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Biomedical subjects

S Sen

Publications and source records attributed to S Sen.

At least 37 records · Page 2Linked to original sources

Treatment of unstable angina pectoris (European experience).

Unstable angina pectoris is used to describe accelerated angina, new onset of angina, or prolonged angina. The natural history of the angina varies according to clinical presentation. The 1-year mortality rate ranges from 2% to nearly 40%. Specific therapy includes nitrates, beta-adrenergic blockers, and/or calcium antagonists as well as antithrombotic therapy in the form of aspirin. Patients with severe angina at rest and ST- and T-wave changes should be admitted to a coronary care unit where full-dose heparin is administered. Coronary angiography should be performed in individuals who fail to respond to the conventional therapy in order to evaluate other therapeutic options, including percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass surgery. In some cases, especially in patients with intracoronary thrombus, thrombolytic therapy may be beneficial.

Angina, Unstable

Comparative efficacy of chlorophyllin in reducing cytotoxicity of some heavy metals.

The potential of chlorophyllin in reducing clastogenicity was studied against two concentrations of each of three potent metallic clastogens (cesium chloride, mercuric chloride and cobalt chloride) in bone marrow cells of mice in vivo. The respective salts and chlorophyllin were administered orally to mice by gavaging in different combinations. Simultaneous administration of chlorophyllin with both concentrations of each salt reduced the clastogenic effects in the order Cs greater than Hg greater than Co. Chlorophyllin could not decrease the clastogenic effects when administered 2 h before the salts.

Animals

Effect of sodium deprivation on cardiac hypertrophy in spontaneously hypertensive rats: influence of aging.

Sodium has been identified as a causal factor in the development of hypertension in experimental animal models as well as in clinical human subjects. Sodium is also known to play a role in modulating myocardial mass and its pattern of myosin isozyme distribution. In the rodent model, the accumulation of V3 myosin isozyme (MI), due to the modulating influence of sodium, has been shown to be associated with persistent cardiac hypertrophy and heart failure. In this paper, we have examined the effect of the restriction of dietary sodium on blood pressure, ventricular weight and myosin isoforms in spontaneously hypertensive rats (SHR) and the relationship of these parameters with age. In 10- to 11-week-old SHR, dietary sodium restriction for 14 weeks resulted in a significant reduction in ventricular mass associated with systolic shifting of myosin isoform from V3 type to V1 type with no change in systolic blood pressure level; dietary sodium restriction also showed a significant reduction in body weight. When the effect of dietary sodium restriction (for 8 weeks) was studied in relation to age (in 11-, 16- and 24-week-old rats) a significant shift in myosin isoform from the V3 to the V1 type was noted in the 11-week-old rats; a slight but significant shift was noted in 16-week-old rats, and no change in myosin isoform distribution was noted in the 24-week-old SHR. The alteration in myosin isoform and myocardial mass in the 11- and 16-week-old rats was independent of changes in systolic blood pressure. This study demonstrates that sodium plays an important role not only in modulating myocardial mass but also in changing the biochemical composition of the heart. This study also suggests that in genetic hypertension, the restriction of sodium at a very young age may fully prevent the development of hypertension and hypertrophy. However, the mechanism by which the sodium ion modulates myocardial mass and the expression of either V1 or V3 myosin genes is unknown; the question of how sodium affects the cardiac function also remains. Some evidence suggests that sympathetic outflow may play an important role, but further studies are needed to validate this.

Aging

Half-life of single-chain urokinase-type plasminogen activator (scu-PA) and two-chain urokinase-type plasminogen activator (tcu-PA) in patients with acute myocardial infarction.

The pharmacokinetics of urokinase (two-chain urokinase-type plasminogen activator, tcu-PA) and single-chain urokinase-type plasminogen activator (scu-PA) were studied in 20 patients with acute myocardial infarction (AMI). Ten consecutive patients received 2.5 million units tcu-PA by bolus injection within 5 min during the first 6 h after AMI (group I). Ten further consecutive patients received 250,000 U tcu-PA within 5 min, followed by 4.5 million U scu-PA by intravenous infusion over 40 min (group II). An enzyme immunoassay was developed for urokinase antigen determinations, and a fibrin plate assay for determinations of fibrinolytic activity was applied. Using a 3-compartment model, in group I 98% of urokinase antigen were cleared with a half-life of 60.8 min. After scu-PA, urokinase antigen was cleared with half-lives (area under the curve in parentheses) of 6.9 min (74.8%), 26.5 min (23.6%), and 329.7 min (2.2%). The half-disappearance times of fibrinolytic activity were 18 and 8 min in group I and II, respectively. A more pronounced decrease of plasminogen was observed after tcu-PA.

Half-Life

Effect of chlorophyllin on mercuric chloride-induced clastogenicity in mice.

The effect of chlorophyllin (1.5 mg/kg body weight) on the clastogenicity of mercuric chloride (HgCl2) was studied in vivo in mouse bone marrow cells. HgCl2 (3.0, 6.0 and 12.0 mg/kg body weight) administered by gavage induced chromosomal aberrations at frequencies directly proportional to the dose. Chlorophyllin was not clastogenic, and significantly reduced the mitotic index when given alone. Chlorophyllin administered simultaneously with HgCl2 significantly reduced the frequencies of chromosomal aberrations in a dose-dependent manner. When given simultaneously with the lowest HgCl2 concentration tested (3.0 mg/kg body weight), chlorophyllin provided total protection. A lower degree of protection was given by chlorophyllin administered 2 hr before HgCl2. The data demonstrate the potential of green plant components to modify the genotoxic activity of HgCl2 when administered orally.

Administration, Oral

Effect of supercoiling on the melting characteristics of heteropolynucleotides.

Considering a supercoiled DNA molecule, having equal numbers of two distinct types of base-pairs, it has been shown theoretically that even for the extreme cases of mixing of the two types of base-pairs in a supercoiled DNA, the melting temperatures as well as the melting curves do not differ significantly. This indicates that these properties are practically independent of the detailed base sequence when the molecule is a covalently closed one and may be replaced by an equivalent homopolynucleotide whose binding energy is equal to the average base-pairing energy of the original DNA. This conclusion has been further supported by comparing the theoretical results with those obtained experimentally in the cases of polyoma DNA and phi X174 DNA. Finally, the effects of supercoiling on the cooperativity of melting and a few aspects of the differential melting characteristics of a supercoiled DNA have been discussed which provide a clear physical understanding of the process.

Chemical Phenomena

Inhibition of clastogenic effects of cesium chloride in mice in vivo by chlorophyllin.

The antagonistic effect of chlorophyllin was tested in reducing the clastogenic action of cesium chloride (CsCl) in vivo on mice bone marrow cells. CsCl induced chromosomal aberration in frequencies directly proportional to the dose administered. Chlorophyllin, when given alone, was not clastogenic even at a concentration of 1.5 mg/kg body wt. of the animal. Simultaneous administration of chlorophyllin and CsCl reduced chromosomal aberrations significantly at 24 h. Exposure to the same dose of chlorophyllin 2 h before exposure to CsCl also decreased clastogenic effects but to a lesser extent. These findings are of importance in view of the uptake of radioactive Cs by green plants after nuclear fallout.

Animals

Flow cytometric analysis of cellular DNA content in paraffin wax-embedded specimens of canine mammary tumours.

Flow cytometric analysis of DNA content was performed on 72 formalin-fixed, paraffin wax-embedded samples of canine mammary tumours. DNA content was correlated with histological appearance, stage of the tumour, and survival after mastectomy. All benign tumours (14 cases) were diploid. Amongst the malignant tumours, a higher incidence of aneuploid tumours (50 per cent) was observed in cases with lymph nodal metastases in comparison with those without metastases (26 per cent). All dogs with benign tumours survived for at least two years after mastectomy and so did 26 (81 per cent) of 32 DNA diploid malignant cases without metastases. A 67 per cent (eight of 12 cases) survival rate was found in the dogs with DNA aneuploid malignant tumours without metastases, while a very low survival rate (17 per cent) was observed in the group with malignant tumours with metastases, independently of the extent of ploidy.

Animals

Intracellular calcium transients in myocardium from spontaneously hypertensive rats during the transition to heart failure.

To investigate the mechanism of impaired myocardial function after long-term pressure overload, we studied cardiac muscle mechanical contraction and intracellular calcium transients using the bioluminescent indicator aequorin. Left ventricular papillary muscle preparations were examined from three groups of rats: 1) aging spontaneously hypertensive rats (SHR) with clinical and pathological evidence suggesting heart failure (SHR-F group), 2) age-matched SHRs with no evidence of heart failure (SHR-NF group), and 3) age-matched normotensive Wistar-Kyoto rats (WKY group). Isometric force development was depressed in both SHR groups relative to the WKY group. Resting [Ca2+]i was lower in the SHR-F group, and the time to peak [Ca2+]i was prolonged in this group. The relative increases in peak [Ca2+]i with the inotropic interventions of increased [Ca2+]o and the addition of isoproterenol were similar among groups. Although inotropy increased in all groups with increased [Ca2+]o, after isoproterenol, inotropy increased only in the WKY group. Thus, in SHR myocardium, [Ca2+]i increased after isoproterenol, but inotropy failed to increase. Myosin isozymes were shifted toward the V3 isoform in both SHR groups; the V3 isoform was virtually 100% in papillary muscles from the SHR-F group. These changes may reflect events directly contributing to the development of heart failure or represent adaptive changes to chronic pressure overload and heart failure.

Aequorin

Alteration of collagen phenotypes in ischemic cardiomyopathy.

Ischemic cardiomyopathy refers to a significant impairment of left ventricular function, a condition resulting from atherosclerotic coronary artery disease. The left ventricular ejection fraction is usually 35% or less, and electron microscopy shows an increased deposition of collagen in the space between the capillaries and the myocytes. The present study shows the alteration in collagen concentration and phenotypes in ischemic cardiomyopathy, and the effect captopril treatment has on these parameters. In patients with ischemic cardiomyopathy, collagen concentration estimated from hydroxyproline increased from 7.96 +/- 1.24 mg/g to 13.9 +/- 1.30 mg/g, P less than 0.05. Ischemic cardiomyopathic patients given captopril therapy had a significantly lower collagen concentration of 10.03 +/- 1.46 mg/g, P less than 0.05. The collagen type I:III ratio decreased from 1.93 +/- 0.52 to 1.23 +/- 0.27 in patients with ischemic cardiomyopathy. Of these patients, those receiving captopril had a collagen type I:III ratio of 1.49 +/- 0.38, which did not differ significantly from the ratio of individuals with normal myocardium. There was no significant difference in type I collagen concentration in the myocardium of normal individuals, patients with ischemic cardiomyopathy, and patients with ischemic cardiomyopathy receiving captopril therapy. The type III collagen concentration increased significantly from 2.56 +/- 0.21 mg/g in normal myocardium to 6.10 +/- 0.58 mg/g in ischemic cardiomyopathic myocardium. Patients receiving captopril had a myocardial collagen type III concentration of 4.87 +/- 0.64 mg/g, which was significantly lower than that found in patients with ischemic cardiomyopathy. An increased deposition of type III collagen may be partly responsible for altering the compliance of the myocardium, resulting in dilatation of the heart and possibly leading to eventual heart failure.

Adolescent

Comparison of dihydropyridine and phenylalkylamine calcium antagonists in patients with coronary heart disease.

To evaluate possible differences between dihydropyridine and phenylalkylamine calcium antagonists in the setting of chronic stable angina, 2 placebo-controlled, double-blind, crossover trials were conducted comparing the effects of gallopamil and nifedipine on exercise tolerance and ischaemic ST depression, using standard as well as slow release formulations. In the first study, 30 patients received standard formulations of gallopamil (50mg 3 times daily) and nifedipine (20mg 3 times daily). This trial was stopped after 9 patients had been enrolled, because of severe exacerbation of angina in 3 nifedipine recipients. 21 patients then entered a second protocol in which the nifedipine dose was reduced to 10mg 3 times daily. Compared with the preceding placebo periods, time to angina onset and total exercise time were statistically significantly (p less than 0.01) prolonged by gallopamil (by 30 and 18%, respectively), and nonsignificantly prolonged by nifedipine (by 20 and 13%, respectively), after 4 weeks' treatment. Increases in heart rate and rate-pressure product at maximal comparable workloads were less with gallopamil than with nifedipine (p less than 0.01). In contrast to nifedipine, gallopamil was associated with very few side effects. The second trial comprised 24 patients who received slow release formulations of gallopamil (100mg twice daily) and nifedipine (20mg twice daily) over 2 weeks. Again, both drugs exhibited significant anti-ischaemic efficacy, as evidenced by reductions in ST depression at maximal comparable workloads and increases in exercise time compared with placebo, but the differences between the treatments were not statistically significant. Side effects were more frequent with nifedipine, but less severe than with the standard formulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

A community-based study into the possible reasons for the high incidence of cardiovascular disease in the west Highland District of Lochaber.

Cardiovascular screening of 726 males in a Fort William group practice was undertaken in an effort to determine possible causes for the high incidence of cardiovascular disease in the area. Sixty-four per cent of those sampled were born outside the area. The mean fasting plasma cholesterol level was surprisingly low at 5.4 mmol/l. Forty-three per cent of the sample were smokers and 22% had diastolic blood pressures above 90 mm Hg, 24% were clinically obese and 29% had a history of ischaemic heart disease amongst first degree relatives. Public awareness of cardiovascular risk factors was found to be low. A local health education programme could prove to be of great benefit.

Adult

Myotrophin: purification of a novel peptide from spontaneously hypertensive rat heart that influences myocardial growth.

Mechanisms involved in the development or the regression of myocardial hypertrophy cannot be fully explained as responses to blood pressure control alone. We had hypothesized that the development of hypertrophy is initiated by a signal (mechanical or humoral) to the myocardium, which in turn produces a soluble factor that triggers protein synthesis and initiates myocardial growth. Using the stimulation of protein synthesis in isolated cardiac myocytes obtained from normal rat hearts as an assay system, we have identified a soluble factor from the hypertrophied myocardium of spontaneously hypertensive rats. This factor, which has been purified to apparent homogeneity, is a protein of 12 kDa. The sequence of three internally liberated peptides containing 7-24 residues was determined. Based on the determined amino acid sequences of these peptides, this factor (designated myotrophin) appears to be a novel protein that shows no homology with any previously described growth factors. Myotrophin is present in human, dog, and rat hypertrophied hearts (28-35% stimulation of protein synthesis over control) and in small amounts in normal hearts (5-6% stimulation). Myotrophin causes two dose-dependent effects in neonatal cardiac myocytes: an increase in the surface area of the myocyte and the appearance of organized myofibrils, which become apparent within 48 h. Myotrophin may play an important role in the pathogenesis of cardiac hypertrophy as well as in the normal development of cardiac myocytes.

Amino Acid Sequence