Effects of docosahexaenoic acid on calcium pathway in adult rat cardiomyocytes.

In this study we examined the effect of polyunsaturated fatty acids (PUFAs), in particular of docosahexaenoic acid (DHA), on calcium homeostasis in isolated adult rat cardiomyocytes exposed to KCl, ET-1 and anoxia. Free [Ca(2+)](i) in rat cardiomyocytes was 135.7 +/- 0.5 nM. Exposure to 50 mM KCl or 100 nM ET-1 resulted in a rise in free [Ca(2+)](i) in freshly isolated cells (465.4 +/- 15.6 nM and 311.3 +/- 12.6 nM, respectively) and in cultured cells (450.8 +/- 14.8 nM and 323.5 +/- 14.8 nM respectively). An acute treatment (20 minutes) with 10 microM DHA significantly reduced the KCl- and ET-1-induced [Ca(2+)](i) increase (300.9 +/- 18.1 nM and 232.08 +/- 11.8 nM, respectively). This reduction was greater after chronic treatment with DHA (72 h; 257.7 +/- 13.08 nM and 192.18 +/- 9.8 nM, respectively). Rat cardiomyocytes exposed to a 20 minute superfusion with anoxic solution, obtained by replacing O(2) with N(2) in gas mixture, showed a massive increase in cytosolic calcium (1200.2 +/- 50.2 nM). Longer exposure to anoxia induced hypercontraction and later death of rat cardiomyocytes. Preincubation with DHA reduced the anoxic effect on [Ca(2+)](i) (498.4 +/- 7.3 nM in acute and 200.2 +/- 12.2 nM in chronic treatment). In anoxic conditions 50 mM KCl and 100 nM ET-1 produced extreme and unmeasurable increases of [Ca(2+)](i.) Preincubation for 20 minutes with DHA reduced this phenomenon (856.1 +/- 20.3 nM and 782.3 +/- 7.6 nM, respectively). This reduction is more evident after a chronic treatment with DHA (257.7 +/- 10.6 nM and 232.2 +/- 12.5 nM, respectively). We conclude that in rat cardiomyocytes KCl, ET-1 and anoxia interfered with intracellular calcium concentrations by either modifying calcium levels or impairing calcium homeostasis. Acute, and especially chronic, DHA administration markedly reduced the damage induced by calcium overload in those cells.

Management of hypertension by general practitioners: an Italian observational study.

Data on patients receiving antihypertensive therapy were collected from 20 general practitioners (GPs) in Campania, Italy, to determine the prescription of different antihypertensive classes and their use with other drugs for concomitant diseases, to investigate the main factors influencing antihypertensive choice, to document treatment outcome, and to assess adverse drug reactions (ADRs). Each GP completed a data card for each consultation that produced an antihypertensive prescription; 1900 cards were collected. The most frequently used antihypertensives were angiotensin-converting enzyme inhibitors (49.6%), calcium antagonists (24.8%), beta blockers (11.7%), angiotensin II-receptor blockers (5.5%), and alpha blockers (0.9%). In 82% of patients, blood pressure was reduced but did not reach normotensive levels. The choice of antihypertensive treatment was influenced by international guidelines (56%), clinical diagnosis (25%), concomitant diseases (8%), cost (4%), compliance (3%), and other factors (5%). ADRs--most often cough (35.7%), edema (22.7%), headache (13.3%), and tachycardia (7.8%)--occurred in 11.8% of patients.

Self-prescribed laxative use: a drug-utilization review.

This study was conducted to determine the reasons for the choice of self-prescribed laxatives and to acquire information on how they were used and tolerated. From November 1999 to February 2000, 70 pharmacies, uniformly located throughout the Campania region of southern Italy, distributed a questionnaire to purchasers of over-the-counter laxatives. The average age of the (mostly female) respondents was 45.9 years; 23.8% were elderly. Among the 7324 individuals who completed the survey, 77.6% selected an oral product; 22.4% preferred rectal administration. A physician influenced the choice of a laxative in 37.7% of the cases, a pharmacist in 20.5%; other suggestions came from relatives (14%), acquaintances (12.1%), advertisements (11.7%), and miscellaneous sources (4%). Only 59.8% of respondents used these drugs correctly, and 58.2% consulted a physician or pharmacist because of constipation. Adverse effects, mainly gastrointestinal symptoms, occurred in 6.1% of those surveyed. The long-term use or abuse of laxatives can cause serious medical consequences, as well as mask diseases, delaying diagnosis and appropriate treatment. Physicians, pharmacists, and other health-care personnel should counsel patients on the proper use of these easily available, ubiquitous drugs.

Synthesis of new N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-thieno[2,3-h]-1-benzopyran-2-ones.

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-thieno[2,3-h]-1-benzopyran-2-ones (4a-f), by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-5-aminomethylene-6,7-dihydrobenzo[b]thiophen-4(5)-ones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. A moderate local anaesthetic activity was observed in the title compounds, particularly in 4e.

3-Arylsulphonyl-5-arylamino-1,3,4-thiadiazol-2(3H)ones as anti-inflammatory and analgesic agents.

Two series of 3-arylsulphonyl-5-arylamino-1,3,4-thiadiazol-2(3H)ones 2 with potential anti-inflammatory and analgesic activity were prepared and tested. Pharmacological results revealed that all the title compounds, endowed with an arylsulphonyl side chain, possess good antalgic activity and fair anti-inflammatory properties. The analgesic profile of the two series, evaluated by the acetic acid writhing test, showed that compounds 2c, 2f and 2h, in particular, were the most active. Structure-activity relationships are briefly discussed.