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T K Ghosh

Publications and source records attributed to T K Ghosh.

At least 55 records · Page 3Linked to original sources
PubMed1996

Development of a transdermal patch of methadone: in vitro evaluation across hairless mouse and human cadaver skin.

A 3-day monolithic polyacrylate adhesive dispersion type delivery system containing methadone was fabricated and in vitro permeation through hairless mouse and human cadaver skins was conducted. The effect of skin permeation enhancers was also investigated. Skin permeation rate across human cadaver skin was found to be lower than that of hairless mouse. Skin permeation profiles across both types of skins showed a membrane permeation controlled cumulative amount permeated (Q) versus time (t) relationship. Skin permeation rate was found to be dependent on both adhesive film thickness and loading dose of the drug in the matrix. Effective skin permeation rate across the hairless mouse skin was obtained from a patch with 1.5 mm thickness and 15% w/w loading dose. n-Decylmethyl sulfoxide and Azone were found to produce an effective skin permeation rate of methadone through human cadaver skin at a 5% w/w concentration. These initial studies demonstrated the feasibility of methadone administration through intact skin from a transdermal patch.

Administration, Cutaneous↗
PubMed1996

Profile and characteristics of animals bites in India.

Animal bites and so also the incidence of rabies in India are on rise. There are regional differences in the animal responsible for the bite. Different practices including use of traditional remedies are prevalent for wound treatment. In India this report analyses the profile and characteristics of animal bites in 869 patients from various regions. Apart from dog and cat, other animals such as cow, monkey, horse, pigs, camel were responsible for bite and could be possible vectors in transmission of rabies. Traditional remedies such as application of chilly paste is still practiced in state of Rajasthan.

Adolescent↗
PubMed1995

Microcirculation of gills and accessory respiratory organs of the walking catfish Clarias batrachus.

BACKGROUND: An ability to extract oxygen directly from the atmosphere enables air-breathing fish to survive otherwise debilitating hypoxic environments. Addition of accessory respiratory organs (ARO) necessitates changes in both the general circulatory system and the microcirculation of the respiratory epithelia. Understanding these modifications provides information on the efficiency of gas exchange organs as well as an indication of the evolutionary processes associated with adaptation to terrestrial habitats. METHODS: Vascular organization and structure of gills and ARO of the facultative air-breathing walking catfish Clarias batrachus were examined by scanning electron microscopy of vascular replicas and fixed tissue. RESULTS: Well-developed filaments are present on all four pairs of gill arches and they possess three vascular pathways: respiratory (arterioarterial), nutrient (arteriovenous), and interlamellar (arteriovenous), typical of teleosts. ARO, consisting of gill fans, dendritic organs on the second and fourth gill arch, and the suprabranchial epithelium are derived from gill tissue and retain structural features and arterioarterial vessels similar to gill filaments. Gill and ARO vessels are in parallel with each other, and together they are in series with the systemic circulation. Nutrients and interlamellar vessels are reduced in ARO. CONCLUSIONS: Other than the presence of multiple ventral aortas, and an additional vessel connecting the suprabranchial epithelium to the dorsal aorta, there are no vascular shunts or anatomical modifications that indicate spatial separation of flow through the heart or between gills and ARO. However, a mechanism is proposed that would prevent unsaturation of dorsal aortic blood by local myogenic vasoconstriction of gill vessels when the fish is in hypoxic water. Despite considerable differences in the gross features of ARO in Clarias and Heteropneustes fossilis (Olson et al. 1990 J. Morphol., 203:165), there are striking similarities in vascular organization and respiratory islet structure that suggest these ARO evolved in a common silurid ancestor and were later modified into an everted arborescent organ or inverted air sac, respectively.

Animals↗
PubMed1995

Transdermal delivery of metoprolol. II: In-vitro skin permeation and bioavailability in hairless rats.

The absolute bioavailability of metoprolol (MP) was evaluated following oral and transdermal administration in hairless rats. The absolute bioavailability of MP following oral administration was 3.48 +/- 1.73%, indicating that MP is subject to extensive hepatic first-pass metabolism. Transdermal delivery of MP, via an adhesive delivery device, resulted in a bioavailability of 30.07 +/- 4.84%, indicating that the transdermal delivery of MP can significantly increase systemic bioavailability compared with oral administration. Preliminary skin irritation studies indicated that neither MP nor the adhesive used in the device caused any appreciable skin irritation in the hairless rats.

Adhesives↗
PubMed1995

Epithelial modulation of afferent nerve endings: differential effects of amiloride on afferent subtypes.

Mechanisms underlying the differing chemosensitivity of laryngeal afferents have not been defined. The role of airway epithelium in transducing the chemical stimuli to neural signals was investigated by using Na(+)- and Cl(-)-channel inhibitors in anesthetized spontaneously breathing cats. Single-fiber action potentials were recorded from the peripheral cut end of the superior laryngeal nerve. Luminal application of amiloride (10(-4) M), an inhibitor of epithelial Na+ channels, reduced the responsiveness of non-respiratory-modulated endings (n = 25) to distilled water (65.76 +/- 5.77 vs. 50.67 +/- 5.13 Hz; P < 0.01). Water responsiveness of these endings was unaffected by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and diphenylamine-2-carboxylate, two Cl(-)-channel blockers. Respiratory-modulated endings (water responsive, n = 8; water nonresponsive, n = 9) were unaffected by Na(+)- and Cl(-)-channel blockers. These results suggest that epithelial Na+ channels play a role in the modulation of non-respiratory-modulated laryngeal endings. The lack of an effect by amiloride on other subtypes may be due to differences in location or intrinsic properties of nerve endings. Cl- channels do not appear to play an important role in the modulation of laryngeal afferents targeted in this study.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Modification of GTP-activated calcium translocation by fatty acyl-CoA esters. Evidence for a GTP-induced prefusion event.

A sensitive and specific GTP-activated Ca2+ translocation process induces rapid Ca2+ movements within cells and appears to reflect G protein-induced membrane fusion or junctional communication between discrete subpopulations of Ca(2+)-pumping organelles (Ghosh, T. K., Mullaney, J. M., Tarazi, F. I., and Gill, D. L. (1989) Nature 340, 236-239). Since fatty acylation can modify G protein action, modification of GTP-induced Ca2+ translocation by fatty acyl-CoA was investigated to throw light on the mechanism underlying Ca2+ transfer. Using permeabilized DDT1MF-2 smooth muscle cells, 2 microM palmitoyl-CoA completely blocked Ca2+ release activated by 20 microM GTP, while having no effect on inositol 1,4,5-trisphosphate-induced Ca2+ release. The IC50 (50% inhibitory concentration) for palmitoyl-CoA was 0.5 microM. Above 3 microM, palmitoyl-CoA inhibited Ca2+ accumulation. Fatty acyl chain length was important, C-13 to C-16 fatty acyl-CoA esters all fully blocking the action of GTP; the IC50 for myristoyl-CoA was also 0.5 microM. C-18 or larger acyl groups had diminished effectiveness as did C-8 or smaller acyl groups. Acetyl-CoA had no blocking effect. In contrast, 10 microM CoA itself blocked GTP-induced Ca2+ release. CoA required a free sulfhydryl group to block, desulfo-CoA having no effect. Removal of ATP by hexokinase and glucose prevented the action of CoA but not palmitoyl-CoA. The free sulfhydryl and ATP requirements indicated CoA was being acylated by endogenous fatty-acyl-CoA synthetase to be effective. The nonhydrolyzable myristoyl-CoA analog, S-(2-oxopentadecyl)-CoA, blocked the GTP effect identically to myristoyl- and palmitoyl-CoA (IC50 = 0.5 microM); thus, fatty acyl transfer is not required, indicating that blockade is due to a direct allosteric modification of a component of the GTP-activated process by acyl-CoA esters. Palmitoyl-CoA not only inhibited but completely reversed GTP-activated Ca2+ release, resulting in the released Ca2+ being taken back up into pools. In the presence of oxalate, GTP-activated Ca2+ transfer results in a substantial increase in Ca2+ accumulation; palmitoyl-CoA also completely reversed this effect resulting in rapid termination of Ca2+ uptake. This reversal provides strong evidence that GTP-activated Ca2+ translocation does not reflect a membrane fusion event. Instead, it likely represents formation of a reversible junction or pore between organelles which may be a required prefusion event.

Acylation↗
PubMed1994

Sphingosine 1-phosphate generated in the endoplasmic reticulum membrane activates release of stored calcium.

Sphingosine and sphingosine derivatives induce Ca2+ release from inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pools in permeabilized cells (Ghosh, T. K., Bian, J., and Gill, D. L. (1990) Science 248, 1653-1656). To further assess the mechanism of sphingoid base-mediated Ca2+ release, the effects of sphingosine and sphingosine derivatives on Ca2+ fluxes were characterized using a microsomal membrane vesicle fraction (B3) enriched in rough endoplasmic reticulum (ER) prepared from cells of the DDT1MF-2 cell smooth muscle line (Ghosh, T. K., Mullaney, J. M., Tarazi, F. I., and Gill, D. L. (1989) Nature 340, 236-239). Addition of 15 microM sphingosine to Ca2+ pump-loaded B3 vesicles induced a delayed but thereafter rapid Ca2+ release from vesicles which was dependent on the presence of ATP and was blocked by ADP. Sphingosylphosphorylcholine (SPC) released Ca2+ to the same extent (more than 80% of pumped Ca2+), but in contrast to sphingosine, there was no lag and the effect was independent of ATP or ADP. The EC50 for sphingosine and SPC in activating Ca2+ release was 1 and 3 microM, respectively. Such observations are consistent with the view that sphingosine, unlike SPC, must be modified by an ATP-requiring kinase activity located within the ER membrane. Sphingoid bases do not appear to release Ca2+ through InsP3 receptors since heparin had no effect on sphingoid base-mediated Ca2+ release. Sphingosine 1-phosphate (sph-1-P), the likely active Ca(2+)-releasing derivative of sphingosine, was synthesized by phospholipase D-catalyzed cleavage of SPC, purified, and tested for Ca(2+)-releasing activity. sph-1-P at 10 microM induced Ca2+ release from both B3 vesicles and permeabilized DDT1MF-2 cells to exactly the same extent as sphingosine. Unlike sphingosine, the effect of sph-1-P was immediate and not blocked by ADP. Using B3 membrane vesicles incubated with [gamma-32P]ATP and sphingosine under the same conditions as Ca2+ flux studies, a labeled band was detected on TLC which ran identically with authentic sph-1-P. Formation of this labeled product was prevented by removal of exogenous sphingosine and blocked by ADP. Sphingosine- but not SPC-mediated Ca2+ release was blocked by 10 mM oxalate. 10 mM oxalate also blocked the formation of 32P-labeled sph-1-P indicating that it is an inhibitor of sph-1-P formation. The studies establish that the ER membrane contains the necessary kinase to convert sphingosine to sph-1-P which functions as a powerful mediator of Ca2+ release through a non-InsP3 receptor-mediated mechanism in the same ER membrane, perhaps reflecting a novel Ca2+ signaling pathway.

Adenosine Diphosphate↗
PubMed1994

Endoplasmic reticulum calcium pump expression and control of cell growth.

Intracellular Ca2+ pump expression and Ca2+ pool function are shown to be closely associated with growth and proliferation of DDT1MF-2 hamster smooth muscle cells. The Ca2+ pump blocker thapsigargin induces sustained Ca2+ pool emptying and entry of cells into a quiescent G0-like state (Short, A. D., Bian, J., Ghosh, T. K., Waldron, R. T., Rybak, S. L., and Gill, D. L. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 4986-4990). Using DDT1MF-2 cells growth-arrested by exposure to 3 microM thapsigargin for 24 h, treatment with 20% serum for 6 h without thapsigargin induced expression of functional Ca2+ pump protein detected as a 110-kDa thapsigargin-sensitive phosphorylated intermediate; 2.5% serum treatment resulted in no functional pump expression. Western analysis revealed only a slight serum-induced increase in total Ca2+ pump protein. New functional Ca2+ pump protein could be detected within 1 h of high serum treatment of thapsigargin-arrested cells, increasing over a 6-h period and correlating with the appearance of new Ca2+ pools. Induction of Ca2+ pools required serum at 10% or higher; no pools appeared with 5% serum or less. Significantly, high serum was required for only a brief but precise period of time. Exposure of thapsigargin-arrested cells to a 45-min pulse of 20% serum followed by continued culture in 2.5% serum was sufficient for full induction of new functional Ca2+ pump protein and Ca2+ pools; in contrast, no pumps or pools were detected after a 30-min serum pulse. A 40-min high serum pulse resulted in arrested cells reentering the cell cycle, synthesizing DNA, and resuming normal proliferation; in contrast, 35 min of serum treatment resulted in cells remaining totally quiescent. The results provide important evidence for the necessity of functional endoplasmic reticulum Ca2+ pumps in serum-induced cell growth and reflect a remarkably precise signaling period during which quiescent cells become committed to a progression of events including Ca2+ pump expression, Ca2+ pool function, reentry into the cell cycle, and cell division.

Animals↗
PubMed1994

Cephalic circulation in the air-breathing snakehead fish, Channa punctata, C. gachua, and C. marulius (Ophiocephalidae, Ophiocephaliformes).

The macrocirculation in the head of three air-breathing species of Channa was examined with the aid of vascular corrosion replicas and a scanning electron microscopic study was conducted on the pseudobranch, choroid gland and lentiform body. Two facultative air-breathing murrels, C. punctata and C. gachua, and one obligate air-breather, C. marulius were examined. In all three, the air-breathing organs (ABO) and systemic circulations were in-parallel, and both were in-series with the branchial circulation. Efferent branchial arteries from the first and second gill arches formed the arterial supply to the ABO, whereas the third and fourth arch efferents perfused systemic tissues. Postbranchial blood from the second gill arch also entered the systemic circulation directly via a shunt from the efferent branchial artery to the lateral aorta and via hypobranchial arteries. Vascular specialization to prevent mixing of oxygenated ABO venous and deoxygenated systemic venous blood was evident in arterial, but not venous circuits. Pseudobranchs of C. gachua and C. punctata are tri-lobed, in C. marulius they have numerous lobules. Pseudobranch lamellae are wider and shorter along the axis of blood flow than gill lamellae and folded perpendicular to this axis. Pseudobranch lamellae appear to be modified to minimize their epithelial surface while retaining an extensive vascular endothelial-pillar cell surface area, counter-current amplification is also possible. The choroid gland is an extensive planar counter-current capillary rete. The lentiform body of the eye is a globular capillary rete but there is no evidence of a counter-current circulation. The choroid and lentiform rete may have distinct physiological functions.

Air↗
PubMed1994

Microcirculation of gills and accessory respiratory organs from the air-breathing snakehead fish, Channa punctata, C. gachua, and C. marulius.

Snakehead fish of the genus Channa have well-developed air-breathing organs (ABO) yet retain their gill arches for respiratory and non-respiratory functions. Alterations in the macrocirculation accompany inclusion of the ABO and appear to enhance gas exchange efficiency (Munshi et al., 1994. Anat. Rec. 238:77-91). In the present study, the microcirculatory anatomy of gill and ABO from two facultative air-breathing Channa, C. punctata and C. gachua, and one obligate air-breather, C. marulius, were examined in detail using scanning electron microscopy (SEM) of vascular corrosion replicas and fixed whole-sectioned tissue. The results show that the circulation in the filaments from the first, second, and third gill arches is similar to that found in water-breathing teleosts. Fourth gill arch microcirculation of C. punctata is not different from the other three, whereas in C. marulius, it has been greatly modified into a network of low-resistance vascular shunts, although remnants of an intralamellar filamental microcirculation remain. The vascular shunts are formed from extensions of afferent and efferent lamellar arterioles and the complete, or nearly complete, loss of a lamellar sinus. The vasculature of the ABO has been highly modified in all species into a coiled-spiral capillary network with a constricted aperture guarding a dilated capillary dome at the epithelial surface. Microvilli are found congregated on the aperture endothelium of C. punctata but they are virtually absent from C. marulius endothelium. Less than 15% of the ABO capillary surface appears to face the epithelium and thereby contributes directly to gas exchange. These findings suggest that the microvascular modifications observed in Channa entail more than a simple increase in the contact surface between ABO vessels and air and they may serve other unknown physiological functions.

Air↗
PubMed1994

Influence of intralaryngeal CO2 on the response of laryngeal afferents to upper airway negative pressure.

Effects of intralaryngeal CO2 on the response of superior laryngeal afferents to negative pressure were investigated in 20 anesthetized spontaneously breathing adult cats. Single-fiber action potentials were recorded from the peripheral cut end of the superior laryngeal nerve. The larynx was exposed to negative pressure during inspiration when the animal breathed against an occluded upper airway. Among the 99 receptors evaluated, 54 were respiratory modulated and 45 were nonmodulated endings. The effect of intralaryngeal CO2 on the response of 39 receptors responding to negative pressure was determined by exposure of the larynx to CO2 or air for 1 min followed immediately by upper airway occlusion. The mean discharge frequency of 22 fibers inhibited by negative pressure was 32.4 +/- 2.6 Hz during air trials compared with 29.9 +/- 2.6 Hz during CO2 trials (P < 0.005). During occlusion of the upper airway after the warm humidified air trial, the discharge frequency of these endings decreased to 24.2 +/- 2.3 Hz compared with 17.5 +/- 2.2 Hz after CO2 trial (P < 0.001). The mean discharge frequencies of 17 fibers stimulated by negative pressure were 3.7 +/- 2.6 and 4.4 +/- 1.8 Hz, respectively, during air and CO2 trials. The mean frequencies increased to 14.7 +/- 3.5 Hz (air) and 18.6 +/- 4.0 Hz (CO2) during upper airway occlusions (P < 0.01). We conclude that intralaryngeal CO2 can alter the response of pressure-sensitive laryngeal afferents, thereby having a role in the maintenance of upper airway patency.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

Safe sex.

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Developing Countries↗
PubMed1993

Intracellular Ca2+ pool content is linked to control of cell growth.

A close correlation was observed between intracellular Ca2+ pool depletion and refilling and the onset of DNA synthesis and proliferation of DDT1MF-2 smooth muscle cells. The intracellular Ca2+ pump inhibitors 2,5-di-tert-butyl-hydroquinone (DBHQ) and thapsigargin (TG) specifically emptied identical inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pools and both arrested cell growth at concentrations corresponding to Ca2+ pump blockade. However, an important distinction was observed between the two inhibitors with respect to their reversibility of action. Upon removal of DBHQ from DBHQ-arrested cells, Ca2+ pools immediately refilled, and 14 hr later cells entered S phase followed by normal cell proliferation; the time for entry into S phase was identical to that for cells released from confluence arrest. Although TG irreversibly blocked Ca2+ pumping and emptied Ca2+ pools, high serum treatment of TG-arrested cells induced recovery of functional Ca2+ pools in 6 hr (via probable synthesis of new pump); thereafter cells proceeded to S phase and normal cell proliferation within the same time period (14 hr) as that following release of DBHQ-arrested cells. The precise relationship between Ca2+ pump blockade and growth arrest indicates that Ca2+ pool emptying maintains cells in a G0-like quiescent state; upon refilling of pools, normal progression into the cell cycle is resumed. It is possible that a specific cell cycle event necessary for G0 to G1 transition depends upon signals generated from the InsP3-sensitive Ca2+ pool.

Animals↗
PubMed1993

Studies on the mechanism of anti-inflammatory and anti-ulcer activity of Pluchea indica--probable involvement of 5-lipooxygenase pathway.

The effect of the methanolic fraction of Pluchea indica Less. root extract was evaluated on various models of inflammation and ulcer in vivo to assess the role of P. indica on the 5-lipoxygenase pathway of prostaglandin synthesis. Studies presented here reveal significant antiinflammatory activity of the fraction on Arachidonic acid, Platelet activation factor and Compound 48/80-induced paw oedema. There was significant inhibition of spontaneous as well as compound 48/80-induced histamine release from mast cells. Ulcer studies revealed significant protective action of the fraction on indomethacin, alcohol and indomethacin-alcohol induced ulceration. There was significant decrease of gastric volume and acidity in pylorus ligated rats. Studies also showed, significant protective action of the same on gastric mucosa.

Animals↗
PubMed1993

Isolation of a toxin from jellyfish Acromitus rabanchatu and its effect on skeletal muscle.

A toxin (T-Ar) from the crude extract of jellyfish Acromitus rabanchatu was purified by (NH4)2SO4 fractionation followed by ion-exchange chromatography on DEAE-cellulose column. The mol. wt of T-Ar was found to be about 182,000. T-Ar reversibly blocked the twitch response of rat diaphragm muscle stimulated either indirectly or directly. It also reversibly blocked the twitch responses of chick biventer-cervicis muscle preparations. T-Ar failed to alter the contractures of the denervated rat diaphragm muscle preparation induced by acetylcholine, potassium chloride and caffeine. Similarly, acetylcholine and carbachol-induced contractures on chick biventer-cervicis muscle preparation were not influenced by T-Ar. The T-Ar-induced blockade of twitch responses of rat phrenic nerve-diaphragm was enhanced in high Na+ or low Ca2+ medium, and reduced in low Na+ or high Ca(2+)-containing medium. The results suggest that the toxin (T-Ar) possesses a direct paralysing effect on the muscle membrane.

Acetylcholine↗
PubMed1993

In-vitro permeation of some beta-blockers across the hairless mouse skin.

To support the development of a suitable transdermal dosage form for beta-blockers, in-vitro, skin permeation studies of nine beta-blockers were conducted at 37 degrees C across the excised abdominal skin of hairless mouse mounted on the receptor compartment of a two-chambered Valia-Chien glass diffusion cell. The drugs varied in lipophilicity, whereas pKa values were comparable. Permeability coefficients were calculated from the steady-state flux values. Agreement was found between the permeability coefficient and the drug lipophilicity, expressed as the octanol-buffer distribution coefficient.

Adrenergic beta-Antagonists↗