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Find video protocols related to scientific articles indexed in Pubmed.
Lack of association between UBE2E2 gene polymorphism (rs7612463) and type 2 diabetes mellitus in a Saudi population.
Acta Biochim. Pol.
PUBLISHED: 10-23-2014
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The ubiquitin-conjugating enzyme E2E 2 (UBE2E2) gene plays an important role in insulin synthe-sis and secretion under conditions in which stress to the endoplasmic reticu-lum is increased in ?-cells. In this case-control study, we have selected rs7612462 polymorphism within UBE2E2 gene to identify in a Saudi population the type 2 diabetes mellitus (T2DM) subjects. In total, 376 subjects with T2DM and 380 controls were enrolled in this study. We have collected 5 mL of peripheral blood from each participant for biochemical and molecular analyses. PCR-RFLP was used to generate genotypes at rs7612462 in all of the study subjects. Clinical data and anthropometric measurements of the patients were significantly different from those of the controls (p < 0.05). All of the subjects used in this study were non-obese (25 < BMI < 30). None of the alleles or genotypes of rs7612462 were associated with T2DM (OR=1.251, 95% CI=0.7703-2.034; p=0.3641). Our data suggest that rs7612462 polymorphism in UBE2E2 does not contribute to T2DM susceptibility in the Saudi population.
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Nature of immobilization surface affects antibody specificity to placental alkaline phosphatase.
J Immunoassay Immunochem
PUBLISHED: 10-17-2014
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Abstract Retention of native conformation of immobilized protein is essential for various applications including selection and detection of specific recombinant antibodies (scFvs). Placental alkaline phosphatase (PAP), an onco-fetal antigen expressed on the surface of several tumors, was immobilized on supermagnetic particles for selection of recombinant antibodies from a human phage display antibody library. The isolated antibodies were found to be cross-reactive to either of the isozymes of alkaline phosphatase i.e. bone alkaline phosphatase (BAP) or intestinal alkaline phosphatase (IAP) and could not be used for tumor targeting. A specific anti-PAP monoclonal antibody H17E2 was tested for retention of specificity under these conditions. Binding of the antibody to magnetic beads conjugated IAP and BAP along with PAP and the ability of the two isozymes to inhibit its binding to PAP depicted the loss of isozyme specificity of the antibody. However, the antibody retained its specificity to PAP immobilized on polyvinyl chloride (PVC) surface. Enzyme activity was observed on both surfaces. This demonstrates that nature of immobilization may affect antigen-antibody binding in subtle ways, resulting in alteration of conformation of the epitopes. This may have consequences for determining the specificity of antibody binding for proteins that share a high degree of homology.
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Tobacco abuse amongst the school going students of 15 to 18 years of almora district, uttarakhand: a cross sectional study.
Oral Health Dent Manag
PUBLISHED: 10-07-2014
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The present study was done to assess the prevalence of tobacco abuse among school going students of the age group 15 to 18 year old in the rural areas of Almora district, Uttrakhand state, India.
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Susac's syndrome: the value of fundus fluorescein angiography.
BMJ Case Rep
PUBLISHED: 10-05-2014
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A 19-year-old woman presented with a 4-week history of headache, ataxia, vertigo, confusion, intermittent blurred vision in the right eye and intermittent hearing loss. MRI revealed white matter lesions and 'pepper pot' lesions of the corpus callosum. The cerebrospinal fluid had raised protein and lymphocytes. Fundal examination revealed multiple peripheral arterial occlusions in the both eyes confirmed with fundus fluorescein angiography (FFA). A diagnosis of Susac's syndrome was made. The patient was initially treated with steroids, followed by azathioprine and intravenous immunoglobulins (IVIg). Clinical improvement was noted, associated with improvement of the retinal circulation on FFA.
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Typhoid Fever surveillance and vaccine use - South-East Asia and Western Pacific regions, 2009-2013.
MMWR Morb. Mortal. Wkly. Rep.
PUBLISHED: 10-03-2014
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Typhoid fever is a serious, systemic infection resulting in nearly 22 million cases and 216,500 deaths annually, primarily in Asia. Safe water, adequate sanitation, appropriate personal and food hygiene, and vaccination are the most effective strategies for prevention and control. In 2008, the World Health Organization (WHO) recommended use of available typhoid vaccines to control endemic disease and outbreaks and strengthening of typhoid surveillance to improve disease estimates and identify high-risk populations (e.g., persons without access to potable water and adequate sanitation). This report summarizes the status of typhoid surveillance and vaccination programs in the WHO South-East Asia (SEAR) and Western Pacific regions (WPR) during 2009-2013, after the revised WHO recommendations. Data were obtained from the WHO/United Nations Children's Fund (UNICEF) Joint Reporting Form on Immunization, a supplemental survey of surveillance and immunization program managers, and published literature. During 2009-2013, 23 (48%) of 48 countries and areas of SEAR (11) and WPR (37) collected surveillance or notifiable disease data on typhoid cases, with most surveillance activities established before 2008. Nine (19%) countries reported implementation of typhoid vaccination programs or recommended vaccine use during 2009-2013. Despite the high incidence, typhoid surveillance is weak in these two regions, and vaccination efforts have been limited. Further progress toward typhoid fever prevention and control in SEAR and WPR will require country commitment and international support for enhanced surveillance, targeted use of existing vaccines and availability of newer vaccines integrated within routine immunization programs, and integration of vaccination with safe water, sanitation, and hygiene measures.
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Molecular docking studies and in vitro cholinesterase enzyme inhibitory activities of chemical constituents of Garcinia hombroniana.
Nat. Prod. Res.
PUBLISHED: 09-15-2014
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Garcinia species are reported to possess antimicrobial, anti-inflammatory, anticancer, anti-HIV and anti-Alzheimer's activities. This study aimed to investigate the in vitro cholinesterase enzyme inhibitory activities of garcihombronane C (1), garcihombronane F (2), garcihombronane I (3), garcihombronane N (4), friedelin (5), clerosterol (6), spinasterol glucoside (7) and 3?-hydroxy lup-12,20(29)-diene (8) isolated from Garcinia hombroniana, and to perform molecular docking simulation to get insight into the binding interactions of the ligands and enzymes. The cholinesterase inhibitory activities were evaluated using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. In this study, compound 4 displayed the highest concentration-dependent inhibition of both AChE and BChE. Docking studies exhibited that compound 4 binds through hydrogen bonds to amino acid residues of AChE and BChE. The calculated docking and binding energies also supported the in vitro inhibitory profiles of IC50. In conclusion, garcihombronanes C, F, I and N (1-4) exhibited dual and moderate inhibitory activities against AChE and BChE.
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The insertion and deletion (I28005D) polymorphism of the angiotensin I converting enzyme gene is a risk factor for osteoarthritis in an Asian Indian population.
J Renin Angiotensin Aldosterone Syst
PUBLISHED: 09-01-2014
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Angiotensin I converting enzyme (ACE) insertion and deletion (I/D) polymorphism has been implicated in the pathogenesis of osteoarthritis (OA). In recent years, numerous genetic factors have been identified and implicated in OA. In this Asian Indian population-based study, we aimed to evaluate the relationship between ACE (I28005D) gene polymorphism and primary OA. We performed a case-control association study to identify and explore the correlation between clinically, radiologically diagnosed individuals with primary knee OA and the ACE I/D polymorphism.
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Prevalence of glucose-6-phosphate dehydrogenase deficiency and the role of the A- variant in a Saudi population.
J. Int. Med. Res.
PUBLISHED: 08-28-2014
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To estimate the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among Saudi men, and to establish the frequency of the two mutations/polymorphisms associated with the G6PD A- mutation--G to A at nucleotide 202 (G202A) and A to G at nucleotide 376 (A376G)--in those found to have G6PD deficiency.
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Effect of the cation on the interactions between alkyl methyl imidazolium chloride ionic liquids and water.
J Phys Chem B
PUBLISHED: 08-21-2014
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A systematic study of the interactions between water and alkyl methyl imidazolium chloride ionic liquids at 298.2 K, based on activity coefficients estimated from water activity measurements in the entire solubility range, is presented. The results show that the activity coefficients of water in the studied ILs are controlled by the hydrophilicity of the cation and the cation-anion interaction. To achieve a deeper understanding on the interactions between water and the ILs, COSMO-RS and FTIR spectroscopy were also applied. COSMO-RS was used to predict the activity coefficient of water in the studied ionic liquids along with the excess enthalpies, suggesting the formation of complexes between three molecules of water and one IL molecule. On the basis of quantum-chemical calculations, it is found that cation-anion interaction plays an important role upon the ability of the IL anion to interact with water. The changes in the peak positions/band areas of OH vibrational modes of water as a function of IL concentration were investigated, and the impact of the cation on the hydrogen-bonding network of water is identified and discussed.
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Renal allograft transplant recipient with ruptured hydatid native kidney.
Urol Ann
PUBLISHED: 08-16-2014
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Echinococcosis of the kidneys in a renal transplant recipient is extremely rare and its occurrence being related to immunosuppression is a possibility which needs further characterisation. Ruptured renal hydatid in a renal transplant recipient is not reported so far to our best knowledge. We present a 42-year-old renal allograft receipient who presented one year after transplant with left flank pain, palpable left lumbar mass and gross hydatiduria. Investigations revealed a ruptured native hydatid kidney. Patient was managed with a combination of chemotherapy and left native nephrectomy and discharged in a satisfactory condition.
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Acute effect of sorghum flour-containing pasta on plasma total polyphenols, antioxidant capacity and oxidative stress markers in healthy subjects: A randomised controlled trial.
Clin Nutr
PUBLISHED: 08-14-2014
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It has been previously reported that pasta containing wholegrain sorghum flour exhibits high content of polyphenols and antioxidant capacity and hence might enhance antioxidant status and reduce markers of oxidative stress in vivo; however no clinical studies have yet been reported. Therefore, the present study assessed the effect of pasta containing red or white wholegrain sorghum flour on plasma total polyphenols, antioxidant capacity and oxidative stress markers in humans. The study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN: 12612000324819).
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Association of a polymorphism in the BIRC6 gene with pseudoexfoliative glaucoma.
PLoS ONE
PUBLISHED: 08-13-2014
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Recently an association was observed between alleles in genes of the unfolded protein response pathway and primary open angle glaucoma (POAG). The goal of the current study is to investigate the role of these two genes, protein disulphide isomerase A member 5 (PDIA5) and baculoviral IAP repeat containing 6 (BIRC6), in different forms of glaucoma. 278 patients with POAG, 132 patients with primary angle closure glaucoma (PACG) and 135 patients with pseudoexfoliative glaucoma (PEXG) were genotyped for single nucleotide polymorphisms (SNPs) rs11720822 in PDIA5 and 471 POAG, 184 PACG and 218 PEXG patients were genotyped for rs2754511 in BIRC6. Genotyping was done by allelic discrimination PCR, and genotype and allele frequencies were calculated. Logistic regression analyses were performed using R software to determine the association of these SNPs with glaucoma. The allele and genotype frequencies of rs11720822 in PDIA5 were not associated with POAG, PACG or PEXG. The TT genotype of rs2754511 in BIRC6 was found to be protective for PEXG (p = 0.05, OR 0.42 [0.22-0.81]) in the Pakistani population, but not for POAG or PACG. This study did not confirm a previously reported association of risk alleles in PDIA5 and BIRC6 with POAG, but did demonstrate a protective role of the T allele of rs2754511 in the BIRC6 gene in PEXG. This supports a role for the unfolded protein response pathway and regulation of apoptotic cell death in the pathogenesis of PEXG.
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Combination of hepatocyte specific delivery and transformation dependent expression of shRNA inducing transcriptional gene silencing of c-Myc promoter in hepatocellular carcinoma cells.
BMC Cancer
PUBLISHED: 08-10-2014
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A specific targeting modality for hepatocellular carcinoma (HCC) could ideally encompass a liver cell specific delivery system of a transcriptional unit that is active only in neoplastic cells. Sendai virosomes, derived from Sendai viral envelopes, home to hepatocytes based on the liver specific expression of asialoglycoprotein receptors (ASGPRs) which are recognized by the Sendai virosomal fusion (F) proteins. As reported earlier by us and other groups, transcriptional gene silencing (TGS) does not require continuous presence of the effector siRNA/shRNA molecule and is heritable, involving epigenetic modifications, leading to long term transcriptional repression. This could be advantageous over conventional gene therapy approaches, since continuous c-Myc inactivation is required to suppress hepatocarcinoma cells.
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Antibacterial activity of honey in north-west Pakistan against select human pathogens.
J Tradit Chin Med
PUBLISHED: 08-09-2014
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To investigate the antimicrobial activity of commercially available honey and raw honey samples in Khyber Pakhtunkhwa, Pakistan, against pathogenic bacterial strains.
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Simultaneous quantification of eight bioactive secondary metabolites from Codonopsis ovata by validated high performance thin layer chromatography and their antioxidant profile.
J Pharm Biomed Anal
PUBLISHED: 08-07-2014
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Chemical investigation of Codonopsis ovata resulted in the isolation and identification of ?-sitosterol-3-O-glycoside, luteolin, apigenin, gentiacaulein, swertiaperenine, ?-sitosterol, taraxeryl-3-acetate, and 3?-acetoxyoleanane-12-one. A rapid, precise, sensitive and validated HPTLC method for simultaneous quantification of these natural products (NPs) was developed on silica-gel 60F254 plate using ternary solvent system, n-hexane:ethyl acetate:formic acid (10.5:3.5:0.43, v/v/v). Markers were quantified after post chromatographic derivatization with cerric ammonium sulfate reagent. The method was validated for accuracy, precision, LOD, LOQ and all calibration curves showed a good linear relationship (r>0.9924) within test range. Precision was evaluated by intra- and inter-day tests with RSDs <2.59%, accuracy validation recovery 92.43-99.50% with RSDs <1.00%. Apigenin was found major component (natural abundance: 1.103%) and ?-sitosterol the least (0.0263%). The NPs displayed antioxidant activity with luteolin exhibiting maximum effect at 1?g/mL concentration (75.9% for DPPH and 43.7% for ABTS) and others at 10 and 25?g/mL, suggesting thereby their apparent potential use for the prevention of free radical induced diseases or as an additive element to food and pharmaceutical industry.
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Typhoid fever in Fiji: a reversible plague?
Trop. Med. Int. Health
PUBLISHED: 07-25-2014
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The country of Fiji, with a population of approximately 870 000 people, faces a growing burden of several communicable diseases including the bacterial infection typhoid fever. Surveillance data suggest that typhoid has become increasingly common in rural areas of Fiji and is more frequent amongst young adults. Transmission of the organisms that cause typhoid is facilitated by faecal contamination of food or water and may be influenced by local behavioural practices in Fiji. The Fijian Ministry of Health, with support from Australian Aid, hosted a meeting in August 2012 to develop comprehensive control and prevention strategies for typhoid fever in Fiji. International and local specialists were invited to share relevant data and discuss typhoid control options. The resultant recommendations focused on generating a clearer sense of the epidemiology of typhoid in Fiji and exploring the contribution of potential transmission pathways. Additionally, the panel suggested steps such as ensuring that recommended ciprofloxacin doses are appropriate to reduce the potential for relapse and reinfection in clinical cases, encouraging proper hand hygiene of food and drink handlers, working with water and sanitation agencies to review current sanitation practices and considering a vaccination policy targeting epidemiologically relevant populations.
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Epiglottic hypoplasia: a natural model for supraglottic laryngoplasty.
J Coll Physicians Surg Pak
PUBLISHED: 07-24-2014
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Non-syndromic hypoplasia of the epiglottis presenting without symptoms at middle age is an extremely rare entity. We report a 50 years female who presented with oral ulcers and incidentally was found to have an asymptomatic rudimentary epiglottis and thickened bilateral aryepiglottic folds forming an inverted funnel shaped supraglottis protecting the airway from any aspiration. This case demonstrated a functional model of natural supraglottic laryngoplasty which can be used in treating intractable aspiration, similar to the Steam boat modification of Biller's technique of supraglottic laryngoplasty. This natural example can be used to design or scrutinize the existing models of supraglottic laryngoplasty in the treatment of intractable aspiration.
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An energy efficient simultaneous-node repositioning algorithm for mobile sensor networks.
ScientificWorldJournal
PUBLISHED: 07-23-2014
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Recently, wireless sensor network (WSN) applications have seen an increase in interest. In search and rescue, battlefield reconnaissance, and some other such applications, so that a survey of the area of interest can be made collectively, a set of mobile nodes is deployed. Keeping the network nodes connected is vital for WSNs to be effective. The provision of connectivity can be made at the time of startup and can be maintained by carefully coordinating the nodes when they move. However, if a node suddenly fails, the network could be partitioned to cause communication problems. Recently, several methods that use the relocation of nodes for connectivity restoration have been proposed. However, these methods have the tendency to not consider the potential coverage loss in some locations. This paper addresses the concerns of both connectivity and coverage in an integrated way so that this gap can be filled. A novel algorithm for simultaneous-node repositioning is introduced. In this approach, each neighbour of the failed node, one by one, moves in for a certain amount of time to take the place of the failed node, after which it returns to its original location in the network. The effectiveness of this algorithm has been verified by the simulation results.
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Competent statistical programmer: Need of business process outsourcing industry.
Perspect Clin Res
PUBLISHED: 07-03-2014
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Over the last two decades Business Process Outsourcing (BPO) has evolved as much mature practice. India is looked as preferred destination for pharmaceutical outsourcing over a cost arbitrage. Among the biometrics outsourcing, statistical programming and analysis required very niche skill for service delivery. The demand and supply ratios are imbalance due to high churn out rate and less supply of competent programmer. Industry is moving from task delivery to ownership and accountability. The paradigm shift from an outsourcing to consulting is triggering the need for competent statistical programmer. Programmers should be trained in technical, analytical, problem solving, decision making and soft skill as the expectations from the customer are changing from task delivery to accountability of the project. This paper will highlight the common issue SAS programming service industry is facing and skills the programmers need to develop to cope up with these changes.
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Association of apolipoprotein E polymorphism with type 2 diabetes mellitus in a Saudi population.
DNA Cell Biol.
PUBLISHED: 06-30-2014
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Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disorder characterized by persistent hyperglycemia. It is considered to be a major risk factor for obesity and cardiovascular diseases. The cause of T2DM is likely due to a complex interaction between genetic and environmental factors. Apolipoprotein E (ApoE) gene plays a key role in lipid metabolism. The aim of this contemporary study was to investigate the ApoE polymorphism in a Saudi population with T2DM subjects. Two common single-nucleotide polymorphisms, that is, rs429358 and rs7412, in the ApoE gene were genotyped by TaqMan assay in T2DM patients (n=438) and controls (n=460). The results of the present study indicate that ApoE polymorphism was significantly associated with T2DM in a Saudi population with the ?2 and ?4 alleles (p=0.0001). We found statistically significant difference in the genotype distribution between T2DM patients and controls [for E4/E4: OR, 4.39 (95% CI: 2.16-8.92); p=0.0001]. A significant difference was observed in the lipid profile parameters, like triglycerides, low-density lipoprotein, and ApoE alleles (p=0.0001). Further studies are carried out in a Saudi population with different diseases to confirm the risk allele. In conclusion, our study results suggest that ApoE variants constitute risk markers of T2DM in a Saudi population.
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Polycythemia, increased erythropoietin levels in a patient with renal lymphoma.
Adv Biomed Res
PUBLISHED: 06-26-2014
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A young male presented to our clinic with 3 months history of shortness of breathness and progressive distension of abdomen. On investigations, patient had renal failure, polycythemia and nephromegaly. A diagnosis of non-Hodgkin's lymphoma was made on renal and lymph node biopsy. Serum erythropoietin concentrations were physiologically inappropriate. - Erythropoietin immunohistochemistry on renal tissue samples demonstrated positive staining for tumor cells. This patient was managed as a case of infiltrative lymphoproliferative disorder with kidney involvement having polycythemia owing to paraneoplastic Erythropoietin production and possibly local hypoxia produced by tumor cells. With maximum efforts, we could not find such an association in the literature.
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Anti-pruritic activity of pioglitazone on serotonin-induced scratching in mice: Possible involvement of PPAR-gamma receptor and nitric oxide.
Eur. J. Pharmacol.
PUBLISHED: 06-01-2014
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Pioglitazone is a member of peroxisome proliferator-activated receptor gamma (PPAR?) agonists, particularly used in management of type II diabetes. However it also has effects in some dermatological disorders. The current study was designed to investigate the effects of oral administration of pioglitazone and the association of nitric oxide, in serotonin-induced scratching in mice. In order to produce the scratching activity, serotonin (141nm/site) was administered intradermally in the nape of the neck. Pioglitazone in concentrations of 10, 20, 40 and 80mg/kg, was peroral administered (p.o) as a single dose, four h before the serotonin injection. PPAR-? antagonist, GW9662 (2mg/kg, i.p); a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-l-arginine methyl ester (L-NAME; 1mg/kg, i.p); or a nitric oxide precursor, L-arginine (100mg/kg, i.p.); adminstrated 15min before pioglitazone, were analyzed for anti-scratching activity. Results obtained showed that pioglitazone (40 and 80mg/kg, p.o) reduced the scratching in a dose-dependent manner. GW9662 inverted the anti-scratching effect of pioglitazone (80mg/kg). Acute dose of L-NAME (1mg/kg,i.p) also prevented the anti-scratching property of pioglitazone (80mg/kg, p.o); Although L-arginine, was used in sub-effective dose (100mg/kg,i.p), however it potentiated the anti-scratching behaviour when co-injected with pioglitazone (20mg/kg, p.o). The results indicate that, acute pioglitazone has anti-scratching effect on serotonin-induced scratching in mice. It is concluded that anti-scratching outcome of acute pioglitazone is initiated via activation of PPAR-? receptor and to some extent by the NO pathway.
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Effect of sorghum flour addition on in vitro starch digestibility, cooking quality, and consumer acceptability of durum wheat pasta.
J. Food Sci.
PUBLISHED: 05-19-2014
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Whole grain sorghum is a valuable source of resistant starch and polyphenolic antioxidants and its addition into staple food like pasta may reduce the starch digestibility. However, incorporating nondurum wheat materials into pasta provides a challenge in terms of maintaining cooking quality and consumer acceptability. Pasta was prepared from 100% durum wheat semolina (DWS) as control or by replacing DWS with either wholegrain red sorghum flour (RSF) or white sorghum flour (WSF) each at 20%, 30%, and 40% incorporation levels, following a laboratory-scale procedure. Pasta samples were evaluated for proximate composition, in vitro starch digestibility, cooking quality, and consumer acceptability. The addition of both RSF and WSF lowered the extent of in vitro starch digestion at all substitution levels compared to the control pasta. The rapidly digestible starch was lowered in all the sorghum-containing pastas compared to the control pasta. Neither RSF or WSF addition affected the pasta quality attributes (water absorption, swelling index, dry matter, adhesiveness, cohesiveness, and springiness), except color and hardness which were negatively affected. Consumer sensory results indicated that pasta samples containing 20% and 30% RSF or WSF had acceptable palatability based on meeting one or both of the preset acceptability criteria. It is concluded that the addition of wholegrain sorghum flour to pasta at 30% incorporation level is possible to reduce starch digestibility, while maintaining adequate cooking quality and consumer acceptability.
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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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YB-1 expression promotes epithelial-to-mesenchymal transition in prostate cancer that is inhibited by a small molecule fisetin.
Oncotarget
PUBLISHED: 04-29-2014
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Epithelial-to-mesenchymal transition (EMT) plays an important role in prostate cancer (PCa) metastasis. The transcription/translation regulatory Y-box binding protein-1 (YB-1) is known to be associated with cancer metastasis. We observed that YB-1 expression increased with tumor grade and showed an inverse relationship with E-cadherin in a human PCa tissue array. Forced YB-1 expression induced a mesenchymal morphology that was associated with down regulation of epithelial markers. Silencing of YB-1 reversed mesenchymal features and decreased cell proliferation, migration and invasion in PCa cells. YB-1 is activated directly via Akt mediated phosphorylation at Ser102 within the cold shock domain (CSD). We next identified fisetin as an inhibitor of YB-1 activation. Computational docking and molecular dynamics suggested that fisetin binds on the residues from ?1 - ?4 strands of CSD, hindering Akt's interaction with YB-1. Calculated free binding energy ranged from -11.9845 to -9.6273 kcal/mol. Plasmon Surface Resonance studies showed that fisetin binds to YB-1 with an affinity of approximately 35 µM, with both slow association and dissociation. Fisetin also inhibited EGF induced YB-1 phosphorylation and markers of EMT both in vitro and in vivo. Collectively our data suggest that YB-1 induces EMT in PCa and identify fisetin as an inhibitor of its activation.
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Relationship of beam angulation and radiation exposure in the cardiac catheterization laboratory.
JACC Cardiovasc Interv
PUBLISHED: 04-16-2014
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The aim of this study was to analyze the relationship between beam angulation and air kerma in a modern cardiac catheterization laboratory.
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A missense mutation in the splicing factor gene DHX38 is associated with early-onset retinitis pigmentosa with macular coloboma.
J. Med. Genet.
PUBLISHED: 04-15-2014
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Retinitis pigmentosa (RP) is the most frequent inherited retinal disease, which shows a relatively high incidence of the autosomal-recessive form in Pakistan.
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A54T polymorphism in the fatty acid binding protein 2 studies in a Saudi population with type 2 diabetes mellitus.
Lipids Health Dis
PUBLISHED: 03-15-2014
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Fatty acid-binding protein 2 (FABP2) is an intracellular protein expressed exclusively in the enterocytes of proximal small intestine. FABP2 has a high affinity for saturated and unsaturated long-chain fatty acids and is believed to be involved in the absorption and transport of dietary fatty acids.
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EGFRIndb: epidermal growth factor receptor inhibitor database.
Anticancer Agents Med Chem
PUBLISHED: 03-15-2014
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Aberrant activity of epidermal growth factor receptor (EGFR) family proteins has been found to be associated with a number of human cancers including that of lung and breast. Consequently, the search for EGFR family inhibitors, a well established target of pharmacological and therapeutic value has been ongoing. Therefore, over the years several small molecules, which compete for ATP in the kinase domain have been synthesised and some of them have proved to be effective in attenuating EGFR mediated proliferation. Thus, there exists in literature a vast amount of experimental data on EGFR tyrosine kinase inhibitors. In this paper, we describe a comprehensive database EGFRIndb that contains details of the small molecular inhibitors of EGFR family.
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Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and mTOR: findings from 3-D melanoma skin equivalents and computational modeling.
Biochem. Pharmacol.
PUBLISHED: 03-12-2014
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The incidence of melanoma continues to rise. Inspite of treatment advances, the prognosis remains grim once the disease has metastasized, emphasizing the need to explore additional therapeutic strategies. One such approach is through the use of mechanism-based dietary intervention. We previously showed that the flavonoid fisetin inhibits melanoma cell proliferation, in vitro and in vivo. Here, we studied fisetin-mediated regulation of kinases involved in melanoma growth and progression. Time-course analysis in 3-D melanoma constructs that transitioned from radial to vertical growth showed that fisetin treatment resulted in significant decrease in melanocytic lesions in contrast to untreated controls that showed large tumor nests and invading disseminated cells. Further studies in melanoma cultures and mouse xenografts showed that fisetin-mediated growth inhibition was associated with dephosphorylation of AKT, mTOR and p70S6K proteins. In silico modeling indicated direct interaction of fisetin with mTOR and p70S6K with favorable free energy values. These findings were validated by cell-free competition assays that established binding of fisetin to p70S6K and mTOR while little affinity was detected with AKT. Kinase activity studies reflected similar trend with % inhibition observed for p70S6K and mTOR at lower doses than AKT. Our studies characterized, for the first time, the differential interactions of any botanical agent with kinases involved in melanoma growth and demonstrate that fisetin inhibits mTOR and p70S6K through direct binding while the observed inhibitory effect of fisetin on AKT is mediated indirectly, through targeting interrelated pathways.
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Iron(III) catecholates for cellular imaging and photocytotoxicity in red light.
Chem Asian J
PUBLISHED: 03-10-2014
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Iron(III) complexes [Fe(L)(L')(NO3)]--in which L is phenyl-N,N-bis[(pyridin-2-yl)methyl]methanamine (1), (anthracen-9-yl)-N,N-bis[(pyridin-2-yl)methyl]methanamine (2), (pyreny-1-yl)-N,N-bis[(pyridin-2-yl)methyl]methanamine (3-5), and L' is catecholate (1-3), 4-tert-butyl catecholate (4), and 4-(2-aminoethyl)-benzene-1,2-diolate (5)--were synthesized and their photocytotoxic properties examined. The five electron-paramagnetic complexes displayed a Fe(III)/Fe(II) redox couple near -0.4?V versus a saturated calomel electrode (SCE) in DMF/0.1?M tetrabutylammonium perchlorate (TBAP). They showed unprecedented photocytotoxicity in red light (600-720?nm) to give IC50?15??M in various cell lines by means of apoptosis to generate reactive oxygen species. They were ingested in the nucleus of HeLa and HaCaT cells in 4?h, thereby interacting favorably with calf thymus (ct)-DNA and photocleaving pUC19 DNA in red light of 785?nm to form hydroxyl radicals.
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Immune responses to Vi capsular polysaccharide typhoid vaccine in children 2 to 16 years old in Karachi, Pakistan, and Kolkata, India.
Clin. Vaccine Immunol.
PUBLISHED: 03-05-2014
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The geometric mean concentration (GMC) and the proportion maintaining a protective level (150 enzyme-linked immunosorbent assay (ELISA) units [ELU]/ml) 2 years following a single dose of 25 ?g of injectable Vi capsular polysaccharide typhoid vaccine was measured against that of the control hepatitis A vaccine in children 2 to 16 years old in cluster randomized trials in Karachi and Kolkata. The GMC for the Vi group (1,428 ELU/ml) was statistically significantly different from the GMC of the control hepatitis A vaccine group (86 ELU/ml) after 6 weeks. A total of 117 children (95.1%) in the Vi group and 9 (7.5%) in the hepatitis A group showed a 4-fold rise in Vi IgG antibody concentrations at 6 weeks (P < 0.01). Protective antibody levels remained significantly different between the two groups at 2 years (38% in the Vi vaccine groups and 6% in the hepatitis A group [P < 0.01]). A very small proportion of younger children (2 to 5 years old) maintained protective Vi IgG antibody levels at 2 years, a result that was not statistically significantly different compared to that for the hepatitis A group (38.1% versus 10.5%). The GMCs of the Vi IgG antibody after 2 years were 133 ELU/ml for children 2 to <5 years old and 349 ELU/ml for children 5 to 16 years old. In conclusion, Vi capsular polysaccharide typhoid vaccine is immunogenic in children in settings of South Asia where typhoid is highly endemic. The antibody levels in children who received this vaccine remained higher than those in children who received the control vaccine but were significantly reduced at 2 years of follow-up.
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Primary cardiac synovial sarcoma.
Asian Cardiovasc Thorac Ann
PUBLISHED: 03-04-2014
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Approximately 10% of soft tissue sarcomas are synovial sarcomas, and 90% of these occur in the extremities. Among the primary tumors in the heart, 25% are malignant. Primary synovial sarcoma of the heart is an extremely rare entity. A myriad of investigations such as histopathology, immunohistochemistry, electron microscopy, and molecular genetic techniques are required for confirmation of the diagnosis. The tumor is nearly always lethal, but surgical resection with chemotherapy may prolong the life of the patient. We describe the case of a young patient with a primary synovial sarcoma arising from the right ventricle.
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Application of Ethnobotanical Indices on the Use of Traditional Medicines against Common Diseases.
Evid Based Complement Alternat Med
PUBLISHED: 02-22-2014
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The present study was aimed at documenting the detailed ethnomedicinal knowledge of an unexplored area of Pakistan. Semistructured interviews were taken with 55 informants randomly chosen regarding detailed ethnomedicinal and sociocultural information. The study exposed 67 medicinal plant species used to prepare 110 recipes and the major modes of herbal formulation were decoction and powdering (20% each). The disease categories with the highest Fic values were gastrointestinal and dermatological (0.87 each). The study determined 3 plant species, i.e., Acacia modesta Wall., Caralluma tuberculata R.Br., and Withania somnifera (L.) Dunal with a FL of 100%. DMR results showed that Olea ferruginea (Sol.) Steud. ranked first, Morus alba L. ranked second, and Melia azedarach L. ranked third. Among the 55 informants, the male concentration was high (61%) and most of them were over 40 years old while a leading quantity of respondents (45%) was uneducated. There is a dire need to take necessary steps for the conservation of important medicinal plants by inhibiting overgrazing and providing alternate fuel resources. Young generations should be educated regarding the importance of ethnomedicinal knowledge and plants with high Fic and FL values should be further checked chemically and pharmacologically for future exploration of modern medicine.
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Relationship between the paraoxonase 1 gene glutamine 192 to arginine polymorphism and gestational diabetes mellitus in Saudi women.
Clin. Biochem.
PUBLISHED: 02-20-2014
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Gestational diabetes mellitus (GDM) is recognized as an imbalance between insulin resistance and insulin secretion, leading to maternal hyperglycemia. Previous studies in a Saudi population indicated a high frequency of Paraoxonase 1 glutamine 192 to arginine (PON1 Q192R) polymorphism, suggesting this polymorphism as an additional risk factor. The present study was designed to explore the possible association between the PON1 Q192R polymorphism and GDM in a Saudi population.
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Mammalian keratin associated proteins (KRTAPs) subgenomes: disentangling hair diversity and adaptation to terrestrial and aquatic environments.
BMC Genomics
PUBLISHED: 02-19-2014
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Adaptation of mammals to terrestrial life was facilitated by the unique vertebrate trait of body hair, which occurs in a range of morphological patterns. Keratin associated proteins (KRTAPs), the major structural hair shaft proteins, are largely responsible for hair variation.
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Probing the interactions between ionic liquids and water: experimental and quantum chemical approach.
J Phys Chem B
PUBLISHED: 02-07-2014
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For an adequate choice or design of ionic liquids, the knowledge of their interaction with other solutes and solvents is an essential feature for predicting the reactivity and selectivity of systems involving these compounds. In this work, the activity coefficient of water in several imidazolium-based ionic liquids with the common cation 1-butyl-3-methylimidazolium was measured at 298.2 K. To contribute to a deeper insight into the interaction between ionic liquids and water, COSMO-RS was used to predict the activity coefficient of water in the studied ionic liquids along with the excess enthalpies. The results showed good agreement between experimental and predicted activity coefficient of water in ionic liquids and that the interaction of water and ionic liquids was strongly influenced by the hydrogen bonding of the anion with water. Accordingly, the intensity of interaction of the anions with water can be ranked as the following: [CF3SO3](-) < [SCN](-) < [TFA](-) < Br(-) < [TOS](-) < Cl(-) < [CH3SO3](-) [DMP](-) < [Ac](-). In addition, fluorination and aromatization of anions are shown to reduce their interaction with water. The effect of temperature on the activity coefficient of water at infinite dilution was measured by inverse gas chromatography and predicted by COSMO-RS. Further analysis based on COSMO-RS provided information on the nature of hydrogen bonding between water and anion as well as the possibility of anion-water complex formation.
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Carbohydrate-appended tumor targeting iron(III) complexes showing photocytotoxicity in red light.
Inorg Chem
PUBLISHED: 01-27-2014
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Glucose-appended photocytotoxic iron(III) complexes of a tridentate Schiff base phenolate ligand [Fe(bpyag)(L)](NO3) (1-3), where bpyag is N,N-bis(2-pyridylmethyl)-2-aminoethyl-?-D-glucopyranoside and H2L is 3-(2-hydroxyphenylimino)-1-phenylbutan-1-one (H2phap) in 1, 3-(2-hydroxyphenylimino)-9-anthrylbutan-1-one (H2anap) in 2, and 3-(2-hydroxyphenylimino)-1-pyrenylbutan-1-one (H2pyap) in 3, were synthesized and characterized. The complex [Fe(dpma)(anap)](NO3) (4), having bis-(2-pyridylmethyl)benzylamine (dpma), in which the glucose moiety of bpyag is substituted by a phenyl group, was used as a control, and the complex [Fe(dpma)(anap)](PF6) (4a) was structurally characterized by X-ray crystallography. The structure shows a FeN4O2 core in a distorted octahedral geometry. The high-spin iron(III) complexes with magnetic moment value of ?5.9 ?B showed a low-energy phenolate-to-Fe(III) charge-transfer (CT) absorption band as a shoulder near 500 nm with a tail extending to 700 nm and an irreversible Fe(III)-Fe(II) redox couple near -0.6 V versus saturated calomel electrode. The complexes are avid binders to calf thymus DNA and showed photocleavage of supercoiled pUC19 DNA in red (647 nm) and green (532 nm) light. Complexes 2 and 3 displayed significant photocytotoxicity in red light, with an IC50 value of ?20 ?M in HeLa and HaCaT cells, and no significant toxicity in dark. The cell death is via an apoptotic pathway, by generation of reactive oxygen species. Preferential internalization of the carbohydrate-appended complexes 2 and 3 was evidenced in HeLa cells as compared to the control complex 4. A 5-fold increase in the cellular uptake was observed for the active complexes in HeLa cells. The photophysical properties of the complexes are rationalized from the density functional theory calculations.
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Molecular biology of K+ transport across the plant cell membrane: what do we learn from comparison between plant species?
J. Plant Physiol.
PUBLISHED: 01-26-2014
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Cloning and characterizations of plant K(+) transport systems aside from Arabidopsis have been increasing over the past decade, favored by the availability of more and more plant genome sequences. Information now available enables the comparison of some of these systems between species. In this review, we focus on three families of plant K(+) transport systems that are active at the plasma membrane: the Shaker K(+) channel family, comprised of voltage-gated channels that dominate the plasma membrane conductance to K(+) in most environmental conditions, and two families of transporters, the HAK/KUP/KT K(+) transporter family, which includes some high-affinity transporters, and the HKT K(+) and/or Na(+) transporter family, in which K(+)-permeable members seem to be present in monocots only. The three families are briefly described, giving insights into the structure of their members and on functional properties and their roles in Arabidopsis or rice. The structure of the three families is then compared between plant species through phylogenic analyses. Within clusters of ortologues/paralogues, similarities and differences in terms of expression pattern, functional properties and, when known, regulatory interacting partners, are highlighted. The question of the physiological significance of highlighted differences is also addressed.
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Comparison between short- and long-acting erythropoiesis-stimulating agents in hemodialysis patients: target hemoglobin, variability, and outcome.
Int Urol Nephrol
PUBLISHED: 01-22-2014
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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.
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The molecular basis of retinal dystrophies in pakistan.
Genes (Basel)
PUBLISHED: 01-21-2014
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The customary consanguineous nuptials in Pakistan underlie the frequent occurrence of autosomal recessive inherited disorders, including retinal dystrophy (RD). In many studies, homozygosity mapping has been shown to be successful in mapping susceptibility loci for autosomal recessive inherited disease. RDs are the most frequent cause of inherited blindness worldwide. To date there is no comprehensive genetic overview of different RDs in Pakistan. In this review, genetic data of syndromic and non-syndromic RD families from Pakistan has been collected. Out of the 132 genes known to be involved in non-syndromic RD, 35 different genes have been reported to be mutated in families of Pakistani origin. In the Pakistani RD families 90% of the mutations causing non-syndromic RD and all mutations causing syndromic forms of the disease have not been reported in other populations. Based on the current inventory of all Pakistani RD-associated gene defects, a cost-efficient allele-specific analysis of 11 RD-associated variants is proposed, which may capture up to 35% of the genetic causes of retinal dystrophy in Pakistan.
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Association of the genetic variants of insulin receptor substrate 1 (IRS-1) with type 2 diabetes mellitus in a Saudi population.
Endocrine
PUBLISHED: 01-13-2014
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Type 2 diabetes mellitus (T2DM) is a chronic degenerative disease, phenotypically and genetically heterogeneous, characterized by high levels of glucose and metabolic complications. Insulin receptor substrate 1 (IRS-1) plays a key role in the insulin-stimulated signal transduction pathway. A glycine-to-arginine substitution at codon 972 (G972R) (rs1801278) in the IRS-1 gene has been associated with impaired insulin action. Another SNP rs2943641 in the IRS-1 gene has been found to be associated with T2DM and insulin resistance in genome-wide association studies. The aim of the present study was to evaluate whether rs1801278 and rs2943641 are associated with increased risk of T2DM in the Saudi population. The study included 376 T2DM cases and 380 healthy controls. Genomic DNA was isolated using a commercially available kit supplied by Norgen Biotech Corp. Genotyping was performed by PCR and RFLP analysis. There was a significant difference in the genotypic distribution as well as allelic frequency between the T2DM cases and controls in case of both the polymorphisms for rs1801278 (1.752, 95 % CI 1.002-3.121; p = 0.04), and for rs2943641 (OR = 1.482, 95 % CI 1.176-1.867; p = 0.001). In conclusion, both the (rs1801278 and rs2943641) polymorphisms are associated with T2DM in the Saudi population.
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Excellent anti-proliferative and pro-apoptotic effects of (-)-epigallocatechin-3-gallate encapsulated in chitosan nanoparticles on human melanoma cell growth both in vitro and in vivo.
Nanomedicine
PUBLISHED: 01-10-2014
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Earlier we demonstrated the anti-proliferative and pro-apoptotic effects of green tea polyphenol epigallocatechin-3-gallate (EGCG) on human melanoma cells (Int J Cancer. 2005; 114(4): 513-21). The doses used in this study were not physiologically attainable and for chemoprevention the preferred route of administration is oral consumption. To overcome these shortcomings, and taking advantage of our novel concept of nanochemoprevention (Cancer Res. 2009;69(5):1712-6), we developed a nanotechnology based oral delivery system to encapsulate EGCG. Here, using human melanoma Mel 928 cells we demonstrate 8-fold dose advantage of this nanoformulation over native EGCG. Further, nano-EGCG treated cells showed marked induction of apoptosis and cell cycle inhibition along with the growth of Mel 928 tumor xenograft. Nano-EGCG also inhibited proliferation (Ki-67 and PCNA) and induced apoptosis (Bax, PARP) in tumors harvested from the treated mice. These observations warrant further in vivo efficacy studies of nano-EGCG in robust animal models of human melanoma.
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Insulin receptor substrate-1 (IRS-1) Gly927Arg: correlation with gestational diabetes mellitus in Saudi women.
Biomed Res Int
PUBLISHED: 01-10-2014
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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.
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Association of interleukin-6 polymorphisms with obesity and metabolic alterations in young Saudi population.
Mol. Biol. Rep.
PUBLISHED: 01-07-2014
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Rising levels of obesity are a global problem that is being exported from affluent to developing nations through the gradual "westernization of lifestyle". Population of Saudi Arabia is going through a nutrition transition where customary and traditional food is being replaced by fast food high in fat, sugar and salt. Interleukin-6 (IL-6) is a central player in the regulation of inflammation, haematopoiesis, immune response and host defense mechanisms. During the last decade, an accumulating amount of data suggested a pivotal role for IL-6 in metabolic processes, thus fortifying the picture of IL-6 as a multifaceted, pleiotropic cytokine. The Objective is to investigate the relationship between IL-6 (rs1554606) polymorphism and the risk of obesity in young Saudi population. Totally 204 Saudi young obese subjects were involved in this study. Genotyping of IL-6 was performed by the real-time polymerase chain reaction technology, using the Taq Man 5'-allele discrimination assay. IL-6 (rs1554606) AA versus AG (p < 0.01) and AA versus GG (p < 0.01) shows significant difference between Male and female group in genotypic as well as allelic distribution differ significantly, while AG versus GG did not differ significantly (p > 0.5). We have observed significant effects for Genotyping, LDL, CHOL, AST, ALP, BILIT, BMI at 5% (0.05) significance level in the study population. Our results shown that IL-6 polymorphism have significantly differ in both male and females subjects. We have observed that some evidence of interactions of the IL-6 polymorphism and have shown statistical significant association with elevated BMI, Lipid profile and total bilurubin in the study subjects.
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25 years after Vi typhoid vaccine efficacy study, typhoid affects significant number of population in Nepal.
PLoS ONE
PUBLISHED: 01-01-2014
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Salmonella Typhi, first isolated in 1884, results in infection of the intestines and can end in death and disability. Due to serious adverse events post vaccination, whole cell killed vaccines have been replaced with new generation vaccines. The efficacy of Vi polysaccharide (ViPS) vaccine, a new generation, single-dose intramuscular typhoid vaccine was assessed in Nepal in 1987. However, despite the availability of ViPS vaccine for more than 25 years, Nepal has one of the highest incidence of typhoid fever. Therefore we collected information from hospitals in the Kathmandu Valley from over the past five years. There were 9901 enteric fever cases between January 2008 and July 2012. 1,881 of these were confirmed typhoid cases from five hospitals in the Kathmandu district. Approximately 70% of the cases involved children under 15 years old. 1281 cases were confirmed as S. Paratyphi. Vaccines should be prioritized for control of typhoid in conjunction with improved water and sanitation conditions in Nepal and in endemic countries of Asia and Africa.
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ABCA1 C69T gene polymorphism and risk of type 2 diabetes mellitus in a Saudi population.
J. Biosci.
PUBLISHED: 12-04-2013
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Type 2 diabetes mellitus (T2DM) is a disease induced by complex interactions between environmental factors and certain genetic factors. Genetic variants in the Adenosine Binding Cassette Transporter Proteins 1 (ABCA1) have been associated with abnormalities of serum lipid levels of high-density lipoprotein (HDL-C). Decreased serum levels of HDL-C have often been observed in T2DM cases, and this condition has been considered to be involved in the mechanism of insulin resistance (IR). Therefore, we investigated possible association between ABCA1 C69T gene polymorphism and T2DMin a Saudi population. This study was carried out with 380 healthy control subjects and 376 T2DM patients. Genotyping of ABCA1 C69T polymorphism was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique. We observed that the frequency of the T allele of the ABCA1 C69T gene was significantly higher in healthy subjects compared to T2DMpatients (0.28 vs 0.45; p less than 0.0001; OR (95 percent CI) = 0.4624 (0.3732-0.5729), and therefore the T allele may be a protective factor against T2DM in the Saudi population.
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Intestinal cell proliferation and senescence is regulated by receptor guanylyl cyclase C and p21.
J. Biol. Chem.
PUBLISHED: 11-11-2013
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Guanylyl cyclase C (GC-C) is expressed in intestinal epithelial cells and serves as the receptor for bacterial heat-stable enterotoxin peptides (ST) and the guanylin family of gastrointestinal hormones. Activation of GC-C elevates intracellular cGMP, which modulates intestinal fluid-ion homeostasis and differentiation of enterocytes along the crypt-villus axis. GC-C activity can regulate colonic cell proliferation by inducing cell cycle arrest and mice lacking GC-C display increased cell proliferation in colonic crypts. Activation of GC-C by administration of ST to wild type, but not Gucy2c-/- mice, resulted in a reduction in carcinogen-induced aberrant crypt foci formation. In p53-deficient human colorectal carcinoma cells, ST led to a transcriptional up-regulation of p21, the cell cycle inhibitor, via activation of the cGMP responsive kinase PKGII and p38 MAPK. Prolonged treatment of human colonic carcinoma cells with ST led to nuclear accumulation of p21, resulting in cellular senescence and reduced tumorigenic potential. Therefore, our results identify downstream effectors for GC-C that contribute to regulating intestinal cell proliferation. Thus, genomic responses to a bacterial toxin can influence intestinal neoplasia and senescence.
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Association of angiotensin converting enzyme gene insertion/deletion polymorphism and familial hypercholesterolemia in the Saudi population.
Lipids Health Dis
PUBLISHED: 10-26-2013
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The study of the association between genotype and phenotype is of great importance for the prediction of multiple diseases and pathophysiological conditions. The relationship between angiotensin converting enzyme (ACE) Insertion/Deletion (I/D) polymorphism and Familial Hypercholesterolemia (FH) has been not fully investigated in all the ethnicities. In this study we sought to determine the frequency of I/D polymorphism genotypes of ACE gene in Saudi patients with FH.
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Molecular detection of Toxoplasma gondii in water sources of district Nowshehra, Khyber Pakhtunkhwa, Pakistan.
J. Toxicol. Environ. Health Part A
PUBLISHED: 09-24-2013
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Toxoplasmosis is spread through contamination of water sources and results in morbidity globally. In the current study 300 water samples were processed by polymerase chain reaction (PCR) for detection of Toxoplasma gondii. The overall prevalence in different water sources was 6.6% (17/300). Among different water sources the highest prevalence was recorded in drain water at 7% (7/100), followed by tube well water at 7.5% (3/40) and open well water at 5% (5/100) ,and the lowest was recorded in tap water at 3.33% (2/60). The highest prevalence was recorded in summer. Evidence indicates that cleaning and filtration need to be adopted to avoid the health hazards of waterborne zoonotic parasites.
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Differential, dominant activation and inhibition of Notch signalling and APP cleavage by truncations of PSEN1 in human disease.
Hum. Mol. Genet.
PUBLISHED: 09-18-2013
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PRESENILIN1 (PSEN1) is the major locus for mutations causing familial Alzheimers disease (FAD) and is also mutated in Pick disease of brain, familial acne inversa and dilated cardiomyopathy. It is a critical facilitator of Notch signalling and many other signalling pathways and protein cleavage events including production of the Amyloid? (A?) peptide from the AMYLOID BETA A4 PRECURSOR PROTEIN (APP). We previously reported that interference with splicing of transcripts of the zebrafish orthologue of PSEN1 creates dominant negative effects on Notch signalling. Here, we extend this work to show that various truncations of human PSEN1 (or zebrafish Psen1) protein have starkly differential effects on Notch signalling and cleavage of zebrafish Appa (a paralogue of human APP). Different truncations can suppress or stimulate Notch signalling but not Appa cleavage and vice versa. The G183V mutation possibly causing Pick disease causes production of aberrant transcripts truncating the open reading frame after exon 5 sequence. We show that the truncated protein potentially translated from these transcripts avidly incorporates into very stable Psen1-dependent higher molecular weight complexes and suppresses cleavage of Appa but not Notch signalling. In contrast, the truncated protein potentially produced by the P242LfsX11 acne inversa mutation has no effect on Appa cleavage but, unexpectedly, enhances Notch signalling. Our results suggest novel hypotheses for the pathological mechanisms underlying these diseases and illustrate the importance of investigating the function of dominant mutations at physiologically relevant expression levels and in the normally heterozygous state in which they cause human disease rather than in isolation from healthy alleles.
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In vitro antioxidant activities of four medicinal plants on the basis of DPPH free radical scavenging.
Pak J Pharm Sci
PUBLISHED: 09-17-2013
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The present research investigation was aimed at the evaluation of antioxidant activities of methanolic (70%) extracts of whole plant of Pentanema vestitum and fruits of Pistacia integerrima, Withiana somniferra and Withiana coagulans on scavenging of 2, 2-diphenyl-2-picrylhydrazyl (DPPH) free radical. The rank of order of free antioxidant activity of the selected plants was; P. integerrima > P. vestitum > W. somniferra > W. coagulans as compared to standard Ascorbic acid. P. integerrima showed significantly higher activity at all concentrations as compared to Ascorbic acid at P<0.05. The percent inhibition caused by P. integerrima at lowest concentration (40 ppm) was 68.16±0.5 and that of Ascorbic acid was 62.00±0.5. The IC50 value of P. integerrima was 5.75ppm as compared to ascorbic acid having 15.09 ppm. The percent inhibition at all concentrations caused by P. vestitum was not significantly different from Ascorbic acid at P<0.05. The IC50 value of P. vestitum was 13.00ppm and that of Ascorbic acid was 15.09 ppm. The percent inhibitions caused by W. somniferra (IC50=46.85 ppm) and W. coagulans (IC50=84.40 ppm) were most significantly lower than Ascorbic acid at P<0.05. It is inferred from the current study that the methanolic (70%) extracts of the P. integerrima and P. vestitum could be used in preparation of potent antioxidant drugs.
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Mitochondria-Targeting Oxidovanadium(IV) Complex as a Near-IR Light Photocytotoxic Agent.
Chemistry
PUBLISHED: 09-04-2013
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Oxidovanadium(IV) complexes [VO(L(1) )(phen)]?Cl (1) and [VO(L(2) )(L(3) )]?Cl (2), in which HL(1) is 2-{[(benzimidazol-2-yl)methylimino]-methyl}phenol (sal-ambmz), HL(2) is 2-[({1-[(anthracen-9-yl)methyl]-benzimidazol-2-yl}methylimino)-methyl]phenol (sal-an-ambmz), phen is 1,10-phenanthroline and L(3) is dipyrido[3,2-a:2,3-c]phenazine (dppz) conjugated to a Gly-Gly-OMe dipeptide moiety, were prepared, characterized, and their DNA binding, photoinduced DNA-cleavage, and photocytotoxic properties were studied. Fluorescence microscopy studies were performed by using complex 2 in HeLa and HaCaT cells. Complex 1, structurally characterized by X-ray crystallography, has a vanadyl group in VO2 N4 core with the VO(2+) moiety bonded to N,N-donor phen and a N,N,O-donor Schiff base. Complex 2, having an anthracenyl fluorophore, showed fluorescence emission bands at 397, 419, and 443?nm. The complexes are redox-active exhibiting the V(IV)/V(III) redox couple near -0.85?V versus SCE in DMF 0.1?M tetrabutylammonium perchlorate (TBAP). Complex 2, having a dipeptide moiety, showed specific binding towards poly(dAdT)2 sequence. The dppz-Gly-Gly-OMe complex showed significant DNA photocleavage activity in red light of 705?nm through a hydroxyl radical ((.) OH) pathway. Complex 2 showed photocytotoxicity in HaCaT and HeLa cells in visible light (400-700?nm) and red light (620-700?nm), however, the complex was less toxic in the dark. Fluorescence microscopy revealed the localization of complex 2 primarily in mitochondria. Apoptosis was found to occur inside mitochondria (intrinsic pathway) caused by ROS generation.
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Development and evaluation of pluronic- and methylcellulose-based thermoreversible drug delivery system for insulin.
Drug Dev Ind Pharm
PUBLISHED: 08-29-2013
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Abstract The objective of the current work was to develop and evaluate thermoreversible subcutaneous drug delivery system for Insulin. Thermoreversible in-situ gel system was developed and evaluated both in-vitro and in-vivo comprising of pluronic F-127 alone or in combination with methylcellulose in different ratios. The drug release kinetics and mechanism was predicted by applying various mathematical models to the in-vitro dissolution data. Rabbits were used as animal model following subcutaneous injection to predict various pharmacokinetic parameters by applying Pk-Summit® software. The in-vitro and in-vivo data revealed that the formulation IPM 15/3 consisting of the pluronic F-127 (15% w/v) and methylcellulose (3% w/v) was the most robust and capable formulation for extending the drug release and maintaining basal plasma insulin level between 10 and 40?µU/ml for 240?h (10?d).
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Detection and classification of movement-related cortical potentials associated with task force and speed.
J Neural Eng
PUBLISHED: 08-28-2013
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In this study, the objective was to detect movement intentions and extract different levels of force and speed of the intended movement from scalp electroencephalography (EEG). We then estimated the performance of the closed loop system.
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Evaluation of antidiabetic and antihyperlipidemic activity of Artemisia indica linn (aeriel parts) in Streptozotocin induced diabetic rats.
J Ethnopharmacol
PUBLISHED: 07-21-2013
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Diabetes mellitus is a major metabolic disorder affecting a huge population all over the world. Artemisia species have been extensively used for the management of diabetes in folkloric medicine. The present study is designed to investigate the antidiabetic and antihyperlipidemic effects of aeriel parts of Artemisia indica.
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Unilateral pupillary dilatation following septoplasty: cause for concern?
J Coll Physicians Surg Pak
PUBLISHED: 07-05-2013
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We report and explain unilateral pupillary dilatation following routine septoplasty and trimming of inferior turbinates. The unilateral pupillary dilatation was caused by inadvertent instillation of sympathomimetic, (xylometazoline hydrochloride) in the eye during preparation for nasal surgery. The effect was short-lived and the patient made a full recovery. Unilateral pupillary dilatation after sinonasal surgery can be alarming due to the possibility of injury to the globe and intracranial haemorrhage but can also be explained by the mydriatic effect of the sympathomimetic nasal drops and sprays used to decongest the nose. Such possibility should be borne in mind and would help to explain and reduce the anxiety and avoid unnecessary investigations.
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MicroRNAs in skin response to UV radiation.
Curr Drug Targets
PUBLISHED: 06-28-2013
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Solar ultraviolet (UV) radiation, an ubiquitous environmental carcinogen, is classified depending on the wavelength, into three regions; short-wave UVC (200-280 nm), mid-wave UVB (280-320 nm), and long-wave UVA (320- 400 nm). The human skin, constantly exposed to UV radiation, particularly the UVB and UVA components, is vulnerable to its various deleterious effects such as erythema, photoaging, immunosuppression and cancer. To counteract these and for the maintenance of genomic integrity, cells have developed several protective mechanisms including DNA repair, cell cycle arrest and apoptosis. The network of damage sensors, signal transducers, mediators, and various effector proteins is regulated through changes in gene expression. MicroRNAs (miRNAs), a group of small non-coding RNAs, act as posttranscriptional regulators through binding to complementary sequences in the 3´-untranslated region of their target genes, resulting in either translational repression or target degradation. Recent studies show that miRNAs add an additional layer of complexity to the intricately controlled cellular responses to UV radiation. This review summarizes our current knowledge of the role of miRNAs in the regulation of the human skin response upon exposure to UV radiation.
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Involvement of LCA5 in Leber Congenital Amaurosis and Retinitis Pigmentosa in the Spanish Population.
Ophthalmology
PUBLISHED: 06-10-2013
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We aimed to identify novel genetic defects in the LCA5 gene underlying Leber congenital amaurosis (LCA) in the Spanish population and to describe the associated phenotype.
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Profiling Deleterious Non-synonymous SNPs of Smokers Gene CYP1A1.
Cell Biochem. Biophys.
PUBLISHED: 06-05-2013
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CYP1A1 gene belongs to the cytochrome P450 family and is known better as smokers gene due to its hyperactivation as a consequence of long term smoking. The expression of CYP1A1 induces polycyclic aromatic hydrocarbon production in the lungs, which when over expressed, is known to cause smoking related diseases, such as cardiovascular pathologies, cancer, and diabetes. Single nucleotide polymorphisms (SNPs) are the simplest form of genetic variations that occur at a higher frequency, and are denoted as synonymous and non-synonymous SNPs on the basis of their effects on the amino acids. This study adopts a systematic in silico approach to predict the deleterious SNPs that are associated with disease conditions. It is inferred that four SNPs are highly deleterious, among which the SNP with rs17861094 is commonly predicted to be harmful by all tools. Hydrophobic (isoleucine) to hydrophilic (serine) amino acid variation was observed in the candidate gene. Hence, this investigation aims to characterize a candidate gene from 159 SNPs of CYP1A1.
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The use of individually wrapped presterilized small orthopaedic implants increase operating time: a prospective experimental study.
JRSM Short Rep
PUBLISHED: 06-01-2013
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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.
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Topographical and chemical effects of electrochemically assisted deposited hydroxyapatite coatings on osteoblast-like cells.
J Biomater Appl
PUBLISHED: 05-15-2013
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A recently commercialised hydroxyapatite electrochemically assisted chemical deposition technique (BoneMaster) has been shown to induce increased bone apposition; whether this response is caused by the surface topography or chemistry is unknown. An in-vitro examination using human osteoblast-like cells was performed on a series of BoneMaster-coated surfaces. The chemistry was separated from the topography using a thin gold coating; Thermanox coverslips were used as a control. BoneMaster surfaces showed significantly greater alkaline phosphatase activity and osteocalcin production compared with controls; however, no difference was found between the gold-coated and uncoated BoneMaster samples, indicating topography is the main contributing factor.
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Association of human papilloma virus infection and oral squamous cell carcinoma in Bangladesh.
J Health Popul Nutr
PUBLISHED: 04-27-2013
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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.
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A validated high-performance thin-layer chromatography method for the identification and simultaneous quantification of six markers from Platanus orientalis and their cytotoxic profiles against skin cancer cell lines.
J Sep Sci
PUBLISHED: 04-10-2013
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Betulinic acid (1), betulinic acid-3-acetate (2), 3-acetylbetulinaldehyde (3), oleanolic acid-3-acetate (4), 3-?-hydroxy-28,19-?-olenolide (5), and ?-sitosterol (6) were isolated from Platanus orientalis and a high-performance thin-layer chromatography method was developed for their simultaneous quantification. The markers were first derivatized on the chromatogram with ceric ammonium sulfate and then high-performance thin-layer chromatography densitometry was carried out. Chromatographic separation of these markers was carried out on silica gel 60 plates using a ternary solvent system n-hexane/toluene/acetone (6:3.5:1 v/v/v) as a mobile phase. For marker 1, a deuterium (D2) lamp and wavelength of 420 nm was used. A tungsten (W) lamp was used for markers 2 and 3 at 550 nm and for 4-6 at 500 nm. The method was validated for accuracy, precision, LOD, and LOQ. All calibration curves showed a good linear relationship (r > 0.9919). The precision evaluated by an intra- and interday study showed RSDs < 2.51% and accuracy validation recovery between 95.54 and 99.33% with RSDs < 1.55%. The successful application of the validated method showed 1 as the most abundant component (4.63%) and 5 (0.017%) the least. The markers displayed a significant cytotoxic effect against human keratinocyte, mouse melanoma, and human skin epithelial carcinoma cancer cells by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.
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Effects of growth hormone and ultrasound on mandibular growth in rats: MicroCT and toxicity analyses.
Arch. Oral Biol.
PUBLISHED: 03-22-2013
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It has been shown by previous studies that mandibular growth can be enhanced by the systemic administration of recombinant growth hormone (rGH) and/or local application of therapeutic low intensity pulsed ultrasound (LIPUS). The purpose of this study was to determine if local injection of rGH and application of LIPUS to the temporomandibular joint (TMJ) would synergistically enhance mandibular growth. In an animal study, the effect of rGH, LIPUS, and combination of rGH and LIPUS on male Sprague-Dawley rats was observed. Mandibular growth was evaluated by measuring total hemimandibular and condylar bone volume and bone surface area as well as condylar bone mineral density (BMD) after 21 days on dissected rats mandibles using micro-computed tomography (MicroCT). The expression of c-jun mRNA extracted from the liver of each of these rats was also quantified by real-time polymerase chain reaction to evaluate possible systemic effect of local rGH administration. Significant growth stimulation was observed in the mandibular and condylar bone of the animals treated with rGH, LIPUS, and rGH/LIPUS combined when compared with the control group. Bone volume, surface area, condylar bone mineral density, and c-jun expression were also compared between the treatment groups and the control in the liver. The results suggest that mandibular growth may be enhanced by injection of rGH or LIPUS application. The current study although showed synergetic effect of rGH and LIPUS application in increasing mandibular condylar head length, there was no significant changes in mandibular bone volume using both treatments together when compared to the two individual treatments. Moreover, combined rGH and LIPUS decreased condylar bone mineral density than each treatment separately. Future research could be directed to investigate the effects of different rGH doses and/or different LIPUS exposures parameters on lower jaw growth.
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Right ventricular myocardial performance index derived from tissue Doppler echocardiography is useful in differentiating apical ballooning syndrome from cardiomyopathy due to left anterior descending coronary artery disease.
J Am Soc Echocardiogr
PUBLISHED: 03-19-2013
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Apical ballooning syndrome (ABS) and obstructive coronary artery disease of the left anterior descending coronary artery (LAD) can both result in similar left ventricular apical wall motion abnormalities. The right ventricle may more likely be involved in ABS, and its careful evaluation may help differentiate the two conditions. Therefore, the aim of this study was to determine the roles of echocardiographic measures of right ventricular (RV) function, namely, Doppler tissue imaging-derived RV index of myocardial performance (RIMP), RV basal free wall systolic excursion velocity (RV S), and tricuspid annular plane systolic excursion, in differentiating ABS from obstructive LAD disease.
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A prospective randomized pilot study on intermittent post-dialysis dosing of cinacalcet.
Int Urol Nephrol
PUBLISHED: 03-13-2013
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BACKGROUND: Treatment of secondary hyperparathyroidism (SHPT) is important in management of patients with end-stage renal disease on hemodialysis (HD). Calcimimetic agent, cinacalcet provides an option for control of SHPT in patients who fail traditional therapy. It may not have optimal results in non-compliant patients. To enhance compliance, we evaluated effectiveness of post-dialysis dosing of cinacalcet (group AD) as compared to daily home administration (group D) in a prospective randomized trial of HD patients with refractory SHPT. METHODS: After 2-week run-in phase, patients were randomly assigned to two treatment groups. In group AD (N = 12), patients were administered cinacalcet on the day of dialysis (3 times/week) by dialysis staff, while in control group D (N = 11), cinacalcet was prescribed daily to be taken by patients at home. Intact parathyroid hormone (i-PTH), serum calcium, phosphorus, and alkaline phosphatase were followed for 16 weeks and compared to baseline in both groups. Data were analyzed using between-groups linear regression for repeated measures. RESULTS: No significant decline in i-PTH occurred in group AD at 16 weeks as compared to a significant drop in group D (p = 0.006). However, subgroup analysis showed effectiveness of post-dialysis dosing in patients with less severe SHPT (p = 0.04). CONCLUSION: Although daily dosing overall was more effective for treatment of SHPT, dialysis dosing was effective in patients with less severe SHPT. This warrants a larger study considering the limitations of this pilot trial. In the meantime, dialysis dosing can be considered in non-compliant patients with less severe SHPT.
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Synthesis of 3-O-propargylated betulinic acid and its 1,2,3-triazoles as potential apoptotic agents.
Eur J Med Chem
PUBLISHED: 03-11-2013
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Cytotoxic agents from nature are presently the mainstay of anticancer chemotherapy, and the need to reinforce the arsenal of anticancer agents is highly desired. Chemical transformation studies carried out on betulinic acid, through concise 1,2,3-triazole synthesis via click chemistry approach at C-3position in ring A have been evaluated for their cytotoxic potentiation against nine human cancer cell lines. Most of the derivatives have shown higher cytotoxic profiles than the parent molecule. Two compounds i.e. 3{1N(2-cyanophenyl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid (7) and 3{1N(5-hydroxy-naphth-1yl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid (13) displayed impressive IC50 values (2.5 and 3.5 ?M respectively) against leukemia cell line HL-60 (5-7-fold higher potency than betulinic acid). As evident from various biological end points, inhibition of cell migration and colony formation, mitochondrial membrane disruption followed by DNA fragmentation and apoptosis, is demonstrated.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.