A. R. De Los Santos

Effects of cyclooxygenase inhibitor pretreatment on nitric oxide production, nNOS and iNOS expression in rat cerebellum

The therapeutic effect of nonsteroidal anti‐inflammatory drugs (NSAIDs) is thought to be due mainly to its inhibition of cyclooxygenase (COX) enzymes, but there is a growing body of research that now demonstrates a variety of NSAIDs effects on cellular signal transduction pathways other than those involving prostaglandins. Nitric oxide (NO) as a free radical and an agent that gives rise to highly toxic oxidants (peroxynitrile, nitric dioxide, nitron ion), becomes a cause of neuronal damage and death in some brain lesions such as Parkinson and Alzheimer disease, and Huntingtons chorea. In the present study, the in vivo effect of three NSAIDs (lysine clonixinate (LC), indomethacine (INDO) and meloxicam (MELO)) on NO production and nitric oxide synthase expression in rat cerebellar slices was analysed. Rats were treated with (a) saline, (b) lipopolysaccharide (LPS) (5 mg kg−1, i.p.), (c) saline in combination with different doses of NSAIDs and (d) LPS in combination with different doses of NSAIDs and then killed 6 h after treatment. NO synthesis, evaluated by Bred and Snyder technique, was increased by LPS. This augmentation was inhibited by coadministration of the three NSAIDs assayed. None of the NSAIDs tested was able to modify control NO synthesis. Expression of iNOS and neural NOS (nNOS) was detected by Western blotting in control and LPS‐treated rats. LC and INDO, but not MELO, were able to inhibit the expression of these enzymes. Therefore, reduction of iNOS and nNOS levels in cerebellum may explain, in part, the anti‐inflammatory effect of these NSAIDs and may also have importance in the prevention of NO‐mediated neuronal injury.

Primary care role in awareness and control of hypertension: a hospital-based study

To the Editor: Based on survey data, it has been estimated that the prevalence of hypertension in Latin America and the Caribbean countries ranges from 8% to 43% (1–4) and is affected by ethnicity and cultural facts. Yet, little is known about the relationship between general preventive medicine measures taken by the sample population studied and its impact on treatment and control of hypertension. Also, there is a lack of information about the validity of the data conveyed by hypertensive patients about their adherence to consensus dietary guidelines and the real complying. We performed a cross-sectional study in a primary care setting of the Hospital de Clı́nicas, Universidad de Buenos Aires aiming to assess the degree of awareness, treatment status, compliance to dietary recommendations, control rate of hypertension in the whole sample, associated cardiovascular risk factors, and blood pressure (BP) control rate (<140 mm Hg systolic BP and <90 mm Hg diastolic BP) in hypertensive subjects who had previously suffered stroke or myocardial infarction. Also, we intended to test our hypothesis that a calculated general prevention index (PI) based on representative preventive medicine measures and regular physical exercise individually carried out in the last 5 years could serve as a predictor of BP control. Results for 1733 hypertensive subjects, all of them white (578 men and 1155 women, mean age 66.61 ± 12.34 years) consecutively attended were available for analyses. Eightyseven per cent of hypertensive subjects knew their diagnosis, and the prevalence of hypertension was consistently higher in overweight obese than in normal weight subjects (p < 0.001). Overall, the prevalence of pharmacologic treatment of hypertension was 62% but the BP control rate was only 30%. Among knowledgeable-treated hypertensive subjects 80.4% used only one antihypertensive drug; 17.6% used two and 2% used three (p < 0.001). Only 8% of hypertensives carried out consensus recommended dietarian guidelines while 79% asserted that they did. The PI considered patients’ answers about chest x-rays, flu vaccines and faecal occult blood test, digital rectal examination and prostate ultrasonography or prostate-specific antigen level in men, and mammography and papanicolaou in women, performed during the past 5 years. A numeric value was assigned for each variable, zero if answer was negative and one if affirmative, and PI was calculated as summation of the five variables, for each gender. Regular physical activity executed at least once a week during the same period of time was also recorded. Logistic regression model showed that independent variables more likely to be associated with poor BP control were: overweight (OR 1.53, 95% CI: 1.057–2.208), obesity (OR 2.1, 95% CI: 1.307–3.286) and previous stroke (OR 2.9, 95% CI: 1.099– 7.652). Previous myocardial infarction was not associated with poor BP control, whilst the less odds of poor controlled BP were high PI (OR 0.841, 95% CI: 0.725–0.975) and regular physical activity (OR 0.67, 95% CI: 0.449– 0.989). Using a validated index to assist with clinical decision making could help care for hypertensive patients. However, before implementation as a predictor, the model should be validated externally using a different patient population and clinical setting. The poor control rates of BP found in patients who already suffered from stroke suggest that after hospital discharge for that event antihypertensive therapy was inadequate and document the need of a more stringent surveillance.

Effect of Nomifensine on Cortisol, Prolactin and Biogenic Amines in Neurotic Depressed Patients

The effect of nomifensine on plasma levels of cortisol, prolactin, dopamine, noradrenaline, adrenaline and serotonin were studied in neurotic depressive patients. Cortisol levels were elevated in the morning and were significantly decreased by nomifensine treatment. Prolactin levels were within the normal range and nomifensine did not modify them. A significative increase in catecholamine plasma levels was observed at the 6th week of treatment in depressed patients (dopamine: 106%; noradrenaline: 14%; adrenaline: 10%) whose nomifensine plasma levels ranged between 84 and 105 ng/ml. No statistical differences were found between pre- and post-treatment serotonin concentration. Reduction of plasma cortisol and clinical improvement may be related to increased catecholamine levels.