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Our results suggest that HRT with CEE plus MPA is useful for the management of elevated serum Lp(a) concentrations in middle-aged and older women. However, follow-up studies are needed to determine whether this finding is related to the future prevention of coronary heart disease events.

Purpose: Recently, 14-member macrolide antibiotics such as clarithromycin and roxithromycin have been shown to have anticancer and antiangiogenic effects.We investigated the suppressive effect of roxithromycin on accelerated hepatocellular carcinoma growth in a rat hepatocarcinogenetic model and compared results with effects from TNP-470. Experimental Design: Tumor was induced by oral diethylnitrosamine administration for 17 weeks. Normal saline,TNP-470 (50 mg/kg), or roxithromycin (40 or 100 mg/kg) was administered i.p. thrice per week from week 10 to 17. Results: Carcinomatous tissue growing outside dysplastic nodules and a marked expression of placental glutathione S-transferase were detected in rats with induced carcinogenesis. Tumor growth was accompanied by augmented expression of inducible nitric oxide synthase, activation of nuclear factor nB, and increased lipid peroxidation level. All these effects were absent in animals that received roxithromycin or TNP-470. The inhibitory effect of roxithromycin was dose dependent and no clear differences were noted between groups given roxithromycin 100 mg/kg and TNP-470 50 mg/kg. Conclusions: Our results indicate that roxithromycin inhibits oxidative stress, nitric oxide production, and nuclear factor nB activation induced by experimental hepatocarcinogenesis. The data provide additional evidence for the potential use of roxithromycin in treatment of hepatocellular carcinoma prevention.Hepatocellular carcinoma is one of the most common malignancies in the world, especially in Asia and Africa. The vast majority of patients have preexisting cirrhosis at the time they develop hepatocellular carcinoma. Despite many treatments for this disease in recent decades, its long-term therapeutic outcome remains poor. Prevention seems to be the best strategy in lowering the present incidence of the disease. A preventive effect of an acyclic retinoid on the development of a second tumor after ablation of an original tumor has been shown by one group (1, 2). Conflicting results on the potential preventive effect of IFN have also been reported (3-5). To validate and expand the concept of chemoprevention to other therapeutics, the molecular events that contribute to hepatocarcinogenesis in the liver with cirrhosis need to be identified and targeted.It was reported that tumor growth is angiogenesis dependent by the discovery of angiostatin or endostatin, both of which specifically inhibit endothelial proliferation (6, 7). There are several drugs that have angiogenesis inhibitory properties; however, most of these are restricted by excessive toxicity and limited efficacy. Roxithromycin is a new 14-member macrolide antibiotic that has a wide antibacterial spectrum against pathogens and an immunomodulatory effect. Interestingly, on tumor angiogenesis, Yatsunami et al. (8) reported that roxithromycin at concentrations >20 Amol/L inhibited endothelial cell migration and tube formation. Moreover, we previously reported the strong inhibitory effect of roxithromycin on tumor necro...

AimsTo identify donor-related risk factors associated with graft endothelial failure and postoperative endothelial cell density (ECD) reduction after Descemet's stripping automated endothelial keratoplasty (DSAEK).MethodsThis was a single-center retrospective study conducted from July 2006-December 2016. We included 584 consecutive eyes (482 patients) that underwent DSAEK for the treatment of laser iridotomy-related bullous keratopathy (192 eyes), pseudophakic bullous keratopathy (137 eyes), regraft (96 eyes), Fuchs' endothelial corneal dystrophy (FECD; 59 eyes) and others (100 eyes). Twenty-three donor- and recipient-related risk factors potentially associated with graft failure and ECD reduction were assessed using Cox hazard models and linear mixed effect models.ResultsThe median age of the patients was 73.5 years (male; 35.6%). After DSAEK, ECD decreased from 2,674 cells/mm2 (95% confidence interval [CI]; 2,646–2,701) to 1,132 (1,076–1,190) at 12 months and 904 (845–963) at 24 months (P < 0.001). Fifty-five eyes (9.4%) had graft endothelial failure without rejection. This failure was associated with donor pseudophakic lens status (hazard ratio [HR]; 2.67, CI; 1.50–4.76, P = 0.001) and preoperative endothelial folds (HR; 2.82, CI; 1.20–6.62, P = 0.02). The incidence of graft endothelial failure in non-FECD patients was significantly higher among those receiving donor grafts with a pseudophakic lens status and preoperative presence of endothelial folds (P < 0.001). Postoperative ECD loss was significantly greater in eyes with these risk factors compared to those without (P = 0.007).ConclusionsPseudophakic status and/or presence of preoperative endothelial folds are the significant donor risk factors for endothelial failure in non-FECD patients.

The potential spin-triplet heavy-fermion superconductor UTe2 exhibits signatures of multiple distinct superconducting phases. For field aligned along the b axis a metamagnetic transition occurs at μ0Hm ≈ 35 T. It is associated with a spin reorientation inducing magnetic fluctuations that may be beneficial for the field-enhanced superconductivity surviving up to Hm. Once the field is tilted away from the b towards the c axis, a re-entrant superconducting phase emerges just above Hm(θ). However, under pressure this phase detaches from Hm. In order to better understand this remarkably field-resistant phase we investigate magnetic torque and electrical magnetotransport in pulsed magnetic fields. The observed zero-Hall signal evidences the superconducting nature of this distinct high-field phase. We determine its record-breaking upper critical field of μ0Hc2 ≈ 75 T. Furthermore, we provide evidence for a strong angle-dependent reduction of magnetic scattering, likely accompanied by changes in the electronic band structure induced by the tilted field.