcohol and marijuana use with road rage and error behaviours, and also with an increased risk of being involved in road crashes. The reported reasons for using alcohol or marijuana show a general lack of awareness of the hazardous nature of this practice among the commercial driver population.
Conclusion
Alcohol and marijuana use is highly prevalent in Pakistani commercial drivers. The issue needs to be recognized by concerned authorities and methods such as random breath tests and sobriety check points need to be employed for proper law enforcement.
doi:10.1186/1471-2458-12-145
PMCID: PMC3306754  PMID: 22369479
24.  Thrombophilic gene polymorphism studies in G6PD deficient individuals from Saudi population 
Bioinformation  2012;8(25):1255-1259.
We performed a study to evaluate the role of three single nucleotide polymorphisms (SNPs), factor V Leiden G1691A (FVL), prothrombin gene mutation G20210A (PRT or FII-G20210A) and methylenotetrahydrofolate reductase variant C677T (MTHFRC677T), as risk factors for G6PD in Saudi populations. Our results did not show any association with the three Thrombophilic genes with FVL gene, no statistical analysis have shown any association with either allele or genotype frequencies OR=0.566, p=.0.667, (95% CI=0.014-22.48) and OR=0.569, p=0.251¸ (95% CI=0.014-22.96).In PRT gene G20210A for G Vs A, p=0.774; OR=0.566 (95%CI; 0.011-29.6); AA+GA Vs GG; p=0.502; OR=0.569 (95%CI=0.010-2969). G and A allele frequencies were similar between cases and controls with no statistical significance. In the MTHFR gene none of the genotypes or allele frequency cannot show any association OR=1.281, p=.0.667, (95% CI=0.414-3.958) and OR=1.1.172, p=0.800¸ (95% CI=0.343-4.008). Similarly, the difference of T allele frequencies between patients and controls was not found any association. In conclusion, our finding indicates that the prevalence of G1691A, G20210A and C677T mutations in G6PD deficient individuals is not statistically different compared to normal subjects and G6PD is not associated with these thrombophilic mutations in Saudi population.
doi:10.6026/97320630081255
PMCID: PMC3532010  PMID: 23275730
G6PD; FVL; PRT; MTHFR; PCR; Saudi Population
25.  Analysis of G6PD enzyme deficiency in Saudi population 
Bioinformation  2012;8(25):1260-1264.
The evolutionary conservation of a housekeeping gene such as G6PD is greater than that of tissue-specific genes, presumably because the latter may require more specific adaptation to the physiology of individual organisms. The abundance of distinct mutation sites and their clinical manifestations make G6PD ideal for structure-function analysis. Therefore, it is of interest to screen of G6PD deficiency in the blood donors in Kingdom of Saudi Arabia. We report the mean and variation of enzyme activity in a huge set of Suadi to non-Saudi population with reference to the entire population. The sequence level conservation of G6PD among distant species is demonstrated using phylogenetic trees. These observations have implications in the sequence-structure-function understanding of G6PD with reference to its association to several human diseases.
doi:10.6026/97320630081260
PMCID: PMC3532011  PMID: 23275731
G6PD enzyme; Phylogenetic tree; Gene –Gene Distance; Mutations

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