Radical Deuteration with DO: Catalysis and Mechanistic Insights.

Selective incorporation of deuterium atoms into molecules is of high interest for labeling purposes and for optimizing properties of drug candidates. A mild and environmentally benign method for the deuteration of alkyl iodides via radical pathway using DO as source of deuterium has been developed. The reaction is initiated and mediated by triethylborane in the presence of dodecanethiol as a catalyst.

Catechols as Sources of Hydrogen Atoms in Radical Deiodination and Related Reactions.

When used with trialkylboranes, catechol derivatives, which are low-cost and low toxicity, are valuable hydrogen atom donors for radical chain reactions involving alkyl iodides and related radical precursors. The system 4-tert-butylcatechol/triethylborane has been used to reduce a series of secondary and tertiary iodides, a xanthate, and a thiohydroxamate ester. Catechol derivatives are right in the optimal kinetic window for synthetic applications, as demonstrated by highly efficient radical cyclizations.

Total synthesis of aignopsanes, a class of sesquiterpenes: (+)-aignopsanoic acid A, (-)-methyl aignopsanoate A, and (-)-isoaignopsanoic A.

A general strategy for the synthesis of aignopsanes, a new family of sesquiterpene natural products of marine origin, is presented. The total synthesis of (+)-aignopsanoic acid A (1), (-)-methyl aignopsanoate A (2), and (-)-isoaignopsanoic A (3) has been achieved and their absolute configuration confirmed. (+)-Microcionin-1 (4), a structurally related furanosesquiterpene isolated in both enantiomeric forms from marine sponges, was also synthesized and its absolute configuration established in an unambiguous way.

Palladium-catalyzed ortho-selective C-H deuteration of arenes: evidence for superior reactivity of weakly coordinated palladacycles.

We disclose a protocol for the palladium-catalyzed ortho-selective C-H deuteration of arenes. Phenylacetic acids and benzoic acids are suitable substrates for this reaction. This reaction offers a catalytic route to ortho-deuterated phenylacetic acids and benzoic acids and demonstrates the sharp difference in reactivity of palladacycle intermediates held together by weak and strong coordination.

Ligand-accelerated ortho-C-H alkylation of arylcarboxylic acids using alkyl boron reagents.

A protocol for the Pd(II)-catalyzed ortho-C-H alkylation of phenylacetic and benzoic acids using alkylboron reagents is disclosed. Monoprotected amino acid ligands (MPAA) were found to significantly promote reactivity. Both potassium alkyltrifluoroborates and alkylboronic acids were compatible coupling partners.

Hepato-systemic gradient of carbon monoxide in cirrhosis.

Background And Aims: Experimental data suggest that in liver cirrhosis splanchnic and systemic vasculature exhibit marked endothelial Carbon monoxide (CO) overproduction, while recent data demonstrated heme oxygenase (HO) hyperactivity in the liver of rats with cirrhosis. No data are so far available on CO levels in the hepatic veins of cirrhotic patients. We aimed at evaluating whether plasma CO levels differ between systemic (peripheral vein) and hepatic (hepatic vein) circulation in patients with viral cirrhosis with and without ascites.

Radical chain reduction of alkylboron compounds with catechols.

The conversion of alkylboranes to the corresponding alkanes is classically per-formed via protonolysis of alkylboranes. This simple reaction requires the use of severe reaction conditions, that is, treatment with a carboxylic acid at high temperature (>150 °C). We report here a mild radical procedure for the transformation of organoboranes to alkanes.

Elevated plasma levels of urotensin II do not correlate with systemic haemodynamics in patients with cirrhosis.

Background: The hyperdynamic circulation of hepatic cirrhosis is related to decreased systemic vascular resistance due to arterial vasodilation. Urotensin II plasma levels are increased in cirrhotic patients, and have been suggested to play a role in the pathogenesis of systemic haemodynamic alterations.

Aim: To evaluate the relationships between systemic haemodynamics and urotensin II plasma levels.

Role of catechol in the radical reduction of B-alkylcatecholboranes in presence of methanol.

Mechanistic investigations on the previously reported reduction of B-alkylcatecholboranes in the presence of methanol led to the disclosure of a new mechanism involving catechol as a reducing agent. More than just revising the mechanism of this reaction, we disclose here the surprising role of catechol, a chain breaking antioxidant, which becomes a source of hydrogen atoms in an efficient radical chain process.

Increased plasma carbon monoxide in patients with viral cirrhosis and hyperdynamic circulation.

Objectives: Our aim was to measure plasma carbon monoxide (CO) in patients with liver cirrhosis and portal hypertension.

Methods: In 36 cirrhotic patients (24 with ascites) and 9 healthy volunteers, we evaluated CO plasma levels and systemic hemodynamics (using ultra-trace gas chromatography and echocardiography, respectively). Heme oxygenase (HO) activity and expression were measured in isolated polymorphonuclear (PMN) cells.

Transient hepatic attenuation difference (THAD) in biliary duct disease.

Background: THADs are associated with a wide spectrum of hepato-biliary pathologies. The aim of this paper is to find out the role of THADs in the imaging assessment of biliary diseases. We performed a retrospective study to establish the frequency of arterial phenomena in patients with specific biliary diseases.

Hemodynamic alterations in liver cirrhosis.

In cirrhotic patients, portal hypertension is often associated with a hyperdynamic circulatory syndrome, with high cardiac output and reduced systemic vascular resistance and arterial pressure. The hyperdynamic circulatory syndrome is due to arterial vasodilation that mainly occurs in the splanchnic circulation, while vascular resistance in the other circulatory districts is normal or increased, accordingly with the degree of portal hypertension, liver impairment and activation of the renin-aldosterone and sympathetic nervous system. The mechanism(s) leading to splanchnic vasodilation is unclear.

Uveitis in autoimmune hepatitis: a case report.

In this case report we describe for the first time an association between autoimmune hepatitis (AIH) and uveitis, without any doubts about other possible etiologies, such as HCV, since all the old reports describe the association of AIH with iridocyclitis before tests for HCV-related hepatitis could be available. A 38-year-old businessman with abnormal liver function tests and hyperemia of the bulbar conjunctiva was admitted to the hospital. Six years before admission, the patient presented with persistent fever, arthralgias, conjunctival hyperemia, leukocytosis and increased ESR, referred to acute rheumatic fever.

Long-term albumin infusion improves survival in patients with cirrhosis and ascites: an unblinded randomized trial.

Aim: To investigate the effects of long-term albumin administration on survival, recurrence of ascites and onset of other complications.

Methods: One hundred consecutive patients admitted for first-onset ascites were randomized to receive diuretics plus human albumin 25 g/wk in the first year and 25 g every two wk thereafter (group 1) or diuretics alone (group 2). The primary endpoint was survival without liver transplantation.

High CXCL10 expression in rejected kidneys and predictive role of pretransplant serum CXCL10 for acute rejection and chronic allograft nephropathy.

Background: Several experimental models have shown that CXCL10 is required for initiation and development of graft failure caused by both acute and chronic rejection.

Methods: CXCL10 expression and distribution was investigated in tissue specimens obtained from 22 patients suffering from acute rejection (AR) or chronic allograft nephropathy (CAN) by using in situ hybridization. Furthermore, pretransplantation sera of 316 cadaveric kidney-graft recipients were tested retrospectively for serum CXCL10 levels by a quantitative sandwich immunoassay.

Hemodynamic derangement and cardiac dysfunction in cirrhosis.

Liver cirrhosis is characterized by a long course that lasts between 15 and 20 years. The natural history of this disease depends mainly on the occurrence and progression of single complications which are today more fully understood and therefore more treatable. More specifically, those complications involving hemodynamic mechanisms have been extensively studied in recent years.

High pretransplant serum levels of CXCL10/IP-10 are related to increased risk of renal allograft failure.

In experimental models, the chemokine CXCL10/IP-10 is required for graft failure owing to both acute and chronic rejection. In the present study, pretransplantation sera from 316 cadaver kidney graft recipients were tested for serum CXCL10 and CCL22/MDC levels by an ELISA assay. Kidney graft recipients with normally functioning grafts showed significantly lower serum CXCL10 levels than patients who experienced graft failure, whereas no differences for serum CCL22 levels were observed.

Effects of dietary supplementation with arachidonic acid on platelet and renal function in patients with cirrhosis.

Advanced cirrhosis is associated with reduced platelet function and altered renal function and sodium handling. Arachidonic acid (AA) metabolites contribute to platelet aggregation and to maintain the response to diuretics in advanced cirrhosis. In the present study, we tested the effects of a dietary supplementation for 8 weeks with a triacylglycerol (triglyceride) enriched in AA (ARASCO; 4 g/day) or oleic acid (OA) on plasma and membrane fatty acid composition, platelet aggregation and renal prostaglandin (PG) metabolism.

Spiral computed tomography versus ultrasound in the follow-up of cirrhotic patients previously treated for hepatocellular carcinoma: a prospective study.

Background/aims: To assess the value of hepatic-arterial-phase computed tomography (HAP-CT) versus ultrasound (US) plus alpha-fetoprotein (AFP) in the surveillance of cirrhotic patients with previously treated hepatocellular carcinoma (HCC).

Methods: Thirty-six cirrhotic patients, treated for single nodular HCC <4cm with complete response and no evidence of other focal lesions, were enrolled in a prospective study and underwent simultaneous AFP/US/spiral-CT follow-up every 6 months. Focal lesions were considered recurrences when they appeared as globular enhancement areas (EA) at HAP-CT and increased in size during the follow-up.

Multiple immune disorders in unrecognized celiac disease: a case report.

We reported a female patient with unrecognized celiac disease and multiple extra intestinal manifestations, mainly related to a deranged immune function, including macroamilasemia, macrolipasemia, IgA nephropathy, thyroiditis, and anti-b2-glicoprotein-1 antibodies, that disappeared or improved after the implementation of a gluten-free diet.

Effect of antiviral treatment in patients with chronic HCV infection and t(14;18) translocation.

Hepatitis C virus (HCV) may be associated with the mixed cryoglobulinemia syndrome and other B-cell lymphoproliferative disorders (LPDs). The t(14;18) translocation may play a pathogenetic role. Limited data are available regarding the effects of antiviral therapy on rearranged B-cell clones.

Prevalence of bcl-2 rearrangement in patients with hepatitis C virus-related mixed cryoglobulinemia with or without B-cell lymphomas.

Background: Hepatitis C virus (HCV) infection is strictly associated with mixed cryoglobulinemia, a benign B-cell lymphoproliferative disorder that may evolve to lymphoma. An increased prevalence of bcl-2 rearrangement (the t(14;18) translocation) has been shown in patients infected with HCV.

Objective: To evaluate the prevalence of bcl-2 rearrangement in patients with HCV-related mixed cryoglobulinemia and patients with chronic hepatitis but no cryoglobulinemia.

Impaired sympathetic regulation of cerebral blood flow in patients with cirrhosis of the liver.

Continuous recording of mean cerebral blood flow velocity (MCBFV) by Doppler ultrasound allows detection of low-frequency (LF) oscillations, which reflect sympathetic activity in the cerebral circulation. To establish whether the sympathetic drive to the cerebral circulation is altered in patients with compensated cirrhosis, and, if so, where alterations take place, LF oscillations of MCBFV, heart rate (RR interval) and systolic arterial pressure (SAP) were analysed in 10 patients with cirrhosis and 10 control subjects during supine rest and on stimulation of carotid baroreceptors using a neck chamber applying sinusoidal suction. Bivariate analysis was used to study the relationship between pairs of oscillations.

Cardiovascular effects of canrenone in patients with preascitic cirrhosis.

In patients with cirrhosis and portal hypertension, standing induces a reduction in cardiac index (CI) and an increase in systemic vascular resistance index. Our previous studies indicate that this abnormal hemodynamic response to standing is due to an altered myocardial function, because cirrhotic patients are unable to compensate for the reduced preload with an increase in left ventricular (LV) ejection fraction (EF) and stroke volume. To evaluate whether the cardiac dysfunction in cirrhosis is influenced by canrenone, an aldosterone antagonist, 8 patients with preascitic, nonalcoholic cirrhosis, and portal hypertension underwent echocardiographic assessment of LV function and systemic hemodynamics and determinations of plasma volume, urinary sodium excretion, and plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (PNE) when on a 150-mmol/d-sodium diet (baseline), after 1 month on canrenone (100 mg/d) plus a 40-mmol/d-sodium diet and after 1 month on canrenone plus a 150-mmol/d-sodium diet.