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P Saba

Publications and source records attributed to P Saba.

At least 19 recordsLinked to original sources
PubMed1995

The tyramine-labelled vesicular transporter for dopamine: a putative target of pesticides and neurotoxins.

This study defined the ability of a large sample of heterogeneous pesticides and neurotoxins to interact with the [3H]tyramine-labelled vesicular transporter of dopamine in rat striatum. Botanical (with rotenone as the most potent), and organochlorine (Kepone) insecticides, as well as fungicides (Zineb), as a whole, consistently inhibited [3H]tyramine binding, with Ki values ranging from 5 nM to 10 microM. ATP/Mg(2+)-dependent [3H]tyramine uptake to purified striatal synaptic vesicles was also inhibited by rotenone. Organophosphate and carbamate insecticides, and miscellaneous herbicides poorly antagonized [3H]tyramine binding, yielding Ki values exceeding 10 microM. Several, though not all, of the best recognized central neurotoxins tested were major binding antagonists. Their rank order of potency was 1-methyl-4-phenylpyridinium ion (MPP+) > trimethyltin > or = 6-hydroxydopamine > N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) > 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with Ki values ranging from 35 nM to 3 microM. Overall, the potent interaction of selected pesticides and chemicals with the vesicular transporter for dopamine, although, by itself, not synonymous with neurotoxicity, would argue for a likely impairment of transmitter homeostasis, or the putative formation of neurodegenerative toxin pools.

Animals↗
PubMed1994

Antihypertensive and metabolic effects of lacidipine in patients with NIDDM and/or hypertension.

Diabetes mellitus is often associated with hypertension and is an additional cardiovascular risk factor. It is therefore important that antihypertensive drugs should have no negative metabolic effects. We present here the results of two distinct studies investigating the clinical efficacy and the metabolic effects of lacidipine in hypertensive patients without concomitant diabetes. Patients in the first study (group A) were hypertensive with non-insulin-dependent diabetes mellitus (NIDDM) and stable blood glucose levels in the 3 months before entering the study. Patients in the second study (group B) were hypertensive without diabetes mellitus. Before the commencement of the study, antihypertensive treatment was discontinued in all patients for a 4-week washout period, followed by 4 weeks of run-in with placebo. Patients were then treated with lacidipine (4 mg o.d.) for 6 months. After 1-2 months, the dose was doubled in patients with uncontrolled blood pressure. Every 2 months, lipid and carbohydrate metabolism were investigated by blood chemistry analyses. The results demonstrate that lacidipine 4-8 mg o.d. is efficacious and well tolerated in hypertensive patients, even in the presence of diabetes mellitus.

Adult↗
PubMed1993

Antihypertensive effect of once daily sustained release isradipine: a placebo controlled cross-over study.

To evaluate the magnitude and duration of the antihypertensive effect of sustained release (SRO) isradipine, 37 uncomplicated essential hypertensive patients (diastolic blood pressure 100-115 mm Hg after a one month run-in on placebo) were randomised to receive, according to a double-blind cross-over design, isradipine SRO 5 mg once daily and the corresponding placebo for 1 month. At the end of each treatment period, sitting blood pressure and heart rate were measured immediately before and every hour for 6 h after the last dose. Thirty-four patients [16 m, age 54 (7) y] completed the study. As compared to randomised placebo, isradipine SRO significantly reduced the systolic (SBP) and diastolic (DBP) blood pressure. Absolute DBP decrements versus placebo peaked 6 h after dosing (-8.8 mm Hg) and were not significantly lower (-8.2 mm Hg) at the end of the dose interval. At the same times, the absolute decrements in SBP were -9.8 mm Hg and -9.7 mm Hg, respectively. DBP was normalised in 19 patients (56%) at peak and in 17 (50%) at trough time. The trough to peak efficacy ratio in patients with peak DBP < or = 90 mm Hg was 70%. Heart rate was slightly increased by isradipine SRO. Adverse effects monitored with a check-list occurred in 8/36 patients (22%) on isradipine SRO and in 4/35 (11%) on randomized placebo. The data suggest that isradipine SRO is an effective antihypertensive drug, with a trough to peak efficacy ratio supporting once daily administration in most mild to moderate essential hypertensives.

Adult↗
PubMed1993

Potent, extra-channel influence of several calcium-channel modulators on striatal binding of [3H]tyramine.

A number of Ca(2+)-, K(+)-, and Na(+)-channel modulators has been tested with respect to their effects on [3H]tyramine (TY) binding, as a putative marker for the vesicular dopamine (DA) transporter in striatal membrane preparations containing vesicle ghosts. Among organic Ca(2+)-channel modulators, the diphenylalkylamines tested consistently inhibited TY binding: the order of potency was prenylamine > lidoflazine > flunarizine > cinnarizine, with Ki values of 0.1, 0.2, 0.5 and 1.2 microM, respectively. Low (up to 100 nM) concentrations of prenylamine did competitively inhibit TY binding, and higher concentrations provoked a mixed-type inhibition. Furthermore, LIGAND-analysis of competition curves revealed a high- and a low-affinity binding site for prenylamine and flunarizine. The TY binding process was also sensitive to selected K(+)- and Na(+)-channel modulators. Since several Ca(2+)-antagonists are known to affect H(+)-ATPase and the bioenergetics of catecholamine storage vesicles in chromaffin granules, thus affecting monoamine storage, the energy requirements for the formation of the TY/carrier complex were here assessed, assuming similarity between chromaffin granules and synaptic vesicles. TY binding, though not reflecting endovesicle-sequestered TY, was indeed strongly sensitive (with Ki coefficients in the fM or low nM range) to the dissipation of the vesicular transmembrane proton concentration (delta pH), electrical (delta psi), and proton electrochemical (delta microH+) gradients, provoked by a number of specifically targeted agents. It is concluded that Ca(2+)-channel agents of the diphenylalkylamine group may directly affect striatal TY binding due to an extrachannel-regulated competition with TY for the vesicular carrier of DA, as well indirectly, by disruption of the transmembrane energization of the reserpine-sensitive carrier.

Animals↗
PubMed1992

Effects of perindopril on carbohydrate and lipoprotein metabolism in essential hypertension.

Fourteen outpatients with mild-to-moderate essential hypertension were treated with perindopril (4-8 mg once daily) for a 16-week period. It was observed that the drug was effective in lowering blood pressure without inducing changes in blood lipids commonly observed with other hypotensive agents. This lipid neutrality, in addition to the lack of side or toxic effects, confers on perindopril a noteworthy therapeutic value in the treatment of essential hypertension.

Adult↗
PubMed1992

Antihypertensive and metabolic effects of nitrendipine in non-insulin-dependent diabetes mellitus with hypertension.

Fifteen non-insulin-dependent diabetes mellitus hypertensive patients received nitrendipine (20-40 mg) for 24 weeks. Mean systolic and diastolic blood pressure decreased significantly from 177/102 mm Hg before treatment to 153/86 mm Hg (p less than 0.001) after treatment. Meanwhile, the heart rate, body weight, indices of glycemic control (glucose, glycosylated hemoglobin, fructosamine, and serum C peptide levels), and serum lipid fractions did not change. It is concluded that nitrendipine does not impair glucose and lipid metabolism in diabetic patients while exerting its antihypertensive effect.

Aged↗
PubMed1992

Clinical investigation on the hypolipidemic effect of simvastatin in primary hypercholesterolemia.

Simvastatin, 20 mg daily, was given orally to 21 hypercholesterolemic outpatients for 16 weeks. During treatment a significant reduction was found in plasma total and LDL cholesterol; plasma HDL-cholesterol levels increased during the treatment. Results indicate that simvastatin, because of its activity and lack of toxicity and side effects, can be considered a drug of first-choice for the treatment of primary hypercholesterolemia.

Anticholesteremic Agents↗
PubMed1991

The combination of chlorthalidone with nifedipine does not exert an additive antihypertensive effect in essential hypertensives: a crossover multicenter study.

To evaluate whether the combination of nifedipine with chlorthalidone exerts an additive antihypertensive effect when compared to single-drug treatment, 66 uncomplicated essential hypertensives, whose diastolic blood pressure was greater than 100 and less than 115 mm Hg at the end of a 1-month washout placebo period, received, according to a randomized, double-blind, crossover design, nifedipine (20 mg b.i.d.), chlorthalidone (25 mg o.d.), the two drugs combined at the same doses, and the corresponding placebo. When compared to the randomized placebo the three active treatments significantly (p less than 0.001) reduced blood pressure without changing heart rate and body weight. However, blood pressure values were similarly reduced under nifedipine and the combination and were significantly lower (p less than 0.05) than those under chlorthalidone. Moreover, the percentage of responders and normalized patients under nifedipine and the two drugs combined were similar and significantly (normalized, p less than 0.0001; responders, p less than 0.02) greater than those under chlorthalidone. Under chlorthalidone and its combination with nifedipine, plasma potassium tended to decrease and blood glucose and serum uric acid were significantly (p less than 0.05) increased. These data show that the combination of nifedipine with chlorthalidone does not exert any additive antihypertensive effect when compared to nifedipine alone and that this combination increases both blood glucose and serum uric acid. Taken together these findings indicate that the combination of a dihydropyridine calcium antagonist with a thiazide diuretic is devoid of any clinical significance in the treatment of uncomplicated essential hypertensives.

Adult↗
PubMed1990

Central dopaminergic transmission is selectively increased in the limbic system of rats chronically exposed to antidepressants.

Repeated electroconvulsive shock (ECS) exposure produced a decrease of [3H]SCH 23390 binding sites and a reduced response of adenylate cyclase activity to dopamine D-1 receptor stimulation in the rat limbic area analogous to that previously observed in rats chronically treated with imipramine. These effects were completely prevented by the repeated administration of a small dose of alpha-methyl-p-tyrosine (alpha-MPT), associated with the tricyclic compound. Increased dopaminergic transmission seems to be involved in the mechanism of antidepressant action. Rats chronically treated with imipramine showed a decrease of dihydroxyphenylacetic acid (DOPAC) concentration restricted to the limbic area. Finally, both imipramine and desipramine blocked the uptake of [3H]dopamine in the limbic system with a 100-fold greater potency than that observed in the basal ganglia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Chronic imipramine reduces [3H]SCH 23390 binding and DA-sensitive adenylate cyclase in the limbic system.

[3H]SCH 23390 binding and dopamine (DA)-stimulated adenylate cyclase activity were measured in brain membrane preparations from rats chronically treated with imipramine (10 mg/kg twice daily for 14 days). [3H]SCH 23390 binding sites were decreased by 27% in the limbic system but only 14% in the striatum. The responsiveness of adenylate cyclase to DA was reduced by 38% in the limbic system but was not modified in the striatum. Concomitant treatment with alpha-methyltyrosine (alpha-MPT) (50 mg/kg daily for 14 days) prevented the imipramine-induced reduction in both [3H]SCH 23390 binding sites and the responsiveness of adenylate cyclase to DA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Resistance to extrapyramidal effects of opiates in rats chronically treated with SCH 23390.

Rats made tolerant to morphine show neither a change in brain opiate receptor number nor altered sensitivity to the inhibitory effect of opiates on striatal adenylate cyclase (AC) activity. Interestingly, SCH 23390, a selective blocker of D1 dopamine (DA) receptors which, given chronically to rats, induces a 32% increase in D1 receptor number and increases the Vmax of D1-stimulated striatal AC, resulted in marked resistance to acute morphine effects. In particular, rats chronically treated with SCH 23390 failed to show muscular rigidity and increased striatal dihydroxyphenylacetic acid (DOPAC) concentration after morphine. Moreover, basal striatal AC activity in these animals had a significantly reduced sensitivity to opiate inhibition. On the other hand, decreased AC sensitivity to acetylcholine (ACh) inhibition observed in the striatum of rats chronically treated with DFP, an irreversible blocker of acetylcholinesterase, appeared to be secondary to the downregulation of muscarinic receptors and thus did not modify the opiate inhibitory capacity. It was concluded that although a potentiation of striatal AC impairs opiate action, such mechanism is not involved in morphine tolerance.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

The sesamoids of the metacarpo-phalangeal joint of the thumb: an anatomical and clinical study.

Two unusual cases of injury to the sesamoids of the M.P. joint of the thumb are described. An anatomical dissection of the M.P. volar plate region, including the sesamoids, was undertaken to delineate the details of the sesamoids' relationship to the M.P. joint, flexor tendon, flexor tendon sheath and capsule of the joint. Histological studies were carried out to demonstrate a tendinous extension of the muscles that attach to the sesamoids.

Adult↗
PubMed1989

Chlorthalidone does not increase the hypotensive effect of nifedipine in essential hypertensives: a crossover multicentre study.

To determine whether the combination of nifedipine + chlorthalidone exerts an additive antihypertensive effect when compared with single-drug treatment, we studied 66 uncomplicated essential hypertensives, with diastolic blood pressure of greater than 100 and less than 115 mmHg. At the end of a 1-month washout placebo period, using a double-blind crossover design, the patients were randomly allocated to nifedipine (20 mg twice a day), chlorthalidone (25 mg once a day), the two drugs combined at the same doses and the corresponding placebo. Compared with the randomly allocated placebo, the three active treatments significantly reduced blood pressure without changing the heart rate or body weight. Both the absolute and percentage decreases in mean blood pressure induced by nifedipine and the combination compared with placebo were similar and significantly greater than those induced by chlorthalidone. Taken together, these data show that the combination of nifedipine + chlorthalidone does not exert any additive antihypertensive effect compared with nifedipine alone. This finding indicates that the combination of a dihydropyridine calcium antagonist + a thiazide diuretic is probably devoid of any particular clinical significance in the treatment of uncomplicated essential hypertensives.

Adult↗
PubMed1989

Captopril treatment in elderly hypertensive patients: efficacy and tolerability. Captopril Study Group.

Ninety-five elderly (greater than 70 years) hypertensive patients were treated for 3 months with 25-100 mg captopril daily. The mean blood pressure decrease was from 179/101 to 155/87 mmHg (P less than 0.001). The heart rate did not change. The drug was generally well tolerated (patients taking less than 100 mg captopril or captopril + chlorthalidone reported side effects) and there was no change in the biochemical parameters (glucose, uric acid, cholesterol, high density lipoprotein-cholesterol, triglycerides, apoproteins, blood urea nitrogen, creatinine, serum electrolytes). Our open study indicates that captopril is a safe and effective antihypertensive agent in elderly patients. However, some caution is necessary when high doses of captopril (100 mg/day) are used.

Aged↗
PubMed1987

Plasma renin activity does not predict the antihypertensive efficacy of chlorthalidone.

It has been established that angiotensin II stimulation may limit the antihypertensive potential of diuretic therapy in some patients. It is less clear, however, whether renin-angiotensin II stimulation is the cause of the flat blood pressure dose-response relationship to diuretics. To investigate this, 75 out-patients with essential hypertension were treated with chlorthalidone 12.5, 25 or 50 mg o.d. for 3 weeks, in a double-blind, placebo controlled cross-over study. Chlorthalidone significantly reduced blood pressure in all the groups, a plateau being reached at 25 mg o.d. Similarly, plasma renin activity was increased by each dose level of chlorthalidone, but it showed a different trend, being increased to a comparable extent at 12.5 mg and 25 mg o.d., and still higher at 50 mg o.d. Thus, greater stimulation of renin was coincident with the levelling of the blood pressure response to chlorthalidone. However no significant correlation was found between interindividual plasma renin activity and change in blood pressure, either in the entire series, or in each treatment subset. The data suggest overall that renin stimulation may influence the characteristic dose-hypotensive response relationship to diuretic agents in antihypertensive therapy, but it is unlikely that measurement of individual plasma renin activity will provide an useful guide to the optimal dose of a diuretic agents.

Adult↗