Rapid 'one-pot' synthesis of a novel benzimidazole-5-carboxylate and its hydrazone derivatives as potential anti-inflammatory and antimicrobial agents.

A novel series of N-arylidene-2-(2,4-dichloro phenyl)-1-propyl-1H-benzo[d] imidazole-5-carbohydrazides having different substitution on the arylidene part were synthesized in good yield. The core nucleus benzimidazole-5-carboxylate (5) was efficiently synthesized by 'one-pot' nitro reductive cyclization reaction between ethyl-3-nitro-4-(propylamino)benzoate and 2,4-dichlorobenzaldehyde using sodium dithionite in dimethylsulfoxide. This 'one-pot' reaction was proceeded very smoothly, in short reaction time with an excellent yield. All the compounds (7a-r) were screened for their in vivo anti-inflammatory and in vitro antimicrobial activity. Most of the compounds exhibited remarkable paw-edema inhibition in the initial one hour of administration indicating the higher potentiality of these molecules. In particular, compounds 7a, 7d, 7f and 7g displayed a high level of carrageenan-induced paw edema inhibition compared to that of indomethacin. Compound 7p exhibited very good antibacterial activity and antifungal activity with a MIC of 3.12 µg/mL against most of the tested organisms. Furthermore, compounds 7d, 7f, 7h and 7p found to be good inhibitors of Aspergillus niger with MIC of 3.12 µg/mL. Cytotoxicity of the potent compounds 7d, 7f and 7p was checked using MDA MB-231 breast cancer cell line and are found to be non toxic at the highest concentration used (i.e., 10 µg/mL).

SYNTHESIS AND BIOLOGICAL EVALUATION OF N-(SUBSTITUTED PHENYL)-2-(5H-[1,2,4]TRIAZINO[5,6-b]INDOL-3-YLSULFANYL)ACETAMIDES AS ANTIMICROBIAL, ANTIDEPRESSANT AND ANTICONVULSANT AGENTS.

A new series of N-Aryl-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)acetamides were synthesized by condensation of tricyclic compound 2,5-dihydro-3H-[1,2,4]triazino[5,6-b]indole-3-thione with chloro N-phenylacetamides. The tricyclic compound was obtained by condensation of Isatin with thiosemicarbazide. Chloro N-phenylacetamides were obtained from different substituted anilines. Their structures were characterized by IR, 1H NMR, LC-MS and elemental analyses. Newly synthesized compounds were screened for antimicrobial, antidepressant and anticonvulsant activities. Preliminary results indicated that most of the compounds showed lesser MIC value than the standard drug used when tested for antimicrobial activity. Some of the compounds were endowed with very good antidepressant and anticonvulsant activity.

An Updated Review on Molecular Biomarkers in Diagnosis and Therapy of Colorectal Cancer.

Colorectal cancer is one of the most common cancer types worldwide. Since colorectal cancer takes time to develop, its incidence and mortality can be treated effectively if it is detected in its early stages. As a result, non-invasive or invasive biomarkers play an essential role in the early diagnosis of colorectal cancer. Many experimental studies have been carried out to assess genetic, epigenetic, or protein markers in feces, serum, and tissue. It may be possible to find biomarkers that will help with the diagnosis of colorectal cancer by identifying the genes, RNAs, and/or proteins indicative of cancer growth. Recent advancements in the molecular subtypes of colorectal cancer, DNA methylation, microRNAs, long noncoding RNAs, exosomes, and their involvement in colorectal cancer have led to the discovery of numerous new colorectal cancer biomarkers. In small-scale investigations, most biomarkers appear promising. However, large-scale clinical trials are required to validate their effectiveness before routine clinical implementation. Hence, this review focuses on small-scale investigations and results of big data analysis that may provide an overview of the biomarkers for the diagnosis, therapy, and prognosis of colorectal cancer.

Craniosynostosis: A Pediatric Neurologist's Perspective.

Craniosynostosis is premature fusion of sutures of the cranium, resulting in an abnormal skull shape and restriction of brain growth. It may affect either a single suture or multiple sutures. In most cases, craniosynostosis is secondary to an underlying abnormality of the growing brain; however, syndromic craniosynostosis is not uncommon. It might lead to several complications such as raised intracranial pressure, neurological deficits, and neurodevelopmental disabilities. Pediatric neurologists do play a significant role in early identification and treatment, and thereby ensure a better clinical and neurodevelopmental outcome in such children.

Telephone-based follow-up of children with epilepsy: Comparison of accuracy between a specialty nurse and a pediatric neurology fellow.

BACKGROUND: Childhood epilepsy forms a significant burden on the health-care delivery system. Only a few pediatric neurologists available in most of the developing countries and caregivers face a lot of financial and logistic hardships, apart from a long waiting period for initial and follow up visits. Telemedicine is a proposed effective alternative in overcoming this burden. METHODS: Telephonic consultation by a pediatric neurology fellow was compared with that of a specialty nurse; both against face-to-face consultation (gold standard). Care-givers of children 4 months-18 years with epilepsy were telephonically consulted 24-48 hours before their scheduled hospital appointment by one specialty nurse and one pediatric neurology fellow at least 24 h apart in a random sequence. During the hospital visit, another pediatric neurology fellow blinded to the telephonic consultation, documented the same after Face-to-Face interview. RESULTS: In 141 children with epilepsy, 504 critical clinical events were identified. Telephonic consultation by pediatric neurology fellow had a sensitivity of 99 %, 97 %, and 100 % and specificity of 100 % each in detecting whether the child had any breakthrough seizure, any adverse event and whether the drug compliance was adequate or poor respectively, as compared to face-to-face consultation. Telephonic consultation by specialty nurse had a sensitivity of 91 %, 84 %, and 98 % and specificity of 97 %, 99 %, and 81 % in detecting whether the child had any breakthrough seizure, adverse event and whether the drug compliance was adequate or poor respectively. But the specialty nurses fared poorly in identifying atypical seizure semiologies like atonic and myoclonic seizures and documenting an exact number of breakthrough seizures, as well as few subjective adverse effects like behavioral abnormality and scholastic worsening, which was performed excellently by the pediatric neurology fellow. CONCLUSIONS: Telephonic consultation in childhood epilepsy by pediatric neurology fellow has excellent sensitivity and specificity. A specialty nurse has also acceptable sensitivity and specificity in comparison with a face-to-face consultation.

Identification and evaluation of reference genes for accurate gene expression normalization of fresh and frozen-thawed spermatozoa of water buffalo (Bubalus bubalis).

The quantitative real time PCR (qRT-PCR) has become an important tool for gene-expression analysis for a selected number of genes in life science. Although large dynamic range, sensitivity and reproducibility of qRT-PCR is good, the reliability majorly depend on the selection of proper reference genes (RGs) employed for normalization. Although, RGs expression has been reported to vary considerably within same cell type with different experimental treatments. No systematic study has been conducted to identify and evaluate the appropriate RGs in spermatozoa of domestic animals. Therefore, this study was conducted to analyze suitable stable RGs in fresh and frozen-thawed spermatozoa. We have assessed 13 candidate RGs (BACT, RPS18s, RPS15A, ATP5F1, HMBS, ATP2B4, RPL13, EEF2, TBP, EIF2B2, MDH1, B2M and GLUT5) of different functions and pathways using five algorithms. Regardless of the approach, the ranking of the most and the least candidate RGs remained almost same. The comprehensive ranking by RefFinder showed GLUT5, ATP2B4 and B2M, MDH1 as the top two stable and least stable RGs, respectively. The expression levels of four heat shock proteins (HSP) were employed as a target gene to evaluate RGs efficiency for normalization. The results demonstrated an exponential difference in expression levels of the four HSP genes upon normalization of the data with the most stable and the least stable RGs. Our study, provides a convenient RGs for normalization of gene-expression of key metabolic pathways effected during freezing and thawing of spermatozoa of buffalo and other closely related bovines.

Predictors of outcome in patients with diphtheria receiving intensive care.

Forty eight patients with a clinical diagnosis of diphtheria, admitted to the Pediatric Intensive Care Unit (PICU) of a tertiary care teaching hospital, from December 1994 to 2002, were analyzed retrospectively with respect to demographic details, clinical features, immunization status, complications and mortality. Several variables were compared among the survivors and non-survivors to define the predictors of outcome More than half 27 (56.3%). of the patients were unimmunized. Complications seen were: airway compromise 34 (70.8%), myocarditis 32 (66.6%), renal failure 17 (35.4%) and thrombocytopenia 15 (31.3%). Out of the 48 patients, 21 survived and 27 died (56.3%). The immediate cause of death was myocarditis 23 (85%), airway compromise 3 (11.1%) and septic shock due to nosocomial sepsis(1). Inadequate immunization, hypotension at admission and presence of any complication like airway compromise, myocarditis and renal failure had a significant (P <0.05) adverse effect on outcome; multiple regression analysis ascertained that, development of myocarditis was the only independent predictor of death (Adjusted OR 0.061; 95% CI 0.009-0.397; P = 0.003).

Study of menopausal symptoms, and perceptions about menopause among women at a rural community in Kerala.

BACKGROUND: Menopausal health demands priority in Indian scenario due to increase in life expectancy and growing population of menopausal women. Most are either unaware or do not pay adequate attention to these symptoms. AIMS: To find the prevalence of menopausal symptoms and perceptions regarding menopause among menopausal women of Kerala. SETTINGS AND DESIGN: A community based cross-sectional house to house survey was conducted at Anjarakandy a field practice area under Kannur Medical College, Anjarakandy. MATERIALS AND METHODS: The study was conducted among 106 postmenopausal women staying more than 6 months at Anjarakandy with the help of pretested questionnaire administered by a trained social worker from January to October 2009. Before that a pilot study was conducted and required sample size of 100 was calculated. Random sampling of houses was done. STATISTICAL ANALYSIS: Data was coded, entered, and analyzed using SPSS 15. Chi-square test, proportions, and percentages were used. RESULTS: The mean age of attaining menopause was 48.26 years. Prevalence of symptoms among ladies were emotional problems (crying spells, depression, irritability) 90.7%, headache 72.9%, lethargy 65.4%, dysuria 58.9%, forgetfulness 57%, musculoskeletal problems (joint pain, muscle pain) 53.3%, sexual problems (decreased libido, dyspareunia) 31.8%, genital problems (itching, vaginal dryness) 9.3%, and changes in voice 8.4%. Only 22.4% of women knew the correct cause of menopause. CONCLUSIONS: Thus study stated that all the ladies were suffering from one or more number of menopausal symptoms. Ladies should be made aware of these symptoms, their causes and treatment respectively.

Evaluation of effect of three different dental unit waterline antimicrobials on the shear bond strength to dentin - An ex vivo study.

BACKGROUND: In restorative treatment dental unit water is used while irrigating the cavity and also in the use of composite restorations to flush away the etchant to place bonding agent. These antimicrobials may influence the bond strength of the dentine bonding agent to the dentine. AIM AND OBJECTIVE: To evaluate the effect of three different dental units waterline antimicrobials on the shear bond strength of dentin. MATERIALS AND METHODS: Sixty freshly extracted human teeth were taken and the occlusal surfaces were sectioned to obtain a flat dentin surface. Then the teeth were randomized into 4 groups depending on the antimicrobial used: Group 1(Distilled water), Group 2 (Alpron), Group 3 (CitriSil), and Group 4 (Chlorhexidine). The dentine surface was prepared for bonding and composite resin was placed in two increments of 2 mm each. The specimens were stored in distilled water, thermo cycled after 7 days shear test was performed by using the universal testing machine. RESULT: No significant difference between Group 1 and Group 2 with regard to shear bond strength. There was a significant difference in the SBS of Group 1 and Group 3 and Group 4. The SBS of group 2 was higher than Group 3 and Group 4 and the difference was statistically significant. CONCLUSION: Citrisil and Chlorhexidine groups showed affected bond strength whereas Alpron did not vary with bond strength.