Evaluation of anti-psychotic effect of nimodipine using methylphenidate as a model to induce psychosis in albino mice

Background: Schizophrenia is a functional psychotic disorder currently treated by typical and atypical antipsychotic drugs. A large group of patients remain resistant to therapy. Nimodipine has been found effective for treating resistant bipolar mood disorder which is linked genetically with schizophrenia and has a high overlap of neurotransmitters in the etiopathology. Previous studies to evaluate nimodipine’s antipsychotic activity have shown inconsistent results. Methylphenidate, a CNS stimulant like amphetamine, has been shown to induce stereotypy in animals and can be proposed as an alternative model for psychosis.Methods: Methylphenidate 5 mg/kg was given intraperitoneally to induce psychosis in swiss albino mice (n=6). Nimodipine was given alone in doses of 2.5 and 5 mg/kg by i.p route and in combination with haloperidol 0.1 mg/kg and effects were compared with haloperidol 0.2mg/kg. Activity of nimodipine was also assessed on the haloperidol induced catalepsy test. Statistical analysis was done with ANOVA followed by Bonferroni’s test using SPSS v. 20.0.Results: Methylphenidate successfully induced characteristic stereotypy behaviour in mice similar to amphetamine. Both nimodipine 5 mg/kg and haloperidol 0.2 mg/kg showed significant reduction in stereotypy behaviour with no statistical difference between the two; result with nimodipine were only slightly inferior to haloperidol. Nimodipine 5 mg/kg with haloperidol 0.1 mg/kg showed significantly better activity than haloperidol in standard dose of 0.2 mg/kg. Nimodipine did not show significant activity on the haloperidol induced catalepsy test.Conclusions: Methylphenidate has potential to be used as an alternative model for inducing psychosis in animals and nimodipine shows promising results for use as adjuvant antipsychotic drug

Bilharzia in a small irrigation community: an assessment of water and toilet usage

A study on the hygienic usage of pit- latrines to avert bilharziasis in rural Zimbabwe.A questionnaire study was conducted in the Mushandike small scale irrigation schemes in Zimbabwe to investigate the following: 1) to establish whether field latrines are used or not; 2) to find out why people visit natural water bodies for bathing and laundry instead of using water from boreholes for these purposes; 3) to assess people’s knowledge on the transmission and control of schistosomiasis. Results of the study indicated that die field latrines tire utilized and that the borehole water is not preferred for bathing and laundry because of its hardness and oily nature. The results further indicated that the community was aware of schistosomiasis but their knowledge on transmission and control of the disease was limited. Possible reasons for tire observations made tire discussed in die paper and recommendations emanating from the study are stated

Prescription audit to evaluate the pattern and errors in a tertiary care hospital

Background: Medication errors are widespread public health issue. Prescription errors commonly results in medication error. Prescription error can be largely avoidable this study was performed with aim to point out the common mistake in the prescription which may endanger patients.Methods: Our study was cross-sectional and observational, performed in Index Medical College. 320 prescriptions were reviewed. Analysis was done for presence or absence of essential components of prescription like prescriber information’s, patients information’s, details of drug like its dosage form, strength, frequency, total duration of treatment, warnings or instruction for use. The observed data was expressed in number and percentage.Results: Patient information was complete 315 (98.44%) in prescriptions. Prescriber’s information were present in 284 (88.75%). Legibility was seen in 240 (75%). Use of generic drug, capital letters for drug name, warning are seen in 9 (2.81%), 39 (12.19%), 3 (0.94%) respectively. Completeness in terms of the name of drug, dose, strength, route, frequency, duration and dosage forms of prescribed drugs was seen in 252 (78.75%) prescriptions.Conclusions: Properly framed and written prescription can largely prevent medication error. Regular prescription audit must be carried out so that common mistake can be identified and corrective measure with the help of training session, workshop can be taken

A concurrent parallel study to compare the efficacy and safety of oral iron chelators, defrasirox and defriprone in patients of beta thalassaemia major

Background: This study was planned to evaluate all the cases of β thalassaemia major, already receiving one of the oral iron chelators for a comparison among the efficacy, safety and economy of deferasirox and deferiprone to establish the better option in an Indian scenario.Methods: We identified two groups of patients: 38 treated with deferasirox and 35 treated with deferiprone. Laboratory parameters such as serum ferritin, creatinine, SGPT, Hb, CBC and urine were recorded at the time of inclusion and at 1, 3 and 6 months after the inclusion. The primary outcome variable was serum Ferritin level at the start and at the end of study. Serum ferritin level was carried out by microparticle enzyme linked immunoassay.Results: Before the study, the mean hemoglobin level was 7.32±1.50mg/dL ranged from 4 to 10.8 in deferasirox group and 7.54±1.15mg/dL ranged from 5.5 to 8.8 in deferiprone group. At the time of inclusion, study population was characterized by a mean serum ferritin value of 4735.11±450.01 SE in deferasirox and 4315.97±340.75 SE in deferiprone group. After one month the mean serum ferritin increases to 4578.66±371.96 in deferasirox and 4388.82±316.16 in deferiprone group. After three month the mean serum ferritin reduces to 4295.60±377.37 in deferasirox and 3988.88±349.84 in Deferiprone group.Conclusions: Thus, we conclude that deferasirox and deferiprone are well tolerated, have few adverse effects and almost have a comparable effect in lowering of the patient's serum ferritin level. Deferiprone is more cost effective but needs a strict control on compliance owing to requirement in three divided doses per day

Research priorities for improving infant and young child feeding in humanitarian emergencies

Background There are many challenges during emergencies to ensure that optimal infant and young child feeding is protected, promoted and supported, but there is a dearth of evidence on strategies and programmes to improve Infant and Young Child Feeding in Emergencies (IYCF-E) and a need to determine research priorities. Methods Based on interviews with key informants who are experts in the subject, we developed a list of 48 research questions on IYCF-E. A framework, following the Child Health and Nutrition Research Initiative method to set priorities in child health research, was developed to rank the research questions. Four criteria were applied to create a ranking based on answerability, operational relevance, disease burden reduction and prevention, and originality. Using an on-line survey, prioritisation of research questions was done by 27 people from 14 NGOs, universities and research institutions, and UN organisations. Results The top-ten research questions identified focused on the following: • Use of cash-transfer to buy breast-milk substitutes; • Effectiveness of complementary feeding strategies; • Long-term effect of IYCF-E interventions; • Design of IYCF-E programmes in a context where breastfeeding rates are low and breast milk substitutes use is high; • Design of effective re-lactation interventions; • Provision of psychological support to young children’s care-takers; • Determination of number of beneficiaries and coverage of IYCF-E programmes; • Pros and cons of distributing ready-to-use infant formula compared with distributing powdered infant formula plus kit for safer use of BMS, when use of infant formula is necessary; • Assessment of the impact of specific IYCF-E programmes on nutritional status, morbidity and mortality; • Linking and mainstreaming IYCF-E interventions with other sectors such as health, WASH, food security and child protection. Conclusion The questions found by this study could form the basis of future research on IYCF-E and could be integrated into the agenda of relevant stakeholders. Results of studies based on these questions will be fundamental to fill the evidence gap in IYCF-E, improve IYCF-E programming and ultimately contribute to the reduction in morbidity and mortality among infants and young children in humanitarian emergencies

Synthesis of Some New Isoxazoline Derivatives of Chalconised Indoline 2-one as a Potential Analgesic, Antibacterial and Anthelmimtic Agents

A series of novel 1[5”-(2”’-substituted phenyl)-4”,5”’-dihydro isoxazole-3”-yl]-3-[(4 substituted phenyl)imino]1-3-dihydro-2H-indole-2-one were synthesized from different substituted chalconised indole-2,3-dione was prepared from the different chalconised Isatin. The structures of the compounds were elucidated by elemental and spectral (IR, 1H NMR, and MS) analysis. The synthesized compounds were screened for their analgesic activity by the acetic acid induced Writhing method and in vitro antimicrobial activity against the Gram-positive bacteria—Staphylococcus aureus and the Gram-negative bacteria—Pseudomonas auroginosa, Pseudomonas mirabilis, and E. coli by the cup plate agar diffusion method. Compounds 6a1, 6a3, 6b3, and 6b2 were found to be active against bacteria. The compounds 6a1, 6b3, and 6a3 show a significant analgesic activity. Synthesized compounds also screened for anthelmintic activity against Pheretima posthuma. Compounds 6a1, 6b1, and 6b3 show significant anthelmintic activity

Paired phase II trials evaluating cetuximab and radiotherapy for low risk HPV associated oropharyngeal cancer and locoregionally advanced squamous cell carcinoma of the head and neck in patients not eligible for cisplatin

BackgroundAlternative therapeutic strategies are needed for localized oropharyngeal carcinoma. Cetuximab represents a potential option for those ineligible for cisplatin or, until recently, an agent for de‐escalation in low risk HPV+ oropharyngeal carcinoma (OPSCC). Our objective was to define the toxicity and efficacy of cetuximab‐radiotherapy.MethodsWe conducted paired phase II trials evaluating cetuximab‐radiotherapy in two cohorts (a) low risk HPV+ OPSCC and (b) cisplatin ineligible. The mean follow‐up was 48 months.ResultsForty‐two patients were enrolled in cohort A with a 2‐year disease free survival (DFS) of 81%. Twenty‐one patients were enrolled in cohort B prior to closure due to adverse outcomes with a 2‐year DFS of 37%. Severe toxicities were seen in 60% of patients, 30% required enteral nutrition.ConclusionAmong cisplatin ineligible patients, cetuximab treatment engendered poor outcomes. Rates of severe toxicities were on par with platinum‐based regimens suggesting that cetuximab is not a benign treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156234/2/hed26085.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156234/1/hed26085_am.pd

Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression

Multiple, complex molecular events characterize cancer development and progression(1,2). Deciphering the molecular networks that distinguish organ- confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high- throughput liquid- and- gas- chromatography- based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer ( 42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N- methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non- invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine- N- methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.Early Detection Research Network ; National Institutes of Health ; MTTC ; Clinical Translational Science Award ; Fund for Discovery of the University of Michigan Comprehensive Cancer Center ; University of Michigan Cancer Biostatistics Training Grant ; Doris Duke Charitable FoundationWe thank J. Granger for help in manuscript preparation, J. Siddiqui and R. Varambally for help with the clinical database, and A. Vellaichamy and S. Pullela for technical assistance. We thank K. Pienta for access to metastatic prostate cancer samples from the University of Michigan Prostate SPORE rapid autopsy programme. This work is supported in part by the Early Detection Research Network (A.M.C., J.T.W.), National Institutes of Health (A.S., S.P., J.B., T.M.R., D.G., G.S.O. and A.M.C.) and an MTTC grant (G.S.O. and A.S.). A.M.C. is supported by a Clinical Translational Science Award from the Burroughs Welcome Foundation. A. S. is supported by a grant from the Fund for Discovery of the University of Michigan Comprehensive Cancer Center. L. M. P. is supported by the University of Michigan Cancer Biostatistics Training Grant. A. M. C and S. P. are supported by the Doris Duke Charitable Foundation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62661/1/nature07762.pd

P130Cas Attenuates Epidermal Growth Factor (EGF) Receptor Internalization by Modulating EGF-Triggered Dynamin Phosphorylation

BACKGROUND: Endocytosis controls localization-specific signal transduction via epidermal growth factor receptor (EGFR), as well as downregulation of that receptor. Extracellular matrix (ECM)-integrin coupling induces formation of macromolecular complexes that include EGFR, integrin, Src kinase and p130Cas, resulting in EGFR activation. In addition, cell adhesion to ECM increases EGFR localization at the cell surface and reduces EGFR internalization. The molecular mechanisms involved are not yet well understood. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the molecular mechanism by which p130Cas affects the endocytic regulation of EGFR. Biochemical quantification revealed that cell adhesion to fibronectin (FN) increases total EGFR levels and its phosphorylation, and that p130Cas is required for this process. Measurements of Texas Red-labeled EGF uptake and cell surface EGFR revealed that p130Cas overexpression reduces EGF-induced EGFR internalization, while p130Cas depletion enhances it. In addition, both FN-mediated cell adhesion and p130Cas overexpression reduce EGF-stimulated dynamin phosphorylation, which is necessary for EGF-induced EGFR internalization. Coimmunoprecipitation and GST pull-down assays confirmed the interaction between p130Cas and dynamin. Moreover, a SH3-domain-deleted form of p130Cas, which shows diminished binding to dynamin, inhibits dynamin phosphorylation and EGF uptake less effectively than wild-type p130Cas. CONCLUSIONS/SIGNIFICANCE: Our results show that p130Cas plays an inhibitory role in EGFR internalization via its interaction with dynamin. Given that the EGFR internalization process determines signaling density and specificity in the EGFR pathway, these findings suggest that the interaction between p130Cas and dynamin may regulate EGFR trafficking and signaling in the same manner as other endocytic regulatory proteins related to EGFR endocytosis