The ability of a number of prostaglandin F_2α(PGF_2α) analogs to mobilize intracellular Ca²⁺ [Ca²⁺]_i and to compete for [³H]PGF_2α binding to prostaglandin F_2α receptors (FP) was evaluated. Radioligand binding studies measuring displacement of [³H]PGF_2αby a variety of FP prostaglandin analogs yielded the following rank order of affinities: travoprost acid [(+)-16-m-trifluorophenoxy tetranor PGF_2α; (+)-fluprostenol] > bimatoprost acid (17-phenyl-trinor PGF_2α) ≫ unoprostone (13,14-dihydro-15-keto-20-ethyl PGF_2α) = bimatoprost (17-phenyl-trinor PGF_2α ethyl amide) ≥ Lumigan (bimatoprost ophthalmic solution). In FP functional studies, travoprost acid (EC₅₀ = 17.5–37 nM, n = 13), bimatoprost acid (EC₅₀ = 23.3–49.0 nM,n = 6–12), unoprostone (EC₅₀ = 306-1270 nM, n = 4–8), bimatoprost (EC₅₀ = 3070- 3940 nM, n = 4–9), and Lumigan (EC₅₀ = 1470–3190 nM,n = 5–9) concentration dependently stimulated [Ca²⁺]_i mobilization via the rat (A7r5 cells), mouse (3T3 cells), and cloned human ocular FP prostanoid receptors. The rank order of potency of these compounds at the FP receptor of the three species was similar and in good agreement with the determined binding affinities. The agonist effects of these compounds were concentration dependently blocked by the FP receptor-selective antagonist, AL-8810 (11β-fluoro-15-epi-15-indanyl-tetranor PGF_2α) (K_i = 0.6–1.3 μM). These studies have demonstrated that bimatoprost, unoprostone, and bimatoprost acid possess direct agonist activities at the rat, mouse, and human FP prostanoid receptor and that travoprost acid is the most potent of the synthetic FP prostaglandin analogs tested.

The treatment of colorectal cancer continues to improve, but it still remains the second leading cause of cancer-related death in the United States. In 2001, there will be over 135,000 new cases of...

Background Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus, otherwise unexplained deranged liver enzyme levels, and elevated levels of serum bile acid. ICP has been observed more commonly in hepatitis C virus (HCV) infected women than in women with no HCV infection, and some experts advocate testing for HCV infection in all patients with ICP. Aims The aim of our study was to examine the clinical characteristics of pregnant women with ICP and HCV infection. Methods We reviewed the records of pregnant women between 18 and 45 years of age over a period of 6 years with an International Classification of Diseases, Ninth Revision (ICD-9) diagnosis of HCV infection, ICP, or both. We collected demographic, clinical, and financial data on all the patients and compared them with and without a diagnosis of ICP. Results There were 91 pregnant women with a diagnosis of HCV, and 41 (45%) of these women were diagnosed with ICP. HCV-infected patients with ICP had a significantly higher median viral load compared with those without ICP (495 000 vs. 8000 copies/ml, P<0.001). The median total financial charges spent for the care of ICP patients with HCV infection was significantly higher than that spent on ICP patients without HCV infection ($12 753.00 vs. $8970.00, P=0.01). Conclusion We found a high prevalence of ICP among pregnant women infected with HCV, and those with ICP had a higher HCV viral load. Women with suspected ICP should be tested for the presence of HCV.