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Biomedical subjects

R J Griffiths

Publications and source records attributed to R J Griffiths.

49 records · Page 3Linked to original sources
PubMed1985

The effect of 6-oxo-prostaglandin E1 on human platelet aggregation in whole blood in-vitro.

The effect of PGI2, 6-oxo-PGE1 and PGE1 on ADP-induced human platelet aggregation has been assessed in whole blood and in blood centrifuged to prepare platelet-rich plasma (PRP). PGI2 was the most potent anti-aggregatory agent in both media. The concentration of PGI2 required to produce 50% inhibition of platelet aggregation was approximately 0.3 ng ml-1 in each case. In contrast both E series prostaglandins exhibited significantly greater (400-700%) anti-aggregatory activity when tested in whole blood than when tested in PRP. Since whole blood presumably represents a truer reflection of platelet reactivity in-vivo, we believe that the potency of 6-oxo-PGE1 (and PGE1) as inhibitors of platelet aggregation has been underestimated in previous experiments using PRP. In human whole blood 6-oxo-PGE1 has approximately 40% the anti-aggregatory activity of PGI2. The reasons for the increased anti-aggregatory potency of E series prostaglandins in whole blood is not known. We suggest that 6-oxo-PGE1 and PGE1 (but not PGI2) may prevent the release of pro-aggregatory ADP from red blood cells thereby enhancing their ability to inhibit platelet aggregation.

Adult↗
PubMed1984

Enzymatic inactivation of 6-keto-prostaglandin E1 in vitro: comparison with prostaglandin E1.

The inactivation of 6-keto PGE1, a biologically active and stable metabolite of prostacyclin, was studied in 100,000 g cytosolic supernatants by bioassay on rat stomach strip (contraction) and human platelets (inhibition of ADP-induced aggregation). PGE1 was used as a reference compound. Both PGs were inactivated in supernatants from colon, kidney and liver of rat, rabbit and guinea-pig. Inactivation was time- and NAD+ -dependent and was generally greater for PGE1 than 6-keto-PGE1. The enzyme responsible for 6-keto-PGE1 inactivation in cytosolic supernatants is distinct from prostaglandin 15-hydroxydehydrogenase and 9-keto reductase, is not inhibitable by sulphasalazine-like drugs and its activity is recoverable after precipitation by ammonium sulphate. We conclude that 6-keto-PGE1 can be inactivated by enzymes with wide tissue distribution, but further studies are needed for identification of these novel enzymes and the products formed as well as to assess their significance in the intact animal.

Alprostadil↗
PubMed1983

The effect of some flavone drugs on the conversion of prostacyclin to 6-oxoprostaglandin E1.

Flavonoid drugs (rutin, naringenin and quercetin) were compared with indomethacin and sulphasalazine as inhibitors of rat and rabbit renal 9-hydroxyprostaglandin dehydrogenase, prostaglandin synthesis (bovine seminal vesicle microsomes) and inactivation (rabbit colon 100,000 g supernatant), vascular PGI2 formation (rat aortic rings) and for effects on platelet aggregation and on the isolated rat stomach strip. Rutin and naringenin potently inhibited rabbit renal conversion of PGI2 and PGF2 alpha to 6-oxoPGE1 and PGE2, respectively, but had no effect on rat renal 9-hydroxyprostaglandin dehydrogenase activity, prostaglandin breakdown, vascular PGI2 synthesis, platelet aggregation or the anti-aggregatory effect of PGI2 and 6-oxoPGE1. High concentrations (100 microM) of both drugs inhibited the spasmogenic effect of PGI2 on the rat stomach strip. Naringenin and quercetin (1 mM) inhibited whilst rutin (1 mM) stimulated microsomal prostaglandin synthesis. These results suggest that rutin and naringenin may be useful experimental tools to study the biological roles of 6-oxoPGE1.

Alprostadil↗
PubMed1983

Catabolism of 6 keto PGE1: biological activation by the rat kidney in vitro.

An increase in anti-aggregatory but not spasmogenic activity was observed when 6 keto prostaglandin E1 (but not PGE1) was incubated at 37 degrees C with rat kidney 100 000 X g supernatant. No such biological activation was observed in boiled rat kidney supernatant. After high-pressure liquid chromatography two absorbance peaks with anti-aggregatory activity were detected. One peak had a retention time identical to authentic 6 keto prostaglandin E1 whilst the second peak did not coincide with known anti-aggregatory prostaglandins.

Alprostadil↗
PubMed1983

Conversion of prostacyclin to 6 oxo prostaglandin E1 by rat, rabbit, guinea-pig and human platelets.

The enzymatic catabolism of prostacyclin (PGI2) to 6 oxo prostaglandin E1 (6 oxo PGE1) was studied in platelet-rich and platelet-poor-plasma of rat, rabbit, guinea-pig and man. Rat, rabbit and human platelets convert PGI2 to a product with biological activity and thin layer chromatographic mobility identical to that of authentic 6 oxo PGE1. Platelets from these species also converted 9 beta-[3H]-PGI2 to non-radioactive 6 oxo PGE1 as shown by the progressive loss of extracted radioactivity following incubation. Formation of 6 oxo PGE1 was inhibited by the flavonoid drugs, rutin and naringenin. Guinea-pig platelets did not convert PGI2 to 6 oxo PGE1. Rat, rabbit and guinea-pig platelets do not spontaneously release a 6 oxo PGE1-like substance when incubated at 37 degrees C in the absence of added PGI2 or aggregating agents. The relevance of these findings to the possible physiological and pathophysiological roles of 6 oxo PGE1 in the regulation of platelet function is discussed.

Adult↗
PubMed1983

Formation of 6-keto prostaglandin E1 in mammalian kidneys.

1 The metabolism of prostacyclin (PGI2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was studied in cell-free homogenates of rat, rabbit and guinea-pig kidney. 2 Rabbit kidney converted both PGI2 and 6-keto PGF1 alpha to a stable metabolite with chromatographic and biological activity identical to that of authentic 6-keto PGE1. Activity was found in the kidney cortex but not medulla, was inhibited by NAD+ or NADP+ (5 mM) and showed an optimum temperature requirement of 37 degrees C. 3 Guinea-pig kidney converted PGI2 but not 6-keto PGF1 alpha to a labile, biologically active metabolite which was not 6-keto pge1. 4 No conversion of prostacyclin or 6-keto PGF1 alpha to biologically active metabolites occurred in cell-free homogenates of rat kidney, liver and colon or guinea-pig liver and colon. 5 6-keto PGE1 rapidly lost spasmogenic activity on the rat stomach strip following incubation with rabbit or guinea-pig kidney supernatant in the absence of added cofactors. No loss of activity occurred on incubation with rat kidney. 6 Rutin (50 microM) potently inhibited synthesis of 6-keto PGE1 from added PGI2 by rabbit kidney cortex. This reaction was potentiated by a similar concentration of sulphasalazine, carbenoxolone, imidazole, papaverine or indomethacin. 7 The relevance of these findings for the possible physiological and pathological roles of 6-keto PGE1 in the kidney is discussed.

Alprostadil↗
PubMed1983

Effect of aspirin treatment on the hypotensive effect of clonidine in rats.

Rats were pretreated with aspirin (5 mg/kg i.p. 5 days) or saline, anaesthetized with pentobarbitone, and blood pressure recorded from the carotid artery. Clonidine (30 micrograms/kg) was injected intravenously via a cannula inserted into the femoral vein. Aspirin pretreatment significantly reduced the hypotensive effect of clonidine. Spleen, heart brain, kidneys and lung were removed from the animals 60 min after clonidine administration. Prostaglandin biosynthesis from endogenous substrate was determined by homogenizing tissues (1:4 w/v) in either Tris buffer (pH 7.4) or in 1 M formic acid: ethanol (1:V/v). Prostaglandins were extracted into ethyl acetate and bioassayed on the rat stomach strip. Clonidine administration significantly increased the prostaglandin formation in heart, brain and kidney. Animals pretreated with aspirin showed a reduction in the clonidine-induced increase in prostaglandin synthesis in heart, brain and spleen. The results suggest that the hypotensive effect of clonidine in anaesthetized rats may in part be secondary to stimulation of central prostaglandin biosynthesis.

Animals↗
PubMed1982

Interaction of prostaglandins and clonidine in the rat vas deferens.

Stimulation of presynaptic alpha 2-adrenoceptors by clonidine may lead to local synthesis of prostaglandins which contribute to the inhibition of noradrenaline release observed with this drug. The present investigation was undertaken to determine the role of prostaglandins in the effect of clonidine and xylazine on the rat vas deferens. Both drugs inhibited the twitch response to field stimulation in this preparation. Inhibition was reversed by yohimbine. This effect of clonidine (but not xylazine) was reduced by preincubating vasa deferentia in Krebs containing indomethacin for 1h. Clonidine (but not xylazine) stimulated the synthesis of prostaglandin-like activity in pieces of intact vas deferens incubated in Krebs containing arachidonic acid. Such stimulation was prevented by inclusion of yohimbine (but not prazosin) in the incubation medium. Clonidine did not stimulate prostaglandin synthesis in a cell-free preparation of sheep seminal vesicle microsomes incubated with arachidonic acid or inhibit PGE2 catabolism by purified swine lung 15-PGDH. We conclude that clonidine (but not xylazine) stimulates prostaglandin synthesis possibly by activating phospholipase activity and releasing arachidonic acid from membrane phospholipids. This effect on prostaglandin production is secondary to activation of alpha 2-adrenoceptors.

Animals↗
PubMed1982

Pre-synaptic and post-synaptic effects of xylazine and naphazoline on the bisected rat vas deferens.

The effect of the selective alpha 2-adrenoceptor agonists, naphazoline and xylazine, was studied on the field stimulated bisected rat vas deferens. Xylazine inhibited the twitch response to field stimulation in both the prostatic (ID50 = 0.10 microM) and epididymal (ID50 = 0.08 microM) halves of the rat vas deferens. This effect was antagonized by yohimbine (0.01-0.10 microM). Naphazoline also inhibited the response to field stimulation in the prostatic (ID50 = 0.12 microM) but had no such action on the epididymal half of the rat vas deferens. Indeed, low concentrations of naphazoline (threshold, 0.05 microM) contracted the epididymal vas deferens preparation. These contractions were competitively antagonized by prazosin suggesting an action on post-synaptic alpha 1-adrenoceptors. Neither pre-synaptic nor post-synaptic actions of either drug were affected by cocaine (10 microM) or beta-oestradiol (10 microM) added to the Krebs' solution. The results provide further evidence for the existence of two types of post-synaptic alpha 1-adrenoceptors and suggest a different anatomical localization of these receptors between the two ends of the rat vas deferens.

Animals↗
PubMed1971

The effect of sepsis rates of closing and cleaning hospital wards.

Sepsis rates were studied in five hospital wards before and after closure for cleaning. Each ward was closed because of an outbreak of Staph. aureus infection caused by a cloxacillin-resistant strain. The study shows that sepsis rates, especially sepsis caused by hospital strains of Staph. aureus, were greatly reduced in the three-month period following re-opening of the ward, provided that patients infected with such organisms were not readmitted to or allowed to remain in the ward.

Anti-Bacterial Agents↗