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Biomedical subjects

R Rajesh

Publications and source records attributed to R Rajesh.

At least 19 recordsLinked to original sources
PubMed2006

Anticoagulant effect of Naja naja venom 5'nucleotidase: demonstration through the use of novel specific inhibitor, vanillic acid.

The snake venom proteins affect hemostasis by either advancing/delaying blood coagulation. Apart from proteases and phospholipase A(2)s (PLA(2)s), 5'nucleotidase is known to affect hemostasis by inhibiting platelet aggregation. In this study, the possible involvement of Naja naja venom 5'nucleotidase in mediating anticoagulant affect is evaluated. Vanillic acid selectively and specifically inhibited 5'nucleotidase activity among other enzymes present in N. naja venom. It is a competitive inhibitor as evident of inhibition relieving upon increased substrate concentration. Vanillic acid dose dependently inhibited the anticoagulant effect of N. naja venom up to 40%. This partial involvement of 5'nucleotidase in mediating anticoagulant effect is substantiated by concanavalin-A (Con-A) inhibition studies. Con-A, competitively inhibited in vitro protease and 5'nucleotidase activity up to 100%. However, it did not exhibit inhibitory activity on PLA(2). The complete inhibition of anticoagulant effect by Con-A upon recalcification time suggests the participation of both 5'nucleotidase and protease in mediating anticoagulant effect of N. naja venom. Vanillic acid and Con-A inhibition studies together suggest that probably 5'nucleotidase interacts with one or more factors of intrinsic pathway of blood coagulation to bring about anticoagulant effect. Thus, this study for the first time demonstrates the involvement of 5'nucleotidase in mediating N. naja venom anticoagulant effect.

5'-Nucleotidase↗
PubMed2006

Purification and characterization of a 34-kDa, heat stable glycoprotein from Synadenium grantii latex: action on human fibrinogen and fibrin clot.

Latex glycoprotein (LGP) from Synadenium grantii latex was purified by the combination of heat precipitation and gel permeation chromatography. LGP is a heat stable protein even at 80 degrees C showed a sharp single band both in SDS-PAGE as well as in native (acidic) PAGE. LGP is a monomeric protein appears as single band under reducing condition. It is a less hydrophobic protein showed sharp single peak in RP-HPLC with retention time of 13.3 m. The relative molecular mass of LGP is 34.4 kDa. CD spectrum of LGP explains less content of alpha-helix (7%), and high content of beta-pleated sheets (48%) and random coils (46%). The N-terminal sequence of LGP is D-F-P-S-D-W-Y-A-Y-E-G-Y-V-I-D-R-P-F-S. Purified LGP is a fibrinogen degrading protease hydrolyses all the three subunits in the order of Aalpha, Bbeta and gamma. The hydrolytic pattern is totally different from plasmin as well as thrombin. LGP reduces recalcification time from 165 to 30 s with citrated human plasma but did not show thrombin like as well as factor Xa-like activity. Although LGP induces procoagulant activity, it hydrolyses partially cross-linked fibrin clot. It hydrolyses all the subunits of partially cross-linked fibrin clot (alpha- chains, beta-chain and gamma-gamma dimer). LGP is a serine protease, inhibited by PMSF. Other serine protease inhibitors, aprotinin and leupeptin did not inhibit the caseinolytic activity as well as fibrinogenolytic activity. We report purification and characterization of a glycoprotein from Synadenium grantii latex with human fibrino(geno)lytic activity.

Amino Acid Sequence↗
PubMed2006

Multiscaling of correlation functions in single species reaction-diffusion systems.

We derive the multi-scaling of probability distributions of multi-particle configurations for the binary reaction-diffusion system in A + A --> O in d < or =2 and for the ternary system in 3A --> O in d=1. For the binary reaction we find that the probability Pt(N, Delta V) of finding N particles in a fixed volume element Delta V at time t decays in the limit of large time as (ln t/t)N(ln t)-N(N-1)/2 for d=2 and t-Nd/2 t-N(N-1)epsilon/4+O(epsilon2) for d<2. Here epsilon=2-d. For the ternary reaction in one dimension we find that Pt(N, delta V) approximately (ln t/t)N/2(ln t)-N(N-1)(N-2)/6 . The principal tool of our study is the dynamical renormalization group. We compare predictions of epsilon expansions for Pt(N, Delta V) for a binary reaction in one dimension against the exact known results. We conclude that the epsilon corrections of order two and higher are absent in the previous answer for Pt(N, Delta V) for N=1, 2, 3, 4. Furthermore, we conjecture the absence of epsilon2 corrections for all values of N.

Journal Article↗
PubMed2006

Differential action of proteases from Trimeresurus malabaricus, Naja naja and Daboia russellii venoms on hemostasis.

The action of venom proteases and their role in hemostasis has been compared in the venoms of Trimeresurus malabaricus, Daboia russellii and Naja naja from the Southern region of Western Ghats, India. These venoms exhibit varying amounts of proteolytic activity and also influence hemostasis differently. Casein hydrolyzing activity of T. malabaricus venoms was 16 and 24 fold higher than those of N. naja and D. russellii venoms, respectively. With the synthetic substrate TAME, the highest activity was observed in T. malabaricus venom. N. naja venom did not hydrolyze TAME even at higher concentrations. These variations in proteolytic activity also influenced the coagulation process. T. malabaricus and D. russellii venoms are strongly procoagulant and reduce the re-calcification time from 148 to 14 and 12 s, respectively. Similarly, both T. malabaricus and D. russellii venoms reduce the prothrombin time from 12.5 to 6.0 s. On the other hand, N. naja venom is anticoagulant and prolongs re-calcification time to 600 s and prothrombin time to 42 s. In spite of varied effects on hemostasis, all the venoms hydrolyze fibrinogen. T. malabaricus venom hydrolyses both Aalpha and Bbeta subunits. While D. russellii and N. naja venoms hydrolyse only Aalpha. None of these venoms hydrolyze the gamma subunit of fibrinogen. Inhibition studies with specific protease inhibitors revealed that both N. naja and T. malabaricus venoms contain only metalloproteases. D. russellii venom contained both serine and metalloproteases. Only, T. malabaricus venom exhibited thrombin-like activity and induces fibrin clot formation with purified fibrinogen within 58 s. Even though D. russellii venom exhibits procoagulant activity, it did not show thrombin-like activity and may act on other coagulation factors.

Animals↗
PubMed2006

Strong myotoxic activity of Trimeresurus malabaricus venom: role of metalloproteases.

Trimeresurus malabaricus is an endemic snake found in the Southern region of Western Ghats section of India along with the more widely distributed species like Naja naja and Daboia russelii. T. malabaricus venom is not lethal when injected (i.p.) up to 20 mg/kg body weight in mice, but causes extensive local tissue degeneration. N. naja and D. russelii are highly toxic (i.p.) with minimum local tissue damage in experimental mice. In this study a comparative analysis of local tissue damage of T. malabaricus venom is made with N. naja and D. russelii snake venoms of the Southern regions of Western Ghats. T. malabaricus venom exhibits caseinolytic activity 16 and 24 times more than N. naja and D. russelii venom. Inhibition studies with specific protease inhibitors reveal that the major proteases belong to metalloproteases. T. malabaricus venom hydrolyses gelatin and induces strong hemorrhagic activity in mice. Both N. naja and D. russelii fail to hydrolyze gelatin even at very high concentration and did not induce any hemorrhagic activity. With D. russelii venom small hemorrhagic spot was observed at the site of injection. The hemorrhagic activity of T. malabaricus venom is completely neutralized by metalloprotease inhibitors and not by serine protease inhibitor. The i.m. injection of T. malabaricus venom causes extensive degradation of muscle tissue within 24 h. The light microscopic observation of muscle tissue showed congestion of blood vessels and hemorrhage at the early stage followed by extensive necrosis of muscle fibers. The elevated levels of serum CK and LDH activity further supported the muscle degeneration. Such pathological symptoms were not seen with N. naja and D. russelii snake venom. The hemorrhagic and the muscle necrosis was completely neutralized by metalloprotease inhibitors and not by serine protease inhibitor strongly suggests that the major toxin component in the T. malabaricus venom is metalloprotease and its activity can be easily neutralized using chelating agents and its use in the first aid as chelation therapy is beneficial.

Animals↗
PubMed2006

Congenital epulis - congenital granular cell lesion: a case report.

Neumann first described congenital epulis (CE) of newborn in 1871. CE occurs at birth and has a striking predilection for females. It is most frequently located on the anterior maxillary alveolar ridge. CE clinically appears as a pedunculated protuberant mass. In cases with large lesions mechanical oral and nasal obstruction can impair fetal deglutition and neonatal respiratory efforts resulting in polyhydramnios prenatally or respiratory impairment postnatally. Histologically CE shows characteristic large cells with granular cytoplasm and spindle cells resembling fibroblasts. The exact histiogenesis is still uncertain, various theories of origin are epithelial, undifferentiated mesenchymal cells, pericytes, fibroblast, smooth muscle cells and nerve related cells. A newborn female child with CE in the maxillary alveolar ridge reported to our institution is presented with investigation, management and follow-up.

Cytoplasm↗
PubMed2005

Breakdown of Kolmogorov scaling in models of cluster aggregation.

We describe a model of cluster aggregation with a source which provides a rare example of an analytically tractable turbulent system. The steady state is characterized by a constant mass flux from small masses to large. Thus it can be studied using a phenomenological theory, inspired by Kolmogorov's 1941 theory, which assumes constant flux and self-similarity. We prove that such self-similarity is violated in dimensions less than or equal to two. We then use dynamical renormalization group techniques to show that the scaling of multipoint correlation functions implies nontrivial multifractality. The analytical results are supported by Monte Carlo simulations.

Journal Article↗
PubMed2005

Convex lattice polygons of fixed area with perimeter-dependent weights.

We study fully convex polygons with a given area, and variable perimeter length on square and hexagonal lattices. We attach a weight tm to a convex polygon of perimeter m and show that the sum of weights of all polygons with a fixed area s varies as s(-theta(conv))eK(t)square root(s) for large s and t less than a critical threshold tc, where K(t) is a t-dependent constant, and theta(conv) is a critical exponent which does not change with t. Using heuristic arguments, we find that theta(conv) is 1/4 for the square lattice, but -1/4 for the hexagonal lattice. The reason for this unexpected nonuniversality of theta(conv) is traced to existence of sharp corners in the asymptotic shape of these polygons.

Journal Article↗
PubMed2005

Procoagulant activity of Calotropis gigantea latex associated with fibrin(ogen)olytic activity.

The latex of Calotropis gigantea is a rich source of useful components that has medicinal properties and one of the main applications is in controlling bleeding. The crude latex extract contained many proteins, which are highly basic in nature and exhibited strong proteolytic activity. The crude extract hydrolyses casein, human fibrinogen and crude fibrin clot in a dose-dependent manner. The hydrolyzing activity was completely inhibited by IAA indicating they belong to the super family, cysteine proteases. Crude extract hydrolyses Aalpha, Bbeta and gamma subunits of fibrinogen. Among all the subunits the preferential subunit to get hydrolyzed was Aalpha followed by Bbeta and gamma subunit is highly resistant and hydrolyzed at higher protein concentration or over a prolonged incubation time. The crude extract hydrolysis crude fibrin clot strongly compared to trypsin and papain. Pharmacologically the crude extract is hemorrhagic and induces skin hemorrhage at >75 microg and reduces the coagulation time of citrated plasma from 150 to 47 s and promotes blood coagulation. Procoagulation and blood clot hydrolysis are important in wound healing process. This is due to unique cysteine proteases of plant latex and is responsible for the pharmacological actions observed in folk medicine.

Animals↗
PubMed2005

Synthesis and evaluation of trimethoxyphenyl isoxazolidines as inhibitors of secretory phospholipase A2 with anti-inflammatory activity.

A series of trimethoxyphenyl isoxazolidine derivatives, 5a(i-v) and 5b(i-v), bearing different constituents at the 5th position of the isoxazolidine ring were synthesized and evaluated in vitro and in vivo for their inhibitory activity against purified group I and II phospholipase A2 (PLA2) enzymes from snake venom and human inflammatory synovial fluid. Irrespective of modification to the pharmacophore (isoxazolidine ring), they exhibited greater specificity for group II PLA2. The length of alkyl or aryl group at the 5th position, which alters the hydrophobic and aromatic property, was responsible for enhancing the inhibition towards PLA2 enzymes. All of the compounds quench the fluorescent property of the purified PLA2 enzyme, and quenching increases with the increase in length of alkyl or aryl group. The inhibitory effect of compounds appeared to be due to the direct interaction of compounds with the enzyme. Inhibition is substrate-dependent, and the inhibitor likely competes with the substrate for the same binding site of the enzyme. The IC50 value for the most potent interacting inhibitor 5b(v) was 54.8 microM. The most active interacting compounds 5a(v) and 5b(v) from in vitro inhibition of PLA2 activity showed similar potency in in vivo neutralization of PLA2-induced mouse paw edema and hemolytic activity.

Animals↗
PubMed2005

Prevalence of dental caries among school children in Kulasekharam village: a correlated prevalence survey.

The prevalence of the most common dental disease, dental caries has been a subject of intense debate due to its importance in statistical measurement and for the clinical control of this disease. Kulasekharam, a small village, situated in Kanyakumari District has a large number of hospitals and a dental college; yet the people seem to have a very poor knowledge about dental health. This prompted us to do a study among school children in the age group of 6-12 years to assess the prevalence of dental caries and to increase their awareness toward oral health. This paper further strives to find any correlation between patient awareness and prevalence of dental decay. The dental caries prevalence was noted to be low compared to the WHO-recommended values. The fluoride level was also tested and was found to be far below the optimal level.

Attitude to Health↗
PubMed2004

Survival probability of a diffusing test particle in a system of coagulating and annihilating random walkers.

We calculate the survival probability of a diffusing test particle in an environment of diffusing particles that undergo coagulation at rate lambda(c) and annihilation at rate lambda(a) . The test particle is annihilated at rate lambda(') on coming into contact with the other particles. The survival probability decays algebraically with time as t(-theta;) . The exponent theta; in d<2 is calculated using the perturbative renormalization group formalism as an expansion in epsilon=2-d . It is shown to be universal, independent of lambda(') , and to depend only on delta , the ratio of the diffusion constant of test particles to that of the other particles, and on the ratio lambda(a) / lambda(c) . In two dimensions we calculate the logarithmic corrections to the power law decay of the survival probability. Surprisingly, the logarithmic corrections are nonuniversal. The one-loop answer for theta; in one dimension obtained by setting epsilon=1 is compared with existing exact solutions for special values of delta and lambda(a) / lambda(c) . The analytical results for the logarithmic corrections are verified by Monte Carlo simulations.

Journal Article↗
PubMed2004

Stationary Kolmogorov solutions of the Smoluchowski aggregation equation with a source term.

In this paper we show how the method of Zakharov transformations may be used to analyze the stationary solutions of the Smoluchowski aggregation equation with a source term for arbitrary homogeneous coagulation kernel. The resulting power-law mass distributions are of Kolmogorov type in the sense that they carry a constant flux of mass from small masses to large. They are valid for masses much larger than the characteristic mass of the source. We derive a "locality criterion," expressed in terms of the asymptotic properties of the kernel, that must be satisfied in order for the Kolmogorov spectrum to be an admissible solution. Whether a given kernel leads to a gelation transition or not can be determined by computing the mass capacity of the Kolmogorov spectrum. As an example, we compute the exact stationary state for the family of kernels, K(zeta) ( m(1), m(2) )= ( m(1) m(2) )(zeta/2) which includes both gelling and nongelling cases, reproducing the known solution in the case zeta=0. Surprisingly, the Kolmogorov constant is the same for all kernels in this family.

Journal Article↗
PubMed2004

Nonequilibrium phase transitions in models of adsorption and desorption.

The nonequilibrium phase transition in a system of diffusing, coagulating particles in the presence of a steady input and evaporation of particles is studied. The system undergoes a transition from a phase in which the average number of particles is finite to one in which it grows linearly in time. The exponents characterizing the mass distribution near the critical point are calculated in all dimensions.

Journal Article↗
PubMed2004

DSDBASE: a consortium of native and modelled disulphide bonds in proteins.

DSDBASE is a database of disulphide bonds in proteins, which provides information on native disulphides and those that are stereochemically possible between pairs of residues for all known protein structural entries. The modelling of disulphides has been performed, using MODIP, by the identification of residue pairs that can strainlessly accommodate a covalent cross-link. We also assess the stereochemical quality of the covalent cross-link and grade them appropriately. One of the potential uses of the database is to design site-directed mutants in order to enhance the thermal stability of a protein. The proposed sites of mutations can be viewed specifically with respect to active sites of enzymes and across physiological dimers. The occurrence of native and modelled disulphides increases the dimensions of the database enormously. This database can also be employed for proposing three-dimensional models of disulphide-rich short polypeptides. The database can be accessed from http://www.ncbs.res.in/ approximately faculty/mini/dsdbase/dsdbase.html. Supplementary information can be accessed from http://www.ncbs.res.in/ approximately faculty/mini/dsdbase/nar/suppl.htm.

Animals↗
PubMed2004

Anterior inferior cerebellar artery infarct with unilateral deafness.

We report the case of a young man with anterior inferior cerebellar artery infarct causing unilateral deafness. Clinical features and audiometry suggested cochlear localization for deafness. MRI brain showed an infarct in the right AICA territory with involvement of pons. Involvement of the internal auditory artery explains the cochlear deafness.

Adult↗
PubMed2003

Persistence properties of a system of coagulating and annihilating random walkers.

We study a d-dimensional system of diffusing particles that on contact either annihilate with probability 1/(q-1) or coagulate with probability (q-2)/(q-1). In one dimension, the system models the zero-temperature Glauber dynamics of domain walls in the q-state Potts model. We calculate P(m,t), the probability that a randomly chosen lattice site contains a particle whose ancestors have undergone exactly (m-1) coagulations. Using perturbative renormalization group analysis for d<2, we show that, if the number of coagulations m is much less than the typical number M(t), then P(m,t) approximately m(zeta/d)t(-theta), with theta=dQ+Q(Q-1/2)epsilon+O(epsilon(2)), zeta=(2Q-1)epsilon+(2Q-1)(Q-1)(1/2+AQ)epsilon(2)+O(epsilon(3)), where Q=(q-1)/q, epsilon=2-d and A=-0.006....M(t) is shown to scale as M(t) approximately t(d/2-delta), where delta=d(1-Q)+(Q-1)(Q-1/2)epsilon+O(epsilon(2)). In two dimensions, we show that P(m,t) approximately ln(t)(Q(3-2Q))ln(m)((2Q-1)(2))t(-2Q) for m<<t(2Q-1). We also derive an exact nonperturbative relation between the exponents: namely delta(Q)=theta(1-Q). The one-dimensional results corresponding to epsilon=1 are compared with results from Monte Carlo simulations.

Journal Article↗