Cyclooxygenase and 5-lipoxygenase inhibitory activity of 2,6 di-t-butylphenols linked by a sulfur atom to 1,3,4-thiadiazoles and 1,3,4-oxadiazoles

The preparation of a series of 1,3,4-thiadiazoles and 1,3,4-oxadizoles linked by a thioether to 2,6-di-t-butylphenol and the inhibition of cyclooxygenase (CO) and 5-lipoxygenase (5-LO) by these compounds is dicussed.     

A carbon-13 nuclear magnetic resonance investigation of the metabolic fluxes associated withy glucose metabolism in human erythrocytes

We have used [2-¹³C]d-glucose and carbon-13 nuclear magnetic resonance (NMR) spectroscopy to investigate metabolic fluxes through the major pathways of glucose metabolism in intact human erythrocytes and to determine the interactions among these pathways under conditions that perturb metabolism. Using the method described, we have been able to measure fluxes through the pentose phosphate pathway, phosphofructokinase, the 2,3-diphosphoglycerate bypass, and phosphoglycerate kinase, as well as glucose uptake, concurrently and in a single experiment. We have measured these fluxes in normal human erythrocytes under the following conditions: (1) fully oxygenated; (2) treated with methylene blue; and (3) deoxygenated. This method makes it possible to monitor various metabolic effects of stresses in normal and pathological states. Not only has ¹³C-NMR spectroscopy proved to be a useful method for measuring in vivo flux through the pentose phosphate pathway, but it has also provided additional information about the cycling of metabolites through the non-oxidative portion of the pentose phosphate pathway. Our evidence from experiments with [1-¹³C]-, [2-¹³C]-, and [3-¹³C]d-glucoses indicates that there is an observable reverse flux of fructose 6-phosphate through the reactions catalyzed by transketolase and transaldolase, even in the presence of a net flux through the pentose phosphate pathway.     

Vasoconstriction in active skeletal muscles: a potential role for P2X purinergic receptors?

There is evidence that ATP acts as a neurotransmitter in vascular smooth muscle and is coreleased with norepinephrine from sympathetic nerves. We hypothesized that P2X-receptor stimulation with the selective P2X-receptor agonist alpha,beta-methylene ATP would produce vasoconstriction in resting and exercising skeletal muscle. Six mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. The selective P2X agonist alpha,beta-methylene ATP was infused as a bolus into the femoral artery catheter at rest and during mild, moderate, and heavy exercise. Intra-arterial infusions of alpha,beta-methylene ATP elicited reductions in vascular conductance of 54 +/- 5, 49 +/- 8, 39 +/- 8, and 30 +/- 6% at rest, 3 miles/h, 6 miles/h, and 6 miles/h at a 10% grade, respectively. The agonist infusions did not affect blood flow in the contralateral iliac artery. To examine whether nitric oxide is responsible for the attenuated vasoconstrictor response to P2X stimulation, the infusions were repeated in the presence of NG-nitro-l-arginine methyl ester. After nitric oxide synthase blockade, intra-arterial infusions of alpha,beta-methylene ATP elicited reductions in vascular conductance of 56 +/- 7, 61 +/- 8, 52 +/- 9, and 40 +/- 7% at rest, 3 miles/h, 6 miles/h, and 6 miles/h at a 10% grade, respectively. P2X-receptor responsiveness was attenuated during exercise compared with rest. Blockade of nitric oxide production did not affect the attenuation of P2X-receptor responsiveness during exercise. These data support the hypothesis that P2X purinergic receptors can produce vasoconstriction in exercising skeletal muscle.     

Does suppressing luteinising hormone secretion reduce the miscarriage rate? Results of a randomised controlled trial.

OBJECTIVE--To determine whether prepregnancy pituitary suppression of luteinising hormone secretion with a luteinising hormone releasing hormone analogue improves the outcome of pregnancy in ovulatory women with a history of recurrent miscarriage, polycystic ovaries, and hypersecretion of luteinising hormone. DESIGN--Randomised controlled trial. SETTING--Specialist recurrent miscarriage clinic. SUBJECTS--106 women with a history of three or more consecutive first trimester miscarriages, polycystic ovaries, and hypersecretion of luteinising hormone. INTERVENTIONS--Women were randomised before conception to receive pituitary suppression with a luteinising hormone releasing hormone analogue followed by low dose ovulation induction and luteal phase progesterone (group 1) or were allowed to ovulate spontaneously and then given luteal phase progesterone alone or luteal phase placebo alone (group 2). No drugs were prescribed in pregnancy. MAIN OUTCOME MEASURES--Conception and live birth rates over six cycles. RESULTS--Conception rates in the pituitary suppression and luteal phase support groups were 80% (40/50 women) and 82% (46/56) respectively (NS). Live birth rates were 65% (26/40) and 76% (35/46) respectively (NS). In the luteal phase support group there was no difference in the outcome of pregnancy between women given progesterone and those given placebo pessaries. Live birth rates from an intention to treat analysis were 52% (26/50 pregnancies) in the group given pituitary suppression and 63% (35/56) in the controls (NS). CONCLUSIONS--Prepregnancy suppression of high luteinising hormone concentrations in ovulatory women with recurrent miscarriage and hypersecretion of luteinising hormone does not improve the outcome of pregnancy. The outcome of pregnancy without pituitary suppression is excellent.     

Esophageal PCO2 as a monitor of perfusion failure during hemorrhagic shock

Sato, Yoji, Max Harry Weil, Wanchun Tang, Shijie Sun,Jianlin Xie, Joe Bisera, and Hidehiro Hosaka. EsophagealPCO₂ as a monitor of perfusionfailure during hemorrhagic shock. J. Appl.Physiol. 82(2): 558-562, 1997.Measurement ofgastric wall PCO₂(Pg_CO2) bytonometric method has emerged as an attractive option for estimatingvisceral perfusion during circulatory shock. However, gastric acidsecretion obfuscates the tonometric measurement. We, therefore,investigated the option of measuringPCO₂ in the esophagus to minimizethese restraints. Hemorrhagic shock was induced in five Sprague-Dawleyrats, and five rats served as sham controls.Pg_CO2 wasmeasured with an ion-sensitive field effect transistor that wassurgically implanted into the gastric wall. Esophageal luminalPCO₂(Pe_CO2) wasmeasured by a second ion-sensitive field effect transistor sensor.During hemorrhagic shock, mean aortic pressure declined from 150 to 50 mmHg. Gastric blood flow decreased from 58 to 12 ml ^· min^{1 ·} 100 g¹ (21% of preshock) andesophageal blood flow from 44 to 7 ml ^· min^{1 ·} 100 g¹ (16% of preshock).Pg_CO2simultaneously increased from 47 to 116 Torr andPe_CO2 from 47 to 127 Torr. The increases inPg_CO2 werehighly correlated with increases inPe_CO2(r = 0.90). Esophageal tonometry may,therefore, serve as a practical alternative to gastric tonometry.

     

The dental awareness and needs of a Parkinson's disease population

The dental awareness and needs of a population with Parkinson's disease were assessed by means of postal questionnaires sent to members of Parkinson's disease societies of Belfast and London. A total of 228 valid replies were received representing a response rate of 31%. Results showed that dental problems were reported often, xerostomia and burning sensation being at least twice that of the general population. Satisfaction with dental care was high although it was significantly reduced in those with loose dentures and burning sensation. The results of this study support a greater participation by dentists in the planning and provision of healthcare for sufferer of Parkinson's disease.     

Mapping of transfer RNA genes on tobacco chloroplast DNA

Tobacco chloroplast tRNAs have been purified by two-dimensional polyacrylamide gel electrophoresis, identified by aminoacylation, labelled at their 3-end and hybridized to tobacco chloroplast DNA restriction fragments, in order to establish a tRNA gene map. These hybridization studies have revealed the localization of at least seven genes in each inverted repeat region, a minimum of 22 tRNA genes in the large single copy region and one tRNA gene in the small single copy region. Comparison of the tobacco chloroplast tRNA gene map to that of maize shows many similarities, but also some differences suggesting that DNA sequence rearrangements have occurred in the chloroplast genome during evolution.     

Assignment of the gene for uroporphyrinogen decarboxylase to human chromosome 1 by somatic cell hybridization and specific enzyme immunoassay

Summary A specific enzyme immunoassay of uroporphyrinogen decarboxylase was developed and applied to the detection of the human enzyme in man-rodent somatic cell hybrids. This method allowed to assign the gene for uroporphyrinogen decarboxylase to human chromosome 1.     

Erythrocyte choline concentrations and cluster headache.

Erythrocyte choline concentrations were measured in patients with cluster headache and age related control subjects. Concentrations were significantly reduced in the patients with headache both during a cluster period and between clusters, being 58% and 55% of the control value, respectively. After two weeks'' treatment with lithium, choline concentrations in the patients with cluster headache increased to 78 times the control value (mean 369.2 mumol/l (3840 micrograms/100 ml) compared with 4.7 mumol/l (49 micrograms/100 ml]. The presence of depressed erythrocyte choline concentrations during and between cluster attacks indicates that this may be a predisposing condition which results in a cluster attack only when associated with a trigger factor.