Showing papers by "Manipal University published in 2010"
TL;DR: It is demonstrated that inflammation affects the immune properties of MSCs distinctly; whereas IFNγ primed WJMSCs were better suppressors of MLRs, which could utilize unique mechanisms of immune-modulation.
Abstract: Background: Wharton's jelly derived stem cells (WJMSCs) are gaining attention as a possible clinical alternative to bone marrow derived mesenchymal stem cells (BMMSCs) owing to better accessibility, higher expansion potential and low immunogenicity. Usage of allogenic mesenchymal stem cells (MSC) could be permissible in vivo only if they retain their immune properties in an inflammatory setting. Thus the focus of this study is to understand and compare the immune properties of BMMSCs and WJMSCs primed with key pro-inflammatory cytokines, Interferon-γ (IFNγ) and Tumor Necrosis Factor-α (TNFα). Methodology/Principal Findings: Initially the effect of priming on MSC mediated suppression of alloantigen and mitogen induced lymphoproliferation was evaluated in vitro. Treatment with IFNγ or TNFα, did not ablate the immune-suppression caused by both the MSCs. Extent of immune-suppression was more with WJMSCs than BMMSCs in both the cases. Surprisingly, priming BMMSCs enhanced suppression of mitogen driven lymphoproliferation only; whereas IFNγ primed WJMSCs were better suppressors of MLRs. Further, kinetic analysis of cytokine profiles in co-cultures of primed/unprimed MSCs and Phytohematoagglutinin (PHA) activated lymphocytes was evaluated. Results indicated a decrease in levels of pro-inflammatory cytokines. Interestingly, a change in kinetics and thresholds of Interleukin-2 (IL-2) secretion was observed only with BMMSCs. Analysis of activation markers on PHA-stimulated lymphocytes indicated different expression patterns in co-cultures of primed/unprimed WJMSCs and BMMSCs. Strikingly, co-culture with WJMSCs resulted in an early activation of a negative co-stimulatory molecule, CTLA4, which was not evident with BMMSCs. A screen for immune suppressive factors in primed/unprimed WJMSCs and BMMSCs indicated inherent differences in IFNγ inducible Indoleamine 2, 3-dioxygenase (IDO) activity, Hepatocyte growth factor (HGF) and Prostaglandin E-2 (PGE2) levels which could possibly influence the mechanism of immune-modulation. Conclusion/Significance: This study demonstrates that inflammation affects the immune properties of MSCs distinctly. Importantly different tissue derived.
421 citations
TL;DR: A differential gene expression pattern was identified where several stem cells markers and early mesodermal/endothelial genes such as DESMIN, CD34, ACTC were upregulated under hypoxia, suggesting that in vitro culturing of WJ-MSCs under hypoxic conditions leads to adoption of a mesodmal/ endothelial fate.
Abstract: Multipotent mesenchymal stromal cells (MSCs) from Wharton’s jelly (WJ) of umbilical cord bear higher proliferation rate and self-renewal capacity than adult tissue-derived MSCs and are a primitive stromal cell population. Stem cell niche or physiological microenvironment plays a crucial role in maintenance of stem cell properties and oxygen concentration is an important component of the stem cell niche. Low oxygen tension or hypoxia is prevalent in the microenvironment of embryonic stem cells and many adult stem cells at early stages of development. Again, in vivo, MSCs are known to home specifically to hypoxic events following tissue injuries. Here we examined the effect of hypoxia on proliferation and in vitro differentiation potential of WJ-MSCs. Under hypoxia, WJ-MSCs exhibited improved proliferative potential while maintaining multi-lineage differentiation potential and surface marker expression. Hypoxic WJ-MSCs expressed higher mRNA levels of hypoxia inducible factors, notch receptors and notch downstream gene HES1. Gene expression profile of WJ-MSCs exposed to hypoxia and normoxia was compared and we identified a differential gene expression pattern where several stem cells markers and early mesodermal/endothelial genes such as DESMIN, CD34, ACTC were upregulated under hypoxia, suggesting that in vitro culturing of WJ-MSCs under hypoxic conditions leads to adoption of a mesodermal/endothelial fate. Thus, we demonstrate for the first time the effect of hypoxia on gene expression and growth kinetics of WJ-MSCs. Finally, although WJ-MSCs do not induce teratomas, under stressful and long-term culture conditions, MSCs can occasionally undergo transformation. Though there were no chromosomal abnormalities, certain transformation markers were upregulated in a few of the samples of WJ-MSCs under hypoxia.
156 citations
TL;DR: The highest quality cluster RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around younger children.
Abstract: BackgroundViral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a world-wide threat. Antiviral drugs and vaccinations may be insufficient to prevent catastrophe.ObjectivesTo systematically review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses.Search strategyWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 2); MEDLINE (1966 to May 2009); OLDMEDLINE (1950 to 1965); EMBASE (1990 to May 2009); and CINAHL (1982 to May 2009).Selection criteriaWe scanned 2958 titles, excluded 2790 and retrieved the full papers of 168 trials, to include 59 papers of 60 studies. We included any physical interventions (isolation, quarantine, social distancing, barriers, personal protection and hygiene) to prevent transmission of respiratory viruses. We included the following study designs: randomised controlled trials (RCTs), cohorts, case controls, cross-over, before-after, and time series studies.Data collection and analysisWe used a standardised form to assess trial eligibility. RCTs were assessed by: randomisation method; allocation generation; concealment; blinding; and follow up. Non-RCTs were assessed for the presence of potential confounders, and classified into low, medium, and high risks of bias.Main resultsThe risk of bias for the four RCTs, and most cluster RCTs, was high. The observational studies were of mixed quality. Only case-control data were sufficiently homogeneous to allow meta-analysis. The highest quality cluster RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around younger children. Additional benefit from reduced transmission from children to other household members is broadly supported in results of other study designs, where the potential for confounding is greater. Six case-control studies suggested that implementing barriers to transmission, isolation, and hygienic measures are effective at containing respiratory virus epidemics. We found limited evidence that N95 respirators were superior to simple surgical masks, but were more expensive, uncomfortable, and caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to decrease respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. There was limited evidence that social distancing was effective especially if related to the risk of exposure.Authors' conclusionsMany simple and probably low-cost interventions would be useful for reducing the transmission of epidemic respiratory viruses. Routine long-term implementation of some of the measures assessed might be difficult without the threat of a looming epidemic.
155 citations
TL;DR: The primary skin irritation and skin histopathology study indicated that the prepared IPN membranes were less irritant and safe for skin application.
143 citations
TL;DR: The richness of the measured spectrum illustrates that Raman studies of live cells in suspension are more informative than conventional micro-Raman studies where the cells are chemically bound to a glass cover slip.
Abstract: An optical trap has been combined with a Raman spectrometer to make high-resolution measurements of Raman spectra of optically-immobilized, single, live red (RBC) and white blood cells (WBC) under physiological conditions. Tightly-focused, near infrared wavelength light (1064 nm) is utilized for trapping of single cells and 785 nm light is used for Raman excitation at low levels of incident power (few mW). Raman spectra of RBC recorded using this high-sensitivity, dual-wavelength apparatus has enabled identification of several additional lines; the hitherto-unreported lines originate purely from hemoglobin molecules. Raman spectra of single granulocytes and lymphocytes are interpreted on the basis of standard protein and nucleic acid vibrational spectroscopy data. The richness of the measured spectrum illustrates that Raman studies of live cells in suspension are more informative than conventional micro-Raman studies where the cells are chemically bound to a glass cover slip.
135 citations
TL;DR: In this paper, a 355 nm pulsed Nd:YAG laser with a pulse duration of 6 ns focussed onto a copper solid sample in air at atmospheric pressure is studied spectroscopically, and the temperature and electron density characterizing the plasma are measured by time-resolved spectroscopy of neutral atom and ion line emissions in the time window of 300-2000 ns.
Abstract: Plasma produced by a 355 nm pulsed Nd:YAG laser with a pulse duration of 6 ns focussed onto a copper solid sample in air at atmospheric pressure is studied spectroscopically. The temperature and electron density characterizing the plasma are measured by time-resolved spectroscopy of neutral atom and ion line emissions in the time window of 300-2000 ns. An echelle spectrograph coupled with a gated intensified charge coupled detector is used to record the plasma emissions. The temperature is obtained using the Boltzmann plot method and the electron density is determined using the Saha-Boltzmann equation method. Both parameters are studied as a function of delay time with respect to the onset of the laser pulse. The results are discussed. The time window where the plasma is optically thin and is also in local thermodynamic equilibrium (LTE), necessary for the laser-induced breakdown spectroscopy (LIBS) analysis of samples, is deduced from the temporal evolution of the intensity ratio of two Cu I lines. It is found to be 700-1000 ns.
134 citations
TL;DR: This review provides an integrated overview of application of nanotechnology based molecular diagnostics and drug delivery in the development of nanomedicine and ultimately personalized medicine.
Abstract: Nanotechnology is an emerging branch of science for designing tools and devices of size 1 to 100 nm with specific function at the cellular, atomic and molecular levels. The concept of employing nanotechnology in biomedical research and clinical practice is best known as nanomedicine. Nanomedicine is an upcoming field that could potentially make a major impact to human health. Nanomaterials are increasingly used in diagnostics, imaging and targeted drug delivery. Nanotechnology will assist the integration of diagnostics/imaging with therapeutics and facilitates the development of personalized medicine, i.e. prescription of specific medications best suited for an individual. This review provides an integrated overview of application of nanotechnology based molecular diagnostics and drug delivery in the development of nanomedicine and ultimately personalized medicine. Finally, we identify critical gaps in our knowledge of nanoparticle toxicity and how these gaps need to be evaluated to enable nanotechnology to transit safely from bench to bedside.
132 citations
TL;DR: These newly synthesized compounds were characterized by elemental analyses, I.R, NMR and Mass spectral studies, and many of the molecules were found to be potent.
117 citations
TL;DR: A number of ring substituted analogues of curcumin were synthesized and their antioxidant properties were studied using three models, inhibition of lipid peroxidation, scavenging of 1,1′‐diphenyl‐2‐picrylhydrazyl and 2,2′‐azinobis (ABTS+).
Abstract: A number of ring substituted analogues of curcumin were synthesized. Their antioxidant properties were studied using three models, inhibition of lipid peroxidation, scavenging of 1,1′-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethyl-benzthiazoline-6-sulphonate radical (ABTS+).
In all the models, the phenolic analogues were more active than the non-phenolic analogues, some of which were inactive. The highest antioxidant activity was obtained when the phenolic group was sterically hindered by the introduction of two methyl groups at the ortho position. This and several other compounds were more active than the standard antioxidants α-tocopherol and trolox.
This study has demonstrated that the phenolic group is important for the antioxidant activity of curcumin and that the structural features that enhance the antioxidant properties of phenols are optimized in curcumin to a significant extent.
113 citations
TL;DR: Suggestions are made in this paper regarding the methods to determine an optimum sample size in descriptive and analytical studies.
Abstract: Sample size determination is one of the central tenets of medical research. If the sample size is inadequate, then the study will fail to detect a real difference between the effects of two clinical approaches. On the contrary, if the sample size is larger than what is needed, the study will become cumbersome and ethically prohibitive. Apart from this, the study will become expensive, time consuming and will have no added advantages. A study which needs a large sample size to prove any significant difference in two treatments must ensure the appropriate sample size. It is better to terminate such a study when the required sample size cannot be attained so that the funds and manpower can be conserved. When dealing with multiple sub-groups in a population the sample size should be increased the adequate level for each sub-group. To ensure the reliability of final comparison of the result, the significant level and power must be fixed before the sample size determination. Sample size determination is very important and always a difficult process to handle. It requires the collaboration of a specialist who has good scientific knowledge in the art and practice of medical statistics. A few suggestions are made in this paper regarding the methods to determine an optimum sample size in descriptive and analytical studies.
109 citations
TL;DR: This study attempted rapid clinical-scale expansion of WJ-MSCs which would allow these fetus-derived stem cells to be used for various allogeneic cell-based transplantations and tissue engineering.
TL;DR: The study conducted on 240 Rajputs showed a significant correlation between and within the dimensions of hands and feet and may have significance in plastic and reconstructive surgery.
Journal Article•
TL;DR: Mobile phone RF-EMR exposure significantly altered the passive avoidance behaviour and hippocampal morphology in rats and marked morphological changes were observed in the CA3 region of the hippocampus of the mobile phone-exposed rats in comparison to the control rats.
Abstract: Introduction. The interaction of mobile phone radio-frequency electromagnetic radiation (RF-EMR) with the brain is a serious concern of our society. Objective. We evaluated the effect of RF-EMR from mobile phones on passive avoidance behaviour and hippocampal morphology in rats. Materials and methods. Healthy male albino Wistar rats were exposed to RF-EMR by giving 50 missed calls (within 1 hour) per day for 4 weeks, keeping a GSM (0.9 GHz/1.8 GHz) mobile phone in vibratory mode (no ring tone) in the cage. After the experimental period, passive avoidance behaviour and hippocampal morphology were studied. Results. Passive avoidance behaviour was significantly affected in mobile phone RF-EMR-exposed rats demonstrated as shorter entrance latency to the dark compartment when compared to the control rats. Marked morphological changes were also observed in the CA3 region of the hippocampus of the mobile phone-exposed rats in comparison to the control rats. Conclusion. Mobile phone RF-EMR exposure significantly altered the passive avoidance behaviour and hippocampal morphology in rats.
TL;DR: There seems to be a little possibility of obtaining erroneous results while estimating stature from those body dimensions which showed statistically insignificant asymmetry, but it is strongly recommended that the examiner must first identify the side to which the limb part or bone belongs to, and then apply the appropriate formula derived for that particular side.
TL;DR: Several potential protein biomarkers previously known to be increased in ESCC including matrix metalloproteinase 1, transferrin receptor, and transforming growth factor beta-induced 68 kDa were identified as overexpressed in the ESCC-derived secretome, and several novel proteins that have not been previously reported to be associated with ESCC are identified.
Abstract: The identification of secreted proteins that are differentially expressed between non-neoplastic and esophageal squamous cell carcinoma (ESCC) cells can provide potential biomarkers of ESCC. We used a SILAC-based quantitative proteomic approach to compare the secretome of ESCC cells with that of non-neoplastic esophageal squamous epithelial cells. Proteins were resolved by SDS-PAGE and tandem mass spectrometry analysis (LC-MS/MS) of in-gel trypsindigested peptides was carried out on a high-accuracy qTOF mass spectrometer. In total, we identified 441 proteins in the combined secretomes, including 120 proteins with ≥ 2-fold upregulation in the ESCC secretome vs. that of non-neoplastic esophageal squamous epithelial cells. In this study, several potential protein biomarkers previously known to be increased in ESCC including matrix metalloproteinase 1, transferrin receptor and transforming growth factor beta-induced 68 kDa were identified as overexpressed in the ESCC-derived secretome. In addition, we identified several novel proteins that have not been previously reported to be associated with ESCC. Among the novel candidate proteins identified, protein disulfide isomerase family a member 3 (PDIA3), GDP dissociation inhibitor 2 (GDI2) and lectin galactoside binding soluble 3 binding protein (LGALS3BP) were further validated by immunoblot analysis and immunohistochemical labeling using tissue microarrays. This tissue microarray analysis showed overexpression of protein disulfide isomerase family a member 3, GDP dissociation inhibitor 2 and lectin galactoside binding soluble 3 binding protein in 93, 93 and 87% of 137 ESCC cases, respectively. Hence, we conclude that these potential biomarkers are excellent candidates for further evaluation to test their role and efficacy in the early detection of ESCC.
TL;DR: Lead molecules of the 2-quinolone skeleton were designed for binding to the bacterial DNA gyrase subunit A and synthesized and purified compounds were tested for antioxidant and antibacterial activity.
Abstract: As an important class of compounds, 2-quinolones are isomeric to 4-quinolones and isosteric to coumarins. The compounds that have 2-quinolone moiety are associated with interesting biologic activities such as antibacterial, anticancer, antiviral, cardiotonic, and N-methyl-D-aspartate receptor inhibitor functions, among others. In the current study, based on the rational approach, lead molecules of the 2-quinolone skeleton were designed for binding to the bacterial DNA gyrase subunit A. Docking simulations and quantitative structure activity relationship (QSAR) analysis were performed using the Molegro Virtual Docker and Sarchitech softwares. Based on these studies, the 7-amino-4-methylquinolin-2(1H)-one parent compound and its carboxamides (JST 1–15) were synthesized using Conrad Limpach synthesis. The synthesized test compounds then were characterized by thin-layer chromatography and melting point determination, as well as by ultraviolet, infrared (IR), 1H-NMR, and MS studies. All synthesized and purified compounds were tested for antioxidant and antibacterial activity.
TL;DR: A series of novel 2-phenyl-1,3-benzothiazoles were synthesized and characterised by IR, (1)H NMR and mass spectroscopy and showed moderate to good anti-breast cancer activity.
Abstract: Protein tyrosine kinases occupy a central position in the control of cellular proliferation and its inactivation might lead to the discovery of a new generation anticancer compounds. Substituted benzothiazoles have been found to mimic the ATP-competitive binding of genistein and quercetin to tyrosine kinase. A series of novel 2-phenyl-1,3-benzothiazoles were synthesized and characterised by IR, 1 H NMR and mass spectroscopy. All the compounds were tested for their anticancer activity against MCF-7 breast cancer cell line with the MTT assay. Most of the compounds showed moderate to good anti-breast cancer activity. Anticancer activity varied with substitution on the benzothiazole nucleus with halogens and at 4 position, substitution of the 2-phenyl moiety with methyl and methoxy groups was also explored. Among the compounds tested with MTT assay, mono fluoro substitution on benzothiazole nucleus and 4′-methyl variations at 2-phenyl position demonstrated highest percent growth inhibition of MCF-7 cells. Docking studies of the synthesised compounds was done on EGFR using GRIP batch docking method to study their observed activity.
TL;DR: The current global network of pharmacovigilance centers, coordinated by the Uppsala Monitoring Centre, would be strengthened by an independent system of review, which would consider litigious and important drug safety issues that have the potential to affect public health adversely beyond national boundaries.
TL;DR: The outcomes of the study showed that the basic knowledge of palliative care among students was inadequate, and students are unprepared and uncertain in their approach of delivering end-of-life care.
Abstract: Purpose: Quality assurance data worldwide suggests that the current healthcare system is providing inadequate care for the dying. Current health care education focuses entirely on cure and care is almost compromised or nonexistent in end-of-life settings. The purpose of this study was to determine palliative care awareness among Indian undergraduate health care students and assess the need for incorporating palliative medicine education into undergraduate health education. Methods: A non-randomized population based study was conducted using 39-point questionnaire. Undergraduate medical, nursing and allied health students of Manipal University were the target population. Results: 326 students participated in the study. 61.7% of students feel that resuscitation is appropriate in advanced metastatic cancer. 67.5% feel that all dying patients need palliative care and most of the students think that palliative care is equivalent to pain medicine, geriatric medicine and rehabilitation medicine. 89% of students think that Morphine causes addiction in palliative care setting. 60.7% of students feel that prognosis should only be communicated to the family. Conclusion: The outcomes of the study showed that the basic knowledge of palliative care among students was inadequate, and students are unprepared and uncertain in their approach of delivering end-of-life care.
TL;DR: The results suggest that EJ in cancer cells could be negatively regulated by the anti-apoptotic protein, BCL2, and this may contribute toward increased chromosomal abnormalities in cancer.
TL;DR: A cross-sectional questionnaire survey among final year undergraduate medical students in Malaysia, India, Nepal, Pakistan, and Bangladesh found that medical educators should consider revising medical curricula to improve training about tobacco smoking cessation in medical schools.
Abstract: Tobacco smoking issues in developing countries are usually taught non-systematically as and when the topic arose. The World Health Organisation and Global Health Professional Student Survey (GHPSS) have suggested introducing a separate integrated tobacco module into medical school curricula. Our aim was to assess medical students' tobacco smoking habits, their practices towards patients' smoking habits and attitude towards teaching about smoking in medical schools. A cross-sectional questionnaire survey was carried out among final year undergraduate medical students in Malaysia, India, Nepal, Pakistan, and Bangladesh. An anonymous, self-administered questionnaire included items on demographic information, students' current practices about patients' tobacco smoking habits, their perception towards tobacco education in medical schools on a five point Likert scale. Questions about tobacco smoking habits were adapted from GHPSS questionnaire. An 'ever smoker' was defined as one who had smoked during lifetime, even if had tried a few puffs once or twice. 'Current smoker' was defined as those who had smoked tobacco product on one or more days in the preceding month of the survey. Descriptive statistics were calculated. Overall response rate was 81.6% (922/1130). Median age was 22 years while 50.7% were males and 48.2% were females. The overall prevalence of 'ever smokers' and 'current smokers' was 31.7% and 13.1% respectively. A majority (> 80%) of students asked the patients about their smoking habits during clinical postings/clerkships. Only a third of them did counselling, and assessed the patients' willingness to quit. Majority of the students agreed about doctors' role in tobacco control as being role models, competence in smoking cessation methods, counseling, and the need for training about tobacco cessation in medical schools. About 50% agreed that current curriculum teaches about tobacco smoking but not systematically and should be included as a separate module. Majority of the students indicated that topics about health effects, nicotine addiction and its treatment, counselling, prevention of relapse were important or very important in training about tobacco smoking. Medical educators should consider revising medical curricula to improve training about tobacco smoking cessation in medical schools. Our results should be supported by surveys from other medical schools in developing countries of Asia.
TL;DR: The study reveals that the integrated approach of pH adjustment and CyD complexation can be successfully used for improving the CyD solubilizing power towards an ionizable drug such as SQV, thus allowing a smaller quantity of CyD tosolubilize a given amount of drug, offering clear economic and technologic advantages as well.
TL;DR: FPNT was found to be a potent antioxidant when compared to the standard in DPPH, ABTS radical scavenging assays and lipid peroxidation studies.
TL;DR: More frequent use of CBL sessions would not only help the student gain requisite knowledge in microbiology but also enhance their analytic and communication skills, as indicated by the experience.
Abstract: Background: Case-based learning (CBL) is an interactive student-centered exploration of real life situations. This paper describes the use of CBL as an educational strategy for promoting active learning in microbiology. Materials and Methods: CBL was introduced in the microbiology curriculum for the second year medical students after an orientation program for faculty and students. After intervention, the average student scores in CBL topics were compared with scores obtained in lecture topics. An attempt was also made to find the effect of CBL on the academic performance. Student and faculty perception on CBL were also recorded. Results: In a cross sectional survey conducted to assess the effectiveness of CBL, students responded that, apart from helping them acquire substantive knowledge in microbiology, CBL sessions enhanced their analytic, collaborative, and communication skills. The block examination scores in CBL topics were significantly higher than those obtained for lecture topics. Faculty rated the process to be highly effective in stimulating student interest and long term retention of microbiology knowledge. The student scores were significantly higher in the group that used CBL, compared to the group that had not used CBL as a learning strategy. Conclusion: Our experience indicated that CBL sessions enhanced active learning in microbiology. More frequent use of CBL sessions would not only help the student gain requisite knowledge in microbiology but also enhance their analytic and communication skills.
TL;DR: There is significant enhancement in Raman peak intensities corresponding to SS and C-S stretching modes that are induced by oxidative stress, consistent with the formation of mixed disulphides between protein SH groups and low-molecular-mass thiols such as glutathione during oxidative damage to cells.
Abstract: Raman Tweezers have been successfully applied to characterize chemically-induced oxidative stress on optically-trapped live, single erythrocytes. There is significant enhancement in Raman peak intensities corresponding to SS and C-S stretching modes that are induced by oxidative stress. This is consistent with the formation of mixed disulphides between protein SH groups and low-molecular-mass thiols such as glutathione during oxidative damage to cells. Enhancement in glutathione level as a protective response against oxidative stress has been observed. Principal component analysis of the data yields good discrimination between spectra of normal and stress-induced red blood cells.
TL;DR: ACE was found to scavenge DPPH radicals in a concentration‐dependent manner, indicating that the radioprotection afforded by ACE may be in part due to the scavenging of reactive oxygen species induced by ionizing radiation.
Abstract: The effect of various doses (0, 25, 50, 75, 100, 125, 150, 300, 600 and 900 mg kg(-1)) of the alcoholic extract of the plant Ageratum conyzoides Linn. (ACE), on the alteration of radiation-induced mortality in mice exposed to 10 Gy of gamma radiation was studied. The acute toxicity studies showed that the drug was non-toxic up to a dose of 3000 mg kg(-1), the highest dose that could be tested for acute toxicity. Administration of ACE resulted in a dose-dependent decline in radiation-induced mortality up to a dose of 75 mg kg(-1), the dose at which the highest number of survivors (70.83%) was observed. Thereafter, the number of survivors declined with increasing doses of ACE and a nadir was reached at 900 mg kg(-1) ACE. Since the number of survivors was highest for 75 mg kg(-1) ACE, this was considered the optimum dose for radioprotection and used in further studies in which mice were treated with 75 mg kg(-1) ACE before exposure to 6, 7, 8, 9, 10 and 11 Gy of gamma radiation. The treatment of mice with 75 mg kg(-1) ACE reduced the severity of symptoms of radiation sickness and mortality at all exposure doses, and a significant increase in survival was observed compared with the non-treated irradiated group. The ACE treatment effectively protected mice against the gastrointestinal as well as bone marrow related death, as revealed by the increased number of survivors at all irradiation doses. The dose reduction factor was found to be 1.3. To understand the mechanism of action, various doses of ACE were evaluated for their in-vitro scavenging action on 1,1-diphenyl-2-picrylhydrazyl (DPPH), a chemically stable free radical. ACE was found to scavenge DPPH radicals in a concentration-dependent manner, indicating that the radioprotection afforded by ACE may be in part due to the scavenging of reactive oxygen species induced by ionizing radiation.
TL;DR: Results suggest that DVW and DVE-4 inhibits HFD + STZ-induced insulin resistance, lipid abnormalities and oxidative stress indicating that these effects may be mediated by interacting with multiple targets operating in diabetes mellitus.
Abstract: Context: High fat diet (HFD) and low-dose streptozotocin (STZ) is an ideal model for type 2 diabetes mellitus (T2DM) that would closely reflect the natural history and metabolic characteristics of human T2DM and is also suitable for pharmacological screening.Objective: The present study was designed to investigate the effect of the water extract (DVW) and the polar fraction of ethanol extract (DVE-4) of Dodonaea viscosa (L). Jacq. (Sapindaceae) on biochemical parameters in type 2 diabetes induced by a standardized HFD and low dose streptozotocin (25 mg/kg) in rats. Further, to elucidate the mode of action we evaluated its effects on a battery of targets involved in glucose homeostasis (in vitro studies).Materials and methods: Different doses of DVW and DVE-4 were administered once daily for two weeks to HFD + STZ diabetic rats. Quantification of biomarker quercetin was done using HPLC.Results and discussion: Both DVW and DVE-4 dose-dependently reduced blood glucose, serum insulin, homeostatic model assess...
TL;DR: Evidence suggests that specific content and format of prescription drug labels facilitate communication with and comprehension by patients, and efforts to improve the labels should be guided by such evidence, although an additional study assessing the influence of label design on medication-taking behavior and health outcomes is needed.
TL;DR: It is demonstrated that the interfacial activity assisted surface functionalization (IAASF) technique can be used to incorporate reactive functional groups such as maleimide onto the surface of PLGA nanoparticles, which in turn permitted efficient conjugation of biologically active cRGD peptide to thesurface of PL GA nanoparticles.
Abstract: Nanoparticles formulated using poly(d,l-lactide-co-glycolide) (PLGA) copolymer have emerged as promising carriers for targeted delivery of a wide variety of payloads. However, an important drawback with PLGA nanoparticles is the limited types of functional groups available on the surface for conjugation to targeting ligands. In the current report, we demonstrate that the interfacial activity assisted surface functionalization (IAASF) technique can be used to incorporate reactive functional groups such as maleimide onto the surface of PLGA nanoparticles. The surface maleimide groups were used to conjugate cRGD peptide to nanoparticles. The cRGD peptide targets αvβ3 integrins overexpressed on tumor vasculature and some tumor cells, and was used as model targeting ligand in this study. Incorporation of biologically active cRGD peptide on the surface of nanoparticles was confirmed by in vitro cell uptake studies and in vivo tumor accumulation studies. Functionalization of nanoparticles with cRGD peptide incre...