The Ameliorative Effect of Ashwagandha- Withania somnifera (L.) Dunal on park25 Induced Neurodegeneration in Drosophila melanogaster Parkinson’s Disease Model

Ashwagandha - Withania somnifera (L.) Dunal is a perennial shrub belonging to the family Solanaceae. Ashwagandha has been used for over 3000 years in traditional Indian Ayurveda for treatment of various neurological, and stress disorders. The root of Ashwagandha (ASH) is regarded as a tonic, aphrodisiac, narcotic, diuretic, anthelmintic, astringent, thermogenic and stimulant. Ashwagandha with other herbal decoctions was recognized to treat Kampavatha (Parkinson’s Disease) since 18th century. With this wide array of ethnopharmacological relevance, Ashwagandha has been recognized as one of the prominent complementary and alternative medicine to treat many neurodegenerative diseases like Alzheimer’s (AD) and Parkinson’s disease (PD). There is a prominent increase in the cases of AD and PD all over the world and it demands the requirement of complementary and alternative herbal remedies with no/minimal side effects. Many genetic factors are responsible for the onset and progression of PD. Loss-of-function mutations in the parkin gene are a major cause of early onset of autosomal recessive juvenile parkinsonism (AR-JP). Drosophila park25 loss of function mutants exhibit significantly increased number of mitochondria-endoplasmic reticulum contacts and a significantly decreased number of dopaminergic neurons in the adult brain which is the main cause of PD condition. Several studies have demonstrated the ability of Ashwagandha in imparting neuroprotection, improved locomotory ability, memory and learning abilities. The challenge lies in scrutinizing the mechanism and the pathways involved in the neuroprotective properties of this well-known herb. Here in our study, we test the possible neuroprotective effect of Ashwagandha on park25 mutants of Drosophila using lifespan analysis and climbing disability as a disease marker. Parkinson’s mimicking flies were administered with aqueous extraction of Ashwagandha-root mixed with the fly food and subjected to negative geotaxis assay. We observed that there is a prominent increase in the climbing ability in park25 treated flies compared to its age-matched untreated flies. This is the first report showing that, aqueous extraction of Ashwagandha-root extract was able to ameliorate the disease phenotype in the park25 Drosophila Parkinson’s disease model.

Report on Death of Dwarf Sperm Whale, Kogia sima (Order: Cetacea: Family: Kogiidae) in Vedalai Shore of Mandapam, Gulf of Mannar

Aims: Present study aims to highlight an accidental death of a male Dwarf Sperm Whale scientifically known as Kogia sima which found to be as Least Concern (LC) as per IUCN Red List data. Kogia sima represents important higher trophics of marine ecosystem which faced the several threats and conservation need in Gulf of Mannar, India. Study Design: The study undertaken during extensive coral reef monitoring survey was carried out in Gulf of Mannar under the CRAM Project of National Centre for Coastal Research (NCCR). The present report emphasize the Morphometric observation of the dead Kogia sima and try to find out possible cause of death by examining in situ investigation. Place and Duration of Study: The field study was taken in Vedalai Sea shore (N09�.626�, E79�.977�) under the Mandapam Union of Ramnathapuram District of Tamil Nadu. The male whale specimen was found on 5th May, 2019 lying dead on the sandy seashore. Methodology: Animal was photographed and morphological attributes were measured to identify the specimen. Several injuries have been highlighted in the paper which helps in investigating the cause of death. Results: The Dwarf Sperm Whale was infant and has mild damage on the mouth parts including scuff off skin from the body and severe blood clotting at major part of the right side near to pectoral fin. Death of this infant is not clear but it is assumed that the male infant has lost from his parents and came to the inshore area of Mandapam where it gets stuck with running boat or boulder rocks as this immature whale limits its diving capabilities. The necessary morphological characters and measures have been listed in Table 1. Conclusion: This unfortunate death clearly indicated that acute information on ecological behavior of Dwarf Sperm Whale is still under data collection stage in India and that previous conservation efforts in country must be reviewed in terms of role of local authorities, live stranded cetaceans and hunting or incidental killing which in future can build a road map for effective action plans to save this marine mammal.

Effect of Municipal Solid Waste Open Dumping on Soil, Water, Crop, Human Health and Its Prospectives

Characterization of heavy metals in 5 Km2 range of dumping yard in relation to soil, water and crop has been studied. The concentration of Cd (4.05 mg/kg) in soil was higher than the permissible limit of WHO (3 mg/kg) and in descending order of metals in soil was found to be Fe> Cr>Cd>Ni>Zn>Cu>Pb and in bore well water it was Cr, Fe, Pb, Cd, Zn and Cu (23.20, 0.63, 0.31, 1.19 and 0.69 mg/l respectively) than the permissible limit (0.54, 0.40, 0.068, 0.03, 0.22, 0.018 mg/l) and their respective concentration ordered as Fe>Zn>Cu>Pb>Cd>Ni>Cr. Further the vegetables grown nearby dumping yard was highly contaminated by Cr in range (2.78 to 12.78 mgkg-1) in tomato, beans and cabbage and even in ragi and green gram Cr was high (1.78 to 14.96 mgkg-1). i.e., in Tomato; Cd>Fe>Cr>Zn>Pb>Ni>Cu, Beans; Cr>Cd>Pb>Fe>Zn>Cu>Ni, Cabbage; Cr>Cd>Pb>Fe>Zn>Cu>Ni, Ragi; Fe and Zn were below permissible limit and Pb, Ni, Cu, Cd are BDL and Green gram; Cr>Fe>Zn>Pb>Cu > Ni>Cd. In support of results, primary survey was conducted in nearby 20 villages circumventing the dumping yard. A total of 150 respondents were randomly enquired to know their level of knowledge and health status as result of open dumping site. The results revealed that 43.33%, 36% and 20.67% as medium, high and low impact in relation to heath and knowledge aspect of dumping site. Thus there is a considerable impact on environment and humans due to the presence of heavy metal in crop, soil and water.

Acute olanzapine toxicity in a toddler

Olanzapine is an antipsychotic medication, which is approved for treatment of psychiatric illnesses among various age groups of psychiatric patients. Accidental consumption of olanzapine is uncommon among the paediatric age group. We report a case of accidental consumption of 15 tablets of olanzapine (5 mg each) in a two-year-old boy. It is important that clinicians are made aware of these reports of an overdose of olanzapine.

Perception and prejudice about organ donation among medical students in a tertiary healthcare, Mysuru

Background: Today, increase in deaths due to organ failure can be avoided if organ donors are available. Many states in India adopted the transplantation of human organs act and enthusiastic medical professionals and philanthropists joined hands to move the matter further forward. Lack of awareness about organ donation has been noted among the general public including medical professionals. Awareness can be promoted through medical students to bridge the gap of knowledge about organ donation and they can carry the message to the community. Hence an attempt has been made to probe this issue with objective to assess the perception and prejudice about organ donation among medical students.Methods: This cross-sectional study was conducted among medical students in a tertiary healthcare centre, Mysuru. A total of 201 students from 1st and 3rd term, consenting to participate were included in the study. A semi-structured self-administered questionnaire was used to collect data and was analysed using SPSS 22 version.Results: Knowledge about brain death was 73.1%, transplant of harvested organs was 59%, compatibility tests were 89% and organs donated by live donors were 89.6% for kidneys and 66.7% for cornea in cadaver donors. Regarding legal issues 73% knew that organ selling is criminal offence. 90% supported organ donation and related to prejudice 53% agreed that there are no religious constraints to donate organs.Conclusions: Knowledge and awareness regarding procedure, pre-requisites and legal issues related to organ donation needs to be improved among the medical students.

Prevalence and severity of depression among people residing in flood affected areas of Kerala

Background: The world is witnessing significant change in its climate leading to an increase in natural disasters. Kerala state of India recently witnessed its worst Monsoon rainfall in the century. Floods have significant effects on mental health. Screening of psychological problems is necessary in the background of recent floods in Kerala. So this study was done with the objectives to assess the prevalence of depression in the flood affected people of Kerala and to assess the severity of depression among people residing in flood affected areas of Kerala.Methods: Cross sectional study was done four weeks after flood. Individuals aged ≥15 years residing in flood affected areas were included and people not willing to participate were excluded. Purposive sampling was done and 306 participants were studied. Participants were assessed by interview technique using PHQ9 questionnaire. Data was analysed using SPSS-22. Descriptive statistics like percentage were applied. Inferential statistical tests like chi-square test were applied for association.Results: Among the participants 48% showed symptoms of depression. 28.10 % were mildly depressed, 12.74% were moderately depressed, 5.56% had moderately severe and 1.63% had severe depression. Maximum prevalence of depression was observed in geriatric age group.Conclusions: A significant amount of people residing in flood affected areas showed signs and symptoms of depression. An urgent intervention is therefore required to improve mental health status of the flood affected individuals.

Public health concern on occupational hazards among pathologists and microbiologists in Mysuru district, India

Background: Highly qualified and trained medical specialists such as Pathologists and Microbiologists who need to work at the microscope for long hours are at a high risk of musculoskeletal and ophthalmic disorders. This study is an attempt to identify such potential occupational hazards with the objectives to estimate the magnitude of occupational hazards among Pathologists and Microbiologists in Mysuru, and to assess the factors influencing these hazards among the study participants.Methods: This cross-sectional study was conducted among the Pathologists and Microbiologists of Mysuru district over a period of six months, a total of 45 study participants were included. An online self-administered questionnaire was sent to the study participants through e-mail and asked to fill and submit online, keeping complete confidentiality, and with informed consent. The results were analysed using appropriate statistical methods.Results: Pathologists and Microbiologists in almost equal proportions consented and took part in the study. 67% of them reported work related musculoskeletal problems, and 42% had visual refractive errors, mostly myopia. 9% of them reported to have experienced occupational injuries, mostly needle-stick injuries. None of them reported to smoke. Majority were happy with the work atmosphere and environmental conditions. Most of them were positive about the work-related situation in the coming years.Conclusions: This study found that more than half of the pathologists and microbiologists are exposed to occupational hazards and have suffered musculoskeletal, ophthalmic morbidities and had injuries, but none of which were life-threatening. Most of the risk factors are avoidable through ergonomic equipment and training.

Patient based factors influencing drug compliance among hypertensive patients in a tertiary care hospital in Mysore.

Background: Hypertension is deemed as the tip of the iceberg due to the mortality and morbidity associated with it. A major factor accounting for inadequate treatment of hypertension is poor compliance. Methods: Morisky 8-Item Medication Adherence Questionnaire was used for a cross sectional study. The term compliance is defined as the extent to which the patient’s behaviour coincides with the clinical prescription, implying that the patient defaults by not following the advice of the health care provider Results: Mean age of the participants was 59.2yrs (S.D. 10.37 yrs). Compliance was found to be good 71.3% of respondents, medium in 20.4% and poor in 8.3%.52.8% had one or two other ailments (diabetes, asthma etc.). Conclusions: Patient’s medication compliance is a multifactor behaviour in which the role of patient’s attitude is very important. Patients related factors known to affect compliance were equally distributed among good, medium and poorly compliant participants

Enhancement of dissolution rate of etoricoxib through solid dispersion technique.

Etoricoxib, a non-steroidal anti-inflammatory drug, is used to Osteoarthritis, Rheumatoid arthritis and Acute Gouty arthritis. Etoricoxib is practically insoluble in water; hence present study was carried out to enhance dissolution properties of Etoricoxib through the preparation of Solid Dispersions using PEG 6000 as carrier at various proportions by using different techniques like Physical mixtures, Kneading Method and Solvent Evaporation Method. The drug release profile was studied in 0.1N HCl containing 1 % SLS. U.V. Spectrophotometric method was selected for assay as well as in-vitro dissolution studies at 234nm.All the solid dispersions exhibited superior dissolution than pure drug. The drug dissolution studies followed first order kinetics. Solvent evaporation method was found to be superior to other methods.

Structure and function of enzymes involved in the anaerobic degradation of L-threonine to propionate.

In Escherichia coli and Salmonella typhimurium, L-threonine is cleaved non-oxidatively to propionate via 2-ketobutyrate by biodegradative threonine deaminase, 2-ketobutyrate formate-lyase (or pyruvate formate-lyase), phosphotransacetylase and propionate kinase. In the anaerobic condition, L-threonine is converted to the energy-rich keto acid and this is subsequently catabolised to produce ATP via substrate-level phosphorylation, providing a source of energy to the cells. Most of the enzymes involved in the degradation of L-threonine to propionate are encoded by the anaerobically regulated tdc operon. In the recent past, extensive structural and biochemical studies have been carried out on these enzymes by various groups. Besides detailed structural and functional insights, these studies have also shown the similarities and differences between the other related enzymes present in the metabolic network. In this paper, we review the structural and biochemical studies carried out on these enzymes.

Xanthelasma of esophagus and stomach.

Gastric xanthelasma, a benign condition, has been reported before; there has been no documentation of xanthelasma of the esophagus. We report a patient with xanthelasma of the stomach and esophagus.

Source and target enzyme signature in serine protease inhibitor active site sequences.

Amino acid sequences of proteinaceous proteinase inhibitors have been extensively analysed for deriving information regarding the molecular evolution and functional relationship of these proteins. These sequences have been grouped into several well defined families. It was found that the phylogeny constructed with the sequences corresponding to the exposed loop responsible for inhibition has several branches that resemble those obtained from comparisons using the entire sequence. The major branches of the unrooted tree corresponded to the families to which the inhibitors belonged. Further branching is related to the enzyme specificity of the inhibitor. Examination of the active site loop sequences of trypsin inhibitors revealed that here are strong preferences for specific amino acids at different positions of the loop. These preferences are inhibitor class specific. Inhibitors active against more than one enzyme occur within a class and confirm to class specific sequence in their loops. Hence, only a few positions in the loop seem to determine the specificity. The ability to inhibit the same enzyme by inhibitors that belong to different classes appears to be a result of convergent evolution.

Studies on simultaneous inhibition of trypsin and chymotrypsin by horsegram Bowman-Birk inhibitor.

Bowman-Birk inhibitors (BBI) isolated from plant seeds are small proteins active against trypsin and/or chymotrypsin. These inhibitors have been extensively studied in terms of their structure, interactions, function and evolution. Examination of the known three-dimensional structures of BBIs revealed similarities and subtle differences. The hydrophobic core, deduced from surface accessibility and hydrophobicity plots, corresponding to the two tandem structural domains of the double headed BBI are related by an almost exact two-fold, in contrast to the reactive site loops which depart appreciably from the two-fold symmetry. Also, the orientations of inhibitory loops in soybean and peanut inhibitors were different with respect to the rigid core. Based on the structure of Adzuki bean BBI-trypsin complex, models of trypsin and chymotryspin bound to the monomeric soybean BBI (SBI) were constructed. There were minor short contacts between the two enzymes bound to the inhibitor suggesting near independence of binding. Binding studies revealed that the inhibition of one enzyme in the presence of the other is associated with a minor negative cooperativity. In order to assess the functional significance of the reported oligomeric forms of BBI, binding of proteases to the crystallographic and non-crystallographic dimers as found in the crystal structure of peanut inhibitor were examined. It was found that all the active sites in these oligomers cannot simultaneously participate in inhibition.

Sister chromatid exchange studies in oral cancer patients.

Sister chromatid exchange (SCE) was studied in PHA-stimulated peripheral blood lymphocytes from 81 untreated patients with squamous cell carcinoma of the oral cavity and 50 age and sex matched controls. The SCE frequencies were found to be 10.80 +/- 1.38 and 4.15 +/- 1.15 in cancer cases and controls respectively. The SCE values of cancer cases deviate significantly from that of controls. The SCE frequency in patients who were addicted to the single habit of betel with tobacco chewing or bidi/cigarette smoking or combined habits of chewing and smoking was 9.38 +/- 1.28, 12.28 +/- 1.68 and 13.12 +/- 2.13 respectively. The SCE frequency in patients who were habituated to alcohol and tobacco usage was 13.43 +/- 2.16. These values were significantly higher as compared with the SCE values observed in normal controls. Single habit of bidi, cigarette and combined habit of bidi and cigarette smokers had a mean SCE per cell of 12.98 +/- 2.11, 10.18 +/- 1.25 and 13.48 +/- 1.32 respectively, which were significantly higher than the mean value of 4.15 +/- 1.15 found in controls. Higher frequencies of SCE were also observed in individuals who smoked more than 10 bidis or cigarettes per day compared with people who smoked less than 10 bidis or cigarettes per day. Individuals who smoked bidis or cigarettes for more than 10 years also showed an increased frequency of SCE as compared with those who smoked bidis or cigarettes for less than 10 years. Among chewers a significant difference was observed with regard to duration and frequency of chewing when compared to controls. An increase in the mean frequency of SCE for each cancer patient group is directly proportional to the clinical stage of the disease. Interchromosomal distribution of SCE revealed an increased frequency of SCE in almost all the groups of chromosomes in cancer patients when compared to controls.

Primary structure of sesbania mosaic virus coat protein: its implications to the assembly and architecture of the virus.

Sesbania mosaic virus (SMV) is a plant virus that infects Sesbania grandiflora plants in Andhra Pradesh, India. The amino acid sequence of the coat protein of SMV was determined using purified peptides generated by cleavage with trypsin, chymotrypsin, V8 protease and clostripain. The 230 residues so far determined were compared to the corresponding residues of southern bean mosaic virus (SBMV), the type member of sobemoviruses. The overall identity between the sequences is 61.7%. The amino terminal 64 residues, which constitute an independent domain (R-domain) known to interact with RNA, are conserved to a lower extent (52.5%). Comparison of the positively charged residues in this domain suggests that the RNA-protein interactions are considerably weaker in SMV. The residues that constitute the major domain of the coat protein, the surface domain (S-domain, residues 65-260), are better conserved (66.5%). The positively charged residues of this domain that face the nucleic acid are well conserved. The longest conserved stretch of residues (131- 142) corresponds to the loop involved in intersubunit interactions between subunits related by the quasi 3-fold symmetry. A unique cation binding site located on the quasi 3-fold axis contributes to the stability of SMV. These differences are reflected in the increased stability of the SMV coat protein and its ability to be reconstituted with RNA at pH 7.5. A major epitope was identified using monoclonal antibodies to SMV in the segment 201-223 which contains an exposed helix in the capsid structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Crystal structure of cadaverine dihydrochloride monohydrate.

The structure of cadaverine dihydrochloride monohydrate has been determined by X-ray crystallography with the following features: NH3+ (CH2)5NH3+.2Cl-.H2O, formula weight 191.1, monoclinic, P2, a = 11.814(2)A, b = 4.517(2)A, c = 20.370(3)A, beta = 106.56 degrees (1): V = 1041.9(2)A3; lambda = 1.541A; mu = 53.41; T = 296 degrees; Z = 4, Dx = 1.218 g.cm-3, R = 0.101 for 1383 observed reflections. The crystal is highly pseudo-symmetric with 2 molecules of cadaverine, 4 chloride ions and 2 partially disordered water molecules present in the asymmetric unit. Though both the cadaverine molecules in the asymmetric unit have an all trans conformation, the carbon backbones are slightly bent. Between the concave surfaces of two bent cadaverine molecules exists water channels all along the short b axis. The water molecules present in the channels are partially disordered.

Crystal and molecular structure of sym-homospermidine monohydrate.

Sym-homospermidine, [formula; see text] is a naturally occurring rare-polyamine found in relatively large concentration in sandal leaves. As part of our studies on structure and interactions of polyamines, sym-homospermidine was purified from sandal leaves and its structure was determined by single crystal X-ray diffraction technique. The phosphate salt of the molecule crystallized in the triclinic space group P1- with a = 8.246(1)A, b = 8.775(1)A, c = 15.531(2)A, alpha = 74.20(1) degrees, beta = 88.36(1) degrees and gamma = 65.41(1) degrees. The structure was determined by direct methods and refined to a final R factor of 5.4% for 2087 reflections with magnitude of F(obs) greater than 5 sigma [F(obs)]. The amine exists in its most favourable all trans conformation. For each amine molecule three phosphate groups exist in the crystal structure, suggesting that two of the oxygens of each phosphate group are protonated. There is also a single water molecule in the asymmetric unit in contrast to that of spermidine phosphate which has 3 water molecules. These differences probably reflect the hydrogen bonding properties of mono-ionic and di-ionic phosphate groups. The structure is predominantly stabilized by a network of hydrogen bonds.

Naphthol and lens.

Alpha and beta naphthols, the metabolites of naphthalene, a cataractogenic agent, was tested for it's effect on sheep lens proteases and their inhibitors. It reduced protease activities, not that of inhibitor activities of lens proteins. It also increased the efflux of free amino acid from lenses which was retarded by a high concentration of tissue galactose.