Antidepressant like activity of Buspirone but not of ondansetron when administered in combination with Fluoxetine or Desipramine in mice

Background: The involvement of one or more 5-HT receptor sub-types in the pathophysiology of depression is still unclear. The study was performed to investigate the effect of ondansetron and buspirone on depression, and their interaction with fluoxetine or desipramine.Methods: The mice were administered ondansetron, buspirone alone and in combinations with fluoxetine or desipramine for 21 days, and the antidepressant effect was assessed by the immobility period and the sucrose consumption, on the tail suspension test (TST) and the chronic mild stress (CMS) models, respectively.Results: Both ondansetron and buspirone when given alone demonstrated slight non-significant decrease in the immobility time in TST model. Ondansetron when given in combination with fluoxetine (10 mg/kg; i.p.) and desipramine (15 mg/kg; i.p.), showed significant decrease in immobility time in comparison to the control group only. On the other hand, both the combinations of buspirone, either with fluoxetine or desipramine showed significant decrease in the immobility time when compared to the respective group. In CMS, the fluoxetine, desipramine, ondansetron, and buspirone showed gradual increase in the sucrose consumption, at the end of 4th, 5th, and 6th week, but the significant effect was observed only at the end of 6th week, as compared to the control. The combination of buspirone with desipramine but not with fluoxetine showed significant increase in sucrose consumption when compared to respective group.Conclusions: Therefore, the study indicates that both buspirone and ondansetron have a potential antidepressant like action, although buspirone has shown better antidepressant activity than ondansetron as observed in various combination groups

An open randomized study to compare effect of metformin versus acarbose monotherapy on glycemic control and lipid profile in newly diagnosed type 2 diabetes mellitus patients

Background: Type 2 DM is one global health problem and a main cause of morbidity and mortality. It is epidemic in many industrialized and developing areas and is considered to be one of the most challenging health problems of the 21st century. Metformin and acarbose both are used as monotherapy and in combination with other anti-diabetes drugs for treatment of type 2 DM. There are very sparse evidences regarding comparative efficacy and safety of metformin versus acarbose, especially in Asian region. In addition to glycemic control, improvement in lipid profile, weight loss and post-prandial sugar level are important therapeutic objectives for better management of type 2 DM patients.Methods: In this study, 60 newly diagnosed type 2 DM were randomly assigned (1:1) to oral acarbose (titrated doses upto 300 mg daily) or oral metformin (titrated doses up to 2500 mg daily) monotherapy and were followed-up for 12 weeks for effects on glycaemic control [serum HbA1C, fasting blood sugar and post prandial sugar and serum LDL, HDL, triglycerides and total cholesterol.Results: Reduction in FBS, HbA1C and body weight was found significantly greater with metformin while acarbose yielded greater improvement in PPS, total cholesterol and triglyceride levels. Both metformin and acarbose yielded significant improvement in FBS, PPS, HbA1C, lipid profile and body weight after 12 weeks of therapy and yielded similar improvement in LDL and HDL levels.Conclusions: Acarbose can be considered as an alternative initial therapy in newly diagnosed type 2 diabetes patients, particularly those with isolated post-prandial hyperglycemia and those who are intolerant to metformin therapy.

Coenzyme Q10 therapy in current clinical practice

Coenzyme Q10 (CoQ10) is a naturally occurring, lipid soluble, essential compound and is also known as ubiquinone. CoQ10 acts as an intermediate of the electron transport chain situated in membrane of mitochondria and vital for ATP production and cellular respiration. CoQ10 also serves as an intercellular antioxidant. All the clinical use of CoQ10 are based upon these two functions. CoQ10 levels are altered in a number of oncological as well as non-oncological diseases. Furthermore, recent data indicate that CoQ10 has an impact on the expression of many genes involved in metabolism, cellular transport, transcription control, and cell signaling, making CoQ10 a potent gene regulator. CoQ10 supplementation is useful in diseases associated with CoQ10 deficiency which includes primary and secondary CoQ10 deficiencies, fibromyalgia, diabetes mellitus, mitochondrial diseases, neurodegenerative diseases, cardiovascular disease, cancer, male infertility and periodontal disease. Clinical presentations of severe CoQ10 deficiency include severe infantile multisystemic disease, encephalomyopathy, isolated myopathy cerebellar ataxia and Leigh syndrome with growth retardation. Oral CoQ10 administration can correct CoQ10 deficiency since it increases CoQ10 tissue levels. CoQ10 therapy has no serious side effects in humans and new formulations have been developed that increase CoQ10 absorption and tissue distribution. Future trends involving CoQ10 in many diseases needs more clinical trials for better understanding of CoQ10 efficacy

Interpretation of Biochemical Tests for Iron Metabolism in Hyperthyroidism

Objective: Several studies suggest that thyroid hormones may affect erythropoiesis. However the mechanism by which thyroid hormones alter the ferritin concentration is not well known. Therefore, the present case-control study was designed to determine the changes due to hyperthyroidism in serum ferritin, iron and transferrin levels and to investigate the inter-relationship between these parameters.Material: This study was conducted on 50 newly diagnosed hyperthyroid patients and the results were compared with 50 age and sex matched healthy controls. Serum ferritin was assessed by two site sandwich immunoassay using direct chemiluminometric technology. TIBC and serum iron were estimated by colorimetric method.Results: Serum ferritin (314.43 ± 68.7 ng/mL) and iron concentration (159.88 ± 36.28 µg/dL) were found to be increased in hyperthyroid patients as compared to healthy controls (255.23 ± 45.5 ng/mL and 110.52 ± 20.52 µg/dL respectively). There was a significant difference between hyperthyroid patients and healthy controls in serum levels of ferritin and iron (p0.05 for both). Serum ferritin and iron were correlated significantly positive with thyroid parameters while a significant negative correlation was found with transferrin.Conclusion: Our data suggest that alterations in thyroid status in a given individual produce significant changes in serum ferritin, iron and transferrin levels. Increased ferritin levels seem to be protective against increased oxidative stress seen in hyperthyroidism but these also increase atherosclerotic risk. However, a large scale study is recommended to establish the fact

Evaluation of Reid’s Combined Colposcopic Index as a predictor of cervical intraepithelial lesion

Background: Carcinoma cervix is the commonest cancer among women worldwide and in India it accounts for 80% of all genital cancers. Screening methods include cervical cytology, human papilloma virus testing and colposcopy. Objective of present study was to evaluate suspicious cervix colposcopically using Reids Colposcopic Index (RCI) and to correlate RCI with histopathological findings.Methods: This was a prospective cross sectional study done on 125 women with clinical diagnosis of suspicious cervix. Colposcopy was performed and grading of the disease was done according to RCI. Positive cases were subjected to cervical biopsy and endocervical curettage was performed in unsatisfactory colposcopy.Results: Colposcopy was done on 125 women with suspicious cervix. Out of 125, sixty two showed abnormal colposcopic findings which were graded according to RCI into Low grade disease predicting histological diagnosis of CIN1 in 47, Intermediate grade disease predicting histological diagnosis of CIN1/2 in 11 and High grade disease predicting histological diagnosis of CIN2/3 in 4 women. Colposcopy of one women suggested invasive carcinoma and was confirmed on histopathology to be microinvasive squamous cell carcinoma. Six women with unsatisfactory colposcopy showed benign histopathology. Sensitivity, specificity, predictive value and false negative rate of colposcopy for invasive disease was 50%, 100%, 100% and 1.60% respectively with 98.40% diagnostic accuracy. Colposcopic diagnosis of invasive disease and histopathology report showed 100% correlation.Conclusions: Correlation between RCI and histopathology was good. Predictive accuracy of colposcopy increased with increasing severity of disease

Ketamine but not glycine potentiates antidepressant like action of citalopram in mice exposed to chronic mild stress

Background: The present study was designed to investigate the effect of citalopram, ketamine, glycine and their combinations on animal models of depression. Methods: Swiss Albino male mice were subjected to chronic mild stress for 6 weeks for inducing depression, and randomly divided into different groups: citalopram (5 and 10 mg/kg), ketamine (17.5 and 35 mg/kg), glycine (50 and 100 mg/kg), ketamine (17.5 mg/kg) + citalopram (5 mg/kg) and ketamine (17.5 mg/kg) + glycine (50 mg/kg). Two behavioural tests were utilized for the assessment of depression, namely tail suspension test (TST) and forced swim test (FST). Immobility time was recorded for 6 min, before and after administration of drug. Results: Citalopram (10 mg/kg) administration caused significant decrease in the immobility time in TST model only but not in FST. Citalopram (5 mg/kg) and ketamine (17.5 mg/kg) caused insignificant decrease in immobility time in both the models. Moreover, ketamine in combination with Citalopram significantly reduced the immobility time in both the models. Glycine at a dose of 100 mg/kg (but not 50 mg/kg) significantly increased the immobility time in both the models as compared to control group. Further, ketamine when administered with glycine caused increase in the immobility time on both the paradigms, though insignificant. Conclusions: Ketamine demonstrated antidepressant like action in both TST and FST models. Moreover, it potentiated the antidepressant effect of citalopram that might be due to the role of NMDA receptors

The EJC disassembly factor PYM is an intrinsically disordered protein and forms a fuzzy complex with RNA

The discovery of several functional interactions where one or even both partners remain disordered has demonstrated that specific interactions do not necessarily require well-defined intermolecular interfaces. Here we describe a fuzzy protein–RNA complex formed by the intrinsically unfolded protein PYM and RNA. PYM is a cytosolic protein, which has been reported to bind the exon junction complex (EJC). In the process of oskar mRNA localization in Drosophila melanogaster, removal of the first intron and deposition of the EJC are essential, while PYM is required to recycle the EJC components after localization has been accomplished. Here we demonstrate that the first 160 amino acids of PYM (PYM1–160) are intrinsically disordered. PYM1–160 binds RNA independently of its nucleotide sequence, forming a fuzzy protein–RNA complex that is incompatible with PYM’s function as an EJC recycling factor. We propose that the role of RNA binding consists in down-regulating PYM activity by blocking the EJC interaction surface of PYM until localization has been accomplished. We suggest that the largely unstructured character of PYM may act to enable binding to a variety of diverse interaction partners, such as multiple RNA sequences and the EJC proteins Y14 and Mago

Blastoid Variant of Mantle Cell Lymphoma-a Rare Case Report

Abstract Mantle cell lymphoma is now recognised as a rare but distinct entity in the revised WHO classification. It is now well recognised that MCL represent a broad spectrum of different histopathological subtypes. The term blastic or blastoid variant is generally used to describe cases with a homogeneous population of cells displaying lymphoblastic morphology. The blastic form of MCL may be difficult to diagnose however immunophenotyping and molecular analysis show typical mantle cell lymphoma pattern. We present a case of 30 year old male presenting with inguinal mass which was diagnosed as blastic transformation of mantle cell lymphoma based on routine histopathology and immunohistochemistry

Elastic Moduli of Carbon Nanohorns

Carbon nanotube is a special case of carbon nanohorns or carbon nanocones with zero apex angle. Research into carbon nanohorns started almost at the same time as the discovery of nanotubes in 1991. Most researchers focused on the investigation of nanotubes, and the exploration of nanohorns attracted little attention. To model the carbon nanohorns, we make use of a more reliable second-generation reactive empirical bond-order potential by Brenner and coworkers. We investigate the elastic moduli and conclude that these nanohorns are equally strong and require in-depth investigation. The values of Young's and Shear moduli decrease with apex angle

Recognition of fold- and function-specific sites in the ligand-binding domain of the thyroid hormone receptor-like family

Background: The thyroid hormone receptor-like (THR-like) family is the largest transcription factors family belonging to the nuclear receptor superfamily, which directly binds to DNA and regulates the gene expression and thereby controls various metabolic processes in a ligand-dependent manner. The THR-like family contains receptors THRs, RARs, VDR, PPARs, RORs, Rev-erbs, CAR, PXR, LXRs, and others. THR-like receptors are involved in many aspects of human health, including development, metabolism and homeostasis. Therefore, it is considered an important therapeutic target for various diseases such as osteoporosis, rickets, diabetes, etc. Methods: In this study, we have performed an extensive sequence and structure analysis of the ligand-binding domain (LBD) of the THR-like family spanning multiple taxa. We have use different computational tools (information-theoretic measures; relative entropy) to predict the key residues responsible for fold and functional specificity in the LBD of the THR-like family. The MSA of THR-like LBDs was further used as input in conservation studies and phylogenetic clustering studies. Results: Phylogenetic analysis of the LBD domain of THR-like proteins resulted in the clustering of eight subfamilies based on their sequence homology. The conservation analysis by relative entropy (RE) revealed that structurally important residues are conserved throughout the LBDs in the THR-like family. The multi-harmony conservation analysis further predicted specificity in determining residues in LBDs of THR-like subfamilies. Finally, fold and functional specificity determining residues (residues critical for ligand, DBD and coregulators binding) were mapped on the three-dimensional structure of thyroid hormone receptor protein. We then compiled a list of natural mutations in THR-like LBDs and mapped them along with fold and function-specific mutations. Some of the mutations were found to have a link with severe diseases like hypothyroidism, rickets, obesity, lipodystrophy, epilepsy, etc. Conclusion: Our study identifies fold and function-specific residues in THR-like LBDs. We believe that this study will be useful in exploring the role of these residues in the binding of different drugs, ligands, and protein-protein interaction among partner proteins. So this study might be helpful in the rational design of either ligands or receptors