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.

Alpha helix-RNA major groove recognition in an HIV-1 rev peptide-RRE RNA complex.

The solution structure of a human immunodeficiency virus type-1 (HIV-1) Rev peptide bound to stem-loop IIB of the Rev response element (RRE) RNA was solved by nuclear magnetic resonance spectroscopy. The Rev peptide has an alpha-helical conformation and binds in the major groove of the RNA near a purine-rich internal loop. Several arginine side chains make base-specific contacts, and an asparagine residue contacts a G.A base pair. The phosphate backbone adjacent to a G.G base pair adopts an unusual structure that allows the peptide to access a widened major groove. The structure formed by the two purine-purine base pairs of the RRE creates a distinctive binding pocket that the peptide can use for specific recognition.

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.

Hepatic, gut, and renal substrate flux rates in patients with hepatic cirrhosis.

The roles of liver, kidney, and gut in maintaining fuel homeostasis were studied in 28 patients with severe hepatic cirrhosis, 25 of whom had alcohol-induced cirrhosis. Hepatic, portal, and renal blood flow rates were measured and combined with substrate concentration differences across liver, gut, and kidney to calculate the net flux of free fatty acids, ketone bodies, triglycerides, and glucose with selected glucose precursors, including glycerol, lactate, pyruvate, and amino acids. Data from the catheterization studies were related to hepatic histology, glycogen content, and activities of gluconeogenic enzymes and compared with data obtained from control patients. The effects of food deprivation on net flux of fuels across the liver, gut, and kidney were assessed after overnight and after 3d of fasting. Activities of gluconeogenic enzymes were normal, but hepatic glycogen content was diminished in cirrhotic livers, probably as a consequence of extensive hepatic fibrosis. Extrahepatic splanchnic tissues (gut) had only a small influence on total splanchnic flux rates of carbohydrates, lipids and, amino acids. In cirrhotic patients, there was no mean renal glucose contribution to the bloodstream after an overnight or after a 3-d fast. After an overnight fast hepatic glucose production in patients with cirrhosis was diminished as a result of low-rate glycogenolysis. Hepatic gluconeogenesis and ketogenesis were increased. This pattern of hepatic metabolism mimics that seen in "normal" patients after more advanced stages of starvation. After 3 d of starvation, patients with hepatic cirrhosis have hepatic gluconeogenic and ketogenic profiles comparable to those of normal patients undergoing starvation of similar duration. Nevertheless, the total number of caloric equivalents derived from ketone bodies plus glucose corrected for recycled lactate and pyruvate added to the bloodstream by the cirrhotic livers that could be terminally oxidized by peripheral tissues was less than the contributions made by the normal livers, both after and overnight and after a 3-d fast.

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.

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.

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.

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.

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.

Devic's syndrome and systemic lupus erythematosus: a case report with necropsy.

Systemic lupus erythematosus (SLE) rarely occurs coincident with demyelinating disease and, to our knowledge, only one previous case of Devic's syndrome with SLE has been reported.

Peritoneal fine structure of inguinal hernia: a scanning electron microscope study.

Mesothelial cells of the normal human peritoneum of the anterior abdominal wall are covered with numerous surface microvilli. These cells become partially denuded inside the sacs of direct and indirect inguinal hernias and so lose the protective property the microvillar covering may impart on them. These mesothelial cells of hernial sacs also acquire an extensive surface coat of fibrin-like material, presumably due to the loss of that protective property, which may as a result subject them to adhesions. There is a considerable collagen build-up in the subserosal fibrous tissue of sacs of both direct and indirect inguinal hernias. Such a build-up is at variance with the accepted current surgical concept which suggests a defect in collagen synthesis, rather than a build-up, as the cause of direct hernia.

The mechanism of postshunt liver failure.

To determine the influence on postoperative hepatic mass, body weight, ammonia clearance, hepatic urea cycle enzyme activity, and hepatic protein metabolism, 59 dogs were divided into six experimental groups: sham operation end-to-side portacaval shunt, mesocaval shunt with subsequent end-to-side portacaval shunt, distal splenorenal shunt, caval left portal shunt, and portal venous seqregation with juglar vein interposition. Compared to total shunt, selective diversion of portal blood from the liver produces less postshunt liver atrophy, less body weight loss, improved maintenance of urea cycle enzyme activity, improved ammonia tolerance, and less decrease in hepatic deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein content. Segregation of left from right hepatic lobes, in relationship to portal or systemic venous hepatic perfusion or in relationship to gastroduodenopancreaticosplenic or intestinal portal venous drainage, caused little change in enzyme or protein metabolism in respective hepatic lobes.

Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes.

The effect of fenugreek seeds (Trigonella foenum graecum) on blood glucose and the serum lipid profile was evaluated in insulin-dependent (Type I) diabetic patients. Isocaloric diets with and without fenugreek were each given randomly for 10 d. Defatted fenugreek seed powder (100 g), divided into two equal doses, was incorporated into the diet and served during lunch and dinner. The fenugreek diet significantly reduced fasting blood sugar and improved the glucose tolerance test. There was a 54 per cent reduction in 24-h urinary glucose excretion. Serum total cholesterol, LDL and VLDL cholesterol and triglycerides were also significantly reduced. The HDL cholesterol fraction, however, remained unchanged. These results indicate the usefulness of fenugreek seeds in the management of diabetes.

Preliminary morphometric study of tumor necrosis factor-alpha (TNF alpha)-induced rabbit optic neuropathy.

Intravitreal injections of tumor necrosis factor-alpha (TNF alpha) induce morphological changes in the optic nerve suggesting a primary TNF alpha-induced optic neuropathy. A preliminary morphometric analysis of axonal loss and degeneration in optic nerves of a TNF alpha rabbit eye model was conducted. Fifteen rabbits were injected in one eye only with TNF alpha (final doses: 2 U, 20 U and 200 U respectively), and optic nerve cross-sections were examined using a semi-automated image analysis system, at varying time intervals for up to 24 weeks post-injection. Control optic nerves (uninjected or injected with diluent only) were also assessed. Intact, degenerating and demyelinated axons were visible in TNF alpha-exposed optic nerves. Considerable variation was observed between TNF alpha-exposed optic nerves, however the intact axon density consistently decreased in the 200 U TNF alpha group, although not in the 2 U and 20 U groups. Overall, TNF alpha-exposed optic nerves had significantly more degenerating profiles compared to control optic nerves. These observations suggest a dose-dependent axonal loss and degeneration associated with the morphological changes induced in rabbit optic nerves following intravitreal injection of TNF alpha.

Tumor necrosis factor-alpha (TNF-alpha)-induced optic neuropathy in rabbits.

Both in vitro and in vivo studies have implicated a role for tumor necrosis factor-alpha (TNF alpha) in various demyelinating diseases, including HIV-related encephalopathy. To investigate whether intravitreal TNF alpha can induce optic nerve axonal damage in a rabbit eye model, fifteen rabbit eyes were initially injected with TNF alpha (final concentrations: 2U, 20U, and 200U respectively) and studied at varying time intervals for up to 24 weeks post-injection, using light and electron microscopy. Control optic nerves (no injection or diluent injection only) had normal myelinated axons and glia; the myelinated regions, neural retina, retinal glia and vasculature of control retinas were normal. In TNF alpha-exposed optic nerves, intact, degenerating and demyelinated axons were interspersed. Astrogliosis was present, particularly from 8 weeks p.i. and was noted up to 24 weeks. Oligodendrocytes were not severely affected in TNF alpha-exposed optic nerves, and activated macrophages or microglia were not obvious. Axonal degeneration was visible among the more superficial myelinated fibers in TNF alpha-exposed retinas however the neural retina glia were unaffected. These observations suggest that the axonal degeneration induced in TNF alpha-exposed rabbit optic nerves over a 24 week period was most likely related to direct effects of TNF alpha on optic nerve axons, and not primarily due to anterograde degeneration from retinal lesions. In-so-far as neurological pathology in general, and optic nerve degeneration in particular, has been described in AIDS, and TNF alpha levels may be elevated in this disease, it is of great clinical significance that TNF alpha has the capacity to mediate neuronal or axonal injury. If so, strategies to block or inhibit TNF alpha can be pursued for treatment for the neurological symptoms of AIDS.

Ultrastructural disposition of adriamycin-associated magnetic albumin microspheres in rats.

The ultrastructural disposition of intra-arterially administered adriamycin-associated magnetic albumin microspheres has been investigated. The rat tail was used as the target organ and demarcated into the following three parts: T1, the injection site; T2, the target site; and T3, the posttarget site. Adriamycin HCl (2.0 mg/kg) was administered via the carrier through a cannula fixed at T1. The target site, T2, was exposed to a magnetic field of 8000 G for 30 min postdosing. Animals were sacrificed at scheduled time intervals over a 72-h period, and the tissue samples from T2 were observed by light and transmission electron microscopy. Electron microscopy revealed that microspheres traverse the vascular endothelium of the target tissue as early as 2 h after dosing. Gradual loss of tissue organization and cellular components, as a function of drug exposure time, demonstrated that the pharmacodynamic characteristics of the drug are not altered by its entrapment and delivery via the magnetic microspheres. The study confirms second-order drug targeting in the target tissue of healthy animals.

Optic nerve morphometry following axonal degeneration from SAIDS in rhesus monkeys.

In order to further study AIDS (acquired immunodeficiency syndrome) related neuropathologic findings, specifically progressive diffuse leuko-encephalopathy (PDL) and optic neuropathy, ten macaque monkeys (Macaca mulatta) were infected with simian immunodeficiency virus (SIV), observed for varying periods, and then sacrificed and tissue prepared for analysis. A marked difference from human AIDS pathology was found: in all monkeys, there was significant peripheral axonal dropout, as opposed to relatively little dropout in the central areas of the nerves (t stat. = -5.9, p < .001). In those monkeys infected with SIV for over one year, the axonal loss in the periphery was also greater than in the central optic nerve (t stat. = -5.03, p < .001); monkeys infected with SIV for less than one year had slightly less peripheral than central loss (t stat. = -4.5, p = .001). When compared with humans, however, it was found that the overall loss of axons was less (15% in monkeys vs. up to 45% in humans). There was also a lack of discernible retinal pathology, such as cotton wool spots, in the monkey tissue.

Specific immune responses in typhoid fever & after TAB vaccination.

The specific immune responses to Salmonella typhi were investigated in 131 patients suffering from typhoid fever and 34 healthy individuals after TAB vaccination. A proportion of individuals failed to develop either specific humoral or cell mediated immune responses. About 5 per cent of the patients with natural infection and nearly 9 per cent of the vaccine recipients failed to develop both the responses. Frequent reinfection and carrier state, and lack of absolute protection following TAB vaccination could be due to the inability of a proportion of naturally infected and TAB vaccinated individuals to mount sufficient specific immune responses, due to the same mechanism.

Benign synovioma causing internal derangement of the knee. A report of nine cases.

Nine pedunculated benign synoviomata causing mechanical symptoms similar to those of a torn meniscus are described. The average age of the patients was 34.4 years. During the period of study, 2254 meniscal lesions causing mechanical symptoms were identified, giving an incidence of one benign synovioma for every 250 meniscal lesions. All the lesions were removed arthroscopically with relief of symptoms.