Modulation of rat peripheral polymorphonuclear leukocyte response by nitric oxide and arginine

The effect of nitric oxide (NO) on the luminol-dependent chemiluminescence (LCL) response of rat polymorphonuclear leukocytes (PMNLs) was analyzed by using sodium nitroprusside (SNP), a NO donor, and L-arginine (L-arg), a NO precursor. A significant reduction in the LCL intensity was observed in presence of SNP (100 μmol/L) or L-arg (5 or 10 mmol/L) in arachidonic acid (AA) phorbol ester (PMA) and formyl- methionyl-leucyl-phenylalanine stimulated PMNLs. However, opsonized zymosan-induced LCL was not attenuated significantly. Reduction in hydroxyl radical and superoxide generation was also observed in SNP- or L-arg-pretreated cells. D-Arg (10 mmol/L) pretreatment did not inhibit PMNLs' LCL response. Furthermore, methylene blue (5 μmol/L) and L-NG- mono methyl-L-arginine (100 or 300 μmol/L) significantly attenuated the LCL response, as induced by various agonists. Cyclic GMP did not alter the reactive oxygen species generation from rat PMNLs. In addition, AA-induced release of myeloperoxidase, a marker of azurophilic granules, was found to be enhanced in L-arg- (10 mmol/L) pretreated PMNLs. The results suggest that NO inhibits free radical generation from rat PMNLs

Curcumin-Loaded Apotransferrin Nanoparticles Provide Efficient Cellular Uptake and Effectively Inhibit HIV-1 Replication In Vitro

Curcumin (diferuloylmethane) shows significant activity across a wide spectrum of conditions, but its usefulness is rather limited because of its low bioavailability. Use of nanoparticle formulations to enhance curcumin bioavailability is an emerging area of research.In the present study, curcumin-loaded apotransferrin nanoparticles (nano-curcumin) prepared by sol-oil chemistry and were characterized by electron and atomic force microscopy. Confocal studies and fluorimetric analysis revealed that these particles enter T cells through transferrin-mediated endocytosis. Nano-curcumin releases significant quantities of drug gradually over a fairly long period, ∼50% of curcumin still remaining at 6 h of time. In contrast, intracellular soluble curcumin (sol-curcumin) reaches a maximum at 2 h followed by its complete elimination by 4 h. While sol-curcumin (GI(50) = 15.6 µM) is twice more toxic than nano-curcumin (GI(50) = 32.5 µM), nano-curcumin (IC(50)<1.75 µM) shows a higher anti-HIV activity compared to sol-curcumin (IC(50) = 5.1 µM). Studies in vitro showed that nano-curcumin prominently inhibited the HIV-1 induced expression of Topo II α, IL-1β and COX-2, an effect not seen with sol-curcumin. Nano-curcumin did not affect the expression of Topoisomerase II β and TNF α. This point out that nano-curcumin affects the HIV-1 induced inflammatory responses through pathways downstream or independent of TNF α. Furthermore, nano-curcumin completely blocks the synthesis of viral cDNA in the gag region suggesting that the nano-curcumin mediated inhibition of HIV-1 replication is targeted to viral cDNA synthesis.Curcumin-loaded apotransferrin nanoparticles are highly efficacious inhibitors of HIV-1 replication in vitro and promise a high potential for clinical usefulness

Exploring the Fundamental Dynamics of Error-Based Motor Learning Using a Stationary Predictive-Saccade Task

The maintenance of movement accuracy uses prior performance errors to correct future motor plans; this motor-learning process ensures that movements remain quick and accurate. The control of predictive saccades, in which anticipatory movements are made to future targets before visual stimulus information becomes available, serves as an ideal paradigm to analyze how the motor system utilizes prior errors to drive movements to a desired goal. Predictive saccades constitute a stationary process (the mean and to a rough approximation the variability of the data do not vary over time, unlike a typical motor adaptation paradigm). This enables us to study inter-trial correlations, both on a trial-by-trial basis and across long blocks of trials. Saccade errors are found to be corrected on a trial-by-trial basis in a direction-specific manner (the next saccade made in the same direction will reflect a correction for errors made on the current saccade). Additionally, there is evidence for a second, modulating process that exhibits long memory. That is, performance information, as measured via inter-trial correlations, is strongly retained across a large number of saccades (about 100 trials). Together, this evidence indicates that the dynamics of motor learning exhibit complexities that must be carefully considered, as they cannot be fully described with current state-space (ARMA) modeling efforts

Principles of sensorimotor learning.

The exploits of Martina Navratilova and Roger Federer represent the pinnacle of motor learning. However, when considering the range and complexity of the processes that are involved in motor learning, even the mere mortals among us exhibit abilities that are impressive. We exercise these abilities when taking up new activities - whether it is snowboarding or ballroom dancing - but also engage in substantial motor learning on a daily basis as we adapt to changes in our environment, manipulate new objects and refine existing skills. Here we review recent research in human motor learning with an emphasis on the computational mechanisms that are involved

Scale Space Technique for Word Segmentation in Handwritten Manuscripts

Indexing large archives of historical manuscripts, like the papers of George Washington, is required to allow rapid perusal by scholars and researchers who wish to consult the original manuscripts. Presently, such large archives are indexed manually. Since optical character recognition (OCR) works poorly with handwriting, a scheme based on matching word images called word spotting has been suggested previously for indexing such documents. The important steps in this scheme are segmentation of a document page into words and creation of lists containing instances of the same word by word image matching. We have developed a novel methodology for segmenting handwritten document images by analyzing the extent of ``blobs in a scale space representation of the image. The algorithm was been applied to around 30 grey level images randomly picked from different sections of the George Washington corpus of 6,400 handwritten document images. An accuracy of $77-96$ percent was observed with an average accuracy of around $87$ percent. The algorithm works well in the presence of noise, shine through and other artifacts which may arise due aging and degradation of the page over a couple of centuries or through the man made processes of photocopying and scanning. Most existing document analysis systems have been developed for machine printed text. There has been little work on word segmentation for handwritten documents. Most of this work has been applied to special kinds of pages - for example, addresses or ``clean pages which have been written specifically for testing the document analysis systems. Historical manuscripts suffer from many problems including noise, shine through and other artifacts due to aging and degradation. No good techniques exist to segment words from such handwritten manuscripts. Further, scale space techniques have not been applied to this problem before

Evidence for the presence of a plasma factor which acts synergistically to ADP-induced platelet aggregation

This article does not have an abstract

Effect of centbucridine &amp; lignocaine on biochemical changes in isoproterenol induced ischemia in rats

Effect of lignocaine and centbucridine against isoproterenol-induced biochemical changes was studied in the rat. Isoproterenol (40 mg/kg twice) increased the heart weight, level of manolaldehyde (MDA) and activity of acid phosphatase, but decreased the myocardial phospholipid content at 48 h. In addition, increase in plasma triglyceride, cholesterol, MDA and creatine phosphokinase activity was observed. Pretreatment of the animals with lignocaine (10 mg/kg) or centbucridine (1, 3 and 10 mg/kg) protected the animals against these biochemical changes. However, increase in heart weight consequent to isoproterenol treatment could not be prevented. Total protection against creatine phosphokinase release in the blood was also not observed. The results suggest that the two drugs inhibit lipolysis. They may also inhibit phospholipases leading to protection against ischemia-induced changes in the rat

Effect of pulmonary thromboembolism on circulating neutrophils in mice

The role of free radical generation and its scavenging enzymes in circulating mice polymorphonuclear leukocytes (PMNLs) has been studied following pulmonary thromboembolism. Levels of malonaldehyde (MDA), O<SUB>2</SUB> radical generation, activity of superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), myeloperoxidase (MPO) and lysozyme were estimated in lysed neutrophil preparations. Activities of SOD and CAT were increased in neutrophils, while animals showed 60&#177; 4% thrombocytopenia. Levels of MDA in PMNLs were also elevated significantly following thrombosis. However, there was no significant change in superoxide radical generation, after thrombotic challenge, in mice neutrophils. The present study provides evidence for the involvement of free radicals in mice pulmonary thromboembolism

Pulmonary thromboembolism-induced alterations in nitric oxide release from rat circulating neutrophils

We have earlier reported that neutrophils play an important role in pulmonary thromboembolism. The effect of circulating polymorphonuclear leukocytes (PMNL) isolated from normal and thrombotic rats was, therefore, studied on platelet aggregation in platelet-rich plasma. PMNL inhibited the platelet aggregation in a concentration- and time-dependent manner at 37 ° C. The platelet aggregation inhibitory response of PMNL was more pronounced in the presence of superoxide dismutase and was abolished by hemoglobin and methylene blue. These observations suggested that the inhibitory effect of PMNL on platelets was mediated by neutrophil-derived relaxing factor. PMNL, obtained after thromboembolism, inhibited the platelet aggregation response more strongly due to an increased release of nitric oxide from them. It is suggested that PMNL play an important role in the regulation of hemostasis