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21.
Pillai A Veeranan-Karmegam R Dhandapani KM Mahadik SP 《Journal of neurochemistry》2008,107(4):941-951
The role of brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology as well as treatment outcome of schizophrenia. Rodent studies indicate that several antipsychotic drugs have time-dependent (and differential) effects on BDNF levels in the brain. Earlier studies from our laboratory have indicated that long-term treatment with haloperidol (HAL) decreases BDNF, reduced GSH and anti-apoptotic marker, Bcl-xl protein levels and increases the expression of pro-apoptotic proteins in rat frontal cortex. Furthermore, findings from human as well as rodent studies suggest that treatment of schizophrenia must involve the neuroprotective strategies to improve the neuropathology and thereby clinical outcome. In the present study, we investigated the potential of cystamine (CYS), an anti-oxidant and anti-apoptotic compound, to prevent HAL-induced reduction in BDNF, GSH, and Bcl-xl protein levels in mice and the signaling mechanism(s) involved in the beneficial effects of CYS. The results indicated that CYS as well as cysteamine (the FDA-approved precursor of CYS) increased BDNF protein levels in mouse frontal cortex 7 days after treatment. CYS co-treatment prevented chronic HAL treatment-induced reduction in BDNF, GSH, and Bcl-xl protein levels. CYS treatment enhanced TrkB-tyrosine phosphorylation and activated Akt and extracellular signal-regulated kinase (ERK)1/2, downstream molecules of TrkB signaling. In addition, in vitro experiments with mouse cortical neurons showed that CYS prevented the HAL-induced reduction in neuronal cell viability and BDNF protein levels, and increase in apoptosis. BDNF-neutralizing antibody as well as K252a, a selective inhibitor of neurotrophin signaling blocked the CYS-mediated neuroprotection. Moreover, CYS-mediated neuroprotection is also blocked by LY294002, a phosphatidylinositol 3-kinase inhibitor or PD98059, a mitogen-activated protein kinase kinase (MEK) inhibitor. Thus, CYS protects cortical neurons through a mechanism involving TrkB receptor activation, and a signaling pathway involving phosphatidylinositol 3-kinase and MAPK. The findings from the present study may be helpful for the development of novel neuroprotective strategies to improve the treatment outcome of schizophrenia. 相似文献
22.
Nutan D. Mahadik Kulbhushan B. Bastawde Ulka S. Puntambekar Jayant M. Khire Digambar V. Gokhale 《Process Biochemistry》2004,39(12):2031-2034
Mutants of Aspergillus niger NCIM 1207, isolated by subjecting conidia to UV-irradiation, were tested for the production of lipase (glycerol ester hydrolase EC 3.1.1.3). Mutants UV-10 and ANCR-1 showed seven fold and five fold enhanced productivity of enzyme, respectively, over the wild strain in shake flask culture when grown in SOB medium containing 1% olive oil. Maximum lipase activity (41 IU/ml) was obtained in the culture broth when UV-10 was grown in medium supplemented with 0.5% Triton X-100. A higher concentration of oil in the medium did not help lipase production in the case of mutant UV-10. Similarly no increase in enzyme levels was observed when mutant UV-10 was grown in medium supplemented with glucose. However, the addition of glucose in the medium resulted in increased levels of lipase production by wild strain, Aspergillus niger NCIM 1207. 相似文献
23.
The purpose of this research was to evaluate in vitro transnasal sustained-release ability of sorbitan monostearate (SMS)
organogels in isopropyl myristate (IM). Organogels were prepared containing SMS (2.5%–20%) and water (5%–25%) in IM and analyzed
microscopically for phase behavior. The effect of Tween surfactants on gel strength and in vitro nasal diffusion of propranolol
is reported. The in vitro nasal release retardant effect of SMS and Tween 20 was investigated using factorial design. The
microscopic changes in structure of organogel during in vitro nasal diffusion were studied. The water-holding capacity of
SMS organogels in IM increased with SMS concentration. The release retardant effect with incorportation of cosurfactant was
of the order of Tween 80> Tween 60> Tween 20. Gel strengthening and increased viscosity were evident with increased concentration
of SMS and Tween 20. The 3-dimensional network of SMS molecules controls the diffusional drug release. The organogel system
on nasal mucosa during diffusion is dynamic in nature and changes continuously with the time of diffusion. The water penetration
in the organogel network results in percolation and emulsification of organogel, thus affecting the release. Organogels provided
an effective barrier for diffusion of propranolol. The surface epithelium lining and the granular cellular structure of treated
nasal mucosa were intact. 相似文献
24.
The basic objective of this study was to explore the application of Gelucire 43/01 for the design of multi-unit floating systems
of a highly water-soluble drug diltiazem HCl. Diltiazem HCl-Gelucire 43/01 granules were prepared by melt granulation technique.
The granules were evaluated for in vitro and in vivo floating ability, surface topography, and in vitro drug release. Aging
effect on storage was vvaluated using scanning electron microscopy, hot stage polarizing microscopy (HSPM), differential scanning
calorimetry (DSC), and in vitro drug release. Granules were retained in stomach at least for 6 hours. Approximately 65% to
80% drug was released over 6 hours with initial fast release from the surface. Surface topography, HSPM, DSC study of the
aged samples showed phase transformation of Gelucire. The phase transformation also caused significant increase in drug release.
In conclusion, hydrophobic lipid, Gelucire 43/01, can be considered as an effective carrier for design of a multi-unit floating
drug delivery system of highly water-soluble drugs such as diltiazem HCl. 相似文献
25.
Samrat Chakraborty Abhijit Khopade Chandrakant Kokare Kakasaheb Mahadik Balasaheb Chopade 《Journal of Molecular Catalysis .B, Enzymatic》2009,58(1-4):17-23
In this study, we have reported novel α-amylase enzyme from less extensively studied marine Streptomyces sp. D1. Enzyme production was determined by using media containing 2% sucrose, 0.35% peptone and 0.15% of malt extract. Optimum temperature for enzyme production and activity was found to be 45 °C and enzyme retained almost 50% of its activity at 85 °C. Enzyme activity was also retained in presence of commercially available detergent and oxidizing agents. The partially purified enzyme from strain D1 exhibited specific activity of 113.64 U/mg protein that corresponds to 2.8-fold purification. SDS-PAGE and zymogram activity staining showed a single band equal to molecular mass of 66 kDa. The reported enzyme may have wide spread application for detergent and pharmaceutical industry. 相似文献
26.
Sharvil S. Patil Edakkal Venugopal Suresh Bhat Kakasaheb R. Mahadik Anant R. Paradkar 《AAPS PharmSciTech》2015,16(5):1153-1159
The present work explores inner structuration of in situ gelling system consisting of glyceryl monooleate (GMO) and oleic acid (OA). The system under study involves investigation of microstructural changes which are believed to govern the pharmaceutical performance of final formulation. The changes which are often termed mesophasic transformation were analysed by small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), rheology and plane polarised light (PPL) microscopy. The current work revealed transformation of blank system from W/O emulsion to reverse hexagonal structure upon addition of structural analogues of ibuprofen. Such transformations are believed to occur due to increased hydrophobic volume within system as probed by SAXS analysis. The findings of SAXS studies were well supported by DSC, rheology and PPL microscopy. The study established inverse relationship between log P value of structural analogues of ibuprofen and the degree of binding of water molecules to surfactant chains. Such relationship had pronounced effect on sol–gel transformation process. The prepared in situ gelling system showed sustained drug release which followed Higuchi model.KEY WORDS: flurbiprofen, hexagonal phase, ibuprofen, ketoprofen, liquid crystal, sustained drug release 相似文献
27.
—The conversion of plasma glucose into brain proteins in vivo was measured in rats after various periods of food deprivation. Rates of flow of glucose carbon into both soluble and insoluble brain proteins were calculated from the curve representing the decrease of plasma [14C]-glucose specific activity with time, and from the specific activity of brain protein 180 min after intravenous injection of a tracer dose of d -[14C]-glucose. Compared to the post-absorptive rats, food deprivation for 72 h caused a 30 per cent reduction in the rate of flow of glucose carbon into soluble brain proteins but did not affect the flow into insoluble proteins. Results of experiments in which the soluble brain proteins were separated by isoelectric focusing suggest that prolonged fasting in adult rats causes substantial differences in the conversion of glucose to different proteins. 相似文献
28.
The purpose of this research work was to obtain directly compressible agglomerates of ibuprofen with talc by a novel crystallo-co-agglomeration
(CCA) technique, which is an extension of spherical crystallization. Ibuprofen-talc agglomerates were prepared using dichloromethane
(DCM)-water as the crystallization system. DCM acted as a good solvent for ibuprofen as well as a bridging liquid for agglomeration
of crystallized drug with talc. The agglomerates were characterized by differential scanning calorimetry, powder X-ray diffraction,
and scanning electron microscopy and were evaluated for tableting properties and for drug release. The process yielded spherical
agglomerates containing ∼95% to 96% wt/wt of ibuprofen. Agglomerates containing talc showed uniform distribution of hydroxypropylmethylcellulose
and decreased crystallinity, and deformed under pressure. The miniscular form of ibuprofen and the hydrophobicity of talc
governed the drug release rate. The batch containing a higher proportion of talc showed zeroorder kinetics and drug release
was extended up to 13 hours. The CCA technique developed in this study is suitable for obtaining agglomerates of drug with
talc as an excipient. 相似文献
29.
Conclusion The results of this investigation showed that spray drying of CH and HG resulted in free-flowing powder, which exhibited improved
compressibility and compactibility, thereby suggesting the potential of such spray-dried mixtures of CH and HG as binder in
tablets. Optimization of CH:HG ratio needs to be undertaken on a case basis, depending on the presence of other excipients
in the formulation.
Published: October 22, 2005 相似文献
30.
Distribution of Six Synaptic Membrane Antigens in Subcellular Fractions of Rat Brain Cortex 总被引:1,自引:1,他引:0
S. P. Mahadik A. Korenovsky V. Ciccarone M. M. Rapport 《Journal of neurochemistry》1981,36(5):1675-1682
Abstract: The subcellular distribution in rat brain cortex of six synaptic membrane antigens (56K, 58K, 62K, 63K, 64K, 66K) was studied by rocket immunoelectrophoresis, using antiserum to a highly purified synaptic plasma membrane fraction. Initial analysis of the insoluble portion of subcellular fractions showed that these antigens were also present in smooth microsomes, rough microsomes, and synaptic vesicles; that only traces were present in synaptic junctions; and that none was present in nuclei, mitochondria, and myelin. A trace amount of activity was also present in synaptic vesicle cytosol, but none in whole brain cytosol. Quantitative measurements of synaptic plasma membranes, smooth microsomes, and synaptic vesicles showed that all six antigens were present in synaptic plasma membranes and smooth microsomes, but that the 66K antigen was absent from synaptic vesicles. The 56K, 58K, 62K, 63K, and 64K antigens were present in highest concentration in synaptic plasma membranes, whereas the 66K antigen content was highest in smooth microsomes. Only the 58K, 62K, and 63K antigens were detectable in the membrane fraction of whole brain. Their enrichments in synaptic plasma membranes were 10.9, 5.4, and 5.9, respectively. We conclude that the 56K, 58K, 62K, 63K and 64K antigens are primary components of synaptic plasma membranes. The presence of synaptic plasma membrane antigens in smooth microsomes and synaptic vesicles probably represents material being actively transported, consistent with the hypothesis that proteins of synaptic plasma membranes and synaptic vesicles are transported via smooth endoplasmic reticulum. 相似文献