Connecting primary and secondary metabolism: AreB, an IclR-like protein, binds the ARE(ccaR) sequence of S. clavuligerus and modulates leucine biosynthesis and cephamycin C and clavulanic acid production.

A protein binding to the autoregulatory element (ARE) upstream of the regulatory ccaR gene of Streptomyces clavuligerus was isolated previously by DNA affinity binding. The areB gene, encoding this protein, is located upstream and in opposite orientation to the leuCD operon of S. clavuligerus; it encodes a 239-amino-acid protein of the IclR family with a helix-turn-helix motif at the N-terminal region.

Specific integrin labeling in living cells using functionalized nanocrystals.

We present an integrin labeling method using functionalized quantum dots (QDs). Cyclic Arg-Gly-Asp (RGD) peptides and a biotin-streptavidin linkage are used to specifically couple individual QDs to integrins of living cells. The spacer distance between the RGD sequence and the QD surface is a crucial parameter to ensure specific binding to individual alpha(v)beta(3) integrins of osteoblast cells.

Protein repellent properties of covalently attached PEG coatings on nanostructured SiO(2)-based interfaces.

In this study, we report the systematic comparison of different poly(ethylene glycol) (PEG) self-assembled monolayers on glass with respect to their protein adsorption and cell adhesion resistance. Combining PEGylation with micellar nanolithography allowed the formation of gold nanoparticle arrays on glass and selective coverage of the free glass area by PEG. The gold nanoparticles serve as anchor points for the attachment of individual proteins and peptides such as the cell-matrix adhesion promoting cyclic RGDfK motif or the kinesin motor protein Eg5.

Long-term outcome of a phase II study of weekly docetaxel with a short course of estramustine and enoxaparine in hormone-resistant prostate cancer patients.

Objective: The objective was to define the toxicity and activity of weekly docetaxel administered with a short course of estramustine and enoxaparine in patients with hormone-resistant prostate cancer (HRPC).

Patients And Methods: Twenty-four patients were treated with the next regimen: weekly docetaxel 36 mg/m(2) iv for three consecutive weeks every 28 days, and estramustine 280 mg three times a day for three consecutive days beginning the day before docetaxel (days 1-3, 8-10 and 15-17). In order to prevent thromboembolic events, 40 mg of subcutaneous enoxaparine was administered daily sc on the same days as estramustine.

Mimicking cellular environments by nanostructured soft interfaces.

We present herein an innovative technique for decorating soft polymer surfaces with metallic nanostructures fabricated by diblock copolymer micelle nanolithography. Thus far, such nanolithography has been limited to plasma-resistant inorganic substrates such as glass. Our new development is based on the transfer of nanopatterns from glass to soft substrates.

Exploring allelic imbalance within paraffin-embedded tumor biopsies using pyrosequencing technology.

Background: The comparison of molecular genetic changes in healthy and pathological tissues has historically led to the identification of oncogenes and tumor suppressor genes. It is very common that studies investigating loss of heterozygosity are carried out retrospectively on paraffin-embedded samples.

Methods: In this study, we evaluated the power of pyrosequencing for determining the loss of heterozygotic regions.

[Endemic goiter and iodine deficiency: are they still a reality in Spain].

Objective: To estimate the prevalence of goiter and iodine deficiency in a health district in the Autonomous Community of Valencia, given the absence of data in this region of Spain.

Material And Methods: We conducted a descriptive, epidemiologic, cross-sectional study, stratified by age and sex, in four interior regions of the province of Valencia. We selected students aged from 6 to 14 years old in 20 centers.

Kinetics of tienilic acid bioactivation and functional generation of drug-protein adducts in intact rat hepatocytes.

Drug-induced autoimmune hepatitis is among the most severe hepatic idiosyncratic adverse drug reactions. Considered multifactorial, the disease combines immunological and metabolic aspects, the latter being to date much better known. As for many other model drugs, studies on tienilic acid (TA)-induced hepatitis have evidenced the existence of bioactivation during the hepatic oxidation of the drug, allowing the identification of the neoantigen of anti-LKM2 autoantibodies and the pathway responsible for its formation.

[Cystic ureteritis in a kidney transplantation candidate].

Cystic ureteritis is a very uncommon pathology, whose pathogenesis is not well established. It is usually asociated with chronic infectious factors. It presents unspecific symptoms but characteristic radiologic findings.

Highly efficient biocatalytic resolution of cis- and trans-3-aminoindan-1-ol: syntheses of enantiopure orthogonally protected cis- and trans-indane-1,3-diamine.

The efficient chemoenzymatic synthesis of enantiopure 1,3-difunctionalized indane derivatives has been achieved. The corresponding cis and trans N-protected amino alcohols were successfully resolved by acetylation using lipase B, which is a biocatalyst isolated from Candida antarctica. All the possible isomers were obtained in very good chemical yields and ee values (>99 %).

[Effects of valproate on sexual development].

Introduction: Valproate use in young girls has been associated with the adverse endocrinological effects of weight gain and hyperandrogenism. Furthermore, polycystic ovaries and hyperinsulinism have been described in adult women. In men and young boys, however, the possible adverse endocrinological effects of valproate have scarcely been analyzed.

Synthesis of (R)-3,4-diaminobutanoic acid by desymmetrization of dimethyl 3-(benzylamino)glutarate through enzymatic ammonolysis.

Lipase B from Candida antarctica is shown to be a highly efficient catalyst for the desymmetrization of dimethyl 3-(benzylamino)glutarate (1) through aminolysis and ammonolysis reactions. Using this procedure, enantiopure monoamides are obtained in high yield. The synthetic value of these compounds is demonstrated by the preparation of an enantiopure nonnatural amino acid, i.

Differential serological testing by simultaneous indirect immunofluorescent antibody test in canine leishmaniosis and ehrlichiosis.

A mixed indirect fluorescence antibody test (IFAT), based on cultured promastigotes Leishmania infantum and formol-inactivated suspension of cells infected with the bacteria Ehrlichia canis, was applied to make a differential diagnosis between canine ehrlichiosis and leishmaniosis. A titre greater than 80 was considered positive for antibodies to E. canis and suggestive of antibodies to L.

Nitric oxide-scavenging properties of some chalcone derivatives.

The implication of NO in many inflammatory diseases has been well documented. We have previously reported that some chalcone derivatives can control the iNOS pathway in inflammatory processes. In the present study, we have assessed the NO-scavenging capacity of three chalcone derivatives (CH8, CH11, and CH12) in a competitive assay with HbO(2), a well-known physiologically relevant NO scavenger.

Involvement of peroxynitrite on the early loss of p450 in short-term hepatocyte cultures.

The biological chemistry of nitric oxide (NO) in the oxygenated cellular environment is extremely complex. It involves the direct interaction of NO with specific biomolecules and the so-called indirect effects, due to secondary more potent oxidant species derived from NO which are also able to react with DNA, lipids, thiols and transition metals (Wink et al., 1996; Nathan, 1992).

Differential sensitivity of rat hepatocyte CYP isoforms to self-generated nitric oxide.

Early loss of P450 in rat hepatocyte cultures appears directly related to nitric oxide (NO) overproduction. This study investigates the influence of endogenously generated NO (or NO-derived species) on the relative expression of cytochrome P450 (CYP) isoforms in rat hepatocytes. Our results support the view that loss of P450 holoenzyme in culture is the ultimate consequence of a NO driven process, activated during the common hepatocyte isolation procedure, that leads to an accelerated and selective degradation of specific CYP apoproteins.

[Nevirapine induces abstinence symptoms in patients on a methadone maintenance program with HIV infection].

The objective of this study was to investigate the potential inductive effect of nevirapine (NVP) with methadone. Eight patients on the methadone maintenance programme with anti-retroviral therapy because of their infection with HIV, well maintained with methadone and without symptoms of abstinence were studied. All were included in a study of measurement of plasma levels of methadone.

Peroxynitrite generated from constitutive nitric oxide synthase mediates the early biochemical injury in short-term cultured hepatocytes.

Early loss of P450 in rat hepatocyte cultures appears directly related to nitric oxide (NO) overproduction. This study provides experimental evidence for the induction - shortly after isolation through the classical procedure - of strong oxidative stress that involves both oxygen-derived and NO-derived species. NO formation at this stage is due to the early activation of liver constitutive NO synthase (cNOS).

Endogenous nitric oxide is responsible for the early loss of P450 in cultured rat hepatocytes.

Loss of P450 during the early hours of monolayer formation is known to be the more serious limitation of primary cultured hepatocytes as an adequate model for the study of drug metabolism, toxicity and P450 induction. This study reports that endogenous nitric oxide (NO) formation is activated shortly after isolation by the classical collagenase-based liver perfusion methods. Both rapid P450 loss and aerobic mitochondrial energy metabolism impairment -- with subsequent changes on glucose metabolism -- are directly related to the high local generation of the radical at this stage.

Methimazole-mediated enhancement of albendazole oral bioavailability and anthelmintic effects against parenteral stages of Trichinella spiralis in mice: the influence of the dose-regime.

The influence of methimazole (MTZ) inhibitor of the microsomal oxidases on the systemic availability of the albendazole sulpho-metabolites (ABZS-MT) albendazole-sulphoxide (ABZSO) and albendazole-sulphone (ABZSO2) and on its anthelmintic effects was investigated in a mouse model for helminthic infections. Plasma concentrations of the ABZS-MT were measured by high performance liquid chromatography (HPLC) following treatment of Swiss CD-1 mice with albendazole (ABZ) alone or ABZ plus MTZ, at both single and repeated doses. The anthelmintic effects were assessed in age-matched mice similarly treated following infection with Trichinella spiralis.

Albendazole versus ricobendazole (albendazole-sulphoxide) against enteral and parenteral stages of Trichinella spiralis in mice.

Comparison of the anthelmintic activity and pharmacokinetic profiles following albendazole (ABZ) and albendazole-sulphoxide (ricobendazole = RBZ) administration was made in a mouse model for helminthic infections. Swiss CD-1 mice were experimentally infected with Trichinella spiralis and treated with either ABZ or RBZ at 3 different stages of the parasite life-cycle: pre-adult (day 1 p.i.

Concentrated ascitic fluid reinfusion in cirrhotic patients: a simplified method.

A new method for ascites filtration and reinfusion, which uses a single Cuprophan filter and is performed in the dialysis unit, is reported. Thirty-one procedures were performed in 17 patients with cirrhosis and massive ascites. A mean volume of 8.