Insights on kinetic triplets and thermodynamic analysis of Delonix regia biomass pyrolysis.

The aim of this work was to study the pyrolysis of Delonix regia biomass with non-isothermal thermogravimetric experiments. The targeted objective was to investigate kinetic triplets and thermodynamic parameters. Five iso-conversional methods, namely Differential Friedman, Kissinger-Akahira-Sunose, Ozawa-Flynn-Wall, Starink, and Distributed Activation Energy, have been considered. In the adopted heating rates of 5-55 °C min-1, the average activation energy and pre-exponential factor varied in the range 202.34-205.89 kJ mol-1 and 4.98 × 1017 - 2.04 × 1020 s-1 respectively. Corresponding average enthalpy and Gibbs free energy varied from 196.84 to 200.87 kJ mol-1 and from 182.64 to 206.41 kJ mol-1 respectively. Pyrolysis mechanism have been confirmed by Avrami-Erofeyev (A4), power-law (P2 and P4) and reaction (F1, F2, and ≥ F5) according to Criado's master plots.

Cisplatin-based Electrochemotherapy Significantly Downregulates Key Heat Shock Proteins in MDA-MB-231-Human Triple-Negative Breast Cancer Cells.

Heat shock proteins (HSPs) are available and/or induced for the survival of all organisms, including eukaryotic, prokaryotic, and plants, from higher temperature stresses. They are the chaperone proteins that protect all cells against heat, as the name implies. In addition to thermal stress, they also protect them from chemical, physical, and other stresses, including exposure to oxidative stress, nutritional deficiencies, ultraviolet radiation, ethanol, viral infection, ischemia-reperfusion injury, and cancer-related stresses. They are classified based on their molecular weights in kDa, such as HSP90 and HSP70. In our label-free, high-throughput, quantitative LC-MS/MS-based proteomic studies of MDA-MB-231, human, triple-negative breast cancer cells, treated with electrical pulses (EP) and cisplatin (CsP), we identified a number of HSPs, such as HSP90AA1, and others to be significantly downregulated in EP + CsP, compared to CsP alone. This indicates that cells will undergo apoptotic cell death and hence could cause effective cancer cure/treatment. Considering that over 2 million new cases and over 600,000 deaths in 2020, of which ~ 15% are TNBC, heat shock proteins could be the untapped resources, available for the next biomarkers and/or inhibitors for new/additional therapies.

Alkali induced unique partially folded state of bovine serum albumin: qualitative and quantitative insights.

Qualitative and quantitative understanding of partially folded states of protein is essential in gaining deeper insights into folding pathways. We have observed a partially folded state of bovine serum albumin (BSA) in the presence of 2,2,2-trifluoroethanol at pH11.2 which does not resembles the properties of the molten globule state. ThT, a frequently used marker for protein fibrils have two order of greater affinity towards the intermediate state at pH11.2 compared to native BSA at pH7.4. Surprisingly, the binding of ANS with this partially folded state is weaker than that of native state of BSA. Combined fluorescence, circular dichroism spectroscopy and isothermal titration calorimetric studies indicate that for such partially folded state, ThT is a better marker compared to ANS. The results have highlighted the importance of dyes like ThT in characterizing partilally folded states of protein which might appear as intermediates in the funnel moldel describing the protein folding pathway.

Formulation and Evaluation of Niosomal in situ Nasal Gel of a Serotonin Receptor Agonist, Buspirone Hydrochloride for the Brain Delivery via Intranasal Route.

BACKGROUND: Buspirone Hydrochloride is an anxiolytic agent and serotonin receptor agonist belonging to azaspirodecanedione class of compounds used in the treatment of anxiety disorders. It has short half-life (2-3h) and low oral bioavailability (4%) due to extensive first pass metabolism. OBJECTIVE: The nasal mucosa has several advantages viz., large surface area, porous endothelial membrane, high blood flow, avoidance of first-pass metabolism and ready accessibility that lead to faster and higher drug absorption. Keeping these facts in mind, the objective of the present study was to develop Buspirone hydrochloride loaded niosomal in-situ nasal gel. METHODS: Buspirone hydrochloride niosomal in situ nasal gel was formulated, optimized and evaluated with the objective to deliver drug to the brain via intranasal route. Niosomes were prepared by thin film evaporation method and optimized using32 factorial design. Niosomes were characterized for particle size, zeta potential, entrapment efficiency and in vitro drug release. Buspirone hydrochloride loaded niosomes were further incorporated into Carbopol 934P and HPMC K4M liquid gelling system for the formation of in situ gel. The resultant solution was assessed for various parameters, viz., gelling time, gelling capacity, viscosity at pH 5 and pH 6. RESULTS: The vesicle size of all niosomal suspension batches ranges between 168.3 -310.5 nm. The vesicle size of optimized niosomal suspension F5 batch is 181.9±0.36nm. For F5 batch, the value of zeta potential was found to be -15.4 mV; this specifies that prepared niosomes have sufficient surface charge to prevent aggregation of the vesicles. % entrapment efficiency for all batches was found in the range 72.44±0.18% to 87.7±0.66%. The cumulative percent release of niosomal suspension ranges from 66.34±0.39 to 84.26±0.26%. Ex vivo permeation of Buspirone hydrochloride through the sheep nasal mucosa showed that 83.49% w/w drug permeated after 8 h. The SEM and Zeta potential studies showed the formation of stable vesicles. CONCLUSION: Thus, the application of niosomes proved the potential for intranasal delivery of Buspirone hydrochloride over the conventional gel formulations. Overall intranasal drug delivery for Buspirone hydrochloride has been successfully developed.

Alkaloids from aerial parts of Annona senegalensis against Streptococcus mutans.

Antimicrobial potential of medicinal plants have been explored extensively these days. This study was carried out to evaluate the antibacterial potential from aerial parts of plant, called 'Annona senegalensis' and its constituents. Bioassay guided fractionation led to the isolation of four metabolites, (+)-catechin (1), (-)-anonaine (2), (-)-asimilobine (3) and (+)-nornantenine (4). This is the first report on the isolation of compounds 1, 3 and 4 from this plant. Compounds 2 and 4 showed good activity, whereas 1 and 3 displayed weak inhibition against Streptococcus mutans (ATCC 25175). The results showed that compound 2 and 3 showed significant activity with a minimum inhibition concentration (MIC) of 0.12 and 0.25 mg/mL, respectively. The present study reports for the first time the antibacterial activity of the extract of A. senegalensis and its constituents. As S. mutans is a rather resistant bacteria, the MIC obtained during the present study is significant.

Metallic sewing needle ingestion presenting as acute abdomen.

We reported an unusual case of a 26-year-old man presenting to surgical emergency as generalized peritonitis following an ingestion of multiple metallic sewing needles. The X-ray of his abdomen showed pneumoperitoneum and multiple metallic foreign bodies in the abdominal cavity. An ultrasonogram of his abdomen showed multiple metallic foreign bodies in the abdominal cavity and urinary bladder. Emergency exploratory laparotomy was performed. On laparotomy, gastric and duodenal perforation was found through which metallic sewing needles were protruding out. A peritoneal lavage was done, and all the sewing needles were extracted from the perforation site, paracolic gutter, liver parenchyma, and urinary bladder. The primary repair of the perforation with omental patching was done with the drainage of subhepatic space and pelvic cavity. These multiple ingested sewing needles led to the perforation of the stomach and the duodenum, which resulted in perforation peritonitis.

Development and evaluation of tamarind seed xyloglucan-based mucoadhesive buccal films of rizatriptan benzoate.

Mucoadhesive buccal films were developed using tamarind seed xyloglucan (TSX) as novel mucoadhesive polysaccharide polymer for systemic delivery of rizatriptan benzoate through buccal route. Formulations were prepared based on 3(2) factorial design with concentrations of TSX and carbopol 934P (CP) as independent variables. Three dependent variables considered were tensile strength, bioadhesion force and drug release. DSC analysis revealed no interaction between drug and polymers. Ex vivo diffusion studies were carried out using Franz diffusion cell, while bioadhesive properties were evaluated using texture analyzer with porcine buccal mucosa as model tissue. Results revealed that bilayer film containing 4% (w/v) TSX and 0.5% (w/v) CP in the drug layer and 1% (w/v) ethyl cellulose in backing layer demonstrated diffusion of 93.45% through the porcine buccal mucosa. Thus, this study suggests that tamarind seed polysaccharide can act as a potential mucoadhesive polymer for buccal delivery of a highly soluble drug like rizatriptan benzoate.

Skin prick testing and immunotherapy in nasobronchial allergy: our experience.

In the present study of 331 patients suffering from signs/symptoms of nasal allergy, 9 nasal polyps, allergic conjunctivitis and allergic asthma, who were referred by clinician, were taken up for diagnosis of allergy with skin prick test (Ten et al. Mayo Clin Proc 70(8):783-784, 1995) and subjective improvement of patients by immunotherapy. Out of 331 patients tested 321 patients showed significant positive results and rest of them tested negative for allergy. High incidences of positive results were noted in third and fourth decade age of patients. Dust and pollen allergens were positive in most of the patients compare to insect's antigens. Among the pollen antigens tested, those of Parthenium hysterophorus was found to be the most common (30%) followed by Prosopis julifora (25%). 75.22% patients were positive to house dust, 19.33% patients were positive to Aspergillusmoulds. D. farinae was the most common offender amongst the mites. Patients who attended, allergy clinic in Kamineni Hospitals during the last 4 years were referral patients, who had been on prolonged treatment without much relief. Immunotherapy was advised to patients who were having perineal allergy, in whom, medical treatment had become only palliative. Immunotherapy injections were administered subcutaneously, and their results were monitored.

Screening fetal echocardiography in diabetic mothers with normal findings on detailed anatomic survey.

OBJECTIVES: To evaluate the benefit of second-trimester fetal echocardiography for women with diabetes whose fetuses had no obvious heart disease on a detailed anatomic survey performed at skilled, high-volume obstetric centers, and to investigate the technical limitations of fetal echocardiography in this patient population. METHODS: This was a retrospective descriptive review of fetal echocardiograms performed at Children's Hospital Boston from 2000 to 2005. All women referred during the second trimester for fetal echocardiography because of maternal diabetes were included. Those with severe heart disease suspected on obstetric ultrasound examination were excluded. RESULTS: There were 584 initial fetal echocardiograms. No patients were diagnosed with severe heart disease prenatally. Nineteen were diagnosed with suspected mild heart disease (such as small ventricular septal defect), five of whom had normal follow-up fetal evaluation and five of whom had normal postnatal evaluation. Most of these pregnancies did not have a postnatal cardiac evaluation. Forty-seven fetuses had benign cardiac findings. Nearly one third of patients had imaging that was felt to be limited or incomplete, mostly due to poor acoustic windows. Forty-eight patients were asked to return for at least one follow-up visit, most due to the inability to complete the exam at the initial visit. CONCLUSIONS: In an environment with access to high-volume, skilled comprehensive ultrasound services, fetal echocardiography by a pediatric cardiology program adds little to the care of women with diabetes and no suspected heart disease on a detailed anatomic survey. Poor acoustic windows frequently necessitate multiple visits.

In vitro culture methods in sorghum with shoot tip as the explant material.

Twenty-four diverse genotypes of sorghum were evaluated for response to callus induction and plant regeneration with two media viz., MS and NBKNB using shoot tips as the start material to identify a model genotype. None of the genotypes tested showed promising results. Therefore, alternative methods of in vitro pathways using shoot meristem isolated from shoot tips were explored. Shoot apical meristems were isolated and were induced to multiple shoots or multiple shoot buds pathway by manipulation of thidiazuron (TDZ), 6-benzyl adenine (BAP) and 2, 4-dichlorophenoxy acetic acid (2, 4-D). Choice of the pathway whether large-scale multiplication of shoots or production of target tissues for transformation can be exercised based on the needs and applications. A simple procedure, for large scale handling of shoot tips is described in detail. Electron microscopic studies revealed that meristems isolated from 7-day-old seedlings are superior because of possessing greater number of transformation competent cells.

Structural, optical, physical and electrical properties of V2O5.SrO.B2O3 glasses.

The present work aims to study the structure and variation of optical band gap, density and dc electrical conductivity in vanadium strontium borate glasses. The glass systems xV2O5.(40-x)SrO.60B2O3 and xV2O5.(60-x)B2O3.40SrO with x varying from 0 to 20 mol% were prepared by normal melt quench technique. Structural studies were made by recording IR transmission spectra. The fundamental absorption edge for all the glasses was analyzed in terms of the theory proposed by Davis and Mott. The position of absorption edge and hence the value of the optical band gap was found to depend on the semiconducting glass composition. The absorption in these glasses is believed to be associated with indirect transitions. The origin of Urbach energy is associated with the phonon-assisted indirect transitions. The change in both density and molar volume was discussed in terms of the structural modifications that take place in the glass matrix on addition of V2O5. dc conductivity of the glass systems is also reported. The change of conductivity and activation energy with composition indicates that the conduction process varies from ionic to polaronic one.

Better mental health care for older people in India.

Demographic aging will soon lead to a sudden increase in the number of older people with dementia and depression in India. We need to develop services to meet the mental health needs of the aged in the population. Geriatric Psychiatry section of IPS has initiated a process of consultations to address this emerging public health issue. Health professionals involved in the care of older people with mental health problems took part in focus group discussions Their opinion and suggestions regarding development of psychogeriatric services and research were gathered. Urgent action is needed to improve the existing low levels of public awareness about mental health problems of older people. Home based care needs to be supported through formal services in the community. If sensitised properly clinicians, can be more effective in managing depression and dementia at primary care level. Research initiatives can be facilitated by networking of researchers and active efforts at dissemination of important research findings. Community health workers could be trained to identify and provide help to older people with mental health problems and their carers. Community outreach programmes for elderly could be particularly relevant in the rural areas where as development of clinic based psycho-geriatric services may be feasible in urban settings. Good research can influence and shape policies which in turn can result in better mental health care for older people.

Revealing a hidden problem. An evaluation of a community dementia case-finding program from the Indian 10/66 dementia research network.

BACKGROUND: Dementia in India is largely a hidden problem with no community awareness and little help seeking from affected families, despite high levels of strain. Cases must therefore be identified before practical help can be offered. METHOD: After two and a half hours of formal training, local community health workers in rural Kerala were asked to identify possible cases of dementia from the community they served. Diagnoses were then verified by a senior local psychiatrist with clinical and research interests in old age psychiatry. RESULTS: The community health workers identified 51 out of 1979 over 60 year old residents (a prevalence of 2.6%) as suspected cases of dementia. Following the psychiatrist's assessment, 33 met DSM-IV criteria for dementia. The majority of confirmed cases were of the Alzheimer's Disease sub-type. Most "non-cases" were found to be suffering from other major psychiatric disorders, with substantial unmet need. The positive predictive value of the community health workers informal screening was 64.7%. CONCLUSIONS: This simple cost-effective case-finding method can be of practical use in the development of community based dementia care services in India and other developing countries with similar health care systems.

People'S participation in mental health planning the kerala initiative.

Kerala state branch of IPS sought suggestions from the public regarding the state policy on mental health. The letters received from the people were analysed and most suggestions were found to be useful. Suggestions made by the people and the psychiatrists were similar in content. This observation highlights the usefulness of 'user-provider collaboration' in mental health planning. Both user as well as the 'providers' need to be consulted in order to establish user-friendly mental health services.

Discovery of a novel series of selective MMP inhibitors: identification of the gamma-sulfone-thiols.

We have discovered a new series of potent MMP Inhibitors that are selective for MMP-13 over MMP-1 incorporating a gamma-sulfone thiol.

Prediction of maximal aerobic power in healthy Indian males 21-58 years of age.

An attempt has been made in this paper to predict maximal aerobic power (VO2max) in healthy Indian males by three important physical characteristics (viz. age, height and body weight) using the technique of multivariate regression analysis for a wide age group ranging from 21 to 58 years. It has been observed that these characteristics can contribute significantly to the prediction of maximal aerobic power. Three combinations of predictors of two predictors at a time have also been tried to predict maximal aerobic power. Out of these three combinations, the combination of age and body weight has the maximum multiple correlation (R = 0.536, P < 0.001) for a group of 146 subjects of healthy Indian males. A nomogram has been constructed to predict VO2max from age and body weight in order to make the developed multiple linear regression equation of more practical utility to the biomedical scientists who may not be well acquainted with the statistical computational work.

A thermodynamic investigation of reactions catalyzed by tryptophan synthase.

Microcalorimetry and high-performance liquid chromatography have been used to conduct a thermodynamic investigation of the following reactions catalyzed by the tryptophan synthase alpha 2 beta 2 complex (EC 4.2.1.20) and its subunits: indole(aq) + L-serine(aq) = L-tryptophan(aq) + H2O(1); L-serine(aq) = pyruvate(aq) + ammonia(aq); indole(aq) + D-glyceraldehyde 3-phosphate(aq) = 1-(indol-3-yl)glycerol 3-phosphate(aq); L-serine(aq) + 1-(indol-3-yl)glycerol 3-phosphate(aq) = L-tryptophan(aq) + D-glyceraldehyde 3-phosphate(aq) + H2O(1). The calorimetric measurements led to standard molar enthalpy changes for all four of these reactions. Direct measurements yielded an apparent equilibrium constant for the third reaction; equilibrium constants for the remaining three reactions were obtained by using thermochemical cycle calculations. The results of the calorimetric and equilibrium measurements were analyzed in terms of a chemical equilibrium model that accounted for the multiplicity of the ionic states of the reactants and products. Thermodynamic quantities for chemical reference reactions involving specific ionic forms have been obtained. These quantities permit the calculation of the position of equilibrium of the above four reactions as a function of temperature, pH, and ionic strength. Values of the apparent equilibrium constants and standard transformed Gibbs free energy changes delta r G'(m) degree under approximately physiological conditions are given. Le Châtelier's principle provides an explanation as to why, in the metabolic pathway leading to the synthesis of L-tryptophan, the third reaction proceeds in the direction of formation of indole and D-glyceraldehyde 3-phosphate even though the apparent equilibrium constant greatly favors the formation of 1-(indol-3-yl)glycerol 3-phosphate.

Novel biologically active nonpeptidic inhibitors of myristoylCoA:protein N-myristoyltransferase.

A new class of biologically active nonpeptidic inhibitors of Candida albicans NMT has been synthesized starting from the octapeptide ALYASKLS-NH2 (2). The synthetic strategy entailed the preparation of novel protected Ser-Lys mimics 9 and 12 from (S)- or (R)-3-iodotyrosine and then grafting key enzyme recognition elements in a stepwise manner. Like 2, compounds 16, 17, and 18 are competitive Candida NMT inhibitors that bind to the peptide recognition site of the enzyme. Moreover, 16-18 have an affinity comparable to that of 2 even though they are devoid of peptide bonds. In contrast to 2, these nonpeptidic inhibitors exhibit antifungal activity.