Mechanism of action of a new prostaglandin antihypertensive, viprostol [CL 115 347; (dl)-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester]: (I). Vasodilation.

Viprostol [(dl)-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester; CL 115 347], injected directly into coronary, renal, mesenteric, femoral and carotid arteries of the anaesthetized beagle dogs at doses which did not lower the systemic arterial blood pressure, increased blood flow of the vascular beds being studied. Viprostol was as potent as I-prostaglandin E2 (I-PGE2) in the renal bed, but less potent in the other vascular beds. Viprostol was as potent as I-PGE2 in relaxing smooth muscle of the perfused isolated central ear artery of the rabbit. Viprostol maintained its antihypertensive effect in spontaneously hypertensive rats (SHR) pretreated with indomethacin, chlorpheniramine plus cimetidine, atropine or propranolol, suggesting that the vasodilating effects of viprostol were not mediated through the endogenous prostaglandin, histamine, cholinergic nervous system or beta-adrenergic nervous system. The antihypertensive effects of viprostol were not altered in SHR with bilateral nephrectomy or bilaterally ligated ureters, suggesting that the action of viprostol was not dependent on the secretory or excretory functions of the kidneys. In conclusion, viprostol exerts its antihypertensive action mainly by vasodilation in a way similar to the natural PGE2.

Synthesis of 2-alkyl- and 2-carboxy-p-tert-butylcalix[4]arenes via the lithiation of tetramethoxy-p-tert-butylcalix[4]arene.

[reaction: see text]. Tetramethoxy-p-tert-butylcalix[4]arene reacts readily with n-butyllithium to give a putative monolithiated intermediate that is substituted with alkyl halides and carbon dioxide to give in 60-75% yield conformationally mobile calix[4]arenes monosubstituted at the methylene bridge (2-position). 2-Alkyl- and 2-benzyl-substituted tetramethoxycalix[4]arenes are converted in 62-68% overall yield to the corresponding tetrahydroxy-p-tert-butylcalix[4]arenes by treatment with boron tribromide. The tetrahydroxy-p-tert-butylcalix[4]arenes exist in the cone conformation at room temperature in CDCl3 as judged by NMR spectroscopy.

Argon laser use in papillomas of the larynx.

Papillomas of the larynx are discussed, including the use of lasers. Argon lasers' differences from CO2 lasers and techniques are outlined. Case reports are given in which laryngeal papillomas were removed from two patients with the argon laser and examined by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and stereoscanning electron microscopy (SSEM). The depth and width of morphological change are noted. Peripheral to the laser impact site, four zones were observed: 1. coagulation necrosis, 2. contracted epithelial cells, 3. minimally damaged epithelial cells, and 4. morphologically undamaged epithelial cells. In Zone 2, cells were violently popped-off as heat was conducted through the epithelium. The potential for spread of papillomas was discussed and suction of the vapor plume recommended when removing laryngeal papillomas with the argon laser.

Stereoscanning electron microscopy of argon laser excised laryngeal papilloma.

Laryngeal papillomas were removed from two patients with the argon laser and examined by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and stereoscanning electron microscopy (SSEM). Two techniques, lipid-carbohydrate retention for TEM specimens and sonication for SEM, were applied in studying the papillomas. Lipid-carbohydrate retention results were in agreement with previous work in papilloma ultrastructure. The char interface was observed with the sonication technique. Peripheral to the laser impact site, four zones were observed: 1. coagulation necrosis, 2. contracted epithelial cells, 3. minimally damaged epithelial cells, and 4. morphologically undamaged epithelial cells. In Zone 2, cells were violently popped-off as heat was conducted through the epithelium. The potential for spread of papillomas is discussed and suction of the vapor plume recommended when removing laryngeal papillomas with the argon laser.

AIDS-related Kaposi's sarcoma displays differential expression of endothelial surface antigens.

The authors studied 11 cases of Kaposi's sarcoma (KS) in patients with the acquired immunodeficiency syndrome (AIDS) for their reactivity with two monoclonal antibodies (B721 and E431) that recognize endothelial cell surface antigens. Reactivity of these antibodies with KS was compared with the reactivity of other known endothelial markers (F8rAg, Ia, HCL-1). Staining was done with avidin-biotin-alkaline phosphatase immunohistochemistry on acetone-fixed frozen sections. In all samples of tumor both the spindle cell component and the vascular lining cells stained with both B721 and E431. In general, the spindle cells stained less intensely than did the vascular lining cells. There was both intratumor and intertumor variability. B721 and E431 are proposed as two additional markers for KS, and it is suggested that their reactivity with the tumor supports the hypothesis that KS is derived from vascular endothelium. The possibility is also raised that the variability of staining for vascular markers could have diagnostic possibilities, and further studies for investigation of this hypothesis are suggested.

Antihypertensive activity of dl-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl prostaglandin E2 methyl ester (CL 115,347), a new orally and transdermally long-acting antihypertensive agent.

CL 115,347 [dl-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl prostaglandin E2 methyl ester] has a broad spectrum of antihypertensive activity in many animal hypertension models in every species tested. In conscious spontaneously hypertensive rats, CL 115,347 at 0.25 to 10 mg/kg orally produced 31 to 53 mm Hg lowering of the mean arterial blood pressure (MABP) with a duration of action of 1 to greater than 8 hr. When applied transdermally, CL 115,347 was more potent and longer acting than by the oral route. At 0.03 to 1 mg/kg, topically applied CL 115,347 lowered MABP of spontaneously hypertensive rats 27 to 46 mm Hg. Duration of action was greater than 6 to greater than 24 hr. CL 115,347 was also active in conscious normotensive rats (-27 mm Hg), deoxycorticosterone-salt-induced hypertensive rats (-51 mm Hg) and aorta-coarcted hypertensive rats (-52 mm Hg) when tested at 1 mg/kg orally. At 3 mg/kg orally, CL 115,347 lowered MABP of Dahl "S" salt-sensitive rats 55 mm Hg. CL 115,347 orally and s.c. lowered MABP in two-kidney, one-clip Goldblatt renal hypertensive dogs and was accompanied by tachycardia. CL 115,347, at 0.1 and 0.2 mg/kg orally, maximally lowered the systolic blood pressure of conscious rhesus monkeys 33 to 63 mm Hg with only a slight increase in heart rate. Therefore, CL 115,347 was antihypertensive in animals with low, normal and high plasma renin activity. The present findings suggest that CL 115,347 may be useful for the treatment of human hypertension.