Phorbol-stimulated Ca(2+) mobilization and contraction in dispersed intestinal smooth muscle cells.

This study examined the source of Ca(2+) mobilized by phorbol esters and its requirement for phorbol-induced contraction of smooth muscle cells isolated from the circular and longitudinal layers of guinea pig intestine. Phorbol-12-myristate-13-acetate caused rapid, sustained, concentration-dependent muscle contraction and increase in cystolic free [Ca(2+)](i) in muscle cells from both layers. Maximal contraction was similar to that elicited by receptor-linked agonists, whereas maximal [Ca(2+)](i) was 50% less. The increase in [Ca(2+)](i) was mediated by Ca(2+) release in circular, and Ca(2+) influx in longitudinal muscle cells; only the latter was abolished by methoxyverapamil and in Ca(2+)-free medium. [Ca(2+)](i) was essential for contraction in both cell types: contraction in longitudinal muscle cells was abolished by methoxyverapamil and in Ca(2+)-free medium; contraction in circular muscle cells was abolished only after depletion of Ca(2+) stores. Contraction was abolished by the protein kinase C (PKC) inhibitor calphostin C (1 microM), but was not affected by the myosin light chain kinase inhibitor KT5926 (1 microM), suggesting that activation of myosin light chain kinase was suppressed by phorbol-12-myristate-13-acetate or via PKC. Phorbol-induced contraction of permeabilized circular and longitudinal muscle cells was abolished by pretreatment with a common antibody to Ca(2+)-dependent PKC-alpha,beta,gamma, but was not affected by pretreatment with a specific PKC-epsilon antibody. This study demonstrates the ability of phorbol esters to mobilize Ca(2+) from different sources in different smooth muscle cell types and establishes the requirement of Ca(2+) for phorbol-induced contraction; the latter is exclusively mediated by Ca(2+)-dependent PKC isozymes.

Risk of bleeding after endoscopic biopsy or polypectomy in patients taking aspirin or other NSAIDS.

The present study was performed to determine if the risk of bleeding after endoscopic biopsy or polypectomy was increased in patients taking aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Of 694 patients who underwent either upper gastrointestinal endoscopy with biopsy or colonoscopy with biopsy or polypectomy, 320 (46%) had recently consumed NSAIDs. Postprocedure bleeding was assessed by both written questionnaire and telephone follow-up. A total of 32 patients (4.6%) reported bleeding. Minor, self-limited, clinically insignificant bleeding occurred in 20/320 (6.3%) patients taking NSAIDs and 8/374 (2.1%) control patients (p = .009). Major bleeding requiring hospitalization or treatment occurred in only 4 patients (0.58%) (2 from the control group and two from the drug group), each of whom had undergone colonic polypectomy. The risk of bleeding increased with polyp size, but this did not seem to be affected by NSAID use. We conclude that the risk of significant gastrointestinal bleeding after endoscopic biopsy or poly removal is small (< 1%). Although use of NSAIDs did increase the incidence of minor self-limited bleeding, an increase in the rate of major bleeding was not observed.

Hepatic artery aneurysm in corticosteroid-treated, adult Kawasaki's disease.

We describe a single case of Kawasaki's disease (mucocutaneous lymph node syndrome) with the rare complication of a hepatic artery aneurysm which was surgically repaired. Unusual features include arterial aneurysmal formation in the hepatic arteries rather than in coronary arteries, the unusual morphology of the hepatic artery aneurysm, and the expansion of the aneurysm after corticosteroid therapy.

Small intestinal motility: normal and abnormal function.

This review outlines the properties and function of intestinal smooth muscle and the mechanisms that underlie contraction and relaxation. Both tonic and phasic (rhythmic) contraction are mediated by an increase in intracellular calcium. Phasic contraction is paced electrically by rhythmic changes in membrane potential (slow waves) which, upon reaching a threshold, lead to opening of membrane calcium channels and the entry of calcium into muscle cells; this inwardly directed calcium current or spike initiates a cascade of events resulting in contraction. Slow waves and spike potentials and, thus, phasic contraction, are influenced by neurotransmitters, hormones, and drugs. In circular muscle, these agents can also increase calcium by releasing it from intracellular stores, thus inducing tonic contraction. Ingestion of food initiates peristaltic propulsive activity which, in its rhythm, is superimposed on spontaneous phasic activity. The peristaltic reflex consists of two successive phases: relation of circular muscle distal to the distending bolus (descending relaxation) and contraction proximal to the bolus (ascending contraction). In-between meals, a different, slower pattern of muscle activity prevails, known as the migrating motor complex, which helps to maintain the lumen of the intestine free of contents. Improved understanding of normal muscle function is beginning to reflect itself in improved management of patients with motility disorders.