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Biomedical subjects

M Sharma

Publications and source records attributed to M Sharma.

At least 325 records · Page 18Linked to original sources

Circadian rhythms of melatonin and cortisol in aging.

The relationship of age to the circadian rhythms of melatonin and cortisol was investigated in 44 men and 27 women (age range 19-89 years). Subjects were physically and psychiatrically normal. Four hourly serial blood samples were drawn from 8:00 AM until 8:00 AM the next day, with additional samples at 10:00 PM and 2:00 AM. The indoor illumination was restricted to 300 lux during day and 50 lux during the night. Plasma melatonin and cortisol were estimated by radioimmunoassay. Results show that the means of melatonin and cortisol values decreased significantly with age when the subjects were divided into three age groups, i.e., 19-25 years, 42-65 years, and 66-89 years. They also showed a significant negative correlation with age. The acrophases of the two hormonal rhythms, however, showed different relationships to age. The acrophase of melatonin rhythm showed a positive correlation with age (r = 0.38, p less than 0.001), and cortisol showed a negative correlation with age (r = -0.56, p greater than 0.001). It is suggested that this may indicate a weakened responsiveness of the circadian system in the elderly to the day-night cycle and an altered relationship between the pacemakers driving melatonin and cortisol circadian rhythms. This may thus represent a biomarker for the intrinsic process of the aging of the brain.

Adult↗

Effect of colocasia leaves (Colocasia antiquorum) on serum and tissue lipids in cholesterol-fed rats.

Dried colocasia powder (10% and 20%) was fed to hypercholesterolemic rats for a period of one month to explore the effect on serum lipids and tissue lipids. The results indicated that there was a significant increase in total lipids, total cholesterol, and triglycerides levels in the cholesterol fed rats. Liver cholesterol showed a slight reduction which was non-significant, while an increase in liver triglyceride was observed in rats fed with 10% and 20% colocasia leaves diet with or without cholesterol. All these observations indicate an aggravating effect of colocasia leaves on serum and tissue lipids in cholesterol-fed rats.

Animals↗

Pharmacokinetics and disposition of pipecuronium bromide in dogs with and without ligated renal pedicles.

The pharmacokinetics of pipecuronium bromide have been studied in anesthetized beagle dogs with and without ligated renal pedicles. A gas chromatographic assay was used to measure the plasma, urine, bile concentrations, and liver content of pipecuronium, the later of which was obtained 8 h after injection. Following an iv bolus injection of 0.1 mg/kg, pipecuronium disappeared from the plasma exponentially with distribution half-lives of 3.9 +/- 1.1 min and 12.7 +/- 9.5 min (mean +/- SD), and elimination half-lives of 44.8 +/- 2.6 min and 196.7 +/- 102.0 min in animals with and without renal pedicle ligation, respectively. Except for the volume of central compartment, all other pharmacokinetic variables differed significantly between the two experimental groups. The elimination half-life was longer (196.7 +/- 102 (SD) vs. 44.8 +/- 2.6 min), plasma clearance slower (5.9 +/- 0.8 ml.kg-1.min-1 vs. 0.9 +/- 0.1 ml.kg-1.min-1) and mean residence time longer (221 +/- 73 vs. 51.1 +/- 1.8 min) in dogs with ligated renal pedicles. Eight hours after injection, the recovery of the parent form of pipecuronium approximated 77% of the administered dose in the urine, 4.5% in the bile, and 3.3% in the liver of normal animals. In animals with ligated renal pedicles 16% of the unchanged pipecuronium was excreted into the bile and 10% of the administered dose was recovered from the liver. Since the total recovery of unaltered pipecuronium approximated 85% of the administered dose in the intact animals, biotransformation seems to play an insignificant role in disposition of this new neuromuscular blocking drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstane-3,17-diol↗

Nonspecific inhibition of proline dehydrogenase synthesis in Escherichia coli during osmotic stress.

L-Proline, which is accumulated by Escherichia coli during growth in media of high osmolality, also induces the synthesis of the enzyme degrading it to glutamate. To determine if proline catabolism is inhibited during osmotic stress, proline utilization and the formation of proline dehydrogenase were examined in varying concentrations of NaCl and sucrose. Although the specific growth rate of E. coli with proline as the sole nitrogen source diminished as the solute osmolality increased, a comparable reduction in growth rate occurred with ammonium as the primary nitrogen source. Proline catabolism, as measured in whole cells by the conversion of [14C]proline to [14C]glutamate, was only slightly inhibited by solute osmolalities up to 1.0 osmol/kg; more than 50% of the initial activity was still found at 2.0 osmol/kg. By contrast, the specific activity of proline dehydrogenase in bacteria grown in the presence of added solutes decreased to less than 20% of the control level. This reduction was related to a lower rate of synthesis, but was independent of genes currently known to be involved in osmoregulation or proline metabolism. The specific activities of tryptophanase, beta-galactosidase, and histidinol dehydrogenase were also reduced under similar growth conditions. These results indicate that while proline catabolism is not directly inhibited by high solute concentrations, prolonged exposure to osmotic stress leads to its reduction as part of a more general metabolic response.

Escherichia coli↗

Neurochemical and receptor theories of depression.

The neurochemical and receptor theories relate depression to deficient neurotransmission at critical sites in the brain. While this concept has generated a number of theories of depression over the years, the research findings do not fully support any single theory in its entirety. Several issues thus remain controversial or inconclusive. For instance, the monoamine deficit theory is supported by low urinary MHPG in some forms of bipolar, but not unipolar depression. Cerebrospinal fluid MHPG and 5-HIAA studies are inconclusive. Amine metabolite research is also limited in scope because the information derived pertains to pre-synaptic and synaptic events and ignores post-synaptic events. Receptor research, which includes study of both pre-and post-synaptic sites, suggests supersensitivity of Beta-adrenergic receptors in depression. But this research is criticized because it is mostly animal based. Also, the findings of low melatonin in depression contradict the supersensitivity-hypothesis. Abnormally low post-synaptic alpha-2 adrenoceptors is indicated by findings of an attenuated GH response to clonidine. But abnormality of pre-synaptic alpha-2 adrenoceptor functions has not been demonstrated conclusively. Recent findings in depression suggest a dysregulation in the dynamic and interactive relationship between neurotransmitters and receptors. Accordingly, a comprehensive view of the abnormalities of the various neurotransmitter systems in depression requires studies which investigate pre- and post-synaptic events simultaneously, preferably during illness and remission.

Brain↗

Profile of blood pressure in normal school children.

A total of 2073 school children between the age group of 5-14 years were examined to define the normal range of auscultatory blood pressure and prevalence of hypertension. An equal number of children in each age, sex and socio-economic group were studied. Mean figures for systolic and diastolic blood pressure with standard deviation and 95th percentile position for each age group were calculated. Systolic and diastolic blood pressure for both sexes had a direct correlation with age, weight and height. Overall prevalence of hypertension was found to be 2.93%.

Adolescent↗

Chlamydiazyme test for rapid detection of Chlamydia trachomatis.

Endocervical (120) and endourethral (104) swabs collected from patients attending the Gynaecological OPD and STD Clinic of a Hospital, in north India were subjected to the chlamydiazyme test to detect C. trachomatis antigen. This antigen was detected in 25 per cent (30 of 120) of cervical and 20.19 per cent (21 of 104) of urethral specimens. Of the 51 antigen positive cases, 30 (58.8%) presented with the clinical picture of cervicitis, 11 (21.5%) with urethritis, 6 (11.7%) were cases of primary infertility and 4 (7.8%) were healthy controls. The association of C. trachomatis and other sexually manifested microorganisms (Mycoplasma hominis, Ureaplasma urealyticum and Gardnerella vaginalis) was found more commonly in patients of cervicitis, especially those who were C. trachomatis antigen positive.

Antigens, Bacterial↗

Ultraviolet irradiation of nucleic acids: formation, purification, and solution conformational analyses of oligothymidylates containing cis-syn photodimers.

Acetone-photosensitized UV irradiation of three thymine oligomers, d(TpT), d(TpTpT), and d(TpTpTpT), forms predominantly cis-syn cyclobutyl photodimers. C-18 reverse-phase high-performance liquid chromatography is used to purify the following positional isomers: d(TpT[p]T), d(T[p]TpT), d(TpTpT[p]T), d(TpT[p]TpT), d(T[p]TpTpT), and d(T[p]TpT[p]T), where T[p]T represents the cis-syn photodimer. Conformational properties of the cis-syn dimers and adjacent thymine nucleotides have been investigated in solution by using 1H, 13C, and 31P NMR spectroscopy. These studies show that (1) the photodimer conformation in longer oligothymidylates is similar to that in the dinucleoside monophosphate and (2) the cis-syn dimer induces alterations to a greater degree on the 5' side than on the 3' side of the photodimer. Specifically, the photodimer distorts the exocyclic bonds epsilon(C3'-O3') in Tp- and gamma(C5'-C4') in -pT[p]- on the 5' side and slightly alters the furanose equilibrium of the -pT nucleotide on the 3' side of the dimer.

Magnetic Resonance Spectroscopy↗

General methods for modification of sialic acid at C-9. Synthesis of N-acetyl-9-deoxy-9-fluoroneuraminic acid.

Methyl 5-acetamido-3,5-dideoxy-2-O-methyl-D-glycero-D-galacto-2-nonulopyrano sate was converted into the 9-O-trityl derivative and the remaining hydroxyl groups were protected as benzyl ethers. Removal of the trityl group, followed by treatment with diethylaminosulfur trifluoride gave the 9-deoxy-9-fluoro derivative, and deprotection N-acetyl-9-deoxy-9-fluoroneuraminic acid (8). In another procedure, coupling of 2-acetamido-2,6-dideoxy-6-fluoro-D-glucopyranose with potassium di(tert-butyl) oxaloacetate, followed by hydrolysis and decarboxylation gave 8. Some of the derivatives were active as inhibitors of growth of mouse mammary adenocarcinoma (TA3) and L1210 cells in culture.

Indicators and Reagents↗

Synthesis and application of fluorescent labeled nucleotides to assay DNA damage.

A facile method was developed to covalently attach a fluorophore to the 5'-phosphate of a nucleic acid. The procedure, illustrated by coupling 5'-dNmp (N = A,C,G,T) with 5-dimethylaminonaphthalene 1-sulfonyl chloride, commonly known as Dansyl chloride, involves 5'-phosphoramidation with ethylenediamine (EDA) followed by conjugation of the free aliphatic amino group of the phosphoramidate with Dansyl chloride. This method is also applicable to multi-incorporation of fluorescent labels in the nucleic acids. The reaction of 5'-Amp with a polyamine such as poly L-lysine (PLL, mol. wt., 4000) resulted in a phosphoramidate with multiple amino groups, which after isolation and conjugation with fluorescamine gave dAmp with multilabeled fluorophores. A condition was devised to separate the four dansylated mononucleotides of DNA, conjugated via ethylenediamine linker, by reverse phase HPLC. The elution profile could be monitored with a variable wavelength detector at 254 nm and 340 nm corresponding to the absorption of the nucleotides and the dansyl moiety, respectively. The detection limit was 2 nmol at 254 nm. The use of a fluorescence detector enhanced the detection sensitivity to a sub-picomole level (200 fmol). Samples of a DNA model, d(pCpGpTpA) and calf-thymus DNA were digested enzymatically to 5'-mononucleotides and labeled with Dansyl chloride. HPLC analysis of the dansylated digests from these samples, both before and after irradiation, suggests that the combination of enzymatic digestion and fluorescence postlabeling could be a novel approach to assay DNA damage.

Chemical Phenomena↗

Molecular aspects, physiological function, and clinical significance of metallothioneins.

Metallothioneins (MTs) are well-characterized low molecular weight, heat-stable cytosolic proteins with exceptional high content of cysteinyl sulfur and are known to bind heavy metals like cadmium (Cd), zinc (Zn), and copper (Cu). Since these proteins are induced on exposure to heavy metals, it is now accepted that they have a detoxifying role during heavy metal toxicity. It has also been suggested that the primary function of Mt is in the homeostasis of the essential metals Zn and Cu. Recently, a role MT in selenium metabolism in primates has been established. Further, MT has gained considerable importance in the clinical disorders related to trace metal metabolism.

Amino Acid Sequence↗

Molecular and catalytic properties of angiotensin converting enzyme-I from bovine seminal plasma.

Angiotensin converting enzyme [EC 3.4.15.1] was shown to exist in two distinct forms in bovine seminal plasma. The higher molecular weight form of the enzyme (angiotensin convering enzyme I) was purified to homogeneity by Sephadex G-200 gel filtration, and DEAE-Sepharose, blue Sepharose, and concanavalin A-Sepharose column chromatography. Final recovery of the enzyme was 9.0. The molecular weight of the enzyme was estimated to be 8 x 10(5) by the gel filtration method. A value of 4.6 x 10(5) was obtained for the reduced and denatured enzyme by dodecylsulfate polyacrylamide gel electrophoresis. The Stokes' radius, diffusion coefficient, and intrinsic viscosity of the purified enzyme were determined to be 95 A, 2.3 x 10(-7) cm2/s, and 6.76 ml/g. The enzyme had a specific activity of 105.12 mumol/min/mg protein for hippurylhistidylleucine. The Km value for hippurylhistidylleucine was found to be 20 mM. Studies with EDTA suggest that metal ions which are tightly bound are required for its activity. The enzyme was inhibited by some heavy metal ions but did not required sulfhydryl groups for its activity. Trypsin treatment of the urea-denatured enzyme produced a catalytically active fragment with an Mr of 30,000. Chemical hydrolysis of the native enzyme did not produce any active fragment.

Angiotensin-Converting Enzyme Inhibitors↗