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Biomedical subjects

N A Shaikh

Publications and source records attributed to N A Shaikh.

36 records · Page 2Linked to original sources
PubMed1989

Adriamycin action on human breast cancer cells: enhancement by medroxyprogesterone acetate.

Exposure of cultured human breast cancer cells (MCF-7) to medroxyprogesterone acetate (MPA) prior to treatment with adriamycin (ADR) enhanced the effect of the cytotoxic drug on cell yield after further growth of viable cells. Pretreatment with oestradiol (E2) produced similar synergism, but no such effect was observed using dexamethasone. Exposure to ADR before MPA led to an additive effect, but not to synergism. When cells resistant to the growth-inhibitory action of MPA were examined, progestogen/drug synergism could still be demonstrated. We conclude that the effects of ADR, like those of methotrexate and vincristine, can be enhanced by pre-treatment with MPA and that further clinical trials of such a regimen are needed.

Antineoplastic Agents↗
PubMed1989

The effects of sequential treatment with ethynyloestradiol and medroxyprogesterone acetate on oestrogen and progestogen receptors in breast cancer.

As part of a clinical study designed to modulate oestrogen and progestogen receptor (ER and PR) binding site concentrations prior to chemotherapy ER and PR levels have been estimated immediately before treatment, after ethynyloestradiol (EE, 10 micrograms/day, 1 week) and after medroxyprogesterone acetate (MPA, 500 mg/day i.m., 2 weeks) in tumour tissue from 14 women with advanced breast cancer. There was no consistent change after EE treatment. MPA tended to decrease ER and PR levels, though some increases were also seen. Responses (10 complete and 3 partial remissions) to sequential cyclical hormono-chemotherapy were not related to ER or PR levels prior to chemotherapy.

Aged↗
PubMed1989

Relationship between epidermal growth factor and dehydroepiandrosterone and its sulphate in breast cyst fluid.

Gross cystic breast disease is a common condition. Women with apocrine breast cysts may be at higher risk of breast cancer than women with cysts which are lined by flattened epithelium. Apocrine cysts have been shown to be associated with higher intracystic levels of dehydroepiandrosterone sulphate and intracystic sodium to potassium ratios of less than 3. In this study we measured the concentrations of epidermal growth factor, dehydroepiandrosterone and its sulphate in breast cyst fluid. The concentrations of all three analytes were significantly higher in cysts with intracystic Na+/K+ ratios of less than 3 than in cysts with electrolyte ratios of greater than or equal to 3 (P less than 0.001). The higher levels of EGF in cysts with low intracystic electrolyte ratios may provide an explanation of why women with apocrine cysts may be at greater risk of breast cancer. Positive correlations were obtained between concentrations of EGF and DHAS and between EGF and DHA, compatible with the view that intracystic EGF levels may be androgen-modulated. A positive correlation was also obtained between DHA and DHAS concentrations which supports the view that DHA in cyst fluid may be derived from the metabolism of DHAS in the breast cyst wall.

Dehydroepiandrosterone↗
PubMed1988

Antiarrhythmic potential of chloroquine: new use for an old drug.

Amiodarone and chlorpromazine are phospholipase inhibitors which produce cytoplasmic inclusion bodies and have important electrophysiologic properties. Chloroquine also inhibits phospholipase activity, resulting in similar inclusion bodies, but electrophysiologic information about this drug is lacking. In this study, the cellular electrophysiologic effects of two doses of chloroquine were examined in sheep Purkinje fibres and ventricular muscle cells. Both concentrations produced a significant reduction in maximum velocity of upstroke of the action potential and prolongation of the action potential duration and refractory period in Purkinje fibres. These effects were observed in the absence of significant changes in threshold of stimulation or action potential amplitude and were partially reversible following washout of the lower drug concentration. In addition to these experimental data, clinical evidence of antiarrhythmic action was determined by administering 500 mg chloroquine daily over nine weeks to six subjects with frequent asymptomatic ventricular premature complexes. In four patients there was a reduction in ventricular ectopy, which recurred when the drug was discontinued, while a fifth patient reverted to sinus rhythm from atrial fibrillation previously resistant to other antiarrhythmic medication. Thus, chloroquine has important electrophysiologic properties. The underlying mechanism of this action remains unproven at the present time.

Action Potentials↗
PubMed1988

Postirradiation angiosarcoma of the breast--a case report.

Angiosarcoma of the breast is an uncommon neoplasm but coincident angiosarcoma with infiltrating ductal carcinoma is not yet reported. This paper describes a case of angiosarcoma which developed after 4 years of a wide excision and adjuvant radiotherapy for a ductal carcinoma of the breast. Due to latent period of only 4 years radiotherapy cannot be blamed as an aetiological factor in this case but neither is it possible to exclude it as a causative factor.

Aged↗
PubMed1987

Amiodarone--an inhibitor of phospholipase activity: a comparative study of the inhibitory effects of amiodarone, chloroquine and chlorpromazine.

Amiodarone, an antiarrhythmic drug, like chloroquine and chlorpromazine, is a tertiary amine with amphiphilic properties. Chloroquine and chlorpromazine are known inhibitors of phospholipases. All three drugs produce characteristic microcorneal deposits consistent with lysosomal accumulations of phospholipid. Similar lysosomal bodies were found in leukocytes of 15 patients on chronic amiodarone treatment as well as 3 patients each on chloroquine and chlorpromazine, suggestive of widespread systemic inhibition of lysosomal phospholipases. These lysosomal inclusions were similar in morphology, irrespective of the drug given, and were of four types: multilamellar, amorphous dense, amorphous light, or a combination of 2 or more of the preceding types. There was no simple relationship between the number of inclusion bodies per cell and the cumulative dose of amiodarone (r = 0.02) or amiodarone serum levels (r = 0.11). An in vitro assay was used to compare the effects of the three drugs on Ca2+-dependent phospholipase A2 and C activities. Phospholipase A2 activity was inhibited in a dose-dependent fashion (1-8 mg/assay) by all three drugs in the order: chlorpromazine greater than amiodarone greater than chloroquine. The inhibitory effect on phospholipase C was more pronounced with all three drugs, producing almost total inhibition at 8 mg/assay. In a Ca2+-independent lysosomal phospholipase A system, amiodarone had a greater effect, producing 85% inhibition at 1.2 mg/assay. These observations suggest that amiodarone, like other cationic amphiphiles, induces a generalized phospholipidosis by inhibiting phospholipid catabolism. Its therapeutic and toxic effects may be due to its ability to modulate both Ca2+-dependent membrane phospholipases and Ca2+-independent acid phospholipases.

Amiodarone↗
PubMed1987

Effects of chronic amiodarone treatment on cat myocardial phospholipid content and on in vitro phospholipid catabolism.

Amiodarone is used extensively for the chronic treatment of life-threatening arrhythmias caused by ischemic heart disease. However, chronic therapy with this agent results in phospholipidosis in various tissues and it has been suggested that the inhibition of lysosomal phospholipase A by this drug contributes to this abnormality. Exogenous amiodarone has been shown to inhibit purified rat liver lysosomal phospholipase A1, as well as acid phospholipase activities of alveolar macrophage homogenates and those of snake venom phospholipase A2 and bacterial phospholipase C. The effects of drug treatment on heart have not been explored. The results described here demonstrate that amiodarone also significantly increases (37%, p less than 0.001) phospholipid content in cat hearts. This increase is proportionately distributed to all major phospholipid classes, with the exception of sphingomyelin which appears to increase more than the others. In addition, the data also show that following amiodarone treatment, the endogenous drug levels in the heart were sufficient to reduce in vitro losses of membrane phospholipid at 37 degrees C by inhibiting a variety of endogenous phospholipases at physiological (7.4), ischemic (6.2) and acidic (5.0) pH values. This protection is more pronounced at acidic pH values than at physiological pH. Endogenous amiodarone also affects myocardial phospholipase activities towards exogenous phosphatidylcholine and again the extent of inhibition is more at acidic pH. These results suggest that amiodarone induces phospholipidosis in the heart by inhibiting phospholipid catabolism and that its antiarrhythmic properties may reside in its ability to modulate alkaline, neutral and acid phospholipase activities in ischemia. To what extent amiodarone metabolites (desethylamiodarone and bis-desethylamiodarone) are involved in these actions remains to be determined.

Administration, Oral↗
PubMed1984

Ultrastructural changes of ischemic injury due to coronary artery occlusion in the porcine heart.

Using the ultrastructural criteria established by Schaper et al. 1979 [27] for distinguishing between different degrees of ischemic change in dog myocardium, slight ischemic changes are observed in the pig suboendocardium as early as 1 min after occlusion of the LAD artery. Moderate change throughout the thickness of the myocardium is seen after 6 to 12 min of ischemia and continues to be found up until 20 min after commencement of the ischemic period. 20 to 30 min ischemia produces severe ischemic damage and more than 30 min leads to irreversible damage. The changes are uniform at all stages of ischemia and there is no evidence of a transmural gradient of ultrastructural damage. Of particular interest in the early part of the ischemic period is the observation of ultrastructural changes in the subendocardial specialized conducting tissue. In these specialized cells, although morphological features consistent with slight and moderate ischemia are found as early as 1 to 2 min after occlusion, spontaneous recovery occurs and is complete by 15 min. This biphasic time course parallels the electro-physiological changes known to occur in ischemic Purkinje fibres.

Animals↗
PubMed1983

Further evidence for enhanced phospholipid synthesis by rat jejunal villus cells during fat absorption.

The effect of fat absorption on the phospholipid turnover of rat intestinal mucosa was determined in animals receiving single fatty meals by stomach tube or multiple meals in the form of corn-oil-soaked laboratory chow diet. The specific activity and relative specific activity of the total phospholipids and of individual phospholipid classes were measured in the isolated jejunal villus cells of fasting and fat-fed animals following an injection of radioactive inorganic phosphate 0.5-31 h prior to sacrifice, which was scheduled to coincide with the peak of fat absorption (2.5-3 h after the last meal). It was shown that the relative specific activity of the fat-absorbing cells increased by about 33% when the samples were taken 0.5 h after intravenous injection of radioactive phosphate. Samples taken 11 and 31 h after the introduction of the radioactive phosphate showed about 16% decrease in the relative specific activity of the phospholipids of the fat-absorbing cells when compared with the fasting controls. These changes in the relative specific activity of the total phospholipids included all phospholipid classes and corresponded to the recently described expansion of the cellular phospholipid pool owing partly to increased de novo synthesis of the membrane phospholipids. The present results are consistent with the known biochemical and physiological changes taking place in the mucosal cells during fat absorption and transport and find support in various less direct biochemical and morphometric measurements.

Animals↗
PubMed1982

Expansion of phospholipid pool size of rat intestinal villus cells during fat absorption.

The effect of fat absorption upon the phospholipid pool size of the intestinal mucosal cells was determined in rats receiving fatty emulsions as a bolus by stomach tube or as multiple meals in the form of fat-laden laboratory chow. The phospholipid content of the mucosal scrapings and of the isolated villus cells was determined 3 to 34 h after the meals and was compared with the phospholipid content of cells from similar animals receiving water alone or 10% sucrose in water. It was shown that continuously fed animals averaged 5-10% and single meal fed animals up to 40% higher phospholipid content in their mucosal cells than the corresponding controls, when compared per milligram cell protein. The expansion of the phospholipid pool involved all phospholipid classes and correlated well with the phospholipid composition of prechylomicrons and of microsomal membranes, which undergo a significant proliferation during fat absorption. The apparent lower expansion of the phospholipid pool in the continuously fed animals correlated with the lower triacylglycerol content of the lumen and of the cells at these times.

Animals↗
PubMed1981

Time course of changes in porcine myocardial phospholipid levels during ischemia. A reassessment of the lysolipid hypothesis.

This study was performed to determine the early and delayed metabolic effects of myocardial ischemia on the major membrane phospholipids and to reassess the potential role of lysophospholipids in the genesis of malignant dysrhythmias induced by ischemia. Samples taken from in situ hearts before ant at various intervals up to 40 minutes after abrupt ligation of LAD were extracted by the classical Folch technique with modifications to avoid artifactual lysophospholipid production and losses. Following thin layer chromatography of lipid extracts, phospholipid fractions were quantified by phosphorus estimation and lysophospholipids by a more sensitive method employing gas liquid chromatography. The total phospholipid content with the exception of lysophospholipids remained essentially constant throughout the early phases of acute ischemia, but fell by 6 and 14% after 8 and 24 ours, respectively. At 8 minutes, lysophospholipid levels n ischemic myocardium were significantly increased by 60% compared to pre-occlusion controls in the ischemic zone and by 25% in post-occlusion controls. They changed little thereafter. The molecular species of lysophospholipids remained unchanged throughout the period of ischemia studied. The mole fraction of other phospholipids as well as their fatty acyl and aldehyde profiles also were unchanged. Despite significant elevations in lysophospholipids levels, their absolute quantities were very small (0.6% of total phospholipid P) and 15-fold smaller than that reported in vitro to simulate electrophysiological manifestation of ischemia. However, such small amounts in vivo, if produced in the microenvironment of certain membrane-bound enzymes along with acidosis, hypoxia, and fatty acids, could be potentially deleterious to cell functions.

Animals↗
PubMed1980

Comparative determination of plasma phospholipids by automated gas--liquid chromatographic and manual colorimetric phosphorus methods.

Plasma samples obtained during a prevalence study of hyperlipemia in a free-living urban population were analyzed for phosphatidylcholine, sphingomyelin and lysophosphatidylcholine content by automated high-temperature gas--liquid chromatographic (GLC) and manual colorimetric phosphorus (thin-layer chromatographic, TLC) methods. The GLC estimates were obtained from a quantitative analysis of the diacylglycerol, ceramide and monoacylglycerol moieties released from the parent phospholipids by digestion with phospholipase C, while the TLC estimates were derived by manual colorimetric phosphorus analyses of the individual phospholipid classes resolved by TLC. On samples analyzed over a two-year period the methods gave excellent correlation for the total phospholipids (r = 0.98), phosphatidylcholine (r = 0.98) and sphingomyelin (r = 0.90), but resulted in a poor agreement for lysophosphatidylcholine (r = 0.69). Comparable results were obtained for estimates of these phospholipids in plasma very low density, low density and high density lipoproteins. The between-method coefficient of variation ranged from 3 to 5% for phosphatidylcholine and from 5 to 10% for sphingomyelin. The relative error for the estimates of lysophosphatidylcholine ranged from 10 to 25%, and was due to the inclusion in the GLC estimates of a variable proportion of plasma free monoacylglycerols. Other differences between the two methods are due to various analytical errors and biases inherent in the two techniques. The within-day, within GLC, relative error averaged 1% for phosphatidylcholine, 3% for sphingomyelin and 5% for lysophosphatidylcholine. The apparent high precision and accuracy of the GLC method recommend it as an alternative to conventional direct methods of phospholipid analyses based on TLC isolation of lipid classes and colorimetric measurements of their phosphorus content. The GLC analyses of the plasma phospholipids are particularly convenient in conjunction with GLC measurements of plasma cholesterol and triacylglycerols, where a smaller throughput of samples is not a limitation and where both total amount and relative proportion of the lipids are of interest.

Autoanalysis↗
PubMed1979

Lipid absorption and metabolism.

Metabolic processes occurring within the mucosal cell are critical in determining results of interactions between environmental agents and the alimentary tract. The absorption, metabolism, and transport of lipids affects most those agents which are lipid soluble. The understanding of the process involved in lipid absorption and transport is therefore important for both appreciation of the mechanism of uptake of these toxins and for an effective interference with it. Most of the detailed mechanisms of lipid absorption and transport have been proposed from in vitro studies with soluble cell-free systems. The present review integrates these results with recent in vivo and in vitro findings with intact animal tissues and isolated mucosal cells. While there is much general agreement occasional startling differences are also observed, which may have a bearing on the mechanism of normal fat absorption and on the understanding of the transport of the fat-soluble toxins across the mucosal villus cell.

Animals↗