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Biomedical subjects

W Paul

Publications and source records attributed to W Paul.

At least 127 records · Page 7Linked to original sources
PubMed1982

Effects of lindane treatment on drug metabolizing enzymes and liver weight of CF1 mice in which it evoked hepatomas and in non-susceptible rodents.

In CF1 mice lindane treatment led to a significant increase in liver tumor incidence whilst in Osborne-Mendel rats it was not carcinogenic. Although somewhat less clear, the test in B6C3F1 mice led to the conclusion that under the conditions of the bioassay lindane was not carcinogenic for this strain. In this study, the specific activities of some enzymes which are thought to be involved in the metabolism of lindane were studied in these different strains in order to investigate whether differences exist in the activities of these enzymes. Because the enzyme pattern may change after lindane treatment during the carcinogenicity studies, we also investigated the enzyme activities in animals treated for 3 days or 3 months with various doses of lindane. The influence of lindane treatment on the relative liver weight was also determined. B6C3F1 mice showed no increase in absolute or relative liver weight even after 3 months of treatment with the highest tolerated dose of lindane. However, in the susceptible CF1 strain lindane led to a large increase of the absolute and relative liver weight in both sexes, whilst a smaller increase was observed in Osborne-Mendel rats. Basal glutathione-S-transferase activity was higher in males than in females in all three strains, bearing no apparent relationship to susceptibility for tumor formation. However, after treatment with the highest dose of lindane a 5-6-fold induction of this enzyme activity was observed in female CF1 mice, which then together with the male CF1 mice had a higher glutathione-S-transferase activity than untreated and treated B6C3F1 mice and Osborne-Mendel rats. Whether lindane or one of its metabolites is activated by conjugation with glutathione remains to be established. After treatment of the animals with high doses of lindane detergent-treated rat liver microsomes showed a higher UDP-glucuronosyltransferase activity than mouse liver microsomes. This high activity could lead to a rapid conjugation of phenols derived from lindane. The most striking difference observed in this study was the fact that together with the larger increase in absolute and relative liver weight, untreated and treated CF1 mice showed higher monooxygenase activity and, after treatment with lindane, lower epoxide hydrolase activity than rats. Whether the high monooxygenase and rather low epoxide hydrolase activity will lead to an accumulation of reactive epoxides derived from lindane remains to be clarified.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1982

Clomiphene and dexamethasone in women unresponsive to clomiphene alone.

Twelve oligomenorrhic women with polycystic ovary syndrome (PCO) in whom clomiphene (250 mg daily for 5 days) and 10,000 IU human chorionic gonadotropin had failed to induce ovulation were treated with clomiphene and dexamethasone. Eight of the 12 women underwent complete hormonal assessment during treatment. Six of the 12 ovulated and 1 conceived. Serum total and unbound estradiol and testosterone (T), serum dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding-globulin binding capacity (SHBG-BC), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were measured during clomiphene and dexamethasone therapy. SHBG-BC increased in response to clomiphene whether or not ovulation occurred. After treatment with clomiphene and dexamethasone there was a significant decrease in serum T, unbound T, and DHEA-S 2 weeks after dexamethasone administration, but there were no change in LH, FSH, or PRL. In patients who ovulated after clomiphene and dexamethasone, T and unbound T increased again after clomiphene was begun despite the continuation of dexamethasone. The women who ovulated after clomiphene and dexamethasone treatment had significantly higher pretreatment levels of DHEA-S than those who did not ovulate. Clomiphene and dexamethasone treatment may be beneficial to women who have elevated levels of DHEAS and who fail to ovulate with maximum doses of clomiphene.

Anovulation↗
PubMed1981

Leucotrienes, SRS-A and the vascular manifestations of PCA.

In order to study possible mediators of the vascular manifestations of passive cutaneous anaphylaxis (PCA), several arachidonic acid metabolites were injected into guinea-pig skin. SRS-A, LTB4, LTC and LTD increased vascular permeability, responses to LTs being enhanced by PGE2. Mepyramine inhibited responses to histamine, but not those to SRS-A and LTs; the latter were inhibited by the SRS-A antagonist FPL-55712. Both mepyramine and FPL-55712 exert limited inhibitory effects on vascular permeability during PCA. Leukotrienes may contribute towards vascular permeability during PCA.

Animals↗
PubMed1981

Vascular volumes in isolated perfused guinea pig placenta.

Maternal and fetal vascular volumes were determined in 13 isolated artificially perfused guinea pig placentas by measuring mean transit times of an intravascular indicator (Evan's blue dye) at constant flow rates. When both maternal and fetal flow rates were 3.1 ml/min, the average maternal volume of the placenta was 1.85 +/- 0.54 (SD) ml, and the mean fetal volume was 0.92 +/- 0.2 (SD) ml. If calculated maternal volumes were corrected for the myometrial vascular volume and for the interlobium volume, the remaining volume attributable largely to the labyrinth averaged approximately 1.2 ml. When flow rates were changed on the fetal or the maternal side between 0 and 6.2 ml/min, vascular volumes also changed. For example, volumes increased directly with flow rates on that side of the placenta in which the flow change was introduced; in most cases, it decreased on the opposite side where the flow rates had not been altered. This intraplacental volume shift may be regarded as the basic event for the sluice flow phenomenon in placentas.

Animals↗
PubMed1980

Actions of locally administered adrenoceptor agonists on increased plasma protein extravasation and blood flow in guinea-pig skin.

1 Bradykinin-induced increased plasma protein extravasation (IPPE) and blood flow have been assessed in guinea-pig skin by isotopic methods. 2 alpha-Adrenoceptor agonists inhibited IPPE and reduced cutaneous blood flow. The potency of alpha-agonists as inhibitors of IPPE correlated with their vasoconstrictor effects. The actions of noradrenaline on both IPPE and blood flow were blocked by phentolamine but not by propranolol. 4 beta-Adrenoceptor agonists inhibited IPPE at doses which either increased or caused little change in cutaneous blood flow. Isoprenaline inhibition of IPPE was reduced by propranolol but was unaffected by phentolamine. 5 The inhibitory action of alpha-agonists on IPPE can be explained by a reduction in blood flow to the affected site. Beta agonist inhibition is not due to effects on blood flow but is probably caused by a reduction in permeability of the microvessels.

Adrenergic alpha-Agonists↗
PubMed1978

Anti-inflammatory drug actions on allergic responses in guinea-pig skin.

Five non-steroidal anti-inflammatory drugs (indomethacin, naproxen, meclofenamic acid, feprazone and phenylbutazone: NSAIDs) and three glucocorticosteroids (dexamethasone, hydrocortisone and prednisolone) have been tested as local inhibitors of increased vascular permeability in guinea-pig skin. Lesions were induced by histamine or by antigen to evoke type I (passive cutaneous anaphylaxis), type III (reverse passive Arthus) and type IV (delayed hypersensitivity) allergic reactions. NSAIDs and glucocorticosteroids caused either weak, inconsistent inhibition or slight, high-dose inhibition of the response to histamine. None of the drugs tested showed significant inhibition of the type IV response. The NSAIDs caused dose-related inhibition of both type I and type III responses whereas glucocorticosteroids were ineffective. Maximum inhibition with the NSAIDs was never greater than 50--60% Feprazone, meclofenamic acid and indomethacin were the most potent inhibitors of histamine, PCA and Arthus responses respectively. The possible significance of the effects of these anti-inflammatory agents on vascular permeability is discussed.

Animals↗
PubMed1978

Prostaglandin production in arthritis.

Inflammatory cell populations from synovial effusions or synovial villi in rheumatoid arthritis have been cultured in vitro. Prostaglandin productive capacity, measured by radioimmunoassay, showed the polymorphonuclear leucocyte rich populations from synovial effusions to be poor sources of PGE production whereas the synovial fragments produced substantial amounts of PGE activity. It is suggested that the macrophage is the major source of local prostaglandin formation both in gout and rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1977

Circulating inhibitor of sodium-potassium-activated adenosine triphosphatase after expansion of extracellular fluid volume in rats.

1. Serum was collected from normal rats and from rats volume-expanded with isotonic sodium chloride solution. 2. The serum was fractionated by gel filtration on Sephadex G-25 and each fraction was tested for inhibitory activity against sodium-potassium-activated adenosine triphosphatase prepared from rat kidney homogenate. 3. A single low-molecular-weight fraction, eluting after the salts and after exogenously added lysine-vasopressin, had significantly greater enzyme inhibitory activity when obtained from serum of volume-expanded animals than from control serum. 4. As this fraction has been shown in previous independent studies to contain a natriuretic factor, it may be concluded that one property of this factor is the ability to inhibit sodium-potassium-activated adenosine triphosphatase.

Adenosine Triphosphatases↗
PubMed1976

[In vitro studies on the effect of alpha-chymotrypsin on hemostasis].

Postoperative bleeding was observed in 2 patients for whom alpha-chymotrypsin had been prescribed to prevent haematoma or oedema formation. In vitro experiments with citrated blood added with alpha-chymotrypsin evidenced (thrombelastogram, hirudin tolerance test, euglobulin-lysis time) an action on haemostasis. As compared to blanks, the application of an alpha-chymotrypsin dose which was 100-fold higher than those currently used in therapy resulted in a significant shortening of the r-time (thrombelastogram), delayed blood clotting (hirudin tolerance test) and a shortening of the euglobulin-lysis time. In vivo experiments are needed for further elucidation.

Chymotrypsin↗
PubMed1975

A simple dichromatic densitometer for repeated measurements of cardiac output in small animals.

The construction of a simple device for continuous monitoring and recording of plasma indocyanine green concentration in small animals is described. The apparatus is designed to hold a vascular bed such as the ear or the omentum and to transilluminate it with white light from a fiber optic bundle. The transmitted light is divided by a dichroic mirror. Appropriate filters select a narrow band of frequencies from each segment. There are two photovoltaic cells, one sensitive to the dye and the other insensitive to it. Both are approximately equally reactive to changes in transilluminence caused by changes in blood content or hematocrit and are relatively insensitive to changes in oxygen saturation of the transilluminated blood. Reproducible estimates of cardiac output have been obtained with the injection of 300 mug indocyanine green in a volume of 20 mul with the densitometer applied to the small intestine or to the ear of the animal. The device responds linearly to increasing plasma indocyanine green concentrations and can be calibrated with less than 0.1 ml of blood.

Animals↗