Soft phonation index — a sensitive parameter?

Objective  The diagnosis of voice disorders is based on perceptual and acoustic paradigms. Modern acoustic analysis systems are relatively inexpensive and user friendly. One aspect of laryngeal function that is of great interest is the extent of vocal fold closure. Soft phonation index (SPI) is the parameter in Multi Dimensional Voice Program, which reflects the approximation of vocal folds. High values of SPI are stated to correlate with incomplete vocal fold adduction and are a better indicator of breathiness than EGG. This study aims to determine the sensitivity of this acoustic parameter of SPI, as a reflective indicator of incomplete vocal fold adduction in male patients diagnosed with unilateral vocal nodules. Methodology  60 participants were included in the study; 30 with normal vocal fold functioning in the control group and 30 with unilateral vocal nodules in the experimental group. The phonation sample of vowel /a/ was recorded into CSL 4150 of Kay Elemetrics, in a sound treated room. The readings of SPI on the MDVP analysis was extracted and subjected to statistical analysis using independent samples ‘t-test’ using SPSS Version 11. Results  The results of the study reveal that there was a statistically significant difference between the means of the SPI values between the control and the experimental groups. Discussion  It can be understood that SPI is a sensitive parameter to detect abnormalities in vocal fold approximation in the considered population of individuals with vocal nodules. This is in coherence with a study done on patients with vocal fold palsy and cordectomy, wherein SPI was found to be a good indicator of breathiness. The SPI mean obtained for participants in the control group was higher than the Western normative mean specified in MDVP, which highlights the importance of establishing normative values for Indian population. Conclusion  It can be concluded that SPI was sensitive to detect changes affecting vocal fold closure in unilateral vocal nodules. But this conclusion has to be generalized with caution keeping in mind that only one population with vocal pathology was studied. The factors of vocal fold physiology and mechanical properties of vocal tract, which may contribute to individual variations in SPI values, have to be considered for further research.     

Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: design,synthesis, and X-ray cocrystal structure

A series of novel compounds have been designed that are potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1), and the activity and physical properties have been characterized. The new structural classes, 3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-ones and 3,4-dihydropyrrolo[4,3,2-de]isoquinolin-5-(1H)-ones, have conformationally locked benzamide cores that specifically interact with the PARP-1 protein. The compounds have been evaluated with in vitro cellular assays that measure the ability of the PARP-1 inhibitors to enhance the effect of cytotoxic agents against cancer cell lines.     

Evaluation of a novel shape-based computational filter for lead evolution: application to thrombin inhibitors

A novel shape-feature-based computational method is described and used to rapidly filter compound libraries. The computational model, built using three-dimensional conformations of active and inactive molecules, consists of a collection of whole molecule shapes and chemical feature positions that are ranked according to their correlation with activity. A small ensemble of these shapes and features is used to filter virtual compound libraries. The method is applied to two thrombin data sets and is shown to be efficient in identifying novel scaffolds with enhanced hit rates.     

Grape seed proanthocyanidins improved cardiac recovery during reperfusion after ischemia in isolated rat hearts

BACKGROUND: Increasing evidence shows that red wine consumption has cardioprotective effects. These effects have been attributed to the polyphenolic compounds in grapes. OBJECTIVE: We studied the effects of red grape seed proanthocyanidins on the recovery of postischemic function in isolated rat hearts. DESIGN: Two groups of rats were fed different doses of proanthocyanidin-rich extract for 3 wk and another group was untreated and served as controls. The animals were then anesthetized and the hearts were isolated and subjected to 30 min of ischemia followed by 2 h of reperfusion. Coronary effluents were collected during the third minute of reperfusion for measurement of oxygen free radicals by using electron spin resonance spectroscopy. RESULTS: In rats treated with 50 and 100 mg grape seed proanthocyanidins/kg, the incidence of reperfusion-induced ventricular fibrillation was reduced from its control value of 92% to 42% and 25%, respectively (P < 0.05 for both). The incidence of ventricular tachycardia showed the same pattern. In rats treated with 100 mg proanthocyanidins/kg, the recovery of coronary flow, aortic flow, and developed pressure after 60 min of reperfusion was improved by 32% +/- 8%, 98% +/- 8%, and 37% +/- 3%, respectively (P < 0.05 for all) compared with untreated control rats. Electron spin resonance studies indicated that proanthocyanidins significantly inhibited the formation of oxygen free radicals. In rats treated with 100 mg proanthocyanidins/kg, free radical intensity was reduced by 75% +/- 7% (P < 0.05) compared with the control rats. CONCLUSION: Grape seed proanthocyanidins have cardioprotective effects against reperfusion-induced injury via their ability to reduce or remove, directly or indirectly, free radicals in myocardium that is reperfused after ischemia.     

Randomized study of the dopamine receptor agonist piribedil in the treatment of mild cognitive impairment

OBJECTIVE: Age-related decrease in dopamine D(2) receptors is associated with cognitive decline in healthy elderly individuals. This study was an investigation of whether the dopamine receptor agonist piribedil improves global cognitive function in patients with mild cognitive impairment. METHOD: In a 90-day randomized double-blind study, treatment with piribedil was compared to placebo in 60 patients with clinically diagnosed mild cognitive impairment and a Mini-Mental State Examination (MMSE) score of 21 to 25. The primary outcome was change in MMSE score. RESULTS: Of the 30 patients randomly assigned to each treatment group, 19 (63.3%) of those taking piribedil and eight (26.7%) of those treated with placebo had increases in MMSE scores, to 26 or more. The response rate and the mean increase in MMSE scores were significantly greater with piribedil. CONCLUSIONS: Patients with mild cognitive impairment had improvement in global cognitive function when treated with the dopamine receptor agonist piribedil. The results support the role of age-related dopamine decline in cognitive impairment of the elderly.