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Biomedical subjects

S C Tripathi

Publications and source records attributed to S C Tripathi.

At least 19 recordsLinked to original sources

EPR investigations on radiation induced chemical transformations in Pd(ClO4)2/i-PrOH/HClO4 system from 77 to 300 K.

The EPR studies have been carried out on gamma irradiated samples of Pd(ClO4)2 in 9 M/4M HClO4 in the presence and absence of isopropanol [i-PrOH (5%, v/v)], in the temperature range of 77-300 K. The EPR studies revealed the formation of Pd+ complex, Pd3+ complex and several radicals such as H., OH., ClO3., ClO4. and O3- on radiolysis of these systems. Reduction of Pd2+ to Pd clusters could not be observed in the absence of i-PrOH and warming of the irradiated sample finally resulted in recovery of Pd2+ complex. However, in the presence of 5% i-PrOH, strongly oxidizing radicals like OH., ClO3. and ClO4. are suppressed and (CH3)2C.OH radical was produced along with reducing species like H.. EPR spectra in these strongly reducing conditions showed formation of Pd+ complex, which on heating above 230 K, disproportionated into Pd0 and Pd2+ complex and finally lead to formation of Pd metal aggregates. Simultaneously, pulse radiolysis technique has been employed as an alternative method to verify the EPR observations.

Electron Spin Resonance Spectroscopy↗

Regulatory considerations for preclinical development of anticancer drugs.

The entry of new anticancer treatments into phase I clinical trials is ordinarily based on relatively modest preclinical data. This report defines the battery of preclinical tests important for assessing safety under an Investigational New Drug application (IND) and outlines a basis for extrapolating starting doses of investigational anticancer drugs in phase I clinical trials from animal toxicity studies. Types of preclinical studies for the support of marketing of a new anticancer drug are also discussed. This report addresses differences and similarities in the preclinical development of cytotoxic drugs (including photosensitizers and targeted delivery products), drugs used chronically (chemopreventive drugs, hormonal drugs, immunomodulators), and drugs intended to enhance the efficacy (MDR-reversing agents and radiation/chemotherapy sensitizers) or diminish the toxicity of currently used anticancer therapies. Factors to consider in the design of preclinical studies of combination therapies, alternative therapies, and adjuvant therapies in the treatment of cancer, and to support changes in clinical formulations or route of administration, are also discussed.

Animals↗

Hepatoprotective activity of Boerhaavia diffusa L. roots--a popular Indian ethnomedicine.

The roots of Boerhaavia diffusa L., commonly known as 'Punarnava', are used by a large number of tribes in India for the treatment of various hepatic disorders. In the present study the effect of seasons, thickness of roots and form of dose (either aqueous or powder) were studied for their hepatoprotective action to prove the claims made by the different tribes of India. The hepatoprotective activity of roots of different diameters collected in three seasons, rainy, summer and winter, was examined in thioacetamide intoxicated rats. The results showed that an aqueous extract (2 ml/kg) of roots of diameter 1-3 cm, collected in the month of May (Summer), exhibited marked protection of a majority of serum parameters, i.e. GOT, GPT, ACP and ALP, but not GLDH and bilirubin, thereby suggesting the proper size and time of collection of B. diffusa L. roots for the most desirable results. Further, the studies also proved that the aqueous form of drug (2 ml/kg) administration has more hepatoprotective activity than the powder form; this is probably due to the better absorbtion of the liquid form through the intestinal tract.

Alanine Transaminase↗

Arachidonic acid metabolism and cell proliferation in rat mammary carcinoma cells treated with indomethacin.

To determine the specificity of action of indomethacin as an inhibitor of cyclooxygenase in the mammary epithelium, cell proliferation and levels of PGE2 and LTB4 were quantitated in 13762 MAT rat mammary carcinoma cells treated with 10(-4) to 10(-10) M concentrations of drug. Suppression of proliferation of 13762 MAT cells by indomethacin was associated with reduced levels of both PGE2 and LTB4. The antiproliferative activity of indomethacin in rat mammary carcinoma cells may be modulated through inhibition of both cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism.

Animals↗

Mechanical stress mechanisms and the cell. An endothelial paradigm.

There are important physiological and pathological cardiovascular consequences related to endothelial biomechanical properties. The endothelium, however, is not unique in responding to external forces; virtually all cells accommodate or respond to the mechanical environment.

Biomechanical Phenomena↗

Characterization of GP110, a neutrophil surface protein.

Localized juvenile periodontosis is associated with a defect of neutrophil chemotaxis that is characterized by selective depletion of a surface protein with a molecular mass of 110 kDa (GP110). Data on partial characterization of GP110 suggest that it is a glycoprotein which is enriched in Lys, Glu, His, Leu, and Ala residues.

Amino Acids↗

A new method for estimating population doubling time of vertebrate cells.

Based upon the fact that the amount of DNA doubles after each cycle, a technique was developed in which the population doubling time for cell cultures was determined from the ratio of its DNA content to [3H]thymidine incorporation under conditions in which cell numbers cannot be readily determined. This technique may be useful in determining what proportion the sample is of the total cell population.

Animals↗

Antihepatotoxic properties of picroliv: an active fraction from rhizomes of Picrorhiza kurrooa.

The hepatoprotective activity of picroliv, the irridoid glycoside mixture from Picrorhiza kurrooa, was determined in adult male albino rats. Pretreatment with picroliv prevented the hepatotoxic effects of paracetamol and galactosamine as evidenced by various biochemical and histopathological observations. Maximum hepatoprotective effect was observed with daily oral doses of 6 and 12 mg/kg for 7 or 8 days. The antihepatotoxic action of picroliv seems likely due to an alteration in the biotransformation of the toxic substances resulting in decreased formation of reactive metabolites.

Acetaminophen↗

Locomotory behavior of fibroblasts in "sail-sheets".

The locomotory behavior of fibroblasts in two-dimensional cultures (e.g., on culture dishes, cover slips, etc.) was first reported by Abercrombie's group. This paper describes some of the features of movement of fibroblasts in a unique culture system known as sail-sheet cultures (SSCs). Cells in SSCs grow mostly on one another in a three-dimensional form that resembles, to some extent, the in vivo situation. We grew chicken heart fibroblasts (CHFs) as SSCs and studied their locomotory behavior by time-lapse filming extended for periods ranging from 12 h to several days. It was found that CHFs grown as sail-sheets exhibit many features of movement as observed in conventional two-dimensional cultures (CCs). However, we observed that CHFs in SSCs, like those in vivo, lack leading lamella directing their movement. Furthermore, locomotion is significantly slower in SSCs than in CCs. Based on data on the movement of CHFs within the mesh holes of inert grids, we suggest that the mesenchymal cells in SSCs, in addition to their individual movement, move in sheets and that their movement in sheets results in the closure of the mesh holes, a situation that resembles the phenomenon of healing of wounds. Thus SSCs provide a model system for the study of healing of wounds. The presence of collagenlike extracellular matrix (CLECM) between cellular layers in SSCs suggests that CLECM may be involved in guiding the locomotory behavior of CHFs in SSCs.

Animals↗

Effect of mechanical stress on cellular morphology.

Mechanical stress occurs within and between cells during embryogenesis, wound healing and in the repetitive processes performed by various muscles of the body and, therefore, an experimental system to study the effects of mechanical stress was needed. Effects of mechanical stress on cell cycle are documented elsewhere (Curtis and Seehar, 1978). This study intends to investigate whether mechanical stress affects the cellular morphology. Chicken heart fibroblasts were grown as 'Sail-Sheets' a situation that approximates the in vivo organization of cells and provides an appropriate material for studying the effects of mechanical factors. Sail-Sheets were stressed using a low-frequency sine-wave oscillator and a glass rod attached to a piezoelectric ceramic probe. Electron microscopy (both SEM and TEM) was carried out on both mechanically stressed and control cultures. It was found that low frequency mechanical stress (1.0 Hz) may result in a decrease in the number and size of microprocesses (m).

Animals↗

Effect of retinal impulse blockage on cytochrome oxidase-rich zones in the macaque striate cortex: I. Quantitative electron-microscopic (EM) analysis of neurons.

Our previous light-microscopic study indicates that unilateral retinal impulse blockage with tetrodotoxin (TTX) causes a reversible decrease of cytochrome oxidase (CO) in alternating rows of metabolically active zones (puffs) in the adult macaque striate cortex (Wong-Riley & Carroll, 1984b). The goal of the present study was to determine if TTX blockade adversely affects all neurons or only a subpopulation of neurons within the puffs. Three major neuronal types were identified based on mitochondrial CO activities and morphological characteristics. Type A neurons were the most prevalent, consisting of small pyramidal and nonpyramidal neurons that received only symmetrical axosomatic synapses. They had little cytoplasm and relatively low levels of CO activity, and showed the least change with TTX treatment. Type B cells were medium-to-large pyramidal neurons that received exclusively symmetrical axosomatic synapses and were moderately reactive for CO. Impulse blockage caused a decrease in mitochondrial size and packing density, but somal size remained within the control range. Type C cells were medium-sized nonpyramidal neurons contacted by both asymmetrical and symmetrical axosomatic synapses. They contained abundant darkly reactive mitochondria and presumably are metabolically the most active. This cell type suffered the greatest decrease in somal size and packing density of mitochondria, particularly the darkly reactive ones. A rare fourth cell type, type D, was a small, darkly reactive nonpyramidal variety that gave rise to somatodendritic synapses. Their low occurrence prevented statistical analysis under normal and TTX-treated conditions. These data indicate that retinal impulse blockade is most detrimental to the metabolically most active neurons in the adult primate cortical puffs. The alterations are not permanent, because the effects of TTX are fully reversible (Carroll & Wong-Riley, 1987).

Animals↗

Effect of retinal impulse blockage on cytochrome oxidase-rich zones in the macaque striate cortex: II. Quantitative electron-microscopic (EM) analysis of neuropil.

Unilateral retinal impulse blockage with tetrodotoxin (TTX) induces reversible shrinkage and decreased cytochrome oxidase (CO) activity in alternate rows of supragranular, CO-rich puffs in the adult macaque striate cortex (Wong-Riley & Carroll, 1984b: Carroll & Wong-Riley, 1987). The present study extended the findings to the electron-microscopic (EM) level to determine if various neuropil profiles in control puffs exhibit heterogeneous levels of CO activity, and whether specific processes were more susceptible to intravitreal TTX than others. Within the neuropil of control puffs, 60% of the total mitochondrial population resided in dendrites, and the majority of dendritic mitochondria were highly reactive for CO. Axon terminals forming symmetrical synapses also contained darkly reactive mitochondria, whereas those forming asymmetrical synapses possessed very few and mainly lightly reactive mitochondria. Unmyelinated axon trunks, myelinated axons, and glia all exhibited low levels of CO activity. Synaptic count revealed a 3:1 ratio of asymmetrical to symmetrical synapses. Intravitreal TTX for 2-4 weeks adversely affects dendrites and symmetrical terminals much more so than other neuropil processes. There was a general decrease in darkly and moderately reactive mitochondria and an increase in lightly reactive mitochondria throughout the puffs, especially in dendrites. This indicates that afferent blockade is more detrimental to processes of higher metabolic activity. Changes also differed between central and peripheral regions of puffs, and indications of axonal and synaptic reorganization were more evident in the latter. Thus, stabilization of neuronal structure and synapses appears to be activity-dependent even in the adult. A working model of these metabolic and morphological responses to chronic TTX is proposed.

Animals↗

A possible role of actin in the mechanical control of the cell cycle.

Sail-sheet Cultures (SSC) are those in which the cells are i) grown within the meshes of inert grids ii) exposed to nutrients from most sides iii) attached to one another only at the edges like sail of a yacht (hence, the name 'sail-sheet') and iv) have the advantage of three-dimensional structure similar to an in vivo situation. We grew fibroblasts from chicken heart explants as SSC and studied the effect of mechanical stretching on the F-actin content of these cells. This study was designed to investigate the hypothesis that the effect of tension on the cell cycle may be channeled through the microfilaments. Data from this preliminary study suggested that short-term mechanical stretching of sail-sheets, using low frequency tension (1.0 Hz), diminishes F-actin. Thus, it may be possible to relate the decrease in the F-actin content of these cells to the slowing down of their locomotory activity, possible rounding up, and division. This study might contribute to the understanding of the mechanical control of the cell cycle and be of relevance in the phenomena such as healing of wounds and control of the cell division in tumors.

Actins↗