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Find video protocols related to scientific articles indexed in Pubmed.
Impact of the Follicular Lymphoma International Prognostic Index risk categorization on survival of patients with follicular lymphoma in Pakistani population: a single centre experience.
J Pak Med Assoc
PUBLISHED: 10-03-2014
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To determine the impact of Follicular Lymphoma International Prognostic Index risk categorisation on the survival of patients with follicular lymphoma treated in one centre.
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HIV associated lupus like nephropathy.
Ethiop J Health Sci
PUBLISHED: 09-04-2014
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Human immunodeficiency virus type 1 (HIV-1)-seropositive patients are at a high risk for the development of a variety of acute and chronic renal diseases. Most patients with HIVAN are of African descent, presenting late in the course of their HIV-1 infection. The only reliable test to establish or rule out the presence of HIVAN (HIV associated nephropathy) is renal biopsy. The most common lesion associated with HIV is a focal segmental glomeruloscelerosis, but several times, other biopsy findings may also be seen. Our patient had lupus nephritis like pathology picture. The therapeutic agents with the most promise are angiotensin-converting enzyme inhibitors and antiretroviral medications. Role of steroids are less well-defined although they have been used with success many times.
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Functional Non-Nucleoside Adenylyl Cyclase Inhibitors.
Chem Biol Drug Des
PUBLISHED: 08-29-2014
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In this study, we describe the synthesis of novel functional non-nucleoside adenylyl cyclase inhibitors, which can be easily modified with thiol containing biomolecules such as tumour targeting structures. The linkage between inhibitor and biomolecule contains cleavable bonds to enable efficient intracellular delivery in the reductive milieu of the cytosol as well as in the acidic environment within endosomes and lysosomes. The suitability of this synthetic approach was shown by the successful bioconjugation of a poor cell-permeable inhibitor with a cell-penetrating peptide. Additionally, we have demonstrated the excellent inhibitory effect of the compounds presented here in a live-cell Förster resonance energy transfer-based assay in human embryonic kidney cells.
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Bone disease in multiple myeloma: pathophysiology and management.
Cancer Growth Metastasis
PUBLISHED: 08-10-2014
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Myeloma bone disease (MBD) is a devastating complication of multiple myeloma (MM). More than 80% of MM patients suffer from destructive bony lesions, leading to pain, fractures, mobility issues, and neurological deficits. MBD is not only a main cause of disability and morbidity in MM patients but also increases the cost of management. Bone destruction and lack of bone formation are main factors in the development of MBD. Some novel factors are found to be involved in the pathogenesis of MBD, eg, receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) system (RANKL/OPG), Wingless (Wnt), dickkopf-1 (Wnt/DKK1) pathway. The addition of novel agents in the treatment of MM, use of bisphosphonates and other supportive modalities such as radiotherapy, vertebroplasty/kyphoplasty, and surgical interventions, all have significant roles in the treatment of MBD. This review provides an overview on the pathophysiology and management of MBD.
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Is atomic rearrangement of type IV PHA synthases responsible for increased PHA production?
J. Biomol. Struct. Dyn.
PUBLISHED: 08-01-2014
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Background: Type IV PHA synthase is a key enzyme responsible for catalyzing the formation of non-toxic, biocompatible, and biodegradable short-chain-length polyhydroxyalkanoates (scl-PHA) under the growth-limiting conditions in the members of the genus Bacillus. Results: The comparative in vitro and in silico analysis of the phaC subunit of type IV PHA synthases among Bacillus cereus FA11, B. cereus FC11, and B. cereus FS1 was done in our study to determine its structural and functional properties. Conserved domain analysis demonstrated that phaC subunit belongs to the alpha/beta (?/?) hydrolase fold. The catalytic triad comprising of cysteine (Cys), histidine (His), and aspartate (Asp) was found to be present at the active site. A shorter inter-atomic distance was found between the carboxyl (-COO) group of Asp and amino (NH2) group of His. Furthermore, slightly long inter-atomic distances between sulfhydryl (SH) group of Cys and NH2 group of His may be pointing toward the broader substrate specificity of type IV PHA synthases. However, a shorter distance between the SH group of Cys and NH2 group of His in case of B. cereus FC11 leads to a higher enzymatic activity and maximum PHA yield (49.26%). Conclusion: The in silico study verifies that the close proximity between SH group of Cys and NH2 group of His in phaC subunit of type IV PHA synthases can be crucial for synthesis of scl-PHA. However, the catalytic activity of type IV PHA synthases declines as the distance between the sulfur (S) atom of the SH group of Cys and the nitrogen (N) atom of NH2 group of His increases.
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Biocontrol efficacy of different isolates of Trichoderma against soil borne pathogen Rhizoctonia solani.
Pol. J. Microbiol.
PUBLISHED: 07-19-2014
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In this study, the biocontrol abilities of water-soluble and volatile metabolites of three different isolates of Trichoderma (T. asperellum, T. harzianum and Trichoderma spp.) against soil borne plant pathogen Rhizoctonia solani were investigated both in vitro and in vivo. The results showed for the first time that mycelial growth inhibition of the pathogen was 74.4-67.8% with water-soluble metabolites as compared to 15.3-10.6% with volatile metabolites in vitro. In vivo antagonistic activity of Trichoderma isolates against R. solani was evaluated on bean plants under laboratory and greenhouse conditions. We observed that T. asperellum was more effective and consistent, lowering disease incidence up to 19.3% in laboratory and 30.5% in green house conditions. These results showed that three isolates of Trichoderma could be used as effective biocontrol agents against R. solani.
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Polyhydroxyalkanoates - what are the uses? Current challenges and perspectives.
Crit. Rev. Biotechnol.
PUBLISHED: 06-26-2014
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Abstract Over the past few decades, a considerable attention has been focused on the microbial polyhydroxyalkanoates (PHAs) owing to its multifaceted properties, i.e. biodegradability, biocompatibility, non-toxicity and thermo-plasticity. This article presents a critical review of the foregoing research, current trends and future perspectives on the value added applications of PHAs in the biomedical, environmental and industrial domains of life.
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Association of the rs1042522 polymorphism with increased risk of prostate adenocarcinoma in the Pakistani population and its HuGE review.
Asian Pac. J. Cancer Prev.
PUBLISHED: 06-18-2014
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Prostate adenocarcinoma is one of the leading causes of cancer related mortality in men but still limited knowledge is available about its associated functional SNPs including rs1042522 (Pro72Arg). The present study was undertaken to explore the association of this SNP with susceptibility to prostate adenocarcinoma along with its structural and functional impacts in the Pakistani population in a case-control study. Three-dimensional structure of human TP53 with Pro72Arg polymorphism was predicted through homology modeling, refined and validated for detailed structure-based assessment. We also carried out a HuGE review of the previous available data for this polymorphism. Different genetic models were used to evaluate the genotypes association with the increased risk of PCa (Allelic contrast: OR=0.0.34, 95%CI 0.24-0.50, p=0.000; GG vs CC: OR=0.17, 95%CI 0.08-0.38, p=0.000; Homozygous: OR=0.08, 95%CI 0.04-0.15, p=0.000; GC vs CC: OR=2.14, 95%CI 1.01-4.51, p=0.046; Recessive model: OR=0.10, 95%CI 0.05-0.18, p=0.000; Log Additive: OR=3.54, 95%CI 2.13-5.89, p=0.000) except the Dominant model (OR=0.77, 95%CI 0.39-1.52, p=0.46). Structure and functional analysis revealed that the SNP in the proline rich domain is responsible for interaction with HRMT1L2 and WWOX. In conclusion, it was observed that the Arg coding G allele is highly associated with increased risk of prostate adenocarcinoma in the Pakistani population (p=0.000).
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Application of Short Tandem Repeat markers in diagnosis of chromosomal aneuploidies and forensic DNA investigation in Pakistan.
Gene
PUBLISHED: 05-30-2014
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Short Tandem Repeat (STR) genetic markers hold great potential in forensic investigations, molecular diagnostics and molecular genetics research. AmpFlSTR® Identifiler™ PCR amplification kit is a multiplex system for co-amplification of 15 STR markers used worldwide in forensic investigations. This study attempts to assess forensic validity of these STRs in Pakistani population and to investigate its applicability in quick and simultaneous diagnosis and tracing parental source of common chromosomal aneuploidies.
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Identification of proteins found to be significantly altered when comparing the serum proteome from Multiple Myeloma patients with varying degrees of bone disease.
BMC Genomics
PUBLISHED: 05-12-2014
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Bone destruction is a feature of multiple myeloma, characterised by osteolytic bone destruction due to increased osteoclast activity and suppressed or absent osteoblast activity. Almost all multiple myeloma patients develop osteolytic bone lesions associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Biomarkers of bone remodelling are used to identify disease characteristics that can help select the optimal management of patients. However, more accurate biomarkers are needed to effectively mirror the dynamics of bone disease activity.
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Quinoxaline derivatives: novel and selective butyrylcholinesterase inhibitors.
Med Chem
PUBLISHED: 05-10-2014
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Alzheimer's disease (AD) is a progressive brain disorder which occurs due to lower levels of acetylcholine (ACh) neurotransmitters, and results in a gradual decline in memory and other cognitive processes. Acetycholinesterase (AChE) and butyrylcholinesterase (BChE) are considered to be primary regulators of the ACh levels in the brain. Evidence shows that AChE activity decreases in AD, while activity of BChE does not change or even elevate in advanced AD, which suggests a key involvement of BChE in ACh hydrolysis during AD symptoms. Therefore, inhibiting the activity of BChE may be an effective way to control AD associated disorders. In this regard, a series of quinoxaline derivatives 1-17 was synthesized and biologically evaluated against cholinesterases (AChE and BChE) and as well as against ?- chymotrypsin and urease. The compounds 1-17 were found to be selective inhibitors for BChE, as no activity was found against other enzymes. Among the series, compounds 6 (IC50 = 7.7 ± 1.0 µM) and 7 (IC50 = 9.7 ± 0.9 µM) were found to be the most active inhibitors against BChE. Their IC50 values are comparable to the standard, galantamine (IC50 = 6.6 ± 0.38 µM). Their considerable BChE inhibitory activity makes them selective candidates for the development of BChE inhibitors. Structure-activity relationship (SAR) of this new class of selective BChE inhibitors has been discussed.
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A two-phase hyperelastic-viscoplastic constitutive model for semi-crystalline polymers: application to polyethylene materials with a variable range of crystal fractions.
J Mech Behav Biomed Mater
PUBLISHED: 04-23-2014
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Polyethylene-based polymers as biomedical materials can contribute to a wide range of biomechanical applications. Therefore, it is important to identify, analyse, and predict with precision their mechanical behaviour. Polyethylene materials are semi-crystalline systems consisting of both amorphous and crystalline phases interacting in a rather complex manner. When the amorphous phase is in the rubbery state, the mechanical behaviour is strongly dependent on the crystal fraction, therefore leading to essentially thermoplastic or elastomeric responses. In this study, the finite deformation stress-strain response of polyethylene materials is modelled by considering these semi-crystalline polymers as two-phase heterogeneous media in order to provide insight into the role of crystalline and amorphous phases on the macro-behaviour and on the material deformation resistances, i.e. intermolecular and network resistances. A hyperelastic-viscoplastic model is developed in contemplation of representing the overall mechanical response of polyethylene materials under large deformation. An evolutionary optimization procedure based on a genetic algorithm is developed to identify the model parameters at different strain rates. The identification results show good agreement with experimental data, demonstrating the usefulness of the proposed approach: the constitutive model, with only one set of identified parameters, allows reproducing the stress-strain behaviour of polyethylene materials exhibiting a wide range of crystallinities, the crystal content becoming the only variable of the model.
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Submental/Transmylohyoid route for endotracheal intubation in maxillofacial surgical procedures: a review.
J Int Oral Health
PUBLISHED: 03-04-2014
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Patients with severe panfacial injuries usually require long-term airway management. Nasal intubation may be contraindicated in case of nasoorbitoethmoidal fractures and also there may be a need for intraoperative and short-term postoperative intermaxillary fixation to achieve optimum reduction of fractures. The need for unobstructed access to the perinasal area during bimaxillary orthognathic procedures is felt many a time and to avoid a tracheostomy with its attending morbidity, many techniques have evolved that involve a submandibular/transmylohyoid or submental approach for temporary oroendotracheal intubation. In this article, we present our experience of patients by using submental/transmylohyoid route for endotracheal intubation. technique gives the surgeon and the anesthetist comfortable control over their respective domains, is easy to learn and implement in the operating protocol with no added costs. How to cite the article: Prakash VJ, Chakravarthy C, Attar AH. Submental/transmylohyoid route for endotracheal intubation in maxillofacial surgical procedures: A review. J Int Oral Health 2014;6(3):125-8.
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Penicillium verruculosum SG: a source of polyketide and bioactive compounds with varying cytotoxic activities against normal and cancer lines.
Arch. Microbiol.
PUBLISHED: 02-23-2014
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A newly isolated fungus Penicillium verruculosum SG was evaluated for the production and characterization of bioactive colored secondary metabolites using solid-state fermentation along with their cytotoxic activities against normal and cancer cell lines. Logical fragmentation pattern following column chromatography, thin layer chromatography and liquid chromatography and mass spectrometry of crude culture filtrate of fungus revealed the presence of different polyketide pigments and other bioactive compounds. Cytotoxicity of the selected colored fractions of fungal filtrate containing different compounds revealed IC50 (?g/ml) values ranging from 5 to 100. It was significantly higher in case of orevactaene (5 + 0.44) and monascorubrine followed by pyripyropene (8 + 0.63) against cancer cell line KA3IT. Overall, these compounds considerably showed less toxicity toward normal cell lines NIH3T3, HSCT6, HEK293 and MDCK. XRD of a yellow crystalline compound (224.21 m/z) confirmed its 3-dimensional structure as phenazine 1 carboxylic acid (C13H8N2O2) (broad spectrum antibiotic), and it is first time reported in fungi.
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Quantum chemical assessment of benzimidazole derivatives as corrosion inhibitors.
Chem Cent J
PUBLISHED: 01-18-2014
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The majority of well-known inhibitors are organic compounds containing multiple bonds and heteroatoms, such as O, N or S, which allow adsorption onto the metal surface. These compounds can adsorb onto the metal surface and block active surface sites, reducing the rate of corrosion.
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Identification of recurrent c.742G>T nonsense mutation in ECM1 in Pakistani families suffering from lipoid proteinosis.
Mol. Biol. Rep.
PUBLISHED: 01-04-2014
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Lipoid proteinosis (LP) is one of the rare, recessive autosomal disorders clinically characterized by widespread deposition of hyaline-like material in the skin, mucosa and viscera. Classical features include beaded eyelid papules, laryngeal infiltration and hoarseness of voice caused by pathogenic mutations in the ECM1 gene located on 1q21.2. In present study ethnically different, three consanguineous Pakistani families with typical cutaneous features of LP were analysed to investigate the underlying molecular basis. PCR based linkage analysis using microsatellite markers localized the families to locus 1q21.2, harboring ECM1 gene. To identify the mutation in the candidate gene (ECM1), Sanger sequencing was carried out. All the families were found to carry c.742 G>T nonsense mutation in exon 7 of the ECM1 gene that resulted in a truncated ECM1 protein containing 247 amino acids instead of 540 (p.E248X). To further investigate the impact and importance of mutation in LP pathogenesis we applied different bioinformatics tools. In silico studies has predicted lack of functional domains and 65 % shorter ECM1 mutant protein. It is the first report of recurrence mutation from Pakistan as c.742G>T nonsense mutation was found in three ethnically different Pakistani families with LP. Study strengthens the conclusion that c.742G>T mutation is the pathological cause of LP. Furthermore, data also support the fact that exon 7 is one of the most common hot spots of pathological mutations in ECM1. The absence of functional domains and truncated sequence most likely contribute to the lack of ECM1 function and thereby influence several aspects of dermal homeostasis that leads to LP pathogenesis.
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Missense mutations (p.H371Y, p.D438Y) in gene CHEK2 are associated with breast cancer risk in women of Balochistan origin.
Mol. Biol. Rep.
PUBLISHED: 01-04-2014
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CHEK2 encodes a serine/threonine-protein kinase which plays a critical role in DNA damage signaling pathways. CHEK2 directly phosphorylates and regulates the functions of p53 and BRCA1. Most women with breast and/or ovarian cancer are not carriers of mutant BRCA1 or BRCA2. Multiple studies have shown that a CHEK2*1100delC confers about a two-fold increased risk of breast cancer in unselected females and a tenfold increase in males. Moreover, studies have shown that first-degree relatives of bilateral breast cancer cases who carried the CHEK2*1100delC allele had an eight-fold increased risk of breast cancer. It has been suggested that CHEK2 functions as a low-penetrance susceptibility gene for cancers and multiplies the risks associated with other gene(s) to increase cancer risk. The main goal of this study was to evaluate and to compare the role of truncating mutations, splice junction mutations and rare missense substitutions in breast cancer susceptibility gene CHEK2. Present study was performed on 140 individuals including 70 breast cancer patients both with and without family history and 70 normal individuals. Written consent was obtained and 3 ml intravenous blood was drawn from all the subjects. DNA was extracted from all the samples through inorganic method published already. Primers were synthesized for all the 14 exons of CHEK2 gene. Coding and adjacent intronic sequences of CHEK2 gene were amplified and sequenced. Two genetic variants (p.H371Y, p.D438Y) were found in exon 10 and exon 11 of gene CHEK2 which were not found in any of the 70 control individuals from same geographical area and ethnic group. The genetic variant c.1312G>T (p.D438Y) identified in a patient with a family history of breast cancer. To our knowledge, this is first mutation scanning study of gene CHEK2 from Balochistan population.
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Two new compounds from the aerial parts of Bergenia himalaica Boriss and their anti-hyperglycemic effect in streptozotocin-nicotinamide induced diabetic rats.
J Ethnopharmacol
PUBLISHED: 01-03-2014
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Bergenia himalaica Boriss is mainly distributed in the temperate Himalayas between altitudes of 900 and 3000m ranging from the southeastern regions in central Asia and northern regions in South Asia. The plant has a long history of its use in traditional medicine for the treatment of various diseases such as diabetes, urinary complaints, kidney stones, hemorrhagic diseases and epilepsy. The aim of this study is to isolate pure compounds from Bergenia himalaica Boriss, elucidate their structures and determine their blood glucose lowering activity to obtain additional scientific evidence for its usage in traditional medicine for the management of diabetes.
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Novel structural hybrids of pyrazolobenzothiazines with benzimidazoles as cholinesterase inhibitors.
Eur J Med Chem
PUBLISHED: 01-01-2014
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Two series of novel pyrazolobenzothiazine-based hybrid compounds were efficiently synthesized starting from saccharin sodium salt. Pyrazolo[4,3-c][1,2]benzothiazine scaffolds were N-arylated by using p-fluorobenzaldehyde, followed by the incorporation of a benzimidazole or similar ring systems by treatment with arylenediamines. These phenylene-connected hybrid compounds were investigated as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Compounds 12d and 12k were the most potent AChE inhibitors with IC50 values of 11 and 13 nM, respectively, while 6j (IC50 = 17 nM) proved to be the most active inhibitor against BuChE with remarkable selectivity for BuChE over AChE. Molecular docking studies were also performed on human AChE and BuChE to suggest possible binding modes in which the inhibitor's extended structure is accommodated along the active site gorge of both enzymes.
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Vitamin D deficiency and exogenous vitamin D excess similarly increase diffuse atherosclerotic calcification in apolipoprotein E knockout mice.
PLoS ONE
PUBLISHED: 01-01-2014
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Observational data associate lower levels of serum vitamin D with coronary artery calcification, cardiovascular events and mortality. However, there is little interventional evidence demonstrating that moderate vitamin D deficiency plays a causative role in cardiovascular disease. This study examined the cardiovascular effects of dietary vitamin D deficiency and of vitamin D receptor agonist (paricalcitol) administration in apolipoprotein E knockout mice.
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Taguchi's experimental design for optimizing the production of novel thermostable polypeptide antibiotic from Geobacillus pallidus SAT4.
Pak J Pharm Sci
PUBLISHED: 01-01-2014
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Polypeptide antimicrobials used against topical infections are reported to obtain from mesophilic bacterial species. A thermophilic Geobacillus pallidus SAT4 was isolated from hot climate of Sindh Dessert, Pakistan and found it active against Micrococcus luteus ATCC 10240, Staphylococcus aureus ATCC 6538, Bacillus subtilis NCTC 10400 and Pseudomonas aeruginosa ATCC 49189. The current experiment was designed to optimize the production of novel thermostable polypeptide by applying the Taguchi statistical approach at various conditions including the time of incubation, temperature, pH, aeration rate, nitrogen, and carbon concentrations. There were two most important factors that affect the production of antibiotic including time of incubation and nitrogen concentration and two interactions including the time of incubation/pH and time of incubation/nitrogen concentration. Activity was evaluated by well diffusion assay. The antimicrobial produced was stable and active even at 55°C. Ammonium sulphate (AS) was used for antibiotic recovery and it was desalted by dialysis techniques. The resulted protein was evaluated through SDS-PAGE. It was concluded that novel thermostable protein produced by Geobacillus pallidus SAT4 is stable at higher temperature and its production level can be improved statistically at optimum values of pH, time of incubation and nitrogen concentration the most important factors for antibiotic production.
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In vitro synergistic effect of ciprofloxacin with aminoglycosides against multidrug resistant-Pseudomonas aeruginosa.
Pak J Pharm Sci
PUBLISHED: 09-17-2013
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Pseudomonas aeruginosa is an increasingly prevalent nosocomial human pathogen. Infections with multidrug-resistant (MDR) P. aeruginosa are currently a treatment challenge and requires search for better treatment options.
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Modeling in vitro inhibition of butyrylcholinesterase using molecular docking, multi-linear regression and artificial neural network approaches.
Bioorg. Med. Chem.
PUBLISHED: 09-10-2013
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Butyrylcholinesterase (BChE) has been an important protein used for development of anti-cocaine medication. Through computational design, BChE mutants with ?2000-fold improved catalytic efficiency against cocaine have been discovered in our lab. To study drug-enzyme interaction it is important to build mathematical model to predict molecular inhibitory activity against BChE. This report presents a neural network (NN) QSAR study, compared with multi-linear regression (MLR) and molecular docking, on a set of 93 small molecules that act as inhibitors of BChE by use of the inhibitory activities (pIC50 values) of the molecules as target values. The statistical results for the linear model built from docking generated energy descriptors were: r(2)=0.67, rmsd=0.87, q(2)=0.65 and loormsd=0.90; the statistical results for the ligand-based MLR model were: r(2)=0.89, rmsd=0.51, q(2)=0.85 and loormsd=0.58; the statistical results for the ligand-based NN model were the best: r(2)=0.95, rmsd=0.33, q(2)=0.90 and loormsd=0.48, demonstrating that the NN is powerful in analysis of a set of complicated data. As BChE is also an established drug target to develop new treatment for Alzheimers disease (AD). The developed QSAR models provide tools for rationalizing identification of potential BChE inhibitors or selection of compounds for synthesis in the discovery of novel effective inhibitors of BChE in the future.
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Association of HLA-DRB1 and -DQB1alleles and haplotypes with rheumatoid arthritis in a Pakistani population.
Arthritis Res. Ther.
PUBLISHED: 08-22-2013
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Rheumatoid arthritis is an autoimmune disease with poorly understood pathophysiology. Genetic components of disease etiology, especially human leukocyte antigen (HLA) associations, are well known. Ethnic differences account for a number of variations in disease association with the HLA locus and there seem to be differences in various studies regarding its genetic predisposition. This study was aimed at determining the contribution of DRB1 and DQB1 components of HLA class II in rheumatoid arthritis in a Pakistani cohort.
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Echomorphology of cardiomyopathy: review of 217 cases from 1999 to 2010.
J Pak Med Assoc
PUBLISHED: 08-03-2013
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To study echocardiogram features of different types of cardiomyopathy presenting over a 12 year period at a single centre in Peshawar.
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In silico characterization of a novel pathogenic deletion mutation identified in XPA gene in a Pakistani family with severe xeroderma pigmentosum.
J. Biomed. Sci.
PUBLISHED: 07-23-2013
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Xeroderma Pigmentosum (XP) is a rare skin disorder characterized by skin hypersensitivity to sunlight and abnormal pigmentation. The aim of this study was to investigate the genetic cause of a severe XP phenotype in a consanguineous Pakistani family and in silico characterization of any identified disease-associated mutation.
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Identification of sulfonic acids as efficient ecto-5-nucleotidase inhibitors.
Eur J Med Chem
PUBLISHED: 07-08-2013
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Ecto-5-nucleotidase (CD73) is well known for its implication in cancer. Inhibition of ecto-5-nucleotidases is thought to provide an attractive approach to cancer therapy. This study identifies sulfonic acid compounds as efficient inhibitors of ecto-5-nucleotidases. The compounds were tested against recombinant human and rat ecto-5-nucleotidases. The most potent new sulfonic acid inhibitor 6-amino-4-hydroxynaphthalene-2-sulfonic acid (1) of ecto-5-nucleotidase had an IC50 of 1.32 ± 0.09 ?M for the human and 10.4 ± 3.3 ?M for the rat enzyme. Generally, all compounds were more active against the human enzyme. Plausible binding mode models were developed for this new class of inhibitors. Furthermore, several sulfonic acid inhibitors were efficient cytotoxic agents when tested on H157 cancer cell lines. Hence, new ecto-5-nucleotidases inhibitors displayed significant potential for further development as compounds for anti-cancer therapy.
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Review on the demographic and social impact of methadone-medication therapy on Malaysian patients.
Pak J Pharm Sci
PUBLISHED: 07-02-2013
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This study is an observational cross-sectional study aimed to examine the possible demographic and social characteristics of patients enrolled at the Methadone Maintenance Therapy Adherence Clinic (MMTAC) in Malaysia. Medical records from year 2009 - 2011 were Reviewed. Demographic, social characteristics and laboratory examinations such as age, gender, race, clinic attendances and urine analysis were recorded. Subjects were selected by means of convenient sampling but based on the specified inclusion and exclusion criteria. Data were analyzed by either Chi-square test, Fishers exact test Mann-Whitney U-test, with the limit of significance was set at p < 0.05. Demographically, this study found that the ratio of Malays, Chinese and Indian enrolled to the MMTAC program is similar to the distribution of races in Malaysia. Their starting age for drug use was between 14-35 years and the age to enrolment between 30-58 years. Socially, many are unemployed, lowly educated and married. Most are drug users with a high percentage of HCV accompanied with impaired liver function. Retention rate was 87% but illicit drug use was at 57.50%. However, percentage of employment increased significantly after therapy. The study managed to identify several demographical and social distributions of patients attending the MMTAC. Although attendance rate was high, many were on illicit drug use. Nevertheless, employment rate improved significantly.
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Isolation and molecular characterization of polyvinyl chloride (PVC) plastic degrading fungal isolates.
J. Basic Microbiol.
PUBLISHED: 05-20-2013
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The recalcitrant nature of polyvinyl chloride creates serious environmental concerns during manufacturing and waste disposal. The present study was aimed to isolate and screen different soil fungi having potential to biodegrade PVC films. After 10 months of soil burial experiment, it was observed that a number of fungal strains were flourishing on PVC films. On morphological as well as on 18rRNA gene sequence and phylogenetic basis they were identified as Phanerochaete chrysosporium PV1, Lentinus tigrinus PV2, Aspergillus niger PV3, and Aspergillus sydowii PV4. The biodegradation ability of these fungal isolates was further checked in shake flask experiments by taking thin films of PVC (C source) in mineral salt medium. A significant change in color and surface deterioration of PVC films was confirmed through visual observation and Scanning electron microscopy. During shake flask experiments, P. chrysosporium PV1 produced maximum biomass of about 2.57?mg?ml(-1) followed by A. niger PV3. P. chrysosporium PV1 showed significant reduction (178,292?Da(-1) ) in Molecular weight of the PVC film than control (200,000?Da(-1) ) by gel permeation chromatography. Furthermore more Fourier transform infrared spectroscopy and nuclear magnetic resonance also revealed structural changes in the PVC. It was concluded that isolated fungal strains have significant potential for biodegradation of PVC plastics.
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Molecular events on tooth socket healing in diabetic rabbits.
Br J Oral Maxillofac Surg
PUBLISHED: 05-11-2013
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Healing of extraction sockets involves complex cellular events such as repair and regeneration of tissue. These events are precisely controlled and regulated by specific signalling molecules such as transforming growth factor beta (TGF-?), vascular endothelial growth factor (VEGF), bone morphogenetic protein (BMP), and insulin-like growth factor (IGF), which are well-conserved proteins involved in the initial response to injury and repair in soft and hard tissues. We studied 48 rabbits, which were divided into 3 groups of 16 each: the control group, the untreated diabetic group, and the insulin-treated diabetic group. The lower incisor of each rabbit was extracted and, after 2, 10, 20, and 30 days of healing, the expression of TGF?-3, VEGF, IGF-1R, and BMP-4 in the sockets was measured immunohistochemically. Rabbits with untreated diabetes expressed less TGF?-3 than the other groups throughout the healing periods, whereas IGF-1R expression was higher than that in the other groups. This increase in IGF-1R expression was responsible for increasing the healing time in rabbits in the untreated group. The healing of bone in diabetic rabbits that were not treated with insulin was prolonged because of a delay in the onset of cell proliferation and osteoblast differentiation, and the insulin treatment had a direct effect on the expression of TGF?-3 and IGF-1R, which accelerated healing of the socket.
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Synthesis of poly-(3-hydroxybutyrate-co-12 mol % 3-hydroxyvalerate) by Bacillus cereus FB11: its characterization and application as a drug carrier.
J Mater Sci Mater Med
PUBLISHED: 04-29-2013
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The synthesis of microbial polyhydroxyalkanoate is investigated in this work for it potential application as drug carrier for cancer therapy. The bacterial isolate Bacillus cereus FB11 has synthesized poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer under nutrient stress conditions using glucose as a sole carbon source. The FTIR spectrum of the purified copolymer showed the characteristic absorption bands at 1,719, 1,260 and 2,931 cm(-1) attributing to C=O, C-O stretching and C-H vibrations, respectively. The result of (1)H-NMR confirmed that it was composed of 88 mol % of 3-hydroxybutyrate and 12 mol % of 3-hydroxyvalerate monomeric subunits. The nanoparticles were fabricated from copolymer and used as a carrier for anticancer drug ellipticine. The in vitro drug release studies showed that % inhibition of A549 cancer cell line receiving ellipticine loaded poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles was two-fold higher in comparison to ellipticine alone. This drug delivery system offers exciting possibilities for cancer therapy by increasing the bioavailability of anti-neoplastic drug to the tumor site.
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P53 (Pro72Arg) polymorphism associated with the risk of oral squamous cell carcinoma in gutka, niswar and manpuri addicted patients of Pakistan.
Oral Oncol.
PUBLISHED: 04-08-2013
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The chewing habit of paan, chhaliya, and tobacco is common in the traditional culture of Pakistan. Currently, niswar, gutka and manpuri are also commercially available in the Pakistani market. Epidemiologic evidences and increased rate of oral squamous cell carcinoma (OSCC) cases may indicate a direct relationship of these chewing habits with oral carcinogenesis. The p53 gene has been known to be a tumor suppressor gene that is found mutated in common human cancers. The p53 gene contains a single nucleotide polymorphism at codon 72 of exon 4 which encodes either proline (Pro) or arginine (Arg). The aim of the present study was to investigate association of p53 gene codon 72 polymorphism with patients of oral squamous cell carcinoma consuming these carcinogenic chewable materials.
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In vitro bactericidal and TEM study of the interaction of Ag-modified titania with coliform bacteria.
Int J Environ Health Res
PUBLISHED: 04-05-2013
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This research aimed to investigate in vitro photocatalytic bactericidal effect of Ag-TiO2 nanocomposite using Escherichia coli as a model organism. Highly dispersed, Ag-TiO2 nanocomposite is used with an average particle size of less than 20 nm. Bactericidal analysis was carried out in Luria Bertani medium on solid agar plates with various illumination time and different concentrations of Ag-TiO2 nanocomposite. Transmission electron microscopic analysis of bacterial section was used to detect the effect of irradiation of Ag-TiO2 nanocomposite on the ultra structure of the bacterial cell in order to reveal possible cellular damage. The mechanism underlying the action of photoexcited Ag-TiO2 nanocomposite on E. coli cell membrane is also evaluated. The results confirmed that E. coli cells after the contact with Ag-TiO2 nanocomposite were damaged since they showed membrane disorganization. This causes the enhanced level of membrane permeability leading to the build-up of Ag-TiO2 nanocomposite in the bacterial membrane and also cellular internalization of these nanoparticles.
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Isolation and molecular characterization of potentially pathogenic Acanthamoeba genotypes from diverse water resources including household drinking water from Khyber Pakhtunkhwa, Pakistan.
Parasitol. Res.
PUBLISHED: 04-04-2013
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Acanthamoeba, an opportunistic protozoan pathogen, is ubiquitous in nature, and therefore plays a predatory role and helps control microbial communities in the ecosystem. These Acanthamoeba species are recognized as opportunistic human pathogens that may cause blinding keratitis and rare but fatal granulomatous encephalitis. To date, there is not a single report demonstrating Acanthamoeba isolation and identification from environmental sources in Pakistan, and that is the aim of this study. Acanthamoeba were identified by morphological characteristics of their cysts on non-nutrient agar plates seeded with Escherichia coli. Additionally, the polymerase chain reaction (PCR) was performed with genus-specific primers followed by direct sequencing of the PCR product for molecular identification. Furthermore, our PCR and sequencing results confirmed seven different pathogenic and nonpathogenic genotypes, including T2-T10, T4, T5, T7, T15, T16, and T17. To the best of our knowledge, we have identified and isolated Acanthamoeba sp., for the first time, from water resources of Khyber Pakhtunkhwa, Pakistan. There is an urgent need to address (1) the pathogenic potential of the identified genotypes and (2) explore other environmental sources from the country to examine the water quality and the current status of Acanthamoeba species in Pakistan, which may be a potential threat for public health across the country.
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Inhibitory effects of Olea ferruginea crude leaves extract against some bacterial and fungal pathogen.
Pak J Pharm Sci
PUBLISHED: 03-05-2013
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This work aimed to evaluate the inhibitory effects of Olea ferruginea crude leaves extract that are commonly used as remedy to cure infections in the tribal (Khyber Agency) areas of Pakistan against some of bacterial and fungal pathogens. The crude n-hexane fraction was appreciably active against both gram positive and negative microorganisms (MIC ranged from 7.5 to 15 mg/ml) followed by butanol fraction (MIC 15 to 30 mg/ml). Conversely least biological activity was shown by chloroform (30mg/ml) and methanol (15 to 30mg/ml) crude fractions. The MBC observed for all crude fractions was same or 2 times higher when compared with MIC for all crude extract fractions. Likewise all the fractions showed activity against Aspergillus niger and maximum zones of inhibition were shown by the n-hexane fraction (14 ± (0.02), butanol (13 ± (0.02) followed by methanol (9 ± (0.05) and chloroform fractions (7 ± (0.02). These results clearly imitate the antibacterial and antifungal potential of Olea ferruginea and hence we recommend the whole plant for further futuristic studies.
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Bacterial succession and degradative changes by biofilm on plastic medium for wastewater treatment.
J. Basic Microbiol.
PUBLISHED: 02-28-2013
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Biofilms contain a diverse range of microorganisms and their varying extracellular polysaccharides. The present study has revealed biofilm succession associated with degradative effects on plastic (polypropylene) and contaminants in sludge. The wet weight of biofilm significantly (p?80%) and in chemical parameters (decrease in COD, BOD5 of 73.32 and 69.94%) representing diminution of organic pollutants. Energy dispersive X-ray spectroscopy (EDS) of plastic revealed carbon and oxygen contents, further surface analysis of plastic by scanning electron microscopy (SEM) revealed emergence of profound bacterial growth on the surface. Fourier transform infrared (FTIR) spectroscopy conforms its biotransformation under aerobic conditions after 8 weeks. New peaks developed at the region 1050 and 969?cm(-1) indicating C?O and C?C bond formation. Thus plastic with 6 weeks old aerobic biofilm (free of pathogens, max. weight, and OD, efficient COD & BOD removal ability) is suggested to be maintained in fixed biofilm reactors for wastewater treatment.
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No evidence for cardiac dysfunction in Kif6 mutant mice.
PLoS ONE
PUBLISHED: 01-23-2013
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A KIF6 variant in man has been reported to be associated with adverse cardiovascular outcomes after myocardial infarction. No clear biological or physiological data exist for Kif6. We sought to investigate the impact of a deleterious KIF6 mutation on cardiac function in mice. Kif6 mutant mice were generated and verified. Cardiac function was assessed by serial echocardiography at baseline, after ageing and after exercise. Lipid levels were also measured. No discernable adverse lipid or cardiac phenotype was detected in Kif6 mutant mice. These data suggest that dysfunction of Kif6 is linked to other more complex biological/biochemical parameters or is unlikely to be of material consequence in cardiac function.
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Yield, chemical composition and nutritional quality responses of carrot, radish and turnip to elevated atmospheric carbon dioxide.
J. Sci. Food Agric.
PUBLISHED: 01-08-2013
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Future concentration of carbon dioxide in the atmosphere is very important due to its apparent economic and environmental impact in terms of climate change. However, a compressive assessment of its effect on the nutritional and chemical characteristics of food crops has yet to be established. In the present study the impact of elevated atmospheric CO2 on the yield, chemical composition and nutritional quality of three root vegetables, carrot (Daucus carota L. cv. T-1-111), radish (Raphanus sativus L. cv. Mino) and turnip (Brassica rapa L. cv. Grabe) has been investigated.
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Monitoring of growth and physiological activities of biofilm during succession on polystyrene from activated sludge under aerobic and anaerobic conditions.
Environ Monit Assess
PUBLISHED: 01-02-2013
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The present research work monitored the successive biofilm development and its catabolic role in the degradation of polystyrene (PS). PS material was artificially colonized with biofilm by incubating it with activated sludge under aerobic and anaerobic conditions. Biofilm formation was monitored by gravimetric weight analysis, spectrophotometric absorbance technique, heterotrophic plate count, and scanning electron microscopy under aerobic and anaerobic conditions. The wet weight (1.59 and 1.17 g) and dry weight (0.41 and 0.08 g) of a biofilm showed a significant constant increase under aerobic and anaerobic conditions, respectively, from first till 9 weeks of incubation. Plate count of the selected bacteria (Escherichia coli, Salmonella typhimurium, Shigella dysenteriae, Pseudomonas aeruginosa) considerably declined (90-99 %) in the biofilm after seventh and fifth weeks of incubation under aerobic and anaerobic conditions, respectively, indicating a positive shift from pathogenic to beneficial microbial community. While most probable number index of fecal coliforms and E. coli in the sludge showed more reduction (98 and 99 %) under aerobic as compare to anaerobic conditions (86 and 91 %) after 9 weeks of biofilm formation on PS cubes. Correspondingly, the decreasing levels of chemical oxygen demand and biochemical oxygen demand (up to 73 %) showed signs of sludge digestion. Scanning electron microscope coupled with energy dispersive X-ray spectroscope revealed nature of PS media containing high carbon content. However, biofilm development proved to be involved in the biochemical transformation of the PS medium as indicated by Fourier transform infrared spectroscopy.
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Combined efficacy of biologically synthesized silver nanoparticles and different antibiotics against multidrug-resistant bacteria.
Int J Nanomedicine
PUBLISHED: 01-01-2013
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Biological synthesis of nanoparticles is a growing innovative approach that is relatively cheaper and more environmentally friendly than current physicochemical processes. Among various microorganisms, fungi have been found to be comparatively more efficient in the synthesis of nanomaterials. In this research work, extracellular mycosynthesis of silver nanoparticles (AgNPs) was probed by reacting the precursor salt of silver nitrate (AgNO3) with culture filtrate of Aspergillus flavus. Initially, the mycosynthesis was regularly monitored by ultraviolet-visible spectroscopy, which showed AgNP peaks of around 400-470 nm. X-ray diffraction spectra revealed peaks of different intensities with respect to angle of diffractions (2?) corresponding to varying configurations of AgNPs. Transmission electron micrographs further confirmed the formation of AgNPs in size ranging from 5-30 nm. Combined and individual antibacterial activities of the five conventional antibiotics and AgNPs were investigated against eight different multidrug-resistant bacterial species using the Kirby-Bauer disk-diffusion method. The decreasing order of antibacterial activity (zone of inhibition in mm) of antibiotics, AgNPs, and their conjugates against bacterial group (average) was; ciprofloxacin + AgNPs (23) . imipenem + AgNPs (21) > gentamycin + AgNPs (19) > vancomycin + AgNPs (16) > AgNPs (15) . imipenem (14) > trimethoprim + AgNPs (14) > ciprofloxacin (13) > gentamycin (11) > vancomycin (4) > trimethoprim (0). Overall, the synergistic effect of antibiotics and nanoparticles resulted in a 0.2-7.0 (average, 2.8) fold-area increase in antibacterial activity, which clearly revealed that nanoparticles can be effectively used in combination with antibiotics in order to improve their efficacy against various pathogenic microbes.
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Predictors of depression in patients presenting with dyspeptic symptoms in a GI clinic.
J Ayub Med Coll Abbottabad
PUBLISHED: 10-01-2011
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The association between dyspepsia, H. pylori and psychological distress has remained a topic of intense debate over the past several decades. In Pakistan, where depression is highly prevalent and dyspepsia is possibly present in a high percentage of population, little data exist about these common health problems. This study was conducted to determine the frequency and predictors of depression among patients presenting with dyspeptic symptoms in the Gastrointestinal (GI) Clinic of a tertiary care hospital in Pakistan.
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Facile one-pot synthesis of gold nanoparticles and their sensing protocol.
Chem. Commun. (Camb.)
PUBLISHED: 09-30-2011
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This communication reports facile one pot synthesis of amoxicillin and sodium salt of amoxicillin stabilized gold nanoparticles (Au-NPs). Primarily the cyclic thioether linkage i.e. the thiozolidine ring of amoxicillin is utilized for sequestering Au(III). Fluorescence quenching of these clusters makes it an efficient protocol for sensing Cu(2+) at nano scale levels.
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Prevalence of class A and AmpC ?-lactamases in clinical Escherichia coli isolates from Pakistan Institute of Medical Science, Islamabad, Pakistan.
Jpn. J. Infect. Dis.
PUBLISHED: 05-28-2011
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In this study, 121 Escherichia coli samples isolated from clinical specimens obtained from Pakistan Institute of Medical Science, Islamabad, Pakistan, were analyzed for extended-spectrum ?-lactamases (ESBLs) and AmpC ?-lactamases using disk-diffusion assay and polymerase chain reaction. Of the isolates, 78 and 43 were identified as ESBL and AmpC producers, respectively. The highest resistance (89%) was observed against cefotaxime, followed by ciprofloxacin (87.6%) and cefepime (87%). Genetic analysis showed the presence of different class A and class C ?-lactamase genes, either alone (44.7%) or in combination (53.6%). CTX-M (57.7%) was the most prevalent among class A, followed by TEM (20.3%) and SHV (15.4%). CIT (including LAT-1 to LAT-4, CMY-2 to CMY-7, and BIL-1) and MOX (including MOX-1, MOX-2, CMY-1, and CMY-8 to CMY-11) family-specific plasmid-mediated AmpC ?-lactamases were the most prevalent among these isolates. Our study showed that both class A and class C ?-lactamases contributed to cephalosporin resistance in the E. coli isolates, thereby limiting therapeutic options. Co-expression of these enzymes may further hinder the identification of ESBLs, which is a critical step for designing a successful treatment for multidrug-resistant E. coli.
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Molecular analysis of lipoid proteinosis: identification of a novel nonsense mutation in the ECM1 gene in a Pakistani family.
Diagn Pathol
PUBLISHED: 05-17-2011
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Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood that is caused by homozygous or compound heterozygous mutations in the ECM1 gene located on chromosome 1q21. The aim of the study was to investigate the molecular genetic defect underlying lipoid proteinosis in a consanguineous Pakistani family.
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The effect of pregnancy and childbirth on pelvic floor muscle function.
Int Urogynecol J
PUBLISHED: 05-02-2011
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The effect of pregnancy and mode of delivery on pelvic floor muscle function (PFMF) is unclear. Our aim was to prospectively evaluate the effect of pregnancy and childbirth on PFMF.
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Understanding, perceptions and self-use of complementary and alternative medicine (CAM) among Malaysian pharmacy students.
BMC Complement Altern Med
PUBLISHED: 04-14-2011
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In recent times the basic understanding, perceptions and CAM use among undergraduate health sciences students have become a topic of interest. This study was aimed to investigate the understanding, perceptions and self-use of CAM among pharmacy students in Malaysia.
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H7 avian influenza virus vaccines protect chickens against challenge with antigenically diverse isolates.
Vaccine
PUBLISHED: 04-12-2011
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Vaccination has been a critical tool in the control of some avian influenza viruses (AIV) and has been used routinely in Pakistan to help control sporadic outbreaks of highly pathogenic (HP) H7 AIV since 1995. During that time, several AIV isolates were utilized as inactivated vaccines with varying degrees of success. In order to evaluate which H7 AIV strains may serve as optimal vaccines for diverse H7 AIVs from Pakistan we conducted vaccination-challenge studies with five H7 vaccines against challenge with two HPAIVs: A/chicken/Murree/NARC-1/1995 H7N3 and A/chicken/Karachi/SPVC-4/2004 H7N3. To further characterize the isolates antigenic cartography was used to visually demonstrate the antigenic relationships among the isolates. All vaccines provided similar protection against mortality, morbidity and shedding of challenge virus from the respiratory tract. However, some minor (not statistically significant) differences were observed and correlated with antibody levels induced by the vaccine prior to challenge.
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Total sleep deprivation study in delayed sleep-phase syndrome.
Indian J Med Sci
PUBLISHED: 04-01-2011
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Delayed sleep-phase syndrome (DSPS) is characterized by delayed sleep onset against the desired clock time. It often presents with symptoms of sleep-onset insomnia or difficulty in awakening at the desired time. We report the finding of sleep studies after 24 h total sleep deprivation (TSD) in a 28-year-old DSPS male patient. He had characteristics of mild chronic DSPS, which may have been precipitated by his frequent night shift assignments. The TSD improved the patients sleep latency and efficiency but all other sleep variables showed marked differences.
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Synthesis and DPPH radical scavenging activity of 5-arylidene-N,N-dimethylbarbiturates.
Med Chem
PUBLISHED: 03-22-2011
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Twenty-four derivatives of N,N-dimethylbarbituric acid 1-24 were screened for their DPPH radical scavenging activity. These compounds showed an excellent antioxidant activity. A structure-activity relationship has been discussed, while all the synthetic compounds were characterized by spectroscopic techniques and elemental analysis.
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Paigen diet-fed apolipoprotein E knockout mice develop severe pulmonary hypertension in an interleukin-1-dependent manner.
Am. J. Pathol.
PUBLISHED: 02-23-2011
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Inflammatory mechanisms are proposed to play a significant role in the pathogenesis of pulmonary arterial hypertension (PAH). Previous studies have described PAH in fat-fed apolipoprotein E knockout (ApoE(-/-)) mice. We have reported that signaling in interleukin-1-receptor-knockout (IL-1R1(-/-)) mice leads to a reduction in diet-induced systemic atherosclerosis. We subsequently hypothesized that double-null (ApoE(-/-)/IL-1R1(-/-)) mice would show a reduced PAH phenotype compared with that of ApoE(-/-) mice. Male IL-1R1(-/-), ApoE(-/-), and ApoE(-/-)/IL-1R1(-/-) mice were fed regular chow or a high-fat diet (Paigen diet) for 8 weeks before phenotyping for PAH. No abnormal phenotype was observed in the IL-1R1(-/-) mice. Fat-fed ApoE(-/-) mice developed significantly increased right ventricular systolic pressure and substantial pulmonary vascular remodeling. Surprisingly, ApoE(-/-)/IL-1R1(-/-) mice showed an even more severe PAH phenotype. Further molecular investigation revealed the expression of a putative, alternatively primed IL-1R1 transcript expressed within the lungs but not aorta of ApoE(-/-)/IL-1R1(-/-) mice. Treatment of ApoE(-/-) and ApoE(-/-)/IL-1R1(-/-) mice with IL-1-receptor antagonist prevented progression of the PAH phenotype in both strains. Blocking IL-1 signaling may have beneficial effects in treating PAH, and alternative IL-1-receptor signaling in the lung may be important in driving PAH pathogenesis.
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A mechanistic approach for islet amyloid polypeptide aggregation to develop anti-amyloidogenic agents for type-2 diabetes.
Biochimie
PUBLISHED: 01-05-2011
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Type-2 diabetes mellitus (DM-2) is a conformational disease involving intrinsically disordered islet amyloid polypeptide (IAPP), in which a structural transition from physiological polypeptide to pathological deposits takes place. Different factors acquired or inherited, contribute to endoplasmic reticulum stress and/or impair mitochondrial function which leads to conformational changes in IAPP intermediates and ultimately produces oligomers of an anti-parallel crossed ?-pleated sheets that eventually accumulate as space-occupying lesions within the islets. Clusters of IAPP monomers form a pore which is linked to channel-like behavior in planar bilayers, indicating that these oligomeric IAPP pores could become incorporated into membranes and alter its barrier properties. Identification of nucleating residues and the residues responsible for this oligomeric tendency could improve understanding of structure-function relationships as well as the molecular mechanism of folding and aggregation of IAPP contributing to the onset of DM-2. A combination of biological, chemical or physical approaches is required to be extensively pursued for the development of a successful anti-amyloidogenic agent to prevent this malady. Exploring the hypothesis of ?-stacking may be a better option to control IAPP aggregation if researchers go through the mechanism of ?-? interaction, which provides entropy driven energy and direction for self-assembly to control amyloidogenic aggregation.
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Molecular basis of the selectivity of the immunoproteasome catalytic subunit LMP2-specific inhibitor revealed by molecular modeling and dynamics simulations.
J Phys Chem B
PUBLISHED: 09-04-2010
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Given that immunoproteasome inhibitors are currently being developed for a variety of potent therapeutic purposes, the unique specificity of an ?,?-epoxyketone peptide (UK101) toward the LMP2 subunit of the immunoproteasome (analogous to ?5 subunit of the constitutive proteasome) has been investigated in this study for the first time by employing homology modeling, molecular docking, molecular dynamics simulation, and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations. On the basis of the simulated binding structures, the calculated binding free energies are in qualitative agreement with the corresponding experimental data, and the selectivity of UK101 is explained reasonably. The observed selectivity of UK101 for the LMP2 subunit is rationalized by the requirement for both a linear hydrocarbon chain at the N terminus and a bulky group at the C terminus of the inhibitor, because the LMP2 subunit has a much more favorable hydrophobic pocket interacting with the linear hydrocarbon chain, and the bulky group at the C terminus has a steric clash with the Tyr 169 in ?5 subunit. Finally, our results help to clarify why UK101 is specific to the LMP2 subunit of immunoproteasome, and this investigation should be valuable for rational design of more potent LMP2-specific inhibitors.
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Sero-epidemiological study of visceral leishmaniasis in Basrah, Southern Iraq.
J Pak Med Assoc
PUBLISHED: 06-10-2010
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To study selected epidemiological aspects of visceral leishmaniasis, assess direct agglutination test (DAT) as a diagnostic method and the sero-epidemiological prevalence of the disease among apparently healthy children in Basrah, Iraq.
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Outcome and prognostic factors of uterine sarcoma in 59 patients: single institutional results.
J Egypt Natl Canc Inst
PUBLISHED: 06-01-2010
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Uterine corpus sarcomas are rare heterogeneous tumors characterized by rapid progression and poor response to treatment. This series investigated treatment options, relapse pattern, survival and prognostic factors.
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Role of brown-rot fungi in the bioremoval of azo dyes under different conditions.
Braz. J. Microbiol.
PUBLISHED: 04-26-2010
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The present study is vital to the understanding of bioremediation of structurally different azo dyes by some unusual Brown-rot fungi. Bioremoval of each dye (20 mg l(-1)) was tested in two different culture media under static and shaking conditions by taking inocula from different fungi. Fungal strains showed varying dyes removal abilities, though considerable high in case of Acid Red (AR) 151(di-azo) as compared to Orange (Or) II (mono-azo). With an exception of Aspergillus tereus SA3, all the fungal isolates showed higher removal of dyes in SDB. Under static condition, the maximum decolorizing fungal strains were; Aspergillus flavus SA2 (67%) and Alternaria spp. SA4 (57%) in AR 151, while Penicillium spp. (34 and 33 %) in Orange II, in SDB and STE, respectively. Bioremoval of dyes was considerably increased when experiments were shifted from static to shaking mode. It was specifically increased (%) in; AR 151 (255) with Penicillium spp., Or II with A. flavus SA2 (112) and Alternaria spp. (111). The primary mechanism of dyes removal proved to be fungal biosorption. However, reduction of dyes (onto fungal) with formation of their products (?. naphthol, sulphalinic acid and aniline) furthermore revealed that dyes (specifically azo) were actually biodegraded.
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Sequence and phylogenetic analysis of H7N3 avian influenza viruses isolated from poultry in Pakistan 1995-2004.
Virol. J.
PUBLISHED: 04-02-2010
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Avian influenza virus (AIV) infections have caused heavy economic losses to the poultry industry in Pakistan as well as numerous other regions worldwide. The first introduction of H7N3 AIV to Pakistan occurred during 1995, since then H7N3, H9N2 and H5N1 AIVs have each been sporadically isolated. This report evaluates the genetic origin of the H7N3 viruses from Pakistan collected 1995-2004 and how they disseminated within the country. To accomplish this we produced whole genome sequences for 6 H7N3 viruses and data for the HA and NA genes of an additional 7 isolates. All available sequence from H7N3 AIV from Pakistan was included in the analysis.
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Ethambutol resistance of indigenous Mycobacterium tuberculosis isolated from human patients.
Braz. J. Microbiol.
PUBLISHED: 03-03-2010
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The present study was conducted to find out the ethambutol resistance pattern of indigenous isolates of Mycobacterium tuberculosis from Tuberculosis diagnosed human patients. A total of 172 specimens were collected from six different sources and comprised of 84.9% sputum, 10.5% pus and 4.7% bronchial washings. There were 70.9% males and 29.1% females with 84.30% pulmonary and 15.69% extra-pulmonary tuberculosis. The Mycobacterium tuberculosis isolates collected from primary culture were further studied to determine their pattern and level of resistance. The inoculums were prepared using 0.5 Mac Farland turbidity standards. Five different concentration of ethambutol were used in Lowenstein Jensen (LJ) medium i.e. 2µg/ml, 4µg/ml, 6µg/ml, 8µg/ml and 10µg/ml for sensitivity testing. Data showed 10 (5.8%) resistant and 162 (94.2%) sensitive Mycobacterium tuberculosis out of total 172 clinical isolates. The growth was not inhibited at 1(st) (2µg/ml) and 2(nd) (4µg/ml) drug levels, while growth of 50% isolates inhibited at 3(rd) level (6µg/ml), 30% inhibited at 4(th) level (8µg/ml) and 20% at 5(th) level (10µg/ml). The last three levels are above the therapeutic index and not recommended in actual clinical practice. It is thus conceivable to explore some other more effective chemotherapeutic agents, modify combinations or find more effective procedures to stop morbidity and mortality due to ethambutol resistant Mycobacterium tuberculosis.
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Management of hypospadias cripples with two-staged Brackas technique.
J Plast Reconstr Aesthet Surg
PUBLISHED: 02-16-2010
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Patients labelled as hypospadias cripples pose a challenge to reconstructive surgeons because of the complexity of the problem and limited options for reconstruction. The two-staged Bracka method is a versatile technique that is relatively easy to learn and applicable in difficult cases of salvage hypospadias. Over a period of 8 years, we applied this technique to 100 patients with hypospadias cripples who had previously undergone multiple (3-16) procedures. In the first stage, a full-thickness graft of skin or buccal mucosa was used for urethral plate reconstruction after release of chordee. Stage II was carried out at least 6 months after the first procedure. Meatal opening at the tip of the glans was achieved in 94 patients, straightening of the penis in 96 and proper urinary stream in 92 patients. Fistula formation occurred in nine patients. In our opinion, the two-staged Bracka technique is a useful strategy to deal with the myriad abnormalities encountered in crippled hypospadias. This technique not only creates a neourethra successfully, but also gives the penis a near-normal shape and appearance.
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Bacteriocinogenic potential of newly isolated strains of Enterococcus faecium and Enterococcus faecalis from dairy products of Pakistan.
J. Microbiol. Biotechnol.
PUBLISHED: 02-06-2010
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Present study was carried for the isolation of bacteriocin producing Enterococci from indigenous sources. Gram positive enterococci are known for having the ability to produce enterocins with good antimicrobial potential. A total of 34 strains were isolated from processed dairy products of Pakistan and seven out of them were found to be member of genus enterococci on selective enumeration. Biochemical and molecular characterization revealed that four of these isolates (IJ-03, IJ-07, IJ-11 and IJ-12) were Enterococcus faecalis while three (IJ-06, IJ-21 and IJ-31) were Enterococcus faecium. Local processed cheese was the source of all enterococcal isolates, except E. faecium IJ-21 and IJ-31 which were isolated from indigenous yoghurt and butter samples respectively. Bacterial isolates were sensitive to commonly used antibiotics except methicillin and kanamycin. They also lack critical virulence determinants mainly cytolysin (cyl), gelatinase (gel), enterococcal surface protein (esp) and vancomycin resistance (vanA and vanB). Polymerase chain reaction amplification identified that enterocin A and P genes were present in the genome of E. faecium IJ-06 and IJ-21 while E. faecium IJ-31 genome showed only enterocin P genes. No amplification was observed for genes that corresponded with the enterocins 31, AS-48, L50A, L50B and ent 1071A and 1071 B. Also there were no signals of amplification found for E. faecalis IJ-11 indicating that the antimicrobial activity was because of an enterocin different from those checked by PCR. So the indigenous bacterial isolates have great potential for bacteriocin production and they had antibacterial activity against a variety of closely related species.
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Production, characterization, and antimicrobial activity of a bacteriocin from newly isolated Enterococcus faecium IJ-31.
J. Food Prot.
PUBLISHED: 01-07-2010
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This work aimed to isolate and characterize Enterococcus spp. from indigenous dairy products in Islamabad, Pakistan. By classical microbiological techniques, one strain from a butter sample was identified to be Enterococcus faecium, and we designated it E. faecium IJ-31. The precise identity of this strain was then established by determining the sequence of its 16S and 23S rRNA genes. The sequence homology searches revealed matches with a number of previously reported strains, such as E. faecium HN-N3 and HN-N29, both isolated from swine intestines in China. The newly isolated strain was tested for hemolysis and antibiotic sensitivity; it was nonhemolytic on sheep and human blood and sensitive to vancomycin. Consistent with its vancomycin sensitivity, repeated attempts to amplify the vancomycin resistance genes vanA and vanB failed. Similar attempts to amplify the virulence genes gelE, agg, and cyl also failed, suggesting the absence of these genes. In contrast, the enterocin-P gene, entP, readily amplified with primers based on the previously reported sequences, and the deduced sequence showed near identity with a number of reported sequences from E. faecium. Further, the 71-residue enterocin-P sequence from strain IJ-31 is only the second complete sequence reported. The enterocin was partially purified and tested for antibacterial activity. It showed potent inhibitory activity against many bacteria, including Listeria monocytogenes, a routinely used test strain. Further, the enterocin showed potent activity against Bacillus subtilis and Bacillus cereus. The enterocin retained antibacterial activity even following heating to 121 degrees Celsius for 15 min. Further, it also retained activity after exposure to pH values ranging from 4 to 10. However, proteinase K treatment rendered the peptide nonfunctional.
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Physicochemical characterization and Bioremediation perspective of textile effluent, dyes and metals by indigenous Bacteria.
J. Hazard. Mater.
PUBLISHED: 07-25-2009
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Physicochemical and bacteriological status of a local textile mill effluent showed considerably high values of temperature (40 degrees C), pH (9.50), EC (3.57mus/m), BOD (548mgl(-1)), COD (1632mgl(-1)), TSS (5496mgl(-1)), TDS (2512mgl(-1)), heavy metals ions (0.28-6.36mgl(-1)) and color above the prescribed fresh water limits. However, a considerable decline in almost all pollution indicators from source to sink indicated signs of natural remediation. Ten bacteria strains isolated from effluent showed comparatively higher resistance (MRL) (mgl(-1)) (average) for 10 heavy metals than against four structurally different dyes tested on solid media of mineral salt. Overall bacterial resistance was quite high against Fe(3+) (2820), Cr(3+) (1203), Zn(2+) (1122), Mn(2+) (804) and Pb(2+) (435), whereas, it varied amid 300-500 in four dyes. Bacterial decolorization/degradation of dyes indicated on solid media was confirmed through experiments carried out in liquid broth.
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Report: antibiotic production by thermophilic Bacillus specie SAT-4.
Pak J Pharm Sci
PUBLISHED: 06-26-2009
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Production of antimicrobial compounds seems to be a general phenomenon for most bacteria. The prevalence of antimicrobial resistance among key microbial pathogens is increasing at an alarming rate worldwide. Current solutions involve development of a more rationale approach to antibiotic use and discover of new antimicrobials. Bacillus species produce a large number of biological compounds active against bacteria, fungi, protozoa and viruses. The process of production usually involves screening of wide range of microorganisms, testing and modification. Production is carried out using fermentation. Thermophilic spore-forming, gram positive, motile rod bacterial strains were isolated from the Thar Desserts, Sindh Province, Pakistan. These strains were screened and checked for antibacterial activity. The best activity was observed by SAT4 against Micrococcus luteus, Staphylococcus aureus and Pseudomonas aeroginosa. The activity was only observed against gram positive bacteria and no activity was seen against Pseudomonas aeroginosa. Thermophilic Bacillus specie SAT4 was found to be active in the fermentation process to produce the antimicrobial agents. Further optimizations of different conditions (time of incubation, media, pH, glucose concentrations, nitrogen concentrations, and temperature) for antimicrobial production by the selected bacterial strain was performed. Agar diffusion assay was performed to evaluate the antibacterial activity. Optimum conditions for the production of antimicrobials by selected isolate were observed to be 48 hour, pH 5, temperature 55 degrees C, 2% glucose and 1.5% nitrogen concentration. This newly isolated bacterial strain has great potential for antimicrobial production at industrial scale.
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Photocatalytic decolourization of dyes on NiO-ZnO nano-composites.
Photochem. Photobiol. Sci.
PUBLISHED: 03-12-2009
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NiO-ZnO nanocomposite photocatalysts were synthesized by co-precipitation/co-gel formation techniques using potassium hydroxide (KOH), sodium carbonate (Na(2)CO(3)) and oxalic acid (H(2)C(2)O(4)) as precipitating agents. X-Ray diffraction (XRD) analysis was employed for the determination of crystallite size and phase purity, while BET surface areas were estimated by nitrogen physisorption analysis. The photocatalytic activities of the NiO-ZnO nanocomposites, evaluated using the photo-decolourization of two structurally different dyes, methyl orange and methylene blue, were correlated with the variation in the crystallite size of the constituents of the composites. All the three synthesized nanocomposites showed appreciable activity for the decolourization of dyes. NiO-ZnO nanocomposite derived by KOH exhibited maximum activity for the decolourization of both the dyes and the decolourization rate of methylene blue was found to be comparable with that of Degussa P-25 TiO(2). Finally, the activity of the most active NiO-ZnO composite with relatively large crystallite sizes was compared with the pure components and their physical mixture, synthesized by the identical synthetic route, in the same molar ratio as that of nanocomposite.
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Endoscopic removal of retained T- tube fragment.
BMJ Case Rep
PUBLISHED: 03-05-2009
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T-tube usage is common following common bile duct exploration for calculi and other complex biliary surgeries to ensure proper biliary diversion and healing. A 25-year-old woman was referred from a surgical unit with a history of open cholecystectomy and common bile duct exploration for cholelithiasis and choledocholithiasis with T-tube placement in the common bile duct for postoperative biliary diversion. While retrieving the T-tube, it got fractured and the fragment remained in the bile duct. We report a rare case of retained T-tube fragment after T-tube removal that was retrieved endoscopically.
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Methods for detection and characterization of lipases: A comprehensive review.
Biotechnol. Adv.
PUBLISHED: 03-04-2009
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Microbial lipases are very prominent biocatalysts because of their ability to catalyze a wide variety of reactions in aqueous and non-aqueous media. The chemo-, regio- and enantio-specific behaviour of these enzymes has caused tremendous interest among scientists and industrialists. Lipases from a large number of bacterial, fungal and a few plant and animal sources have been purified to homogeneity. This article presents a critical review of different strategies which have been employed for the detection, purification and characterization of microbial lipases.
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Antibacterial activities of Dodonaea viscosa using contact bioautography technique.
Molecules
PUBLISHED: 02-18-2009
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The crude ethanolic extract and n-hexane, dichloromethane, ethyl acetate, n-butanol and aqueous fractions of Dodonaea viscosa were analyzed for antibacterial potential against four Gram positive bacteria: Bacillus subtilis, Bacillus cereus, Micrococcus luteus, Staphylococcus aureus, and three Gram negative bacteria: Escherichia coli, Salmonella typhi, Pseudomonas aeruginosa. Preliminary screening showed inhibition against Staphylococcus aureus, Micrococcus luteus, Escherichia coli and Pseudomonas aeruginosa. The thin layer chromatograms of the fractions were then subjected to contact bioautography, which showed inhibition zone at different R(f) values against Bacillus subtilis, Micrococcus luteus, Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa, indicating the presence of antibacterial components. The MIC of each fraction was determined through a 96-well micro-titer plate method. The non-viability of the organisms was ascertained by determining the MBC of the fractions.
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Production of peptide antibiotics by Bacillus sp. GU 057 indigenously isolated from saline soil.
Braz. J. Microbiol.
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A total of 112 soil samples were taken from differents areas of district D.I.Khan and Kohat (KPK) Pakistan and screened for production of antibiotics against the Micrococcus luteus and Staphylococcus aureus. Widest zone of inhibition (18mm) was produced by microorganism isolated from saline soil. The strain was later identified as Bacillus GU057 by standard biochemical assays. Maximum activity (18mm inhibition zone) was observed against Staphylococcus aureus after 48 hours of incubation at pH 8 and 4% concentration of glucose. The antibiotic was identified by autobiography as bacitracin. The Bacillus strain GU057 was confirmed as good peptide antibiotic producer and can effectively be indulged as biocontrol agent.
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Encapsulation of Ellipticine in poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) based nanoparticles and its in vitro application.
Mater Sci Eng C Mater Biol Appl
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Biodegradable, biocompatible, renewable and non-toxic polyhydroxyalkanoates (PHAs) based nanoparticles are the novel nanotherapeutic tool which are used for the encapsulation of antineoplastic drugs for cancer therapy. In this study, poly-3-hydroxybutyrate-co-5 mol% 3-hydroxyvalerate (PHBV-S), poly-3-hydroxybutyrate-co-11 mol% 3-hydroxyvalerate (PHBV-11) and poly-3-hydroxybutyrate-co-15 mol% 3-hydroxyvalerate (PHBV-15) were used as a nanocarrier for encapsulation of Ellipticine (EPT). EPT is a model anticancer drug. Physicochemical characteristics such as particle size, its morphology and zeta potential of blank and EPT loaded PHBV-S, PHBV-11 and PHBV-15 nanoparticles were studied. In vitro cytotoxicity tests confirmed that the blank PHBV-S, PHBV-11 and PHBV-15 nanoparticles were demonstrating significant biocompatibility without affecting the survival of cancer cell line A549. The loading efficiency of EPT in PHBV nanoparticles was observed in the range of 39.32 to 45.65%. The % inhibition of cancer cell line A549 ranged from 64.28 to 67.77% in comparison to EPT alone in which % inhibition found to be ?45.11%. The IC50 value for each of three different formulations of EPT loaded PHBV nanoparticles ranged from 1.00 to 1.31 ?g/mL. The order of % inhibition of cancer cell line A549 for drug loaded nanoparticles was EPT-PHBV-15>EPT-PHBV-S>EPT-PHBV-11. This system had demonstrated a great potential to increase the cytotoxic effect of EPT by increasing its bioavailability.
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Reliability of 1-repetition maximum estimation for upper and lower body muscular strength measurement in untrained middle aged type 2 diabetic patients.
Asian J Sports Med
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The 1-repetition maximum (1-RM) test is the gold standard test for evaluating maximal dynamic strength of groups of muscles. However, safety of actual 1-RM testing is questionable in clinical situations such as type 2 diabetes (T2D), where an estimated 1-RM test is preferred. It is unclear if acceptable test retest reliability exists for the estimated 1-RM test in middle aged T2D patients. This study examined the reliability of the estimated 1-RM strength test in untrained middle aged T2D subjects.
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