Randomized, single-dose, two-period, two-sequence crossover bioequivalence study evaluating two oral formulations of lamotrigine in healthy volunteers

Background: Lamotrigine is an anti-epileptic medicine used to treat epilepsy and bipolar disorder. The mechanism of action is to block voltage activated sodium channels. The aim of this study was to evaluate the bioequivalence of 2 oral formulations of lamotrigine 25 mg in healthy volunteers.Methods: A single-dose, two-period, randomized crossover study design in - healthy Indian adult volunteers was conducted at Amaris Clinical, a division of Caplin Point Laboratories Ltd., Chennai. A validated high performance liquid chromatography in conjunction with mass spectrometry was used. Lamotrigine concentration in plasma. Adverse events were determined by measuring vital functions after dosing. A total of 24 subjects were included.Results: The mean and 90% confidence intervals of the test / reference ratios for these parameters were as follows: The mean Cmax and Tmax of the test were 758.606 (157.453) ng / ml and 1.17 (0.50-5.00) hours, respectively. The mean Cmax and Tmax of the reference were 775.993 (151.654) ng / ml or 0.88 (0.25-4.00) hours. The mean AUC0-72 was 24142. 031±3641.691 (ng.hr/mL) for the test formulation and 24202.099±3742.957 (ng. h / ml) for the reference formulation. The mean test / reference ratios for Cmax and AUC0-72 were 97.92 and 99.82 respectively. The 90% parametric CIs for Cmax and AUC0-72 were 90.17-105.68% or 97.87-101.81%.Conclusions: The 90% confidence intervals ranged from 80-125% and it was concluded that the test product was bioequivalent to the reference product in these healthy adult male volunteers.

Изменение диэлектрических потерь резин на основе этилен-пропиленовых каучуков со временем ионизационного старения

В работе изучалось влияние вулканизующей группы и наполнителя на диэлектрические потери резин на основе этилен-пропиленовых каучуков и изменение диэлектрических потерь со временем ионизационного старения. Установлено, что диэлектрические потери и изменения их со временем ионизационного старения в значительной степени зависят от типа вулканизующей группы и наполнителя

'जिन्दा पत्थर’ (लाइव रॉक) की स्थापना और अनुरक्षण

कृपया पूरा लेखा पढ

Prevalence, severity, causes and drugs used for depression, stress and anxiety among junior doctors in a tertiary care teaching hospital in South India

Background: Due to various reasons, junior doctors experience high level of stress in their workplace. However, very few studies have been done to analyze the stress levels and pertinent causative factors among junior doctors in India. So the present study was done to investigate the prevalence, severity and causes of depression, stress and anxiety among junior doctors along with the drugs used to mitigate them.Methods: A cross sectional, questionnaire based study was conducted on a total of 114 junior doctors who include 80 interns and 34 post graduates belonging to  2013-14 batch, utilizing the 21-item depression, anxiety and stress scale (DASS 21). A personal interview was also conducted to enquire into the causes responsible for the stress and the medications employed by them to overcome it.Results: Among the interns, the mean depression score was 5.64±3.85, mean anxiety score was 6.69±3.86 and mean stress score was 7.33±3.22. Among the post graduates, the mean depression score was 4.73±2.15, mean anxiety score was 5.18±3.19 and mean stress score was 7.82±2.68. The percentage of junior doctors who had severe or extremely severe scores of depression was 11.40%, anxiety was 40.35% and stress was 9.65%. Alcohol was the most commonly used psychotropic drug (60.87%). Frequent calls during night duties and late working hours were the leading causes for stress among junior doctors.Conclusions: Overall higher stress was observed among post graduates compared to interns and females compared to males. Anxiety was more severe compared to depression and stress among junior doctors. Reducing working hours and increasing workplace flexibility are some measures to reduce stress among the junior doctors

Early Harappan interaction between Sindh and Gujarat, as evidenced by lithic tools

The spread and development of the Indus Valley Civilisation, also known as the Harappan civilisation, one of the oldest civilisations of the world, is still an enigma. Indus Valley Civilisation was spread over modern day India and Pakistan. The civilisation has been divided into three phases, Early or Pre-Harappan, Mature or Urban Harappan and Post- or Late Harappan. The Urban phase is very well studied and understood. However, this phase is the culmination of a process that started much earlier. A lot of effort during recent years has led to new discoveries and clues regarding the interactions during the Early Harappan period between now politically divided areas. Unfortunately, this struggle to understand the spread of Early Harappan cultural traits between these distinct regions is one on-going and far from over. Explorations and subsequent excavations at the site of Juna Khatiya, situated in Kachchh district of Gujarat, India have brought to light noteworthy evidence of the Early Harappan period in terms of artefacts and burials. Other than the ubiquitous pottery, these indications include a lithic blade industry comprising of various types of blades, various types of scrapers, points and associated lithic debitage. The tools are made out of locally available raw material (mostly chalcedony). However, the discovery of a few blades of chert imported from the Rohri hills (situated about 500 km as-the-crow-flies from Gujarat) in modern Pakistan is important. Rohri chert blades are significant since they are very distinct and easily identifiable. The wide distribution of standardised Rohri chert blades is also often regarded as a testimony to the Harappan efficiency in long distance trade and craft production. The technique used in the manufacturing of these blades is known as the crested guiding ridge, a technique not observed in Gujarat before this contact between Sindh (in modern Pakistan) and Gujarat (in modern India) developed. This paper highlights the contributions of lithic artefacts to understand the Early Harappan interactions between these two politically divided but culturally united regions

Lymphoid priming in human bone marrow begins before expression of CD10 with upregulation of L-selectin.

Expression of the cell-surface antigen CD10 has long been used to define the lymphoid commitment of human cells. Here we report a unique lymphoid-primed population in human bone marrow that was generated from hematopoietic stem cells (HSCs) before onset of the expression of CD10 and commitment to the B cell lineage. We identified this subset by high expression of the homing molecule L-selectin (CD62L). CD10(-)CD62L(hi) progenitors had full lymphoid and monocytic potential but lacked erythroid potential. Gene-expression profiling placed the CD10(-)CD62L(hi) population at an intermediate stage of differentiation between HSCs and lineage-negative (Lin(-)) CD34(+)CD10(+) progenitors. CD62L was expressed on immature thymocytes, and its ligands were expressed at the cortico-medullary junction of the thymus, which suggested a possible role for this molecule in homing to the thymus. Our studies identify the earliest stage of lymphoid priming in human bone marrow

Loop diuretic-induced hyponatremia: a case report

Hyponatremia is the most common encountered electrolyte abnormality where the serum sodium concentration is <136 mEq/L. The most common causes are either the concurrent illnesses or the medications. Diuretics top the list of drugs inducing hyponatremia and this occurs more frequent within 2 weeks of initiating therapy. Though thiazide diuretics are frequently the culprits of inducing hyponatremia, the role by/risk with loop diuretics cannot be ignored. Prompt diagnosis and management of hyponatremia needs a sound knowledge with which permanent neurologic sequelae and morbidity could be prevented. Here, we report a case of hyponatremia induced by loop diuretic and spironolactone combination, where the presenting complaints of the patient were only intractable nausea and altered taste. The patient was successfully managed with hypertonic saline and the vasopressin receptor antagonist, tolvaptan, which belongs to a new class of drugs called aquaretics

Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer

Increased numbers of myeloid-derived suppressor cells (MDSCs) are positively correlated with poor prognosis and reduced survivals of cancer patients. They play central roles in tumor immune evasion and tumor metastasis. However, limited data are available on phenotypic/transcriptomic characteristics of the different MDSCs subsets in cancer. These cells include immature (I-MDSCs), monocytic (M-MDSCs), and polymorphonuclear/granulocytic (PMN-MDSCs). Phenotypic characterization of myeloid subsets from 27 colorectal cancer (CRC) patients was assessed by flow cytometric analyses. RNA-sequencing of sorted I-MDSCs, PMN-MDSCs, and antigen-presenting cells (APCs) was also performed. We found that the levels of I-MDSCs and PMN-MDSCs were increased in tumor tissues (TT), compared with normal tissues (NT) in colorectal cancer. Our functional annotation analyses showed that genes associated with histone deacetylase (HDAC) activation- and DNA methylation-mediated transcriptional silencing were upregulated, and histone acetyl transferase (HAT)-related genes were downregulated in tumor-infiltrating I-MDSCs. Moreover, pathways implicated in cell trafficking and immune suppression, including Wnt, interleukin-6 (IL-6), and mitogen-activated protein kinase (MAPK) signaling, were upregulated in I-MDSCs. Notably, PMN-MDSCs showed downregulation in genes related to DNA methylation and HDAC binding. Using an ex vivo model, we found that inhibition of HDAC activation or neutralization of IL-6 in CRC tumor tissues downregulates the expression of genes associated with immunosuppression and myeloid cell chemotaxis, confirming the importance of HDAC activation and IL-6 signaling pathway in MDSC function and chemotaxis. This study provides novel insights into the epigenetic regulations and other molecular pathways in different myeloid cell subsets within the CRC tumor microenvironment (TME), giving opportunities to potential targets for therapeutic benefits