Clotrimazole (CLT) is a drug known to interfere with cellular calcium homeostasis, which in turn is reported to intervene in cell proliferation and in the reactivity of small blood vessels. Experiments were designed to test the influence of CLT on the proliferative and vasorelaxant effect of bradykinin (BK) and on calcium homeostasis in smooth muscle cells (SMC). To this purpose two model systems were employed: (i) cultured human smooth muscle cells (HSMC), and (ii) isolated resistance arteries maintained in an organ bath. The effect of various concentrations of CLT (2-15 microM) on BK-induced proliferation of HSMC was quantitated by spectrometry following [3H]-thymidine incorporation, and intracellular calcium [Ca+]i was determined by spectrofluorimetry using Fura 2-AM assay. In other experiments the roles of BK receptor (AB2) and of thapsigargin were assessed. The reactivity of the resistance arteries was measured by the myograph technique, and the effects of BK, CLT, and NO synthase blocker, L-NAME were evaluated. The results showed that 10 microM CLT: (i) inhibits the BK-induced proliferation of HSMC by 45-50%: (ii) prevents the rise of [Ca2+]i induced by BK (120.8 +/- 12.4 nM vs. 235.8 +/- 34.1 nM), an cffect similar to that of "classic" L-type calcium channels blockers: (iii) reduces the release of Ca2+ entry induced by thapsigargin suggesting a possible inhibition of the capacitative Ca2+ entry. Organ bath assays showed that CLT enhanced the BK-induced relaxation of the resistance arteries by an endothelium NO-independent pathway. Together, these data suggest that the mechanism of action of CLT on SMC implies mainly a modification of intracellular calcium homeostasis, with a minor contribution of BK B2 receptors. These new distinctive features of CLT effects suggest the potential use of this drug in the therapy of cardiovascular diseases associated with SMC increased proliferation and impeded relaxation in small arteries, such as atherosclerosis and restenosis.

Arteriosclerosis↗

PubMedDate not supplied

A case of hepatocellular carcinoma (HCC): treatment with local application of alcohol and interleukin 2 (IL-2).

A case of an inoperable hepatocellular carcinoma due to liver cirrhosis is presented. Surgical treatment was not clinically warranted. So we decided to induce tumor necrosis by intratumoral injections of 10 mL of ethanol followed by two treatments with 9 x 10(6) U Chiron interleukin-2 with an interval of 1 month. This ethanol-interleukin-2 cycle was repeated three times with intervals of 6 months. Interleukin-2 injections were given by a fine needle, under ultrasound control in the periphery and in the center of the tumor. The initial size of the tumor was 55-60 mm. During the follow-up period of 2 years the tumor size remained relatively unchanged. The patient died due to gastric hemorrhage. The treatment elicited no adverse clinical effects. The clinical status improved greatly after this treatment. Local interleukin-2 application after alcohol-induced tumor ablation might be an alternative if surgical treatment is not warranted.

Aged↗

PubMedDate not supplied

[Jackson's laryngotracheobronchitis suffocans in a 14-year old boy].

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Adolescent↗