Manserin as a novel histochemical neuroendocrine marker in prostate cancer

ObjectivesTo investigate the presence of manserin in human prostate cancers and to correlate manserin expression with pathologic outcomes and progression-free survival.MethodsEighty-seven patients with recent prostate cancer were classified into 4 groups based on Gleason score, and manserin immunohistochemistry was correlated with Gleason sum grade. To investigate the validity of manserin as a prognostic factor, the Cox proportional hazards regression model was performed on 48 patients in our cohort with T3 or T4 prostate cancer who were initially treated with androgen deprivation therapy.ResultsThe manserin-positive rates of patients with Gleason sums of 6, 7, 8, and ≥9 were 0%, 20.0%, 35.0%, and 48.1%, respectively. Manserin-positive rates were positively correlated with Gleason sums (P = 0.0001). Median times to cancer progression in groups with (n = 8) and without (n = 40) manserin expression were 8 months and 28 months, respectively (P = 0.01). Univariate Cox analysis revealed that manserin expression, clinical stage T4, and high Gleason sum were significantly associated with progression. Multivariate analysis revealed that only 2 factors, manserin expression (hazard ratio (HR) 4.99, P = 0.01) and clinical stage T4 (HR 4.77, P = 0.03), were independent risk factors for progression.ConclusionsThis is the first report of manserin expression in human prostate cancers. Manserin may serve as a marker of prostate cancer progression.     

Stereospecific polymerization of higher α-olefins with the solvay type catalyst TiCl3/Cp2Ti(CH3)2

Polymerizations of higher α-olefins (C₁₀–C₂₀) were carried out at 40°C in heptane, using the following three catalysts which differ in the isospecificity for propene polymerization: Solvay type TiCl₃/Cp₂TiMe₂((A) highly isospecific), Solvay type TiCl₃/AlEt₃((B) isospecific) and TiCl₃.3Py/MgCl₂/AlEt₃((C) aspecific). The isospecificity of the catalysts was found to decrease in the following order: (A) ? (B) ? (C), which agrees well with the results obtained in propene polymerization. The crystallinity of these polymers is discussed in brief.     

Evaluation of 266 cases of hepatobiliary-pancreatic carcinoids

A review was undertaken to clarify the characteristics of carcinoids of the hepatobiliary-pancreatic (HBP) system (in the gallbladder, liver, choledochus, and pancreas) in terms of clinicopathological features, based on information obtained from a statistically reliable number of cases that to date had been unavailable. The material reviewed included 266 cases of HBP carcinoids (239 ordinary and 27 atypical varieties) cited in 338 international articles published in approximately 30 countries since 1920. The details of each case were carefully read and then computerized and analyzed in the analyzing system for gut-pancreatic endocrinoma (Niigata Registry). To avoid duplication, cases without individual identification (such as the age and sex of patients, and the institution providing the mateiials) were excluded. Where thought to be relevant for comparison, cases from the overall gastrointestinal series, consisting of 4789 cases (4606 excluding atypical varieties) similarly input into the same Registry, were referred to for comparative purposes. We found that the characteristics of HBP carcinoids were: female preponderance, except in the choledochus, small lesions (20 mm or less) in the gallbladder and choledochus, and large tumors (exceeding 50mm) in the liver at detection, a higher incidence of hematogenous compared to lymphogenous spread overall, a high incidence of carcinoid syndrome in the pancreas, compared to the other sites, and a relatively unfavorable postoperative prognosis overall.     

Polymerization of olefins with the TiCl4/SiO2 catalyst system modified with MgCl2

MgCl₂/TiCl₄/SiO₂ catalysts were prepared by treating TiCl₄/SiO₂ with MgCl₂ · 2THF (THF: tetrahydrofuran) at different Mg/Ti ratios. The catalysts were analysed by X-ray, electron spin resonance (ESR), atomic absorption spectrometry to determine the crystal structure, oxidation state of titanium and also contents of Ti, Al and Mg. Homo- and copolymerizations of ethylene and propene were conducted with them using Al(i-C₄H₉)₃ as a cocatalyst. The results of polymerization were correlated with the analytical data of the catalyst.     

Synthesis of vinyl-terminated isotactic poly(propylene) using the coupling reaction between Zn-terminated polymer and allyl halides

Propene was polymerized with the TiCl₃/Al(C₂H₅)₂Cl catalyst system using Zn(C₂H₅)₂ as a chain transfer reagent. The resulting Zn-terminated poly(propylene) (PP) was then brought into contact with allyl halides (chloride, bromide and iodide) in the presence of N-methylimidazole to obtain vinyl-terminated PP. Allyl bromide gave the highest conversion among these allyl halides. When the coupling reaction was conducted with allyl bromide at 40°C for 24 h, the conversion to the terminal vinyl groups was over 90% for atactic PP and approximately 60% for isotactic PP. The Zn-polymer bonds of both atactic and isotactic PP were almost quantitatively converted into terminal vinyl groups at 130°C for 3 h.     

Dietary diacylglycerol induces the regression of atherosclerosis in rabbits

Recent studies of the relation between serum triacylglycerol concentration and the risk for coronary artery disease suggest that inefficient clearance of postprandial triacylglycerols promotes atherogenesis. We recently demonstrated that dietary diacylglycerol (DAG), rich in the 1,3-species, suppresses the postprandial increase in serum triacylglycerol levels compared with dietary triacylglycerol (TAG). Here, we investigated the effects of dietary DAG on atherosclerosis in rabbits with cholesterol-induced atherosclerosis. New Zealand White rabbits (n = 20) were fed a diet containing 3% lard and 1.3% cholesterol for 50 d to induce atherosclerotic lesions. Thereafter, the rabbits were assigned to 2 groups and fed 90 g/d nonpurified diet and orally administered 5 g DAG or TAG for an additional 34 d. Reference rabbits (n = 5) were fed only the nonpurified diet throughout the 84-d study. The area of atherosclerotic lesions and aortic lipid concentrations were significantly lower in DAG-fed rabbits compared with TAG-fed rabbits. The VLDL receptor and macrophage antigen-1 mRNA expression levels were significantly lower in DAG-fed rabbits than in TAG-fed rabbits. In the liver of DAG-fed rabbits, the triacylglycerol concentration was lower and the carnitine palmitoyltransferase activity higher than in TAG-fed rabbits. Stimulation of hepatic lipid catabolism might be related to the reduced lipid accumulation in the liver and aorta by reducing the release of triacylglycerol into the circulation. Thus, long-term consumption of DAG, which reduces postprandial lipemia, might be useful for the regression of atherosclerosis by stimulating hepatic lipid catabolism and thereby modulating monocyte/macrophage migration and aortic lipid accumulation.     

Nonmammalian gonadotropin-releasing hormone molecules in the brain of promoter transgenic rats

Mammalian gonadotropin-releasing hormone (GnRH1) and nonmammalian immunoreactive GnRH subtypes were examined in transgenic rats carrying an enhanced GFP (EGFP) reporter gene driven by a rat GnRH1 promoter. Double-label immunocytochemistry was performed on EGFP(+)/GnRH1 brain sections by using antisera against GnRH1, GnRH2 (chicken II), GnRH3 (salmon), or seabream GnRH. EGFP(+)/GnRH1 neurons were in the septal-preoptic hypothalamus but not in the midbrain, consistent with GnRH1-immunopositive neurons in WT rats. Apparent coexpression of EGFP(+)/GnRH1 with other GnRH subtypes was observed. All EGFP(+) neurons in the septal-preoptic hypothalamus were GnRH1-immunopositive. However, only approximately 80% of GnRH1-immunopositive neurons were EGFP(+), which awaits further elucidation. GnRH subtypes-immunopositive fibers and EGFP(+)/GnRH1 fibers were conspicuous in the organum vasculosum of the lamina terminalis, median eminence, and surrounding the ependymal walls of the third ventricle and the aqueduct in the midbrain. These results demonstrate that the expression of the EGFP-GnRH1 transgene is restricted to the bona fide GnRH1 population and provide clear morphological evidence supporting the existence of GnRH1 neuronal subpopulations in the septal-preoptic hypothalamus, which might be driven by different segments of the GnRH promoter. This genetic construct permits analyses of promoter usage in GnRH neurons, and our histochemical approaches open questions about functional relations among isoforms of this peptide, which regulates reproductive physiology in its behavioral and endocrine aspects.     

Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative acute kidney injury

The aim of the present study was to evaluate the usefulness of a closed-loop system (STG-55; Nikkiso, Tokyo, Japan), a type of artificial endocrine pancreas for the continuous monitoring and control of intraoperative blood glucose, for preventing postoperative acute kidney injury (AKI) in patients undergoing hepatectomy. Thirty-eight patients were enrolled in this study. Glucose concentrations were controlled with either a manual injection of insulin based on a commonly used sliding scale (manual insulin group, n = 19) or the programmed infusion of insulin determined by the control algorithm of the artificial endocrine pancreas (programmed insulin group, n = 19). After the induction of anesthesia, a 20-G intravenous catheter was inserted into the peripheral forearm vein of patients in the programmed insulin group and connected to an artificial endocrine pancreas (STG-55). The target range for glucose concentrations was set to 100–150 mg/dL. The mean serum creatinine concentrations of preoperative, postoperative 24 and 48 h were 0.72, 0.78, and 0.79 mg/dL in the programmed insulin group, and 0.81, 0.95, and 1.03 mg/dL in the manual insulin group, respectively. Elevations in serum creatinine concentrations postoperative 48 h were significantly suppressed in the programmed insulin group. The STG-55 closed-loop system was effective for maintaining strict blood glucose control during hepatectomy with minimal variability in blood glucose concentrations and for suppressing elevations in serum creatinine concentrations. Strict blood glucose control by an artificial endocrine pancreas during hepatectomy may prevent postoperative AKI.     

Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans.

Pycnogenol, an extract of bark from the French maritime pine, Pinus pinaster Ait., consists of a concentrate of water-soluble polyphenols. Pycnogenol contains the bioflavonoids catechin and taxifolin as well as phenolcarbonic acids. Antioxidants, such as bioflavonoids, enhance endothelial nitric oxide (NO) synthase expression and subsequent NO release from endothelial cells. The purpose of this study was to determine Pycnogenol's effects on endothelium-dependent vasodilation in humans. This was a double-blind, randomized, placebo and active drug study. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, in healthy young men before and after 2 weeks of daily oral administration of Pycnogenol (180 mg/day) (n=8) or placebo (n=8). FBF was measured by using strain-gauge plethysmography. Neither the placebo nor Pycnogenol altered forearm or systemic hemodynamics. Pycnogenol, but not placebo, augmented FBF response to ACh, from 13.1 +/- 7.0 to 18.5 +/- 4.0 mL/min per 100 mL tissue (p<0.05). SNP-stimulated vasodilation was similar before and after 2 weeks of treatment in the control and Pycnogenol groups. The administration of N(G)-monomethyl-L-arginine, an NO synthase inhibitor, completely abolished Pycnogenol-induced augmentation of the FBF response to ACh. These findings suggest that Pycnogenol augments endothelium-dependent vasodilation by increasing in NO production. Pycnogenol would be useful for treating various diseases whose pathogeneses involve endothelial dysfunction.     

Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways

The biochemistry of cancer cells diverges significantly from normal cells as a result of a comprehensive reprogramming of metabolic pathways. A major factor influencing cancer metabolism is hypoxia, which is mediated by HIF1α and HIF2α. HIF1α represents one of the principal regulators of metabolism and energetic balance in cancer cells through its regulation of glycolysis, glycogen synthesis, Krebs cycle and the pentose phosphate shunt. However, less is known about the role of HIF1α in modulating lipid metabolism. Lipids serve cancer cells to provide molecules acting as oncogenic signals, energetic reserve, precursors for new membrane synthesis and to balance redox biological reactions. To study the role of HIF1α in these processes, we used HCT116 colorectal cancer cells expressing endogenous HIF1α and cells in which the hif1α gene was deleted to characterize HIF1α-dependent and independent effects on hypoxia regulated lipid metabolites. Untargeted metabolomics integrated with proteomics revealed that hypoxia induced many changes in lipids metabolites. Enzymatic steps in fatty acid synthesis and the Kennedy pathway were modified in a HIF1α-dependent fashion. Palmitate, stearate, PLD3 and PAFC16 were regulated in a HIF-independent manner. Our results demonstrate the impact of hypoxia on lipid metabolites, of which a distinct subset is regulated by HIF1α.