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Biomedical subjects

J Sinha

Publications and source records attributed to J Sinha.

17 recordsLinked to original sources
PubMed2002

Quercetin: critical evaluation as an antileishmanial agent in vivo in hamsters using different vesicular delivery modes.

Chemotherapy is still a major challenge for in vivo drug targeting to macrophages. Toxicity remains the major obstacle for the most potent drugs already known in the therapy of leishmaniasis. Thus, new drugs and new delivery systems are sought. By using different vesicular delivery modes e.g. liposomes, niosomes, microspheres and nanoparticles, attempts have been made to deliver an indigenous antileishmanial compound, quercetin, to treat experimental leishmaniasis in the hamster model so as to increase its efficacy as well as to reduce the toxicity. At equivalent quercetin concentration, the nanocapsulated quercetin was found to be the most potent in reducing the parasite burden in the spleen as well as in reducing hepatotoxcity and renaltoxicity compared to free drug or drug in other vesicular forms. An inverse relationship between the efficacy and the size of the vesicles was established. Such a drug vehicle formulation especially in the nanocapsulated form may be considered for clinical trials.

Algorithms↗
PubMed2002

Lowering anti-dsDNA antibodies--what's new?

Antibodies to dsDNA are specific to SLE and are pathogenic, both due to their ability to deposit in tissues through a variety of mechanisms, and to their ability, when present in immune complexes, to activate inflammatory cells. The relationship of serum anti-dsDNA antibody levels to disease activity is a complex one and the factors that determine whether or not such antibodies will be pathogenic in an individual SLE patient are incompletely understood. Although anti-dsDNA antibodies can be made by naïve B cells and B cells belonging to the B1 and marginal zone subsets, pathogenic anti-dsDNA antibodies have the hallmarks of germinal center development and exposure to T cell help, including accumulation of somatic mutations and class switching to the IgG isotype. Epitope spreading may result in aquisition of cross-reactivities with multiple target organ antigens and aquisition of a memory phenotype will allow these B cells to acquire antigen presentation functions that amplify the autoreactive response. In the early stages of disease, or after remission induction protocols, autoreactive B cells may be susceptible to treatments that target T cell costimulation or that deplete or tolerize naïve and mature B cells. Therapeutic approaches targeting innate immune responses or regulatory T cells are starting to be tested in pre-clinical models. In later disease stages, memory and plasma cell accumulation may render patients more resistant to this type of therapeutic approach. Deposition of anti-dsDNA antibodies in target tissues can stimulate an inflammatory cascade that leads to tissue damage. A number of murine models have now been developed that show that interruption of this cascade can prevent or reverse such damage. This type of approach may be beneficial for individuals with established disease. As we learn more about the specific defects that cause SLE, it may become possible to individualize therapy based on patient specific biologic markers.

Animals↗
PubMed2001

Production of inulooligosaccharides from chicory extract by endoinulinase from Xanthomonas oryzae No. 5.

Inulooligosaccharides (IOS) production from chicory extract was carried out using endoinulinase obtained from a new isolate, Xanthomonas oryzae No. 5. The IOS production from chicory extract was maximum when 50 g/liter of chicory extract was utilized as the substrate. As the substrate concentration increased, the IOS production accordingly decreased probably due to substrate inhibition. For a comparative study, enzyme reactions were carried out from pure inulin as substrate. Though total IOS contents indicated higher IOS yield with pure inulin compared to that of chicory extract, the distribution of inulooligosaccharide components between pure inulin and chicory extract was not significantly different; i.e. DP5 and higher oligosaccharides are major products in case of both chicory extract and pure inulin as substrate. A considerable amount of oligofructose (about 30%, w/w), which were originally present in chicory extract, resulted in the change of the enzyme kinetics. A reaction pH 7 was found to be most suitable for enzyme reaction. The initial reaction rates increased with increasing enzyme dosage, although the relative composition of the IOS produced remain unchanged.

Journal Article↗
PubMed2001

Changes in morphology of Paecilomyces japonica and their effect on broth rheology during production of exo-biopolymers.

The influence of Paecilomyces japonica pellet morphology on fermentation broth rheology and exobiopolymer production was investigated in a 5-1 jar fermenter. Rapid formation of pellets was observed after the first day of fermentation; and these slowly increased in size and roughness. This, together with the increase in biomass concentration, altered the transport characteristics and broth rheology towards a pseudoplastic nature which, in turn, influenced cell growth and exo-biopolymer production. At mild agitation, high aeration and optimum substrate concentration, pellets were the most predominant morphological form, compared with free mycelia. The broth rheology showed pseudoplastic behavior; and the fungal morphology was closely related to the rheological properties.

Biopolymers↗
PubMed2001

Liposomal antioxidants in combating ischemia-reperfusion injury in rat brain.

Liposome-encapsulated antioxidants have been tested in vivo to prevent oxidative attack during cerebral ischemia and reperfusion. Oxidative stress is a causal factor in the neuropathogenesis of ischemic-reperfusion injury. From the therapeutic point of view free chemical antioxidants were almost ineffective to protect cerebral tissues from those oxidative attacks. Thus an attempt has been made to prevent the oxidative damage due to the cerebral ischemic insult by the introduction of chemical antioxidants, ascorbic acid and alpha-tocopherol either encapsulated or intercalated in small unilamellar liposomes. The effectiveness of antioxidant-loaded liposomes was tested against an experimental in vivo rat model of global cerebral ischemia. Oxidative free radical attack on cerebral tissues by the ischemic insult and brief reperfusion was accounted for by the amount of diene production per unit of tissue protein. Diene production in ischemic reperfused rat brain increases almost twofold over that of the normal rats. Prevention of excess diene production has been attributed to rats when they were treated either with L-ascorbic acid-encapsulated liposomes or alpha-tocopherol intercalated liposomes 2 hours prior to the cerebral ischemic insult. Complete restriction of excess diene generation has also been achieved when a mixture of alpha-tocopherol and L-ascorbic acid-encapsulated liposomes were injected 3 hours before the ischemic infraction.

Animals↗
PubMed2000

Extractive fermentation for improved production of endoglucanase by an intergeneric fusant of Trichoderma reesei/Saccharomyces cerevisiae using aqueous two-phase system.

Extractive aqueous two-phase fermentation of endoglucanase, a key enzyme for the conversion of cellulosic substances to fermentable sugars, from an intergeneric fusant of Trichoderma reesei/Saccharomyces cerevisiae is a meaningful approach for better production and simple recovery of this enzyme. A phase composition of 6.5% (w/w) dextran and 7.5% (w/w) polyethylene glycol 6000, having a partition coefficient of 2.89 and 1.31 for endoglucanase from an intergeneric fusant of T. reesei/S. cerevisiae and T. reesei (WT) (being a control in this study), respectively, was chosen for extractive fermentation of the enzyme. Endoglucanase production is higher in medium containing polyethylene glycol (PEG) 6000 than in medium without PEG 6000. Comparative analysis of endoglucanase fermentation by fusant and T. reesei was carried out in shake culture and environment-controlled bioreactor conditions. The fusant produced 0.43U of endoglucanase (overall production: 0.34U) in the top phase of an aqueous two-phase system (ATPS), compared to 0.3U in medium without the phase system in shake culture. In a batch reactor, the endoglucanase level for the fusant in the top phase of ATPS was 0.49U (overall production: 0.40U), compared to 0.38U produced in medium without aqueous two-phase components. To corroborate this study, T. reesei produced 8.41U of endoglucanase (overall production: 5.96U) in the top phase of ATPS, compared to 7.18U in the medium without the phase system in shake culture. On the other hand, in a batch bioreactor, T. reesei produced 10.13U of endoglucanase (overall production: 6.90U) in the top phase of ATPS, compared to 8.56U of the enzyme in medium without aqueous two-phase components. The lower overall enzyme production by T. reesei in the two-phase system might be due to limitation in oxygen transfer to the dispersed phase where the enzyme is produced. A higher cell concentration and a reduced lag phase was obtained in ATPS, compared to a similar medium without phase forming polymers for both the intergeneric fusant of T. reesei/S. cerevisiae and T. reesei.

Journal Article↗
PubMed2000

Aqueous two-phase: the system of choice for extractive fermentation.

Extractive fermentation in aqueous two-phase systems is a meaningful approach to overcome low product yield in a conventional fermentation process, and by proper design of the two-phase system it is possible to obtain the product in a cell-free stream. The characteristics of an aqueous two-phase system, various polymers used for forming an aqueous two-phase system, the physicochemical parameters of the aqueous two-phase system, partitioning of biomolecules and cell mass and the effect of individual phase forming polymers on cell growth and product formation are reviewed in this article. The various extractive fermentation processes are also summarised here. At the end, the economic viability and scope of aqueous two-phase fermentation are briefly discussed in relation to the wider application of this topic.

Anti-Bacterial Agents↗
PubMed1999

Quantitative structure-activity relationship study on some nonpeptidal cholecystokinin antagonists.

A quantitative structure-activity relationship (QSAR) analysis has been performed on a series of 1,4-benzodiazepine derivatives, which were found to act as antagonists of cholecystokinin (CCK), a gastrointestinal peptide hormone. The CCK acts with three different receptor subtypes termed as CCK-A, CCK-B, and gastrin receptor, which can be found in peripheral system, brain, and stomach, respectively. With all the three subtypes, the binding of the compounds is found to significantly depend on the lipophilicity of the compounds and their ability to form the hydrogen bonds with the receptor. However, the binding sites in CCK-A receptor seem to be slightly rigid as compared to those in CCK-B or gastrin receptor. The latter two appear to have similar binding features.

Animals↗
PubMed1988

Villous adenomas and carcinoma of the duodenum in Gardner's syndrome.

Patients with Gardner's syndrome are increasingly found to have polyps on routine upper gastrointestinal endoscopy, and their risk of developing periampullary carcinoma is between 3-12%. We report a 45 year old man with Gardner's syndrome who presented with periampullary carcinoma 5 years after colectomy. Review of the literature amassed another 21 cases of periampullary carcinoma in patients with Gardner's syndrome.

Adenocarcinoma↗
PubMedDate not supplied

Targeting of liposomal andrographolide to L. donovani-infected macrophages in vivo.

Despite the rapid development in medicinal and pharmaceutical technology, the targeting of drugs to phagocytic cells in macrophage-related diseases still remains a major unsolved problem. By using the mannosyl-fucosyl receptors on macrophages, attempts were made to target antileishmanial drugs encapsulated in mannosylated or fucosylated liposomes to treat experimental leishmaniasis in the hamster model. Mannosylated liposomes were found to be more potent in delivering antileishmanial drugs to phagocytic cells. Liposomes loaded with an indigenous drug, andrographolide, a labdane diterpenoid isolated from Indian medicinal plant Andrographis paniculata, were prepared and tested against experimental leishmaniasis in a hamster model. Mannosylated liposomes loaded with the drug were found to be most potent in reducing the parasitic burden in the spleen as well as in reducing the hepatic and renal toxicity. In addition, mannosylated drug-loaded liposome-treated animals showed a normal blood picture and splenic tissue histoarchitecture when compared with those treated with free drug or regular liposomal drug. Such a drug-vehicle formulation may be considered for clinical trials.

Animals↗
PubMedDate not supplied

Bacopasaponin C: critical evaluation of anti-leishmanial properties in various delivery modes.

Bacopasaponin C, an indigenous glycoside, was isolated from Indian medicinal plant Bacopa monniera (b. brahmi) and was tested for antileishmanial properties both in free and in various delivery modes, e.g., niosomes, microspheres, and nanoparticles that are used now as alternatives to more commonly used liposomes. The different vesicles were prepared by published protocols. The percent intercalation of Bacopasaponin C in liposomes, niosomes, and micropspheres determined at its absorption maximal (lambda(max) = 238 nm, epsilon = 8.6 x 10(3) M(-1) x cm(-1)) was found to be 30; for nanoparticles it was 50. At equivalent dose of 1.75 mg/kg body weight, every third day for a total of 6 doses in 15 days, Bacopasaponin C in all the vesicular forms was found to be very active. An inverse linear relationship between the efficacy and the size of the vesicles was established. As analyzed from tissue histology, blood pathology, and specific tests related to normal liver and kidney functions, Bacopasaponin C in each of the four vesicular forms was found to be without any side effects. Thus, because of its indigenous origin and non-toxic nature, Bacopasaponin C could very well be considered for application in the clinic through these alternative delivery modes.

Animals↗