Stereoselective Synthesis of Bisfuranoxide (Aurochrome, Auroxanthin) and Monofuranoxide (Equinenone 5',8'-Epoxide) Carotenoids by Double Horner-Wadsworth-Emmons Reaction.

The stereoselective synthesis of C-all--carotenoids with the formal hexahydrobenzofuran skeletons aurochrome, auroxanthin, and equinenone-5',8'-epoxide is reported. The synthesis is based on a one-pot or stepwise double Horner-Wadsworth-Emmons (HWE) reaction of a terminal enantiopure C-5,6-epoxycyclohexadienylphosphonate and a central C-trienedial. The ring expansion of the epoxycyclohexadienylphosphonate, generated by a Stille cross-coupling reaction, to the hexahydrobenzofuran skeleton was promoted by the reaction conditions of the HWE reaction prior to double-bond formation.

Cardiovascular disease risk stratification by the Framigham score is markedly improved by ambulatory compared with office blood pressure.

Introduction And Objectives: Ambulatory blood pressure (BP) better predicts cardiovascular disease (CVD) outcomes than office BP measurements (OBPM). Nonetheless, current CVD risk stratification models continue to rely on exclusively daytime OBPM along with traditional factors, eg, age, sex, smoking, dyslipidemia, and/or diabetes.

Methods: Data from 19 949 participants of the primary care-based Hygia Project assessed by 48-hour ambulatory BP monitoring (ABPM) and without prior CVD events were used to compare the diagnostic accuracy, discrimination, and performance of the original Framingham risk score (RS) and its adjusted version to the Hygia Project study population (RS) with that of a novel CVD risk stratification model constructed by replacing OBPM with ABPM-derived prognostic parameters (RS).

Bedtime hypertension chronotherapy best reduces cardiovascular disease risk as corroborated by the Hygia Chronotherapy Trial. Rebuttal to European Society of Hypertension officials.

Reinhold Kreutz and colleagues in a recent editorial claim the Hygia Chronotherapy Trial lacks credibility because of deficient methods, thereby dismissing both the plausibility and clinical significance of its reported findings. They misstate and misrepresent crucial information, findings and conclusions unambiguously detailed in the published report of the Hygia Chronotherapy Trial. The purpose of this communication is to provide a complete rebuttal to each and every one of the misleading and scientifically unsupported claims by Kreutz et al.

The Hygia Project and Hygia Chronotherapy Trial: insights of we clinical investigators on the impact of the embedded continuing medical education on primary-care practice and improved patient cardiovascular health.

The participating doctors of the Hygia Chronotherapy Trial (HCT) are aware of the criticisms of its published findings, which have been unjustifiably misrepresented in letters to the editors and commentaries, perhaps because of lack of understanding of the foundations of the Hygia Project, in which the HCT is nested. Thus, our purpose through this communication is to highlight the unique features of the Hygia Project and HCT in terms of: (i) organization, management, and quality control, (ii) physician training/continuing medical education, and (iii) impact on every-day primary-care clinical practice specifically improved patient care through 48 h ambulatory blood pressure monitoring to diagnose and optimally manage by bedtime hypertension chronotherapy to markedly improve the cardiovascular health of our patients.

Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial.

Aims: The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction.

Methods And Results: In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.

Asleep blood pressure: significant prognostic marker of vascular risk and therapeutic target for prevention.

Aims: Sleep-time blood pressure (BP) is a stronger risk factor for cardiovascular disease (CVD) events than awake and 24 h BP means, but the potential role of asleep BP as therapeutic target for diminishing CVD risk is uncertain. We investigated whether CVD risk reduction is most associated with progressive decrease of either office or ambulatory awake or asleep BP mean.

Methods And Results: We prospectively evaluated 18 078 individuals with baseline ambulatory BP ranging from normotension to hypertension.

Synthesis of labile all-trans-7,8,7',8'-bis-acetylenic carotenoids by bi-directional Horner-Wadsworth-Emmons condensation.

A new stereoselective synthesis of the C40-bis-acetylenic carotenoids all-trans-(3R,3'R)-alloxanthin and all-trans-3,4,7,8,3',4',7',8'-octadehydro-β,β-carotene, both compounds featuring a stereochemically labile C7-C10 enyne, based on a bi-directional Horner-Wadsworth-Emmons (HWE) reaction of a C15-phosphonate and a central C10-dialdehyde, is reported. The triene unit of the latter fragment was synthesized using the acyclic metathesis/dimerization reaction.

Size fractionation of non-volatile dissolved organic compounds and metal species in German white wines by combining on-line tangential-flow multistage ultrafiltration, a home-built carbon analyser, and inductively coupled plasma mass spectrometry.

Organic metal species and their size fractions in three German white wines were characterized by combining multistage ultrafiltration (MST-UF), determination of non-volatile dissolved organic carbon (NV-DOC) by a home-built carbon analyser, and metal quantification by inductively coupled plasma mass spectrometry (ICP-MS). First, NV-DOC and metal species in selected "dry" German white wines were fractionated on-line using MST-UF in the size range of >100 kDa to <1 kDa. For this purpose a 20 mL sample of the wine under study diluted 1:10 with high-purity water was processed through a cascade system of hydrophilized polyethersulfone-based flat membranes of decreasing cut-off (100, 50, 10, 5, and 3 kDa).

Development of a procedure for the multi-element determination of trace elements in wine by ICP-MS.

An inductively coupled plasma mass spectrometric (ICP-MS) procedure has been developed for the determination of trace elements in wine. The procedure consists in simple 1+1 dilution of the wine and semi-quantitative analysis (without external calibration) using In as internal standard. Thirty-one elements at concentrations ranging from 0.

Plasma levels of the soluble fraction of tumor necrosis factor receptors 1 and 2 are independent determinants of plasma cholesterol and LDL-cholesterol concentrations in healthy subjects.

In the last few years, it has been demonstrated that tumor necrosis alpha (TNF-alpha) has important effects on whole-body lipid metabolism. TNF-alpha administration has been found to produce an increase in serum cholesterol levels and increased hepatic hydro-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase activity in mice. The purpose of this study was to test whether plasma levels of the soluble forms of the TNF-alpha receptors 1 and 2 (sTNFR1, sTNFR2) are associated with lipid abnormalities.

Oxidative stress, mitochondrial respiration, and glycemic control: clues from chronic supplementation with Cr3+ or As3+ to male Wistar rats.

Multiple experiments in male Wistar rats were designed to clarify the role of mitochondrial dysfunction in the mechanisms of oxidative stress-related diseases and toxicity-induced pathologies. In this particular report, 21 male Wistar rats were supplemented ad libitum with either As3+ or Cr3+ salts in drinking water to assess insulin secretion patterns in vivo and in vitro, mitochondrial dysfunction, oxidative stress, liver damage, basal insulin, and glucose tolerance curves, among other parameters. Results were compared with a control group without any metal supplementation.

Further evidence for recessive inheritance of von Willebrand disease with abnormal binding of von Willebrand factor to factor VIII.

A new family with a bleeding diathesis and FVIII deficiency secondary to abnormal binding of von Willebrand factor (vWF) to factor VIII (FVIII) is described. Two propositi of this family, an 18-year-old male and a 33-year-old female, both with a history of epistaxis, bruising, bleeding from the gums, epistaxis, hemarthrosis, and hematoma, were analyzed. Also additional members of the same family with no bleeding history were also studied.

[A clinical and biological study of 11 cases of essential thrombocythemia].

11 patients diagnosed as suffering from essential thrombocytosis at "Hospital Xeral de Lugo" between 1978 and 1986, are presented. 7 patients were female and 4 were male with a median age of 63 years. 6 patients had thrombotic manifestation, 6 had hemorrhagic symptoms, 2 had both manifestations and only one had no thrombo-hemorrhagic clinical symptoms.