Transport and magnetic properties of Fe(x)VSe(2) (x = 0-0.33).

We present the results of the effect of Fe intercalation on the structural, transport and magnetic properties of 1T-VSe(2). Intercalation of iron suppresses the charge density wave transition at 110 K in 1T-VSe(2). And for more than 10% Fe concentration a new kind of first-order transition appears below 160 K in our resistivity results. The transition becomes stronger with a broad hysteresis (80-160 K) for 33% Fe intercalation. The anomalies are absent in the thermopower measurements of polycrystalline Fe(x)VSe(2) compounds (x = 0-0.33). The susceptibility measurements between 2 and 300 K and the magnetization in a high magnetic field up to 14 T at 2 K are reported. The Fe atoms are in the low-spin ( S = 1/2) state of Fe(3+) and the compounds show the absence of any magnetic order at low temperatures.

Kinetoplast DNA minicircles of Leishmania donovani express a protein product.

We describe an unprecedented finding of an open reading frame present in the variable region in one of the minicircle sequence classes of a human pathogenic strain of Leishmania donovani (MHOM/IN/90/RMRI 68) which is transcribed and translated. The encoded protein showed homologies to known transport proteins.

Antioxidant and lipid lowering activities of Indian black tea.

Indian black tea; CTC leaf and dust, produced by Tata Tea Limited, Kolkata, (India) was studiedin vitro as potential scavenger of oxygen free radicals. Super oxide anions were generated in a system containing xanthine-xanthine oxidase (enzymic system) and by NADH- phenozine methosulphate (non enzymic system). Anions were assayed in terms of uric acid formation and reduction of nitroblue tetrazolium salt, which were shown to be suppressed by tea extracts. Extracts from both leaf and dust also inhibted the formation of hydroxyl radicalsin vitro in the enzymic system comprising hypoxanthine-Cu(+2)-sodium ascorbate and xanthine oxidase and in non enzymic system of deoxyribose-Cu(+2)-sodium ascorbate and H(2)O(2) as well as the Cu(+2) induced lipid peroxidation in human low density lipoprotein. Feeding with black tea in normal rats for sixty days increased their antioxidant activity and their liver microsomes were shown to be protected against peroxidation of lipids as stimulated by metal ions with enzymic or non enzymic reactants. Furthermore feeding with tea extracts in normal as well as triton WR-1339 induced hyperlipidemic rats caused decrease in their plasma levels of total cholesterol, phospholipids and triglycerides. The antioxidant and lipid lowering activities of both extracts from CTC leaf and dust tea was comparable and may be due to the presence of natural products like catechin and others.

In vitro cultivation and characterization of axenic amastigotes of Leishmania.

The establishment of axenic cultures of the amastigote stage of Leishmania is important to understand the mechanisms regulating the differentiation, survival and pathogenicity of the parasite with a view to develop and identify molecular and chemotherapeutic targets. Recent developments in axenic culture and the characterization of amastigotes of different species of Leishmania are discussed.

Relative resistance of promastigotes of a virulent and an avirulent strain of Leishmania donovani to hydrogen peroxide.

Sensitivity of promastigotes of Leishmania donovani (Dd-8, virulent: UR-6 avirulent strain) to hydrogen peroxide has been studied in vitro conditions. There was a dose-dependent toxic effect of H2O2 on both strains. The promastigotes of Dd-8 strain, however, were more resistant compared to UR-6 strain. The cell response was not affected by the forms of H2O2 stress, for instance, single-dose exposure with reagent H2O2 or equivalent amount generated over a period of 1 h. Dd-8 promastigotes removed H2O2 from medium at a higher rate (6.43 nmol/min/ 3 x 10(7) cell/ml) compared to UR-6 promastigotes (3.17 nmol/min/3 x 10(7) cells/ml). Hydrogen peroxide metabolism by Dd-8 cells was significantly inhibited by aminotriazole, azide, and thiol reagents, while that of UR-6 cells was sensitive only to thiol reagents. The results are consistent with the negligible activity of glutathione peroxidase and nondetectable catalase in UR-6 promastigotes; both enzyme activities were present in Dd-8 promastigotes. These findings suggest that the ability of the parasite to resist H2O2 toxicity may have a potential role in its virulence.

Symptomatic osteoarthritis in the elderly: a comparative study of sulindac and ibuprofen.

Thirty-two elderly patients with symptomatic osteoarthritis, mainly of the hip and/or knee joints, were treated at random with either 400 mg sulindac or 1200 mg ibuprofen per day for 12 weeks. Clinical assessments were made before, during and after treatment of disease activity, weight-bearing pain, night pain, and pain on active and passive movement. Objective measurements were also made of duration of inactivity stiffness, knee flexion and hip abduction. The results showed that after treatment there was significant symptomatic improvement in the patients in both groups. Apart from night pain, the differences between the groups in the subjective parameters at Week 12 were significant in favour of sulindac. Overall assessment of response to treatment also showed a significant preference for sulindac by patients and physician. Both drugs were well-tolerated although 1 patient on sulindac had to be withdrawn because of a skin rash.

A randomized comparison between sulindac and ibuprofen in osteoarthritis of the aged.

Thirty-two elderly patients with symptomatic osteoarthritis predominantly of the hip and/or knee joints were randomly treated on an open basis for 12 weeks with either 400 mg sulindac or 1200 mg ibuprofen per day. Clinical assessments were made before and after 1, 3, 6, 9 and 12 weeks of treatment, of disease activity, weight bearing pain, and pain on active and passive movement. Objective measurements were also made of duration of inactivity stiffness, knee flexion and hip abduction. The results showed that there was significant symptomatic improvement after treatment in the patients in both groups and that, apart from night pain, the differences between the groups in the subjective parameters at Week 12 were significant in favour of sulindac. Overall assessment of response to treatment also showed a significant preference for sulindac by patients and physician. Sulindac and ibuprofen were well-tolerated during the trial period, although 1 patient on sulindac had to be withdrawn because of a skin rash.

Characterization of kinetoplast DNA minicircles of an Indian isolate of Leishmania donovani.

Characterization of the kinetoplast DNA minicircles in a human pathogenic Indian isolate of Leishmania donovani has not been reported previously. Using inverse PCR, we constructed a library of PCR-amplified minicircle variable region from the kinetoplast DNA of this isolate. A combination of restriction enzyme digestion and nucleotide sequence analysis revealed five minicircle DNA sequence classes within the library, one of which was predominant, representing 75% of the kDNA network. Another distinct sequence class represented 15% of the minicircle network. Other minor sequence classes collectively constituted the remaining 10% of the network. Apart from generating basic information on the organisation and distribution of the different sequence classes within the minicircles, the DNA sequence analysis also revealed unique attributes to our minicircles. One was the surprising homology of our isolate (an Old World sp.) with distantly related New World Leishmania species. Secondly, open reading frames were also identified, indicating the possibility that these minicircles may have more than a structural role to play within the kinetoplast network.

Characterization of intracellular metabolites of axenic amastigotes of Leishmania donovani by 1H NMR spectroscopy.

The intracellular metabolites of long-term in vitro cultured axenic amastigotes of Leishmania donovani (strain Dd8) were determined and compared with those of promastigotes and intracellular amastigotes, employing proton NMR spectroscopy. The presence of two new metabolites, i.e. betaine and beta-hydroxybutyrate were reported. Betaine was detected in all the three stages being highest in the promastigotes while beta-hydroxybutyrate could be detected only in promastigotes and axenic amastigotes. Among other metabolites, succinate and valine were found in higher quantities in intracellular amastigotes and axenic amastigotes than in promastigotes. Acetoacetate was present only in axenic and intracellular amastigotes. The comparative metabolite profile of different parasite forms reveals that axenic amastigotes seem to represent an intermediate stage between promastigotes and intracellular amastigotes in spite of their strong resemblance to intracellular amastigotes in morphology, infectivity, biochemical studies and even in the manifestation of amastigote specific A2 protein.

Protective effect of Picroliv from Picrorhiza kurroa against Leishmania donovani infections in Mesocricetus auratus.

The prevalent drugs for treatment of kala azar viz. sodium stibogluconate (SSG) and pentamidine cause severe toxic side effects and acute immunosuppression in the treated individuals. Picroliv, a standardized mixture of iridoid glycosides, prepared from the alcoholic extract of the root and rhizome of Picrorhiza kurroa has shown strong hepatoprotective activity against several models of hepatotoxicity. Therefore, the present study was undertaken with an objective to study the effects of Picroliv (12.5 mg/kg x 7 days oral) alone and in combination with SSG on parasitemia, lipid peroxidation and hepatic marker enzymes of golden hamsters during Leishmania donovani infection. The results indicated a marked hepatoprotective effect of Picroliv in terms of biochemical markers, and a significant antileishmanial activity implying that it can be utilized as an adjunct to chemotherapy or in combination therapy of kala azar along with sodium stibogluconate, thus enhancing the efficacy of antileishmanials.

Oxy free radical system in heart failure and therapeutic role of oral vitamin E.

Twenty patients of heart failure and ten matched healthy controls were included in the trial. Out of these 20 patients of heart failure, 12 patients were also studied prospectively. Plasma levels of superoxide anion and malonyldialdehyde were increased while the levels of superoxide dismutase, catalase and glutathione reductase were decreased in patients of heart failure as compared to control subjects. The alteration in oxidative stress and antioxidant system did not correlate with the age and sex of patients or the etiology of heart failure. With the increasing severity of heart failure the malonyldialdehyde and superoxide anion increased significantly and catalase, glutathione reductase and superoxide dismutase levels decreased. The group of heart failure patients with ejection fraction < 40% (n = 7) exhibited significantly higher levels of malonyldialdehyde than those with an ejection fraction > 40% (n = 13). The superoxide anion and malonyldialdehyde levels were significantly higher in patients of heart failure in the pre-treatment state as compared to those in post-treatment state. Conversely catalase, glutathione reductase and superoxide dismutase were higher in the post-treatment period as compared to their values before treatment. The addition of vitamin E in doses of 400 mg once a day orally for 4 weeks significantly reduced the malonyldialdehyde and superoxide anion levels and produced an elevation of the antioxidant enzymes. Thus, there is an apparent normalisation of the indices of oxidative stress following treatment of heart failure and a markedly improved response on vitamin E supplementation which may be more beneficial.

Measurement and calculations of laminar flow in a ninety degree bifurcation.

Measurements and numericaL calculations of laminar flow in a plane 90 degrees bifurcation are presented. The corresponding two-dimensional steady flow Navier-Stokes equations solved by a finite-difference procedure employing pressure and velocity as dependent variables. The influence of Reynolds number and mass flow ratio on the velocity field, streamlines, local shear stress and pressure drop are quantified and shown to be substantial. The circulation patterns and shear stresses are examined in view of available data regarding the formation of atherotic plaques in the human circulatory system. The calculated velocity profiles are compared with measurements obtained with laser Doppler anemometry and the agreement is shown to be satisfactory. Calculations outside the range of measurements which are of value to biomechanics are also presented.

Biochemical changes in heat stressed promastigotes of Leishmania donovani.

On exposing promastigotes of L. donovani (Dd-8) to 34 degrees C for 30 hr, the flagella were shed, and size was decreased with 10% viability loss. The in vitro and in vivo infectivity of two forms was more or less similar. The 45Ca2+ uptake by the transformed cells was increased as compared to normal cells. Activity of 5'-nucleotidase was increased while activity of Mg(2+)-ATPase remained same. Parasite antioxidant enzymes were also significantly altered by heat shock. There was significant increase in superoxide dismutase, glutathione reductase and glutathione peroxidase. It was accompanied by decrease in ratio of reduced glutathione to oxidized glutathione.

Effect of (-)epicatechin on cAMP content, insulin release and conversion of proinsulin to insulin in immature and mature rat islets in vitro.

(-)Epicatechin, an active principle in the water extract of the bark of Pterocarpus marsupium increases the cAMP content of the islets which is associated with the increased insulin release, conversion of proinsulin to insulin and cathepsin B activity. The response of the islets to the (-)epicatechin stimulation is more pronounced in immature (one month old) than in mature (12 month old) rats.

Identification of amastigote-specific antigens of Leishmania donovani using kala-azar patient sera.

Antigenic characterization of the soluble fraction of axenic amastigotes of Leishmania donovani ( strain Dd8, causative agent of Indian kala-azar) and their comparison with promastigotes is reported. The axenic amastigotes were assessed for their immunological status employing anti-A2 monoclonal antibody which is extremely specific for L. donovani amastigotes. SDS-PAGE of 35[S] methionine labeled proteins of the two parasite stages exhibited few stage specific and some conserved antigens in both the stages. An increased synthesis of heat shock proteins was observed in axenic amastigotes. Western blot experiments employing sera of kala azar positive patients identified immunodominent antigens of 116,83,26 and 12 kDa in axenic amastigotes which were not present in promastigotes. These amastigote stage specific antigens may have immense potential in immunodiagnosis and prophylaxis of kala-azar.

Effect of sodium stibogluconate on hepatic mixed function oxidase system and marker enzymes of golden hamsters during Leishmania donovani infection.

During L. donovani infection in golden hamsters, tremendous hepatic damage was observed as apparent from increased activities of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, succinate dehydrogenase, glucose-6-phosphatase and acid ribonuclease. The levels of cytochrome P-450 and related monooxygenases, viz. aniline hydroxylase and aminopyrine-N-demethylase registered significant decrease in infected animals. Sodium stibogluconate, a standard antileishmanial drug, though caused the removal of parasites from infected tissues, but did not help in the recovery of deranged hepatic markers. The results explain the higher mortality of stibanate treated infected animals as compared to untreated animals infected with L. donovani.

Virulence of Giardia lamblia: an in vitro study on host-parasite interaction.

Trophozoites of G. lamblia, a human parasite, were lysed by polymorphonuclear leukocytes (PMNL) of healthy individuals during in vitro interaction. However, the parasite damaged PMNL of giardiasis patients. A prior treatment of giardia trophozoites with anti-giardia serum, caused agglutination of pathogen and, thereby, the cytotoxic capacity of the parasite was reduced. Interaction of giardia-trophozoites with peritoneal macrophage, derived from infected mouse, reduced the phagocytic activity of the latter to 43% (against 100% in control). Macrophage activity was, however, stimulated to 131% when the mice were immunized with giardia antigen prior to experimental infection. Giardia extract proved cytotoxic at a dose of 0.7 mg, to HeLa cells in tissue culture. These in vitro studies offer experimental evidence of the cytotoxic and immuno-toxic behaviour of G. lamblia towards the host cells.

In vivo model for dyslipidemia with diabetes mellitus in hamster.

Due to similarities in lipid metabolism to those in humans, hamster is considered as a good model for the study of regulatory mechanisms of plasma lipoproteins in response to cholesterol or fatty acid-enriched diet. This model of hyperlipidemia has been modified to produce dyslipidedmia with diabetes complexities by feeding with high fat diet added with 9% (w/w) fructose. Feeding this diet to hamster for 10 days markedly increases plasma levels of triglyceride, cholesterol, fatty acids followed by a significant increase in glycerol, beta lipoproteins, high density lipoprotein, glucose and glycosylated proteins. This model is being used for research and development of lipid lowering drugs with hypoglycemic activity in collaboration with Novo Nordisk, Denmark. The modified high fat diet formulation has now been prepared (Research diet D.99122211) and supplied by Research Diets Inc, Burnswick USA.

Status of glutathione in lymphoid tissues of golden hamster during Leishmania donovani infection.

During Leishmania donovani infection of golden hamsters, changes in the glutathione levels of lymphoid tissues were observed. While in liver and thymus there was significant decrease in the levels of reduced and oxidised glutathione, that in spleen, bone marrow cells, peritoneal exudate cells and lymph nodes increased, indicating a role for host glutathione in establishing the infection.

Antidyslipidemic and antioxidant activities of different fractions ofTerminalia arjuna stem bark.

Terminalia arjuna (T. arjuna) stem bark was successively extracted with petroleum ether (A), solvent ether (B), ethanol (C) and water (D). The lipid lowering activity of these four fractions A, B, C, and D was evaluatedin vivo in two models viz., triton WR-1339 induced hyperlipemia in rats as well as fructose rich high fat diet (HFD) fed diabetic- dyslipidemic hamsters. Hyperlipidemia induced by triton caused marked increase in the plasma levels of total cholesterol (Tc), triglyceride (Tg) and phospholipids (PL) in rats. After treament withT. arjuna fractions A, B, C, and D at the doses of 250 mg/kg per oral (p.o.),only the ethanolic fraction (C) exerted significant lipid lowering effect as assessed by reversal of plasma levels of Tc, Tg and PL in hyperlipidemic rats. In another experiment, feeding with HFD produced marked dyslipidemia as observed by increased levels of plasma Tc, Tg, glucose (Glu), glycerol (Gly) and free fatty acids (FFA) in hamsters. After treatment withT. arjuna fractions at the doses of 250 mg/kg p.o. only two fraction (B and C) could exert significant lowering in the plasma levels of lipids and Glu. in dyslipidemic hamsters.In vitro experimentT. arjuna fractions at tested concentrations (50-500 µg/ml) inhibited the oxidative degradation of lipids in human low density lipoprotein and rat liver microsomes induced by metal ions. These fractions when tested against generation of oxygen free radicals at the concentrations (50-500 µg/ml), counteracted the formation of superoxide anions (O(-2)) and hydrodyl radicals (OH) in non enzymic test systems. The efficacy ofT. arjuna fractions as antidyslipidemic and antioxidant agents was found, fraction C> fraction B> fraction A.