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Biomedical subjects

A Saxena

Publications and source records attributed to A Saxena.

At least 37 records · Page 2Linked to original sources

Antifilarial activity of Zoanthus species (Phylum Coelenterata, Class Anthzoa) against human lymphatic filaria, Brugia malayi.

The chloroform methanol (1:1) extract of an unidentified green zoanthus (Phylum Coelenterata, Class Anthozoa) showed promising in vitro adulticidal activity with a lethal concentration of 125 microg/ml on Brugia malayi. This extract brought about a 52.2% reduction in circulating microfilariae of B. malayi when administered to infected Mastomys coucha at 250 mg/kg, orally for 5 consecutive days. Further fractionation of the extract led to the recovery of four fractions, which were evaluated simultaneously in both in vitro and in vivo systems against B. malayi. The chloroform fraction at 250 mg/kg orally for 5 days exhibited the highest macrofilaricidal action (42.5%), closely followed by the insoluble n-butanol fraction (34.3%), the soluble hexane fraction (32.4%), and the soluble n-butanol fraction (20.4%). In addition, the hexane soluble fraction caused 44.3% sterilization of the surviving female parasites. Two compounds isolated were found devoid of antifilarial activity.

Animals↗

Origin of magnetic and magnetoelastic tweedlike precursor modulations in ferroic materials.

Based on experimental observations of modulated magnetic patterns in a Co0.5Ni0.205Ga0.295 alloy, we propose a model to describe a (purely) magnetic tweed and a magnetoelastic tweed. The former arises above the Curie (or Néel) temperature due to magnetic disorder. The latter results from compositional fluctuations coupling to strain and then to magnetism through the magnetoelastic interaction above the structural transition temperature. We discuss the origin of purely magnetic and magnetoelastic precursor modulations and their experimental thermodynamic signatures.

Journal Article↗

The influence of solvent composition on global dynamics of human butyrylcholinesterase powders: a neutron-scattering study.

A major result of incoherent elastic neutron-scattering experiments on protein powders is the strong dependence of the intramolecular dynamics on the sample environment. We performed a series of incoherent elastic neutron-scattering experiments on lyophilized human butyrylcholinesterase (HuBChE) powders under different conditions (solvent composition and hydration degree) in the temperature range from 20 to 285 K to elucidate the effect of the environment on the enzyme atomic mean-square displacements. Comparing D(2)O- with H(2)O-hydrated samples, we were able to investigate protein as well as hydration water molecular dynamics. HuBChE lyophilized from three distinct buffers showed completely different atomic mean-square displacements at temperatures above approximately 200 K: a salt-free sample and a sample containing Tris-HCl showed identical small-amplitude motions. A third sample, containing sodium phosphate, displayed highly reduced mean-square displacements at ambient temperature with respect to the other two samples. Below 200 K, all samples displayed similar mean-square displacements. We draw the conclusion that the reduction of intramolecular protein mean-square displacements on an Angstrom-nanosecond scale by the solvent depends not only on the presence of salt ions but also on their type.

Biophysical Phenomena↗

Drotaverine hydrochloride for augmentation of labor.

OBJECTIVES: To study the use of drotaverine hydrochloride for acceleration of labor and relief of labor pains. METHODS: In this double-blind placebo-controlled randomized study, 100 primigravidas in uncomplicated spontaneous labor at term were given drotaverine hydrochloride or placebo (distilled water) intramuscularly. Labor events, including pain (assessed by a visual analog scale and a verbal rating scale), neonatal outcome, and side effects of the drug were recorded. Student's t-test was used for analysis. RESULTS: Forty-four patients in the drug group and 40 in the placebo group had complete data for analysis after decoding. In drotaverine group, there was a mean 15% reduction in the duration of the first stage of labor and a mean 19% reduction in the second stage. The maximum shortening of the first stage (28%) was observed when drotaverine was administered when cervical dilatation was 4 cm (P=0.044). There were no adverse fetal effects, but atonic postpartum hemorrhage was more common in the drotaverine group. There was no relief of pain with the drug except in the fourth stage of labor. CONCLUSIONS: Drotaverine hydrochloride is safe and effective in accelerating labor, but not effective in lessening labor pain.

Adult↗

Clonal B cell populations in a minority of patients with Hashimoto's thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is a risk factor for thyroid lymphoma, and clonal B cell populations in HT support this link. The literature on B cell clonality in HT is controversial. AIMS: To identify clonal B cell populations in HT and to assess their usefulness in differentiating HT from mucosa associated lymphoid tissue (MALT) lymphoma and predicting future development of lymphoma. METHODS: DNA from formalin fixed, paraffin wax embedded blocks of thyroid specimens from 10 patients with HT and two thyroid MALT lymphomas was analysed for B cell clonality by seminested polymerase chain reaction (PCR) using FRIII/LJH and FRIII/VLJH primers to amplify the IgH gene VDJ region. In one case, PCR products were sequenced. Immunohistochemistry was performed by labelled streptavidin-biotin technique using antibodies to: CD45, CD45RO, CD3, CD20, and cytokeratin. RESULTS: The histopathological and clinical findings were characteristic of HT. Clonal bands were seen in three and a polyclonal smear pattern was seen in seven cases. The clonal bands in HT were associated with a background smear, and could not be reproduced from other blocks from the same case or from deeper sections of the same block. The clonal bands in thyroid lymphomas were not associated with a background smear and were reproducible. None of the patients with clonal B cells has developed malignant lymphoma during a follow up of 10-13 years. CONCLUSIONS: B cell clonal bands in HT have different features from those in lymphoma (non-pure and non-reproducible) and do not predict future development of lymphoma.

Adult↗

Ion channels as important targets for antiepileptic drug design.

Ion channels have a critical role in the function of the nervous system, where they instigate and conduct nerve impulses by asserting control over the voltage potential across the plasma membrane. Propagation of electrical impulses occurs by opening of voltage-gated ion channels. Ion channel blockers prevent this from occurring, and can therefore be used in the treatment of central nervous system disorders and neuropathic pain. Recent identification of ion channel gene mutations in Mendelian epilepsies suggests that genetically driven neuronal hyperexcitability plays an important role in epileptogenesis. Studies with animal seizure models have indicated that changes in temporal and spatial expression of voltage-gated sodium channels may be important in the pathology of epilepsy. This paper is aimed at elucidating the organization of the ion channels and covers a review on the antiepileptic drugs, both established and currently under development targeted to the ion channels in order to bring about effective seizure control.

Anticonvulsants↗

Breather lattice and its stabilization for the modified Korteweg-de Vries equation.

We obtain an exact solution for the breather lattice solution of the modified Korteweg-de Vries equation. Numerical simulation of the breather lattice demonstrates its instability due to the breather-breather interaction. However, such multibreather structures can be stabilized through the concurrent application of ac driving and viscous damping terms.

Journal Article↗

Confinement of discrete breathers in inhomogeneously profiled nonlinear chains.

We investigate numerically the scattering of a moving discrete breather on a pair of junctions in a Fermi-Pasta-Ulam chain. These junctions delimit an extended region with different masses of the particles. We consider (i) a rectangular trap, (ii) a wedge shaped trap, and (iii) a smoothly varying convex or concave mass profile. All three cases lead to DB confinement, with the ease of trapping depending on the profile of the trap. We also study the collision and trapping of two DBs within the profile as a function of trap width, shape, and approach time at the two junctions. The latter controls whether one or both DBs are trapped.

Journal Article↗

Spin-polarized conductance induced by tunneling through a magnetic impurity.

Using the zero mode method, we compute the conductance of a wire consisting of a magnetic impurity coupled to two Luttinger liquid leads characterized by the Luttinger exponent alpha(>or=1). We find for resonance conditions, in which the Fermi energy of the leads is close to a single particle energy of the impurity, that the conductance as a function of temperature is G approximately equal (e(2)/h)(T/T(F))(2(alpha-2)), whereas for off-resonance conditions the conductance is G approximately equal (e(2)/h)(T/T(F))(2(alpha-1)). By applying either a gate voltage or a magnetic field or both, one of the spin components can be in resonance while the other is off resonance causing a strong asymmetry between the spin-up and spin-down conductances.

Journal Article↗

Photoexcited breathers in conjugated polyenes: an excited-state molecular dynamics study.

pi-conjugated polymers have become an important class of materials for electronic devices. Design of these devices requires understanding such processes as photochemical reactions, spatial dynamics of photoexcitations, and energy and charge transport, which in turn involve complex coupled electron-vibrational dynamics. Here we study nonlinear photoexcitation dynamics in the polyene oligomers by using a quantum-chemical method suitable for the simulation of excited-state molecular dynamics in extended molecular systems with sizes up to hundreds of atoms. The method is based on the adiabatic propagation of the ground-state and transition single-electron density matrices along the trajectory. The simulations reveal formation of a self-localized vibronic excitation ("breather" or multiquanta bound state) with a typical period of 34 fs and allows us to identify specific slow and fast nuclear motions strongly coupled to the electronic degrees of freedom. The effect of chain imperfections and chemical defects on the dynamics is also investigated. A complementary two-dimensional analysis of corresponding transition density matrices provides an efficient way to monitor time-dependent real-space localization of the photoexcitation by identifying the underlying changes in charge densities and bond orders. Possible correlated electronic and vibrational spectroscopic signatures of photoexcited breathers are predicted, and generalizations to energy localization in complex macromolecules are discussed.

Algorithms↗

Molecular detection of the G(-248)A BAX promoter nucleotide change in B cell chronic lymphocytic leukaemia.

BACKGROUND: A novel single nucleotide polymorphism (SNP), G(-248)A, in the 5' untranslated region of the BAX promoter and its association with reduced protein expression, progression beyond Rai stage 0, and treatment resistance in chronic lymphocytic leukaemia (CLL) has been reported previously. AIM: To develop a restriction enzyme analysis (REA) based method for routine detection of BAX promoter SNP in a clinical laboratory. METHODS: The BAX promoter was analysed in duplicate by REA and sequencing in 90 samples (from 45 patients with CLL, 43 controls, and two cell lines). The promoter region was amplified, digested with restriction endonucleases (Aci I and Tau I), and separated by gel electrophoresis. RESULTS: After digestion, the normal GG genotype samples produced three distinct bands. The homozygous AA replacement abolished the cleavage site, resulting in a single band. Although the heterozygous samples produced three bands, the two smaller visible bands were reduced in intensity (> 50%). The test characteristics of Aci I REA were better than those of Tau I REA, in terms of sensitivity (100% v 77.8%), specificity (98.6% v 92.3%), positive predictive value (95.03% v 87.4%), and negative predictive value (100% v 85.83%). CONCLUSIONS: REA using Aci I is a highly sensitive and specific method for detecting the BAX G(-248)A SNP in CLL.

5' Untranslated Regions↗

Conformational dynamics of photoexcited conjugated molecules.

Time-dependent photoexcitation and optical spectroscopy of pi-conjugated molecules is described using a new method for the simulation of excited state molecular dynamics in extended molecular systems with sizes up to hundreds of atoms. Applications are made to poly(p-phenylene vinylene) oligomers. Our analysis shows self-trapping of excitations on about six repeat units in the course of photoexcitation relaxation, identifies specific slow (torsion) and fast (bond-stretch) nuclear motions strongly coupled to the electronic degrees of freedom, and predicts spectroscopic signatures of molecular conformations.

Journal Article↗

Efficient computation of the structural phase behavior of block copolymers.

A numerical implementation of self-consistent mean-field theory for the structural phase behavior of block copolymers is proposed. Our scheme does not require a priori assumptions of the underlying mesoscopic symmetries. The method potentially enables us to characterize, with high accuracy, the structural phase diagram of block copolymers with significant architectural complexity. We illustrate the method by applying it to a triblock copolymer system.

Computational Biology↗

Nucleation in systems with elastic forces.

Systems with long-range interactions when quenched into a metastable state near the pseudospinodal exhibit nucleation processes that differ from classical nucleation seen near the coexistence curve. In systems with long-range elastic forces the description of the nucleation process can be quite subtle due to the presence of bulk and surface elastic compatibility constraints. We analyze the nucleation process in a simple 2D model with elastic forces and show that the nucleation process generates critical droplets with a different structure than the stable phase. This has implications for nucleation in many crystal-crystal transitions, specifically martensites and shape memory alloys, and for the structure of the final state.

Journal Article↗

Expression of Bcl-x, Bcl-2, Bax, and Bak in endarterectomy and atherectomy specimens.

The regulation of apoptosis in atherosclerosis is not completely defined. The aim of this study was to determine the expression of Bcl-2, Bcl-x, Bax, and Bak in relation to apoptosis in advanced atherosclerotic lesions. In atherectomy (15), endarterectomy (10), and control non-atherosclerotic segments of renal (2) and of coronary and carotid (5) arteries, the extent of apoptosis was determined using TdT dUTP nick end labelling (TUNEL) and nuclear morphology (karyorrhexis/pyknosis) and expression of apoptosis regulators by immunohistochemistry and western blot analysis on paraffin-embedded material. In all specimens, the atherosclerotic involvement was advanced: grade V (n=18) and grade VI (n=7). The apoptotic index was high (mean 30%) in advanced lesions compared with controls (<2%) and smooth muscle cells (SMCs) were the predominant cell type undergoing apoptosis. In all TUNEL-positive apoptotic cells, Bax and Bak were present, while Bcl-x was absent. Bcl-2 was absent in a majority of these cells, but occasional TUNEL-positive cells expressed Bcl-2. In non-apoptotic cells, Bcl-x was present and western blot detected only the long isoform, Bcl-xL, from the plaques. In conclusion, increased Bax and Bak coupled with lack/paucity of Bcl-2 and Bcl-xL are associated with SMC apoptosis in advanced lesions. Bcl-xL in non-apoptotic cells appears to contribute to prolonged cell survival.

Apoptosis↗