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Biomedical subjects

P N Sharma

Publications and source records attributed to P N Sharma.

At least 37 records · Page 2Linked to original sources
PubMed1994

Ultrastructure of the male reproductive system in a rumen amphistome Cotylophoron cotylophorum.

The ultrastructure of various regions of the male reproductive tract and the prostate gland of Cotylophoron cotylophorum (Trematoda: Digenea) is described. The internal lining of the entire male duct system is syncytial in nature, and regional variation is quite evident. The syncytial epithelium of the vas deferens and seminal vesicle is very thin, flat and lamellate and the lumen is packed with spermatozoa. In the pars musculosa (PM) the syncytium is also flat but lamellae are sparsely distributed and anastomosed at places to form loops. The syncytium of the PM is invested by several layers of circular and longitudinal muscle. The pars prostatica (PP) is lined by an uneven but moderately thick syncytial epithelium with nuclei projecting into the lumen. The syncytium bears numerous very long lamellae. The ejaculatory duct epithelium is devoid of lamellae. It is even and moderately thick throughout. The prostate gland cells are uneven in outline and bear long ducts which open into the lumen of the PP. They show an ultrastructural organization suggestive of protein secretion.

Animals↗
PubMed1993

Effectiveness of a unani therapy (sangesarmahi) in management of urinary stone disease.

A Unani medicine called fish stones, an isolate from the skull of Channa sp. when given to stone bearing patient daily in 3 equally divided doses (25 mg/capsule) for 5 days, spontaneously voided the stone in 36% of the stone patients during 5 days of therapy. The therapy did not influence the urinary chemistry and was not a powerful expulsion agent of stone but did effect on ureteric muscles to facilitate the movement of stone down the urinary tract. In guinea pigs, the therapy could not reduce the intensity of experimentally induced hyperoxaluria but showed several other beneficial effects. It decreased urinary uric acid and mucoprotein levels, serum LDH and ALT level; prevented rise in liver LDH and GAO activities and kidney-LDH activity. Histological examination revealed decreased intensity of calcification in liver, kidney and bladder tissues.

Animals↗
PubMed1990

Search for chromosomal variations among gas-exposed persons in Bhopal.

A chromosomal survey using standard lymphocyte cultures employing different media and G-banding techniques was initiated in 1984. This study became particularly important following the tragic gaseous exposure of the population in Bhopal at midnight on 2 December 1984. We have been able to formulate a chromosomal profile for each person whom we have studied; during 1986-1988, 154 persons were examined twice. Among seemingly normal individuals, as many as 20% might possess some chromosomal abnormality; of these, 50% may develop, at a later date, some kind of pathological complication (such as tumours, recurrent abortion or transmission of defects to their offspring). The people exposed to methyl isocyanate have repeatedly shown Robertsonian translocations, mostly in acrocentric chromosomes 13 and 21. Other types of translocations have been studied among all exposed (53) and normal (101) persons; the involvement of chromosomes 5, 9, 11, 14 and 16 is statistically significant (P = less than 0.001). One of the major clinical symptoms is dyspnoea; we have estimated that almost all seriously dyspnoeic patients have developed at least two categories of chromosomal aberrations, one of which is Robertsonian translocation, in at least 10% metaphases. Our chromosomal survey will be of significance because we are able to identify people with chromosomal aberrations that might be correlated with future pathological consequences of the accident. The "chromosomal load" that can be sustained with an apparently normal phenotype can also be measured.

Accidents, Occupational↗
PubMed1989

Mechanism of inhibition of DNA gyrase by quinolone antibacterials: a cooperative drug--DNA binding model.

We have proposed a cooperative quinolone-DNA binding model for the inhibition of DNA gyrase. The essential feature of the model is that bound gyrase induces a specific quinolone binding site in the relaxed DNA substrate in the presence of ATP. The binding affinity and specificity are derived from two unique and equally important functional features: the specific conformation of the proposed single-stranded DNA pocket induced by the enzyme and the unique self-association phenomenon (from which the cooperativity is derived) of the drug molecules to fit the binding pocket with a high degree of flexibility. Supporting evidence for and implications of this model are provided.

Anti-Bacterial Agents↗
PubMed1988

Ultrastructure and cytochemistry of the tegument of Orthocoelium scoliocoelium and Paramphistomum cervi (Trematoda: Digenea).

The tegument of Orthocoelium scoliocoelium and Paramphistomum cervi was examined using histochemical techniques and electron microscopy. On the basis of the distribution of acid and alkaline phosphatase (E.C. 3.1.3.2, E.C. 3.1.3.1), non-specific esterase (E.C. 3.1.1.1), cholinesterase (E.C. 3.1.1.7) and succinate dehydrogenase (E.C. 1.3.99.1) at light microscope level two distinct regions were recognized, an outer and an inner zone. Electron microscopy revealed that the tegument comprises an outer surface syncytium underlain by a thick subsyncytial zone and musculature. Deeper still occur the nucleated "tegumental cells". The latter are in cytoplasmic continuity with the surface syncytium via vacuolated cytoplasmic trabeculae which traverse the muscle layers and the subsyncytial zone. Three types of tegumental cells each lacking mitochondria were observed. The T1 cells synthesize discoid and electron dense T1 bodies while T2 cells produce oval and electron lucent T2 bodies. The third type of tegumental cells apparently produce no secretory bodies and may represent an embryonic cell type. The surface syncytium contains T1 and T2 secretory bodies and is bounded apically by a plasma membrane invested externally by a fuzzy and filamentous glycocalyx. The surface syncytium lacks mitochondria and is traversed by infoldings of the basal plasma membrane. Beneath the surface syncytium the subsyncytial zone is largely comprised of fibrous interstitial material. This zone, which is particularly thick in the amphistomes, is traversed by trabeculae and extensions of underlying parenchymal cells which usually contain mitochondria and lysosomes. The subsyncytial zone overlies numerous circular and longitudinal muscle fibres. The absence of mitochondria and enzymes associated with active transport suggests that the amphistome tegument may be mainly specialized for protection of the worm against mechanical and chemical conditions prevailing in the rumen. Active uptake of nutrients is probably not a primary function.

Acetylcholinesterase↗
PubMed1987

Separation of tubulin-binding and anti-inflammatory activity in colchicine analogs and congeners.

The effects of colchicine and its analogs on the carrageenin-induced footpad edema in rats were investigated. The anti-inflammatory effects of colchicine analogs were measured at 3 and 5 hr after the carrageenin injection. Colchicine, 1-demethylcolchicine and 3-demethylcolchicine markedly inhibited the carrageenin edema whereas 2-demethylcolchicine was much less active. Thiocolchicinoids, having a thiomethyl group at C-10 instead of a methoxy group, were considerably less potent. These results suggest that the presence of methoxy groups at C-2 and C-10 in colchicine is necessary to maintain anti-inflammatory activity. Inactivity of deacetylcolchicine indicates that substitution of the amino group at C-7 with electron withdrawing groups is also important. Significant inhibition of carrageenin edema and strong binding to tubulin in vitro were manifested by colchicine, 3-demethylcolchicine, N-butyryldeacetylcolchicine and colchifoline. On the other hand, N-carbethoxydeacetylcolchicine which did bind well to tubulin, did not show much effect on the carrageenin edema. These results suggest that the anti-inflammatory action of colchicinoids may not be regulated through the microtubule system.

Animals↗
PubMed1987

Chiral DNA gyrase inhibitors. 2. Asymmetric synthesis and biological activity of the enantiomers of 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H- pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid (ofloxacin).

A short and efficient synthesis, starting with (R)- and (S)-alaninol, of the two optical antipodes of the quinolone antimicrobial agent ofloxacin has been devised. Testing in vitro of the products against a range of bacteria and in an assay system incorporating purified DNA gyrase from different bacterial species demonstrates that the S-(-) enantiomer is substantially the more active.

Anti-Bacterial Agents↗
PubMed1986

Chiral DNA gyrase inhibitors. 1. Synthesis and antimicrobial activity of the enantiomers of 6-fluoro-7-(1-piperazinyl)-1-(2'-trans-phenyl-1'-cyclopropyl)-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid.

New quinolone antimicrobial agents (racemic, (1'S,2'R)- and (1'R,2'S)-6-fluoro-7-(1-piperazinyl)-1-(2'-trans-phenyl-1'-cyclopropyl)- 1, 4-dihydro-4-oxoquinoline-3-carboxylic acids) were synthesized, and their in vitro antimicrobial potencies and spectra were determined. As compared to their conceptual parents, these agents retained a considerable amount of the antimicrobial potency and spectra of ciprofloxacin and of 6-fluoro-1-phenyl-7-(1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxy lic acid against Gram-positives. Gram-negatives were considerably less sensitive. The (-)-(1'S,2'R) analogue was the more potent of the enantiomers, but the degree of chiral discrimination by most bacteria was only 4-fold. The 4-fold chiral discrimination was observed also using purified DNA gyrase obtained from Micrococcus luteus, whereas the two enantiomers were essentially equiactive against the enzyme derived from Escherichia coli. These results confirm that there is a substantial degree of bulk tolerance available at N-1 of quinolone antimicrobial agents and suggest that electronic factors controlled by substitution at that site are of considerable importance. On the other hand, chiral recognition brought about by attachment of optically active groups to the N-1 position in these derivatives is relatively small.

Anti-Bacterial Agents↗
PubMed1986

B ring regulation of colchicine binding kinetics and fluorescence.

Several properties of the colchicine-tubulin interaction such as association rate, reversibility, and the promotion of drug fluorescence have been related to the B ring of colchicine. The B ring itself retards the binding rate, and substitution at C-7 leads to further binding rate decreases that appear to be related to both substituent bulk and the presence of a N-acyl group. Thus, the decreasing order of binding rates is 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone greater than deacetamidocolchicine greater than deacetylcolchicine greater than or equal to colcemid greater than colchicine greater than N-benzoyldeacetylcolchicine, etc. The apparent irreversibility of the binding seems more closely related to the presence of an N-acyl group rather than the bulk of the substituent at C-7. Substitution at C-7 also affects the tropolone fluorophore. Thus, amines (deacetylcholchicine, colcemid, or N-methylcolcemid) fluoresce poorly in the presence of tubulin, whereas substitution of the amino group with an acyl group enhances fluorescence. The presence of an N-acyl group at C-7 is essential for enhanced fluorescence. We conclude that, in addition to A- and the C-ring portion of the molecule, the B ring of colchicine is a third determinant recognized by the binding site on tubulin.

Animals↗
PubMed1985

Synthesis and biological effects of novel thiocolchicines. 3. Evaluation of N-acyldeacetylthiocolchicines, N-(alkoxycarbonyl) deacetylthiocolchicines, and O-ethyldemethylthiocolchicines. New synthesis of thiodemecolcine and antileukemic effects of 2-demethyl- and 3-demethylthiocolchicine.

Novel and known analogues of thiocolchicine were evaluated in vitro in a tubulin binding assay and in vivo in mice for acute toxicity and in the P388 lymphocytic leukemia assay. This evaluation included N-acyldeacetylthiocolchicines, N-(alkoxycarbonyl)deacetylthiocolchicines, thiodemecolcine and its methyl carbamate, and O-ethyl ethers of demethylthiocolchicines. Selective ether cleavage of thiodemecolcine with concentrated sulfuric acid at 50 degree C afforded the 2-demethyl congener, characterized as its N,O-diacetyl derivative. Several of the compounds showed high potency in the tubulin binding assay, matching the potency of colchicine. Several N-(alkoxycarbonyl)deacetylcolchicines (carbamates) exhibited strong binding affinity to tubulin but had only weak activities against the P388 tumor system, suggesting that other factors besides tubulin binding may be important for the biological effects. The compounds potent in the tubulin binding assay and in the P388 leukemia assay in mice were generally also toxic to mice in the acute toxicity test, showing thus a similar behavior of thiocolchicines to that observed earlier with colchicines. A considerable amount of data collected for 2-demethyl- and 3-demethylthiocolchicine suggests that the latter represents a broad-spectrum antitumor agent of considerable promise and possibly a less toxic substitute for colchicine.

Animals↗
PubMed1984

Synthesis and binding to tubulin of colchicine spin probes.

Spin probes of deacetylcholchicine (1), 4-(hydroxymethyl)colchicine (2), and colchifoline (3) have been synthesized to study the binding site for colchicine on tubulin. Acylation of 1-3 with (+/-)-2,2,5,5-tetramethyl-1-pyrrolidinyloxy-3-carboxylic acid (4) afforded diastereomeric mixtures of the esters 5-8 and the amides 9 and 10. Pure diastereomers of 3 were synthesized with 4a and 4b, which inhibited the binding of colchicine by 60%. In the presence of calf brain microtubular protein, the colchifoline spin labels underwent reduction of the nitroxide group, which precluded their use to study the topography of the colchicine binding site.

Animals↗
PubMed1984

Measles and age of vaccination.

Measles is responsible for high morbidity and mortality in children particularly in developing countries. Infants, found by analytical studies to constitute a high risk group, are usually not covered by current vaccination programmes. In Kuwait in the epidemic years during the period 1976-1982, the incidence of measles in infants under one year was found to be more than five times that in the population over one year of age, ranging between 758 and 992 per 100000 live births. During this period as many as one fifth of the total cases (13.3-21.7%) and about one-third of the total deaths (35%) occurred in infants. The mean fatality rate for infants under one year was 3.3 while for the population one year and above it was 1.4. As the immunity derived from the mother declines markedly a large majority of children over six months of age become susceptible to measles. There is a strong case for lowering the age of vaccination against measles to protect the infants, at least in the developing countries, and to control and eventually eradicate the disease.

Adolescent↗
PubMed1983

Role of oesophageal glands in the digestive physiology of two rumen amphistomes Orthocoelium scoliocoelium and Paramphistomum cervi.

Histochemical techniques have been used to study the chemical composition of the oesophageal gland secretions of Orthocoelium scoliocoelium and Paramphistomum cervi. Results suggest that the secretions contain numerous enzymes, e.g., non-specific alkaline and acid phosphatases, ATPase, TPPase, esterase (Cathepsin C like), beta-galactosidase, beta-glucuronidase and N-acetyl-beta-glucosaminidase. The role of these enzymes in the digestion of food in these amphistomes is discussed. On the basis of histological and histochemical studies the caecal epithelium of the two amphistomes has been found to be syncytial bearing regularly arranged numerous, long but equal-sized and closely packed cylindrical microvilli. The role of various hydrolytic enzymes in well fed and starved flukes in relation to their gastrodermis and microvilli has also been discussed.

Animals↗
PubMed1983

Biological effects of modified colchicines. 2. Evaluation of catecholic colchicines, colchifolines, colchicide, and novel N-acyl- and N-aroyldeacetylcolchicines.

A series of natural and synthetic colchicine derivatives was examined for their potency in the lymphocytic leukemia P388 screen in mice, for their toxicity in mice, and for their binding to microtubule protein. The natural alkaloids cornigerine and colchifoline and several N,O-substituted analogues of colchifoline were found to be as potent and as toxic as colchicine in the P388 screen with good affinity for tubulin. The 1,2-(methylenedioxy)-substituted isomer of cornigerine was considerably less potent in vivo than could have been anticipated from the in vitro tubulin binding data. Several N-acyl and N-aroyl derivatives prepared from deacetylcolchicine showed high potency in the in vitro and in vivo screens. Colchicide was found to be highly potent in vivo, and N-carbethoxydeacetylcolchicine, a synthetic analogue of colchicine with a N-carbethoxy instead of an N-acetyl function, showed interesting biological properties.

Animals↗
PubMed1982

Morphology, histochemistry, and the biological significance of the lymphatic system of the trematode Orthocoelium scoliocoelium.

The gross morphology and histological and cytological architecture of the lymph system of Orthocoelium scoliocoelium were studied. Each main vessel, near the intestinal bifurcation forms a spindle-shaped sinus. Lymphocytes, similar to the primitive blood cells, have been seen to form aggregates in certain regions of the lymph system. In addition, detailed histochemical observations were made on the localization and distribution pattern of various phosphatases, esterases and dehydrogenases. It is suggested that the lymph system, in addition to the functions already known, may also selectively reabsorb certain important outgoing higher fatty acids from the excretory system. Furthermore, the lymphocytes may also be involved in the defense mechanism of the worm. The nature and function of fine granules in the lymph remain speculative.

Animals↗
PubMed1981

Cytochemical characteristics of the neurosecretory cells of Ceylonocotyle scoliocoelium (Trematoda: Digenea).

Two types of neurosecretory cells (NSC), large alpha cells and small beta cells were detected on the basis of their size and characteristics as shown by aldehyde fuchsin and chrome haematoxylin-phloxin staining. A histochemical survey of the neurosecretory material indicates that it is a glycoprotein. Phosphatases and esterases present in NSC probably help in the transfer of metabolites and their hydrolysis and in the control of secretory material produced in a NSC, while SDH provides the necessary energy for the synthetic activity of the latter. The role of neurosecretion in governing the reproduction of this parasite is discussed.

Animals↗