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Biomedical subjects

N Pivac

Publications and source records attributed to N Pivac.

29 records · Page 2Linked to original sources

Inhibitory effect of diazepam on the activity of the hypothalamic-pituitary-adrenal axis in female rats.

The acute intraperitoneal administration of anxiolytic diazepam (2 mg/kg) inhibits the activity of the hypothalamic-pituitary-adrenal (HPA) axis, i.e., it decreases the concentration of adrenocorticotropic hormone (ACTH) and corticosterone in female rats. This fall of ACTH and corticosterone levels was reversed by an antagonist of central benzodiazepine receptors-flumazenil. The antagonist of peripheral benzodiazepine receptors-PK 11195, failed to affect diazepam-induced decrement of plasma ACTH and corticosterone levels. The suppressed HPA function obtained after diazepam administration was also antagonized by bicuculline, an antagonist of GABA recognition sites, and by picrotoxin, a drug that blocks the GABA-A receptor associated chloride channel. These results suggest that central benzodiazepine receptors, the part of GABA-A macromolecular complex, are involved in diazepam-induced inhibition of the activity of the HPA axis.

Adrenocorticotropic Hormone↗

Immune response of stressed rats treated with drugs affecting serotoninergic and adrenergic transmission.

Stressful conditions interfere with immune response. One of the principal mechanisms is activation of hypothalamo-pituitary-suprarenal axis by central serotoninergic and adrenergic pathways. Alternative mechanisms bypassing the axis also take part in stress-induced immunomodulation. Immunosuppression caused by repeated restraints or over-crowding was usually accompanied by increased metabolism of serotonin in the brain (as indicated by increased level of its metabolite, 5-HIAA) and by increased levels of corticosterone in plasma. Changes in lymphatic tissues of stressed animals that result in suppression of immune response apparently "outlive" fluctuating changes in neurotransmitter and corticosterone levels. Drugs that alter serotoninergic or adrenergic transmission interfere with immunosuppressive effect of stress either synergistically (augmenting suppression) or antagonistically (preventing it). Since immunocompetent cells possess serotoninergic and adrenergic receptors, such drugs may exert their effect either via central neuroendocrine mechanisms, or by direct effects on immunocompetent cells.

Animals↗

[Comparison of the antihypertensive effects of bopindolol and metoprolol in the treatment of arterial hypertension].

A randomized, double blind clinical trial included 40 hypertension patients of both sexes, aged 18-70 years, with diastolic blood pressure persistently above 100 (13.33 kPa) and below 120 mm Hg (15.99 kPa). After a run-in period on placebo, one half of them was treated with bopindolol (single daily dose 1-3 mg), and the other half with metoprolol (100-300 mg daily in two divided doses). After 4 weeks of formal trial both beta blockaders had significantly decreased the elevated arterial pressure, e.g. the mean arterial pressure in the bopindolol group dropped from an average of 129.1 +/- 6.9 (17.20 +/- 0.92) to 111.6 +/- 6.1 mm Hg (14.87 +/- 0.81 kPa) or by 13.6% and in the metoprolol group from 129.8 +/- 7.1 (17.30 +/- 0.94 kPa) to 114.5 +/- 6.4 mm Hg (15.26 +/- 0.85 kPa) or by 11.8% (p less than 0.02). After 12 weeks the mean pressure was ulteriorly lowered to some 104.3 mm Hg (13.90 kPa) on bopindolol and to some 106.0 mm Hg (14.12 kPa) on metoprolol. The heart rate was expectedly slowed down, from an average of 95 to 69 b.p.m. with bopindolol (27.4% decrease, p less than 0.001) and from 99 to 67 b.p.m. with metoprolol (32.3% decrease, p less than 0.001). The other parameters, including the laboratory results did not change appreciably during this study. Clinically relevant side-effects were not registered, and the observed between-group differences did not reach the level of statistical significance. It is concluded that bopindolol and metoprolol are beta-adrenergic blockaders of comparable antihypertensive efficacy.

Adolescent↗

[The vasodilating effect of chlorthalidone in mild hypertension evaluated by impedance venous plethysmography].

Thirty hypertensive outpatients of both sexes having diastolic blood pressure below 110 mmHg were included in a randomized trial. Their mean age was 50.4 +/- 8.6 years. After a two-week placebo period, the patients were treated with chlorthalidone in a single daily dose of 25 or 12.5 mg over the one-month period, and the next month the alternative dose (i.e. 12.5 or 25 mg) was administered. Changes in vascular reactivity were measured by occlusive plethysmography (mercury strain-gauge) at the end of the placebo period, and then post the first and second month of therapy. All the observed parameters, i.e. rest flow (RF), peak flow (PF), venous capacity (VC), and maximal venous outflow (MVO) increased with 25 mg of chlorthalidone, and similar findings were registered when a dose of 12.5 mg was given. There was a significant increase in venous capacity of both groups (from 2.6 to 3.2 and from 3.0 to 3.4 ml/100/min) and in peak flow of the group that was on 25 mg of chlorthalidone as the first dose (from 18.6 to 23.9 ml/100ml/min). Both doses had similar antihypertensive effect. It is concluded that antihypertensive effect of chlorthalidone is partly due to changes in vascular reactivity in the sense of vasodilation which is more prominent at the venous side of the blood flow, Low-dosed chlorthalidone is equipotent in antihypertensive efficiency, its side effects are rare, and the cost of therapy is by far the lowest.

Chlorthalidone↗

[Orthostatic hypotension. Case report of the Bradbury-Eggleston syndrome].

A case of a 71-year-old woman with idiopathic orthostatic hypotension is presented. Several diagnostic procedures which can detect sympathetic pathway lesion are reported. The value of blood pressure measurement and heart rate response to the supine and standing position deep breath, Valsalva maneuver and cold pressor test in differential diagnosis are emphasized. The venoconstriction, venous reflexes and tyramine tests are described, as well. The authors favour an individual therapeutic approach with no limitation of mineralocorticoid dosage. Nonpharmacological measures, such as an increased salt intake, elastic support stockings and swimming are highly recommended.

Aged↗

[Comparison of amlodipine and the nifedipine retard preparation in the treatment of arterial hypertension].

The efficacy and acceptability of amlodipine (5-10 mg o.d.) and sustained-release nifedipine (20-40 mg b.i.d.) were compared in a multicenter, double-blind clinical trial. After a two-week placebo period, 71 essential hypertensives of both sexes, aged 51.7 +/- 8.5 years, having diastolic blood pressure of 95-114 mmHg were randomly allocated to either amlodipine 5 mg once daily (group A) or nifedipine 20 mg twice daily (group B). With respect to the blood pressure response, the initial dose was doubled after two weeks. No significant differences in blood pressures recorded at baseline and at the end of the placebo period were demonstrated. A significant reduction in both systolic and diastolic blood pressures in the supine position was observed already two days after the start of treatment. In the group A it decreased from 163.2 +/- 21.4/102.7 +/- 8.5 to 155.7 +/- 20.7/98.2 +/- 8.9 mm Hg (p < 0.05) and in the group B from 160.5 +/- 16.2/100.5 +/- 12.2 to 152.2 +/- 17.0/95.4 +/- 9.5 mm Hg (p < 0.05). The similar changes of blood pressure were observed in the standing position, as well. At the end of the study, the overall reduction of the supine diastolic blood pressure was 12.5% in the group A versus 5.2% in the group B (p < 0.05). In the standing position, amlodipine decreased diastolic blood pressure by 8.8% and nifedipine by 6.4% (p < 0.05). Furthermore, amlodipine decreased the standing diastolic blood pressure to a greater extent (8.8% versus 6.4%; p < 0.05) than nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amlodipine↗

[How much do we understand about pharmacotherapy of cardiac arrhythmias?].

By an anonymous, multiple-choice questionnaire assessed was the knowledge of cardiac electrophysiology and mechanism of action of some antiarrhythmic drugs among the staff members of a department of medicine from a large regional hospital. The overall results were disappointing (over 55 per cent of inaccurate answers), but improved after 3 months (less than 30 per cent). It is concluded that such a polling increases the level of awareness about target problem (cardiac arrhythmia management in the actual case) and improves the performance of health professionals.

Arrhythmias, Cardiac↗

[Outpatient approach to arterial hypertension: analysis of ambulatory care of hypertonic patients at the Clinical Hospital Center in Split 1988-1990].

A retrospective analysis of 5,088 hypertensives treated by our Outpatient Clinic, Department of Medicine, University Hospital Split from 1988 through 1990 is presented. Male sex was predominant (about 65%) and almost all the patients (over 95%) were overweight and the majority (over 50%) have had mild hypertension. Essential form was by far the most prevalent type of hypertension (over 95%), while curable forms of secondary hypertension were rare indeed (less than 0.2%). Diuretics and beta blockers, the traditional first-line antihypertensives were the most prescribed drugs (over 60%), while the share of ACE inhibitors, calcium antagonists and alpha blockers was steadily increasing. General measures, such as body weight reduction, salt restriction or cessation of smoking, although obligatory part of the treatment and suggested to each hypertensive, are rarely carried out.

Adult↗

[Biochemical changes in hypertensive patients during a 1-year cross-over study of treatment with hydrochlorothiazide and propranolol].

A prospective, randomized, cross-over trial comparing the antihypertensive efficacy and biochemical changes during treatment with either hydrochlorothiazide (HTZ: 25 mg o.d.) or propranolol (PRO: 40 mg t.i.d.), included 55 mild to moderate hypertensives (diastolic blood pressures ranged from 90 to 110 mmHg), aged 25-65 years. Forty patients completed the study; during the first six months 20 of them (12 males and 8 females) were taking HTZ, and the remaining 20 (13 males and 7 females) PRO. After a one-week wash-out period, for the next six months the alternative drug was administered. Antihypertensive efficacy of both drugs was nearly equal: systolic and diastolic blood pressure significantly decreased already after the first month (approximately by 10%), and kept unchanged until the end of the study. The analyzed biochemical parameters, i.e. blood glucose, cholesterol, and triglycerides did not increase significantly, while serum potassium level remained almost unchanged during the trial. Furthermore, during PRO in group B, cholesterol significantly decreased (3rd month), as well as blood glucose during HTZ treatment (10th month). Only the uric acid level, although unsignificantly, increased in group A (from 326.2 to 365.3 +/- 125.2 on HTZ, and to 391.4 +/- 120.0 mumol/l on PRO). It is concluded that HTZ and PRO are comparably effective antihypertensives. During the long-term treatment in small doses these drugs do not induce significant biochemical disturbances.

Adult↗

[Occurrence of thromboembolic complications in patients with dilated cardiomyopathy. Retrospective-prospective study].

The purpose of the present study was to determine the prevalence of thromboembolic events in patients with primary and secondary (ischemic) dilated cardiomyopathy (DC), with regard to basic rhythm, sinus or atrial fibrillation. Retrospectively, over three years, from January 1, 1989 to December 31, 1991, the case histories of 75 inpatients with DC, mean age 56.2 +/- 14.1 years, 41 in sinus rhythm and 34 in atrial fibrillation from Clinic Hospital Split were analyzed and compared to those of 75 controls (heart failure with no DC). The incidence of thrombi, embolisms and mortality in both subgroups was similar, while the prevalence of thromboembolic events was significantly higher in the analyzed than in the control group (decompensated patients with ischemic cardiomyopathy and without cardiomegaly) (9/75:1/75, p < 0.05). Prospectively, between 9 and 22 months, from December 1, 1991 to September 30, 1993 51 consecutive decompensated outpatients with DC, in NYHA class II and III, mean age 54.2 +/- 15 years, were followed-up. Bilirubin, lactic dehydrogenase, prothrombin time and activated partial thromboplastin time were determined. 1-D and 2-D transthoracic echocardiographic exam was performed and clinical status was assessed. There were 24 patients in sinus rhythm and 27 patients in atrial fibrillation. The prevalence of thromboembolic events, thrombi and mortality in both subgroups was similar. The laboratory findings, indicators of possible thrombogenesis or thrombolysis, did not show any significant difference in both subgroups. The incidence of thrombi in both parts of this study was low, amounted to only 9.5% (12/126) with no clear signs of thromboembolism (these patients were anticoagulated!). Altogether 12.6% (16/126) patients suffered thromboembolic events, 9 in retrospective and 7 in prospective part of the trial (more patients were anticoagulated in prospective then in retrospective study, 5 versus 19; p < 0.05). We conclude that thromboembolism in patients with decompensated DC are rare, but appear at significantly higher rate than in decompensated patients with ischemic cardiomyopathy and no cardiomegaly. The beneficial effects of anticoagulant therapy are to be expected in these patients regardless of the basal rhythm. This hypothesis must, however, be assessed in a prospective, multicentric trial.

Anticoagulants↗