Major sources of sinking particulate organic matter in the western Bay of Bengal.

Impacts of river discharge on coastal ocean processes are multi-dimensional. Studies on sinking particle fluxes, composition and their seasonal variability in coastal oceans are very limited. In this study, we investigated the impact of river discharge on seasonal variability in sinking fluxes of total mass, biogenic and lithogenic material in a river-dominated continental margin, western coastal Bay of Bengal. Higher POC, lithogenic and total mass fluxes were found during early southwest monsoon, and are decoupled with peak river discharge and elevated primary production. It is attributed to cross-shelf transport of re-suspended surface sediments from shelf region. Peak river discharge followed by elevated chlorophyll-a suggest nutrients supply though river discharge support primary production. Elemental C:N ratios, δ13C and δ15N results likely suggest that both marine and terrestrial sources contributed to sinking POM, . Overall, higher sinking fluxes during southwest monsoon than rest of the year suggest that seasonal river discharge exerts considerable impact on sinking fluxes in the western coastal Bay of Bengal.

Everolimus-associated Acute Kidney Injury in Patients with Metastatic Breast Cancer.

Recently, everolimus (Evl) has been introduced in the management of hormone receptor-positive metastatic breast cancer, in combination with aromatase inhibitors. Evl-induced acute kidney injury has hitherto been described in other malignancies, especially renal cell cancer, but only once before in a patient with breast cancer. We describe two cases of Evl-associated nephrotoxicity in patients with breast cancer, one of whom underwent a renal biopsy showing acute tubular necrosis. Both our patients improved after withdrawal of the offending agent and have normal renal functions on follow-up.

Role of Perceptual Factors on Endurance Profiles on Treadmill Exercise.

CONTEXT: It is common practice to unravel signs of possible cardiac ischemia by exposing the heart to graded degrees of exercise stress on treadmill under close monitoring and terminating it at safe limit. The safe limit of exercise duration and intensity is based on subjects who report a sense of exhaustion or appearance of any defined adverse sign whichever is earlier. Commonly, endurance is determined by subjective perception of distress leading to discontinuation of exercise. AIM: Scope of favourable manipulation of perception of stress was evaluated to extend the duration of exercise, and thereby the endurance. MATERIALS AND METHODS: The indices of endurance such as duration of exercise, the distance covered and equivalents of O2 consumption (METs) as well as Cardiovascular adaptational changes of 30 young healthy male medical students are compared between two sets of conditions; {1} Routine treadmill exercise without intervention (Mode A) and later {2} same exercise repeated with individualized musical experience to favourably distract the perception of stress (Mode B). RESULT: It has been conclusively demonstrated that perceptual modification of stress in Mode B caused significant improvement in endurance profiles, reflected by sustenance of longer duration of exercise, correspondingly greater cumulative distance covered and greater METs. Cardiovascular parameters of heart rate and blood pressure rise are comparatively less in Mode B, though not significant. The extent of cardiac stress evaluated by Rate-Pressure (R-P) product is also lesser spite of longer duration of exercise, pointing to better cardiovascular adaptational changes under states of perceptual modification (Mode B). CONCLUSION: Its relevance to day-to-day physical activities including exercise is obviously to make them enjoyable, rather than monotonous, for maximal benefit to health and endurance.

Interaction of Glucagon G-Protein Coupled Receptor with Known Natural Antidiabetic Compounds: Multiscoring In Silico Approach.

Glucagon receptor (GCGR) is a secretin-like (class B) family of G-protein coupled receptors (GPCRs) in humans that plays an important role in elevating the glucose concentration in blood and has thus become one of the promising therapeutic targets for treatment of type 2 diabetes mellitus. GCGR based inhibitors for the treatment of type 2 diabetes are either glucagon neutralizers or small molecular antagonists. Management of diabetes without any side effects is still a challenge to the medical system, and the search for a new and effective natural GCGR antagonist is an important area for the treatment of type 2 diabetes. In the present study, a number of natural compounds containing antidiabetic properties were selected from the literature and their binding potential against GCGR was determined using molecular docking and other in silico approaches. Among all selected natural compounds, curcumin was found to be the most effective compound against GCGR followed by amorfrutin 1 and 4-hydroxyderricin. These compounds were rescored to confirm the accuracy of binding using another scoring function (x-score). The final conclusions were drawn based on the results obtained from the GOLD and x-score. Further experiments were conducted to identify the atomic level interactions of selected compounds with GCGR.

Clinical efficacy of a herbal dentifrice on dentinal hypersensitivity: a randomized controlled clinical trial.

BACKGROUND: Dentinal hypersensitivity is a common problem and there is a growing interest in herbal based formulations for the treatment of oral diseases. This study was conducted to assess the efficacy of a commercially available novel herbal dentifrice in reduction of dentinal hypersensitivity. METHODS: A total of 73 subjects (38 males and 35 females; aged 25-60 years) were randomly divided into two groups: Group 1 - a placebo dentifrice (The Himalaya Drug Company Research and Development, Makali, Bangalore) and Group 2 - (test group), a commercially available herbal dentifrice (Hi Ora K, The Himalaya Drug Company Research and Development, Makali, Bangalore). Sensitivity scores for controlled air stimulus and cold water were recorded at baseline, 6 weeks and 12 weeks. RESULTS: The test group was found to be significantly better compared to the placebo group at the end of 6 and 12 weeks in reduction of dentinal hypersensitivity. CONCLUSIONS: The novel herbal dentifrice can be recommended for treatment of dentinal hypersensitivity.

Simvastatin local drug delivery in smokers with chronic periodontitis: a randomized controlled clinical trial.

BACKGROUND: Simvastatin (SMV) is a specific competitive inhibitor of 3-hydroxy-2-methyl-glutaryl coenzyme A reductase. Statins have recently been shown to promote bone formation. This study was designed to investigate the effectiveness of SMV 1.2% in an indigenously prepared biodegradable controlled release gel as an adjunct to scaling and root planing (SRP) in the treatment of smokers with chronic periodontitis. METHODS: Forty patients were categorized into two treatment groups: SRP plus SMV 1.2% and SRP plus placebo. Clinical parameters were recorded at baseline and at 3, 6 and 9 months; they included modified sulcus bleeding index (mSBI), probing depth (PD) and clinical attachment level (CAL). At baseline, after 6 months and 9 months, radiologic assessment of intrabony defect (IBD) fill was done using computer-aided software. RESULTS: Mean probing depth reduction and mean clinical attachment level gain was greater in the SMV group than the placebo group at all visits. Furthermore, significantly greater mean percentage of bone fill was found in the SMV group (32.37 ± 10.23%) compared to the placebo (4.18 ± 5.39%). CONCLUSIONS: There was a greater decrease in mSBI and PD and more CAL gain with significant IBD fill at sites treated with SRP plus locally delivered SMV in smokers with chronic periodontitis.

Local drug delivery of 0.5% azithromycin in the treatment of chronic periodontitis among smokers.

BACKGROUND: Along with conventional periodontal surgical therapy, local delivery of antibiotics may provide more effective treatment in smokers by targeting tissue-invasive bacteria. The aim of this randomized, placebo-controlled, double-masked clinical trial was to evaluate the adjunctive effects of subgingivally delivered 0.5% azithromycin (AZM) as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis in smokers. METHODS: Fifty-four patients were randomized and categorized into two treatment groups: Group 1 - 26 subjects who received (SRP) plus placebo gel and Group 2 - 28 subjects who received (SRP) plus 0.5% azithromycin. Clinical parameters were recorded at baseline, 3, 6 and 9 months. They included Plaque Index (PI), modified Sulcus Bleeding Index (mSBI), probing depth (PD) and clinical attachment level (CAL). RESULTS: Azithromycin resulted in significant improvements. A single application of AZM resulted in attachment gain at 9 months of 2.44 ± 0.64 mm as compared to 0.18 ± 0.68 mm for the placebo. Similarly, pocket depth and PI were significantly reduced but no change in the mSBI was noted. CONCLUSIONS: When compared to the placebo, the adjunctive use of 0.5% AZM resulted in significant improvement in clinical outcome in the treatment of chronic periodontitis among smokers.

Role of naturopathy and yoga treatment in the management of hypertension.

AIM: The primary aim was to study the effect of naturopathy and yoga interventions in treatment of mild to moderate hypertension. DESIGN: The variables of interest were measured at the beginning and end of the intervention using a pre-post design. SETTING: The study was conducted by INYS medical research society in Jindal Nature Cure Institute, Bangalore. SUBJECTS: A total of 104 subjects, already diagnosed with mild to moderate hypertension and on treatment with antihypertensive medicines were included in study. INTERVENTIONS: The intervention consisted of various inpatient administration of different naturopathy treatments, yoga therapies, low calorie and low sodium diet for 21 days. Antihypertensive medicines were withdrawn for some patients in one week based upon response to the treatment. OUTCOME MEASURES: The outcome measures were values of diastolic and systolic blood pressure and body weight. Subjects were followed for a period of one year after every 3 months. RESULTS: After starting nonpharmacological approach of naturopathy and yoga, Systolic blood pressure came down from mean of 139.6 to 129.6 where as it came down from 91.2 to 86.1 for diastolic blood pressure. At the same time favorable effect was also seen in other variables like lipid profile and body weight. At the end of one year out of 57 patients who came for follow-up, 14 cases were found to have blood pressure within normal ranges without any medication over the previous 12 months. CONCLUSION: Naturopathy and yoga therapy can be considered as a valuable nonpharmacological approach in treatment of hypertension.

Multilayer PDMS microfluidic chamber for controlling brain slice microenvironment.

A novel three-layer microfluidic polydimethylsiloxane (PDMS) device was constructed with two fluid chambers that holds a brain slice in place with microposts while maintaining laminar perfusate flow above and below the slice. Our fabrication technique permits rapid production of PDMS layers that can be applied to brain slices of different shapes and sizes. In this study, the device was designed to fit the shape and thickness (530-700 microm) of a medullary brain slice taken from P0-P4 neonatal rats. Medullary slices in this chamber spontaneously produced rhythmic, respiratory-related motor output for up to 3 h, thereby demonstrating that brain slice viability was maintained for prolonged periods. This design is unique in that it achieves independent control of fluids through multiple channels in two separate fluid chambers. The laminar flow exhibited by the microfluidic chamber allows controlled solutions to target specific areas of the brain slice based on the input flow rates. To demonstrate this capability, a stream of Na(+)-free solution was focused on one half of a medullary slice to abolish spontaneous neural activity in only that half of the brain slice, while the other half remained active. We also demonstrated that flow of different solutions can be focused over the midline of the brain slice. The multilayer brain slice chamber design can integrate several traditional types of electrophysiology tools that are commonly used to measure neurophysiological properties of brain slices. Thus, this new microfluidic chamber is advantageous for experiments that involve controlled drug or solution delivery at high spatiotemporal resolution.

Assessing the burden of human rabies in India: results of a national multi-center epidemiological survey.

OBJECTIVE: Human rabies has been endemic in India since time immemorial, and the true incidence of the disease and nationwide epidemiological factors have never been studied. The main objectives of the present study were to estimate the annual incidence of human rabies in India based on a community survey and to describe its salient epidemiological features. METHODS: The Association for Prevention and Control of Rabies in India (APCRI) conducted a national multi-center survey with the help of 21 medical schools during the period February-August 2003. This community-based survey covered a representative population of 10.8 million in mainland India. Hospital-based data were also obtained from the 22 infectious diseases hospitals. A separate survey of the islands of Andaman, Nicobar, and Lakshadweep, reported to be free from rabies, was also undertaken. RESULTS: The annual incidence of human rabies was estimated to be 17,137 (95% CI 14,109-20,165). Based on expert group advice, an additional 20% was added to this to include paralytic/atypical forms of rabies, providing an estimate of 20,565 or about 2 per 100000 population. The majority of the victims were male, adult, from rural areas, and unvaccinated. The main animals responsible for bites were dogs (96.2%), most of which were stray. The most common bite sites were the extremities. The disease incubation period ranged from two weeks to six months. Hydrophobia was the predominant clinical feature. Many of the victims had resorted to indigenous forms of treatment following animal bite, and only about half of them had sought hospital attention. Approximately 10% of these patients had taken a partial course of either Semple or a cell culture vaccine. The islands of Andaman, Nicobar, and Lakshadweep were found to be free of rabies. CONCLUSION: Human rabies continues to be endemic in India except for the islands of Andaman, Nicobar, and Lakshadweep. Dogs continue to be the principal reservoir. The disease is taking its toll on adult men and children, the majority from rural areas, due to lack of awareness about proper post-exposure immunization. The keys to success in the further reduction of rabies in India lies in improved coverage with modern rabies vaccines, canine rabies control, and intensifying public education about the disease.

An epidemiological study of animal bites in India: results of a WHO sponsored national multi-centric rabies survey.

This was a WHO sponsored national multi-centric rabies survey and one of its objectives was to find out the incidence of animal bites, anti-rabies treatment practices, Pet dog population and their care. Twenty-one medical colleges chosen with geoscatter representation conducted the survey during February-August, 2003. The survey was conducted in 18 states, covering a population of 52,731 chosen randomly from 8500 households. The annual incidence of animal bites was high, 1.7% and it was more in rural areas (1.8%), children (2.6%) and poor/low income group (75%). The main biting animal was dog (91.5%), mostly stray (63%), followed by cat (4.7%). A high proportion of bite victims did not wash their wounds with soap and water (39.5%), preferred Government hospitals (59.9%) and nerve tissue vaccine (46.9%). The use of rabies immunoglobulin was low (2.1%). A single animal bite episode led to a loss of 2.2 man-days and the cost of medicines including anti-rabies vaccine was Rs.252 (US$6). The recourse to indigenous treatment (45.3%) and local application to wound (36.8%/) was quite prevalent. About 17% of households reported having a pet/domesticated dog and the pet dog: man ratio was 1: 36. Pet dog care/management practices were not satisfactory with a low veterinary consultation (35.5%) and vaccination (32.9%). The situation was slightly better in urban areas. The people also reported the presence (83%) and menace (22.8%) of stray dogs. It is recommended to initiate appropriate community awareness and dog vaccination campaigns and effective stray dog control measures.

Dual behavior of masked o-benzoquinones in intermolecular Diels-Alder reactions with acyclic dienes: a rapid entry to polyfunctionalized bicyclo[2.2.2]oct-5-en-2-ones and cis-decalins.

The potentiality of the masked o-benzoquinones, i.e., 6,6-dimethoxy-2,4-cyclohexadienones 5-8, to react both as dienes and dienophiles in their intermolecular reactions has been demonstrated. The masked o-benzoquinones (MOBs) 5-8 generated in situ from 2-methoxyphenols 1-4 underwent intermolecular Diels-Alder cycloadditions with acyclic 1,3-dienes 9a-e to provide bicyclo[2.2.2]octenones 10a-f-13a-f along with cis-decalin derivatives 14a-f-17a-f with regio- and stereoselectivity, except in the case of MOB 8. The formation of cis-decalins in these Diels-Alder reactions illustrates the dienophilic character of MOBs, in addition to their general behavior as dienes. The ratio of the two cycloadducts obtained in each reaction as a result of the dual character of MOBs depends on the nature and/or position of the substituents on both the cyclohexadienone moiety and the added conjugated acyclic diene. All of the cycloadducts resulted from the diene property of MOBs in intermolecular Diels-Alder reactions smoothly underwent Cope rearrangement to furnish cis-decalins as sole products in excellent to quantitative yields.

Effect of stimulus intensity and number of treatments on ECS-related seizure duration and retrograde amnesia in rats.

BACKGROUND: Animal models are frequently used to generate and test hypotheses about amnesia resulting from electroconvulsive therapy (ECT). Although many predictors of ECT-induced amnesia are known, their relative effects have been inadequately researched in the context of the animal models. OBJECTIVE: We sought to determine the relative retrograde amnestic effects of electroconvulsive shock (ECS) stimulus intensity (dose) and number on strong memories in rats. We also sought to identify dose-dependent ceiling amnestic effects, if any. METHODS: Adult rats (n = 144) were overtrained in a passive avoidance task using a step down apparatus. The rats were then randomized in a factorial design to receive one, two, or three once-daily bilateral ECS at 0-mC (sham ECS), 30-mC, 60-mC, 120-mC, or 180-mC doses. Recall of the pre-ECS training was assessed 1 day after the last ECS. RESULTS: Retrograde amnesia was observed only in rats that received 3 ECS; dose-dependent amnestic effects did not emerge. Higher stimulus intensity was associated with a small (13%) but significant increase in motor seizure duration, but only at the first ECS; stimulus intensity did not influence the attenuation of seizure duration across repeated occasions of ECS. CONCLUSION: With bilateral ECS, the number of ECSs administered is a more important variable than the ECS dose in weakening a strong, recently acquired, noxious memory; this finding may have important clinical implications. Higher stimulus intensity marginally increases motor seizure duration at the first ECS but does not influence the decrease in seizure duration across repeated ECSs.

Intramolecular Diels-Alder reactions of brominated masked o-benzoquinones. A detour method to synthesize highly functionalized oxatricyclic [m.3.1.0] ring systems from 2-methoxyphenols.

Intramolecular Diels-Alder (IMDA) reactions of masked o-benzoquinones (MOBs) 5a-d to 7a-d and 17a-d to 19a-d generated in situ from 2-methoxyphenols 2-4 and 14-16, respectively, in the presence of alkenols 1a-d, resulting in highly functionalized oxatricyclic [m.3.1.0] ring systems are described. The MOBs 5a-d to 7a-d underwent the IMDA reactions to furnish the adducts 8a-d, 10a-d, and 12a-d (direct method) in poor yields with the concomitant formation of considerable amounts of unexpected byproducts 9a-d, 11a-d, and 13a-d, respectively. To avoid the formation of byproducts and to improve the yields of the desired cycloadducts, a detour method comprising sequential bromination of 2-methoxyphenols 2-4, tandem oxidative acetalization-Diels-Alder reaction, and debromination has been developed. The oxidation of bromophenols 14-16 in the presence of alkenols 1a-d produced the corresponding MOBs 17a-d to 19a-d, which underwent cycloaddition to afford the cycloadducts 20a-d to 22a-d, respectively, as sole products in good to high yields in a highly regio- and stereoselective manner. Treatment of the bromoadducts 20a-d to 22a-d with tributylammonium formate-palladium reagent produced the corresponding debrominated products 8a-d, 10a-d, and 12a-d in high to excellent yields. In general, the latter oxatricycles were obtained in higher overall yields via the detour method than those via the direct method.

Intermolecular Diels-Alder reactions of brominated masked o-benzoquinones with electron-deficient dienophiles. A detour method to synthesize bicyclo[2.2.2]octenones from 2-methoxyphenols.

Intermolecular Diels-Alder reactions of masked o-benzoquinones, i.e., 6,6-dimethoxy-2,4-cyclohexadienones 5-7 and 21-24 generated from 2-methoxyphenols 1-3 and 17-20, respectively, with electron-deficient dienophiles leading to highly functionalized bicyclo[2.2.2]octenones are described. The masked o-benzoquinones (MOBs) 5-7 underwent Diels-Alder cycloadditions with methyl acrylate, methyl methacrylate, and methyl vinyl ketone to provide bicyclo[2.2.2]octenones 13a-c to 15a-c (direct method) in low to moderate yields with the concomitant formation of considerable amounts of dimers 9-11. To retard dimerization and to improve the yields of the requisite bicyclo[2.2.2]octenones, a detour method comprised of sequential bromination of 2-methoxyphenols 1-4, oxidation and Diels-Alder reaction, and debromination has been developed. The oxidation of bromophenols 17-20 produced MOBs 21-24 which are stable enough to be isolated. The MOBs 21-24 underwent cycloaddition with electron-deficient dienophiles in a very efficient manner to afford the corresponding cycloadducts 25a-c to 28a-c in good to high yields without self-dimerization. When the cycloadducts 25a-c to 28a-c were treated with either Bu(3)SnH/AIBN or tributylammonium formate-palladium reagent, the corresponding debrominated products 13a-cto 16a-c were obtained in high to excellent yields. In general, the cycloadducts 13a-c to 15a-c were obtained in 20-40% higher yields via the detour method than those via the direct method. In both routes, the Diels-Alder reactions proceeded in a highly regio- and stereoselective manner to furnish a single cycloadduct in each case.

Microwave assisted high yielding preparation of N-protected 2'-deoxyribonucleosides useful for oligonucleotide synthesis.

A rapid and high yielding method for the synthesis of precursors of synthons for DNA synthesis, N-protected 2'-deoxyribonucleosides is described, which occur under mild conditions using microwave irradiation. The desired material, N-protected nucleosides, was obtained in 93-96% yield in few minutes. The final products were then characterized by 1H-NMR and MALDI-TOF and compared with the standard samples. The method is amenable to small to moderate scale of synthesis.

Quality of drinking water from ponds in villages of Kolleru Lake region.

Kolleru Lake is the largest natural freshwater lake in the districts of East and West Godavari of Andhra Pradesh. The major population centres in the Kolleru Lake region are the 148 villages of which 50 bed villages and 98 belt villages. All bed and belt villages in lake region have at least one drinking water pond. Drinking water ponds are filled with lake water during monsoon season and directly supplied to the public throughout the year. The water samples were collected from village drinking water ponds in a year by covering three seasons and analysed for different physico-chemical parameters to assess the quality of drinking water.

Technique of removal of an impacted sharp object in a penetrating head injury using the lever principle.

Penetrating head injuries can be difficult to manage as the extensive surgery which may be required can result in severe morbidity and mortality in some patients. A conservative surgical approach with a "pull and see" policy was adopted successfully in a described case. Extraction can be achieved by using the mechanical advantage of the lever principle. By this method while removing the object any movements of sharp edges which will cause secondary damage can be reduced to a minimum.

Nuclear magnetic resonance assignment and secondary structure of an ankyrin-like repeat-bearing protein: myotrophin.

Multidimensional heteronuclear NMR has been applied to the structural analysis of myotrophin, a novel protein identified from spontaneously hypertensive rat hearts and hypertrophic human hearts. Myotrophin has been shown to stimulate protein synthesis in myocytes and likely plays an important role in the initiation of cardiac hypertrophy, a major cause of mortality in humans. Recent cDNA cloning revealed that myotrophin has 11B amino acids containing 2.5 contiguous ANK repeats, a motif known to be involved in a wide range of macromolecular recognition. A series of two- and three-dimensional heteronuclear bond correlation NMR experiments have been performed on uniformly 15N-labeled or uniformly 15N/13C-labeled protein to obtain the 1H, 15N, and 13C chemical shift assignments. The secondary structure of myotrophin has been determined by a combination of NOEs, NH exchange data, 3JHN alpha coupling constants, and chemical shifts of 1H alpha, 13C alpha, and 13 C beta. The protein has been found to consist of seven helices, all connected by turns or loops. Six of the seven helices (all but the C-terminal helix) form three separate helix-turn-helix motifs. The two full ANK repeats in myotrophin are characteristic of multiple turns followed by a helix-turn-helix motif. A hairpin-like turn involving L32-R36 in ANK repeat #1 exhibits slow conformational averaging on the NMR time scale and appears dynamically different from the corresponding region (D65-169) of ANK repeat #2.