Synthesis and evaluation of 4-substituted semicarbazones of levulinic acid for anticonvulsant activity

Objective: A series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Methods: All the compounds were evaluated for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test. Results: A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. In the present study 4-(4'-fluoro phenyl) levulinic acid semicarbazone emerged as the most active molecule, showing broad spectrum of activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was found to be inactive in all the screens. Conclusion: The results obtained validate the hypothesis that presence of an aryl group near the semicarbazone moiety is essential for anticonvulsant activity. The results also indicate that the hydrophilic-hydrophobic site can accommodate hydrophilic groups.     

Comparative genomics

An important hallmark of biological research is the aspect of ‘comparisons’. As the complete genome sequences of numerous organisms have become available, the emphasis in biology has shifted to comparisons at the genome level. Indeed, the last few years have witnessed an exponential rise in the number of organisms whose complete genome has been sequenced, and we are still climbing up the graph. The present article, a primer, explains how one can extract a great deal of information from such analyses that is of great value in our research. The subject of comparative genomics impinges on evolutionary biology and phylogenetic reconstructions of the tree of life, drug discovery programs, function predictions of hypothetical proteins and genes, regulatory motifs and other non-coding DNA motifs, and genome flux and dynamics. Finally the article describes how the information one can extract from a comparative analysis of genomes depends to a large extent, on the specific aspect of the genomes that is being compared and the phylogenetic distances of the organisms involved.     

Vergleichsarbeiten und schulische Personalentwicklung – Ausmaß und Voraussetzungen der Datennutzung

The introduction of comparative tests in a low-stakes system was carried out in the expectation that the data feedback to schools would act as a stimulus for the development of the schools and the standard of classroom teaching. By contrast with the use of data to develop teaching, the use of data for personnel development has not yet been studied in Germany. On the basis of an on-line survey of head teachers and a paper-and-pencil survey of teaching staff, the study examines for the first time the extent to which comparative test data is used by head teachers for personnel development and as a means to plan in-service training in subject conferences, and what factors influence whether the data is used in this way. Of the head teacher characteristics which were studied (attitude in relation to the perceived usefulness of the data, qualifications, organisation and age of the head teacher), usefulness is the only characteristic which has a positive effect on the use of the data. The use of comparative test data to plan in-service training in subject conferences is positively influenced by data-wise leadership by the head teacher and by collaborative evaluation.     

Regeneration of Red Cell Cholinesterase Activity Following Pralidoxime (2-PAM) Infusion in First 24 h in Organophosphate Poisoned Patients

Oximes such as pralidoxime chloride reactivate acetylcholinesterase. However their role in management of organophosphate poisoning is controversial. The study was carried out to find effectiveness of pralidoxime chloride (2-PAM) in regenerating red cell acetyl cholinesterase in first 24 h following administration of it in dose recommended by WHO. Eight patients with OPP [chlorpyriphos (3), phorate (3), dichlorvos (1) and monocrotophos (1) who fulfilled the criteria for inclusion were investigated. In addition to decontamination and atropine, all these patients were administered 30 mg/kg body wt of 2-PAM as bolus dose followed by 7.5 mg/kg body wt/h with maximum dose being 500 mg/h as continuous infusion till first 24 h. Red cell AChE activity was estimated every 15 min for first 4 h, one hourly for next 4 h and then 2 hourly till 24 h and subsequently without 2-PAM every 12 h till 7 days or discharge or death which ever earlier. In all the patients maximum increase in activity was observed in first 4 h following which rise was very slow despite continued 2-PAM infusion and reaching a steady state in 20 h in all the cases. The increase in red cell AChE activity observed in diethyl group at 24 h of 2-PAM infusion was 154% vs. 81% in dimethyl group. At 7 days the increase in activity was 215% vs. 118% respectively. However on multiple repeated ANOVA, no statistically significant difference was observed between diethyl and dimethyl groups at admission and discharge (P > 0.05). Similarly no significant difference was observed in three groups when patients were categorized according to WHO classification of organophosphates (P > 0.05). The maximum increase in red cell AChE activity occurs in first 4 h of 2-PAM administration followed by a slow increase despite 2-PAM infusion till 24 h.     

Determination of cancer antigen 125 in ovarian carcinoma

Appropriate therapeutic measures can improve the life expectancy of patients with ovarian malignancy. There has been a pressing need for serodiagnostic assays to enable, the close patient monitoring. Cancer Antigen 125 (CA125) has been described as a useful marker in patient monitoring for ovarian malignancy. Keeping this in view, the present study was planned. 40 consecutive female patients of ovarian carcinoma (mean age 52.4±10.7 years) were selected for serum CA125 analysis during the period of year 1995–2001. The tumour marker concentration was compared with histologic types of ovarian tumour and the FIGO staging of the disease. 25 healthy females (mean age 35.2–10.4 years) served as control. Mean serum CA125 concentrations in patients with papillary serous adenocarcinoma(Mean±%CV 1571±121.5 U/ml) was much higher than patients with mucinous adenocarcinoma(775±78U/ml). Mean serum CA125 concentration in endometrioid carcinoma was very high(2853±136 U/ml). The patient with clear cell carcinoma however had shown moderate increase(60 U/ml). No correlation was found between serum CA125 concentration and the FIGO staging of disease. Quantitation of CA125 was most helpful in monitoring the response of treatment and followup of the patients after completion of their treatment. Posttherapeutically its concentration showed more than 50% reduction in almost all (91.4%) patients (P<0.001). Importantly these patients had also shown significant regression of the disease clinically and radiologically. 8.6% of patients had shown static or increase in serum CA125 concentration which was associated with either clinically static or progressive disease. Recurrence of the disease was noted in patients who had shown increase in serum CA125 concentration (biochemical recurrence) in the followup However, in our test population biochemical recurrence(increase in serum marker concentration) preceded the clinical or radiological recurrence by an average of 6.5 months. Kaplan meier survival analysis for evaluation of overall survival in our test subjects showed an overall survival of 32% at one year and median survival of 9 months with confidence interval of 6.34 to 11.66. We conclude that serum CA125 is a useful marker for monitoring the treatment and predicting an early recurrence of the disease in ovarian carcinoma patients. A study in larger number of patients is needed to define its exact role in the management of the carcinoma ovary.     

Infantile Tremor Syndrome Persistence in Era of Development: An Old Story

Infantile tremor syndrome is seen worldwide more commonly in the developing countries. Although various protein energy malnutrition awareness programme being run in many of these countries including India yet there is persistence of this disease. Here we present a case of 13 month old female child who visited RAPCC paediatrics OPD of Govt. Wenlock Hospital Mangaluru with history of respiratory distress, fever, tremor in limbs and loss of milestones. On examination she had pallor, hyper pigmentation in axilla and toes. Investigatory findings showed megaloblastic erythroid hyperplasia, hemoglobin- 1.6 g % and CT scan of brain showed central atrophic changes.     

Sleep Disturbance and Expressive Language Development in Preschool‐Age Children With Down Syndrome

Recent evidence has suggested that sleep may facilitate language learning. This study examined variation in language ability in 29 toddlers with Down syndrome (DS) in relation to levels of sleep disruption. Toddlers with DS and poor sleep (66%, n = 19) showed greater deficits on parent‐reported and objective measures of language, including vocabulary and syntax. Correlations between sleep and language were found in groups with equivalent medical and social backgrounds and after control for relevant behavioral comorbidities, including autism symptoms. These results emphasize the important role of quality sleep in all children's expressive language development, and may help increase our understanding of the etiology of language deficits in developmental disorders, potentially leading to new treatment approaches.