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Biomedical subjects

S Moncada

Publications and source records attributed to S Moncada.

At least 523 records · Page 29Linked to original sources
PubMed1975

Inhibition of prostaglandin biosynthesis as the mechanism of analgesia of aspirin-like drugs in the dog knee joint.

A method has been developed to measure the analgesic action of aspirin-like drugs in knee joints of anaesthetized dogs. Bradykinin, injected into the joint cavity, induced a reflex rise in blood pressure which was dose-dependent; this was used as a measure of nociceptive activity. The joint cavity became more sensitive to bradykinin as the experiment proceeded, or when a low concentration of prostaglandin E1 or E2 was infused locally. The increase in sensitivity with time was prevented by local injection of aspirin or indomethacin, but that induced by exogenous prostaglandin infusion was not. Injections of carrageenin into dog knee joints increased the prostaglandin E2 content of synovial fluid by up to 160 ng per joint; indomethacin prevented this increase. These experiments support our previous conclusion that local biosynthesis of a prostaglandin (induced by mild trauma) sensitizes pain receptors to mechanical or chemical stimuli. Aspirin-like drugs are analgesic because they prevent prostaglandin biosynthesis, thereby preventing this sensitization.

Analgesia↗
PubMed1973

Some effects of inhibiting endogenous prostaglandin formation on the responses of the cat spleen.

1. Cat isolated spleens release prostaglandins into the venous effluent in response to stimuli such as nerve stimulation, noradrenaline and angiotensin II.2. The release of prostaglandins is abolished by pre-treatment of the spleen with indomethacin (0.3-5 mug/ml).3. The capsular and vascular responses to the different stimuli are augmented after inhibition of prostaglandin release.4. The prevention of prostaglandin release, as well as the augmentation of vascular and capsular responses, are reversible after indomethacin treatment is stopped.5. The role of prostaglandins as modulators of the responses to several stimuli is discussed.

Angiotensin II↗
PubMed1973

Prostaglandins and the mechanism of analgesia produced by aspirin-like drugs.

1. Resting splenic venous outflow from anaesthetized dogs contains prostaglandin-like material: the concentration increases after intra-arterial injections of bradykinin into the spleen, and is abolished by treatment with indomethacin.2. Intra-arterial injections of bradykinin into the spleen of lightly anaesthetized dogs elicit a dose-dependent reflex increase in the blood pressure, which is reduced but not abolished by treatment with indomethacin.3. Addition of prostaglandin E(1) or E(2) either by injections or by infusions restores the reflex increase in the blood pressure due to bradykinin injections after indomethacin treatment.4. The sensitizing action of endogenously released prostaglandins at or near the afferent nerve endings is discussed.5. The analgesic activity of aspirin-like drugs is explained in terms of the removal of the sensitizing activity of prostaglandins.

Analgesia↗
PubMedDate not supplied

Reduction by prostacyclin of acetaminophen-induced liver toxicity in the mouse.

The effect of prostacyclin on acetaminophen-induced liver injury has been investigated in the mouse. Two structurally unrelated thromboxane synthetase inhibitors, OKY 1581 and benzyl imidazole, were also examined in order to investigate the role of the prostacyclin-thromboxane balance in the development of hepatic lesions. Whereas prostacyclin or OKY 1581 given shortly after acetaminophen prevented mortality and reduced liver necrosis, as assessed by serum ALT activity and histology, benzyl imidazole was only effective if given prior to acetaminophen. Acetaminophen overdose resulted in an enhanced prostaglandin and thromboxane generation by liver homogenates. While OKY 1581 inhibited thromboxane production by the liver homogenates, prostacyclin synthesis was increased. Pretreatment with the cyclooxygenase inhibitor indomethacin blocked both the increase in prostacyclin generation and the protective effect of OKY 1581. Benzyl imidazole inhibited the synthesis of thromboxane but did not enhance prostacyclin production. In addition, the protective effect of benzyl imidazole was unaltered by indomethacin pretreatment. Furthermore, whereas benzyl imidazole interfered with hepatic drug metabolism, as assessed by prolongation of the pentobarbitone sleeping time, prostacyclin and OKY 1581 were without activity. Prostacyclin treatment can prevent acetaminophen-induced liver necrosis in mice. Enhanced prostacyclin synthesis by the selective thromboxane synthetase inhibitor OKY 1581 also exerts a protective role in this model.

Acetaminophen↗
PubMedDate not supplied

Prostaglandins, their intermediates and precursors: cardiovascular actions and regulatory roles in normal and abnormal circulatory systems.

The characterization of newly found unstable metabolites of arachidonic acid has provided new perspectives for cardiovascular regulatory mechanisms and new insights into disorders of the circulatory system. Since these intermediates are often more potent on and more specific for cardiovascular structures than the classical prostaglandins, they are more likely candidates as physiologic mediators of circulatory events. Their instability in vitro need not preclude these roles; on the contrary, the limited pharmacology described to date suggests that they function purely as local hormones. As such, changes in the rate of generation of these unstable but potent compounds would provide an excellent control system. The stable prostaglandins may represent only overflow of degradation products of the active mediators associated with pathologic events. For example, the dicovery of prostacyclin and the realization that this prostaglandin and not PGE2 is the primary metabolite of arachidonic acid in blood vessels emphasizes the need to reinterpret many of the previously held hypotheses that proposed that prostaglandins of the E series contributed to the regulation of vessel tone and blood pressure, Moreover, the contribution made by abnormal prostaglandin mechanisms to hypertensive disease should now take into account that a deficiency of prostacyclin and not PGE2 could be a major factor causing the elevated tension developed in vascular smooth muscle and the augmented vessel responsiveness to stimuli associated with hypertension.

Animals↗
PubMedDate not supplied

Inhibition of nitric oxide synthesis in septic shock: how much is beneficial?

Hypotension in septic shock is often resistant to treatment with vasoconstrictors and appears to be mediated by production of nitric oxide (NO). Reversal of endotoxin-induced hypotension in rats was achieved by intravenous injection of 30 mg/kg NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endogenous NO synthesis. A lower dose of 3 mg/kg L-NMMA was ineffective, but 300 mg/kg L-NMMA accelerated and enhanced the fall in blood pressure. NO synthase inhibitors may be helpful in the treatment of hypotension associated with sepsis or therapeutic use of cytokines, but complete inhibition of endogenous NO synthesis may be counterproductive.

Animals↗
PubMedDate not supplied

[Habitual physical activity in a population residing in the city of Barcelona].

OBJECTIVES: To describe the sociodemographic distribution of habitual physical activity and to analyse its relationship with self-perceived health status and occupational status, among the population older that 16 years of age in the city of Barcelona, Spain. METHODS: A sample of 1,885 adult men and 2,196 women answered the Health Interview Survey of Barcelona in 1992. Those whose habitual activity required high physical exertion or walking were considered as active. Bivariate and multivariate analyses adjusting logistic regression models were used to study the relationship between habitual physical activity and the rest of variables, for each occupational situation. RESULTS: Fifty six percent of adults reported being physically active. Physical activity was lower among workers than non workers, although workers reported more physical exertion (14.5% in men and 8.0% in women). Physical activity was associated with occupation and educational level among male workers, but only with occupation among female workers. In the non working population, physical activity was lower among those who perceived their health status as fair or poor, compared with those that described it as good or very good, (ORa in men was 0.2, 95% confidence interval = 0.1-0.5; ORa in women was 0.5, 95% confidence interval = 0.3-0.8). CONCLUSIONS: More than half of the Barcelona population were physically active in an habitual manner. Among workers, this activity was mainly determined by the occupation. Non-workers with a poor self-perceived health status did less physical activity.

Adolescent↗
PubMedDate not supplied

[Gender differences in the influence of housework on health].

OBJECTIVE: To analyze the influence of domestic workload on the health of the working population of Catalonia, taking into account its differential impact on males and females. SUBJECTS AND METHODS: The study population were the 2,164 men and 1,215 women interviewed in the Catalonian Health Survey (ESCA) of 1994, with a paid work who were the main responsible for the family unit. The dependent variable was the self-perceived health status that was dichotomized for the bivariate and multivariate analysis. The domestic workload was measured with the number of people living at home (2, 3, 4 or more than 4), living with children younger than 15 and living with older than 65. The adjusting variables were age and occupational social class. The analysis was separated for men and women and crude, adjusted for age, and for all the predictor variables odds ratios (OR) were calculated with their 95% confidence intervals (95%CI). RESULTS: There was no relation between domestic workload and health status among men. Among women the risk or poor health status increased with the number of people living at home with adjusted OR associated to living with more than four persons of 2.35 (95%CI = 1. 33-4.15), as compared with living only with the spouse. Living with older than 65 was protector for women (adjusted OR = 0.63; 95%CI = 0. 39-1.03). CONCLUSIONS: The risk of poor health status associated to the domestic workload among women with paid work, suggests the need of increasing community resources for caring children, as well as, increasing the participation of men in the domestic work. Future health surveys should collect information about the number of people of different age strata living at home.

Adolescent↗