HIV type 1 diversity from newly diagnosed patients in Santos metropolitan area/Brazil.

HIV-1 from infected subjects has been characterized in order to provide a more accurate view of the strains that are currently found in a given region. In this report, we focused on characterizing the pol gene diversity obtained from newly diagnosed patients in Santos metropolitan area, Brazil. This region is composed of nine cities and an international port.

Antitumor activity of terpenoids against classical and atypical multidrug resistant cancer cells.

Nineteen terpenoids, including macrocyclic diterpenes, diterpenic lactones and other polycyclic diterpenes, steroids and a triterpene isolated from the methanolic extracts of Euphorbia species, were evaluated for their potential antineoplastic activity in various human cancer cell lines that were derived from three tumor entities: gastric (EPG85-257), pancreatic (EPP85-181) and colon (HT-29) carcinomas. Furthermore, different multidrug-resistant variants of these cancer cell lines with over-expression of MDR1/P-gp or no MDR1/P-gp expression were also investigated. In parental drug-sensitive cell lines, the tested compounds showed a moderate/weak antiproliferative effect or were inactive.

Virtual Reality Therapy Controlled Study for War Veterans with PTSD. Preliminary Results.

More than 30 years after signing truces, there are still around 20,000 Portuguese war veterans that fill PTSD (Posttraumatic Stress Disorder) diagnose criteria. Despite many of them attending therapy, the outcome is not cheerful. In this way, a research protocol was devised to investigate the opportunity of adopting virtual reality exposure therapy (VRET) to reduce PTSD symptomathology.

Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor (gamma)t+ and respond preferentially under inflammatory conditions.

Lymph nodes (LNs) have been long considered as comprising few invariant NKT (iNKT) cells, and these cells have not been studied extensively. In this study, we unravel the existence of stable rather than transitional LN-resident NK1.1(-) iNKT cell populations.

iNKT cell development is orchestrated by different branches of TGF-beta signaling.

Invariant natural killer T (iNKT) cells constitute a distinct subset of T lymphocytes exhibiting important immune-regulatory functions. Although various steps of their differentiation have been well characterized, the factors controlling their development remain poorly documented. Here, we show that TGF-beta controls the differentiation program of iNKT cells.

Influence of the multidrug transporter inhibitors on the activity of Kv1.3 voltage-gated potassium channels.

Using the whole-cell patch-clamp technique, the influence of selected multidrug resistance modulators, both plant-derived compounds and derivatives on the activity of voltage-gated potassium channels Kv1.3 was investigated. Twelve compounds with phenolic and terpenic structures were tested: the stilbenes piceatannol (1) and its tetramethoxy (2) and tetracetoxy (3) derivatives, the flavonoids naringenin (4) and its methylated derivatives: naringenin-4',7-dimethylether (5) and naringenin-7-methylether (6), and aromadendrin (7), the coumarins esculetin (8) and scopoletin (9) and ent-abietane diterpenes, helioscopinolide B (10) and its 3beta-acetoxy derivative (11) and helioscopinolide E (12).

Thermopower enhancement in nanowires via junction effects.

We present thermopower measurements on free-standing, straight and "junctioned" gold nanowires using a micromachined thermoelectric workbench. Measurements on straight 70 nm diameter gold nanowires show a thermopower similar to that of bulk gold; however for "junctioned" gold nanowires we observed a hitherto unreported peak in the thermopower near room temperature. The observed enhancement can be explained by approximating the "junctioned" nanowires as tunnel junctions in combination with Coulombic effect of the electrons crossing the junction.

Synergistic interaction between p-glycoprotein modulators and epirubicine on resistant cancer cells.

The macrocyclic lathyrane diterpene latilagascene B, previously isolated from Euphorbia lagascae, was acylated to afford three new diterpene esters, latilagascenes G (1), H (2), and I (3), whose structures were assigned by spectroscopic methods. These acyl derivatives, and the macrocyclic diterpenes of the jatrophane-type, tuckeyanols A (4) and B (5), and euphotuckeyanol (6), isolated from Euphorbia tuckeyana, were tested for P-gp modulating properties on human MDR1 gene-transfected and parental L5178 mouse lymphoma cell lines. All the compounds displayed very strong activity.

Antiplasmodial activity of lignans and extracts from Pycnanthus angolensis.

The dichloromethane, methanol and aqueous ethanol extracts of the stem bark of Pycnanthus angolensis were evaluated for their in vitro activity against the 3D7 Plasmodium falciparum strain. The CH (2)Cl (2) extract was the most active showing an IC (50) = 1.6 microg/mL.

Inhibition of MRP1 transport activity by phenolic and terpenic compounds isolated from Euphorbia species.

Background: A search for inhibitors of multidrug resistance (MDR)-associated protein 1 (MRP1) was performed among the compounds isolated from Euphorbia species, plants traditionally used in folk medicine.

Materials And Methods: Fifteen compounds with terpenic or phenolic structures (macrocyclic and polycyclic diterpenes, coumarins, stilbenes and flavonoids) were isolated from the methanol extracts of Euphorbia lagascae and Euphorbia tuckeyana or obtained by derivatization. A functional test based on measuring the efflux of fluorescent MRP1 substrate (BCECF) from human erythrocytes was employed.

Three new jatrophane polyesters and antiproliferative constituents from Euphorbia tuckeyana.

Three new jatrophane diterpene polyesters named tuckeyanols A and B and euphotuckeyanol, as well as ten known compounds, helioscopinolides A, B, D and E, naringenin, aromadendrin, coniferaldehyde, 4,20-dideoxy-5-hydroxyphorbol 12,13-diisobutyrate, 4,20-dideoxy-5-hydroxyphorbol 12-benzoate-13-isobutyrate and dehydrodiconiferyl diacetate, were isolated from the methanolic extract of Euphorbia tuckeyana. Their structures were elucidated by physical and spectroscopic methods including 1 D and 2 D homo- and heteronuclear NMR techniques (COSY, HMQC, HMBC and NOESY), and HR-mass spectrometry. Four of the isolated compounds were investigated for their antiproliferative activity in three human gastrointestinal cancer cell lines: gastric (EPG85-257), pancreatic (EPP85-181) and colon (HT-29) carcinomas.

Antileishmanial activity of piceatannol isolated from Euphorbia lagascae seeds.

In the search for biologically active compounds from Euphorbia lagascae Spreng, an herbaceous plant native to southeast of Iberic Peninsula, a stilbene, two coumarins and two 12-deoxyphorbol diterpene esters were isolated by chromatographic methods, from the methanol extracts of its defatted seeds. The structures of these compounds were elucidated by a combination of physical and spectral data (IR, MS and high-resolution (1)H-NMR and (13)C-NMR spectroscopy utilizing COSY, HMBC, HMQC and NOESY experiments). The stilbene, piceatannol, was screened for its antileishmanial activity against promastigotes as an extracellular form of Leishmania donovani, Leishmania infantum and Leishmania major, and amastigotes of Leishmania donovani as an intracellular form.

A comparative study of 0.125% racemic bupivacaine (S50-R50) and 0.125% and 0.25% 50% enantiomeric excess bupivacaine (S75-R25) in epidural anesthesia for labor analgesia.

Background And Objectives: Continuous epidural block is used for relief of labor pain and it is associated with a low incidence of complications. Studies with the levorotatory isomer of local anesthetics demonstrated that they are safer regarding the cardiotoxicity. The objective of this study was to compare analgesia and motor blockade of 0.

Antibacterial activity of ergosterol peroxide against Mycobacterium tuberculosis: dependence upon system and medium employed.

Ergosterol peroxide, cycloart-23-en-3beta,25-diol, vanillin and 4-hydroxybenzaldehyde have been isolated and characterized from a crude methanol extract of Euphorbia lagascae. Previous studies have shown contradictory results about the antibacterial activity of ergosterol peroxide against Mycobacterium tuberculosis. In order to clarify this question, the activity of this compound was tested against Mycobacterium tuberculosis H37Rv ATCC 27294 strain using two different systems: BACTEC 460TB (Bactec 460) and BACTEC MGIT 960 system (Bactec 960).

The Idd6.2 diabetes susceptibility region controls defective expression of the Lrmp gene in nonobese diabetic (NOD) mice.

The identification of genes mediating susceptibility to type 1 diabetes (T1D) remains a challenging task. Using a positional cloning approach based on the analysis of nonobese diabetic (NOD) mice congenic over the Idd6 diabetes susceptibility region, we found that the NOD allele at this locus mediates lower mRNA expression levels of the lymphoid restricted membrane protein gene (Lrmp/Jaw1). Analysis of thymic populations indicates that Lrmp is expressed mainly in immature thymocytes.

Macrocyclic lathyrane diterpenes as antitumor promoters.

Human cytomegalovirus (CMV) preferentially infects tumor tissues and the accumulated CMV immediate-early (IE) antigen may lead to tumor promotion and progression. The development of strategies to inhibit human CMV IE antigen expression and/or function is an important goal to prevent and treat certain forms of cancers associated with human CMV. The aim of this study was to search for antitumor promoters from plant sources.

Global reconstruction of the human metabolic network based on genomic and bibliomic data.

Metabolism is a vital cellular process, and its malfunction is a major contributor to human disease. Metabolic networks are complex and highly interconnected, and thus systems-level computational approaches are required to elucidate and understand metabolic genotype-phenotype relationships. We have manually reconstructed the global human metabolic network based on Build 35 of the genome annotation and a comprehensive evaluation of >50 years of legacy data (i.

Lagaspholones A and B: two new jatropholane-type diterpenes from Euphorbia lagascae.

[structure: see text] Two new diterpenes, lagaspholones A (1) and B (2), have been isolated from the methanolic extract of Euphorbia lagascae, along with the known compounds (+)-dehydrovomifoliol, scopoletin, dehydrodiconiferyl diacetate, 3-indolcarbaldehyde, and 4-hydroxy-3,5-dimethoxybenzaldehyde. Their structures were elucidated by spectroscopic methods. Compounds 1 and 2 contain the rare jatropholane-type skeleton, characterized by a 5:6:7:3 fused ring system.

Interaction between doxorubicin and the resistance modifier stilbene on multidrug resistant mouse lymphoma and human breast cancer cells.

The hydroxystilbene trans-3,5,3',4'-tetrahydroxystilbene (piceatannol) (1), isolated from the methanol extract of Euphorbia lagascae defatted seeds, was methylated to yield the derivatives trans-3,5,3',4'-tetramethoxystilbene (2), (trans-3,5-dihydroxy-3',4'-dimethoxystilbene) (3) and trans-3,5,3'-trihydroxy-4'-methoxystilbene (4). The structures of the compounds were assigned by spectroscopic methods (IR, 1H-NMR, 13C-NMR and MS). The ability of piceatannol (1) and the three methylated derivatives to modulate the transport activity of P-glycoprotein (P-gp) and apoptosis induction on the L5178 mouse lymphoma cell line containing the human MDR1 gene was studied by flow cytometry.

Apoptosis induction and modulation of P-glycoprotein mediated multidrug resistance by new macrocyclic lathyrane-type diterpenoids.

The macrocyclic lathyrane diterpenes, latilagascenes D-F (1-3) and jolkinol B (4), were isolated from the methanol extract of Euphorbia lagascae, and evaluated for multidrug resistance reversing activity on mouse lymphoma cells. All compounds displayed very strong activity compared with that of the positive control, verapamil. The structure-activity relationship is discussed.

Changes in blood cell membrane properties in HIV type-1-infected patients.

To evaluate the possible HIV-1 infection-induced changes in cell membrane properties and in calcium signaling, membrane fluidity, acetylcholinesterase (AChE, a glycosylphosphatidylinositol-anchored protein) activity, and intracellular calcium concentration ([Ca2(+)](int)) were evaluated in lymphocytes and erythrocytes of infected individuals, previous to their engagement in antiretroviral therapy. Membrane fluidity was assessed by fluorescence spectroscopy measurements, using the fluorescence probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-(trimethylamino)-phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). AChE activity was determined by the colorimetric Ellman's method and [Ca2(+)](int) using the fluorescent fura-2 acetoxymethyl ester.

Force-deflection spectroscopy: a new method to determine the Young's modulus of nanofilaments.

We demonstrate the determination of Young's modulus of nanowires or nanotubes via a new approach, that is, force-deflection spectroscopy (FDS). An atomic force microscope is used to measure force versus deflection (F-D) curves of nanofilaments that bridge a trench patterned in a Si substrate. The FD data are then fit to the Euler-Bernoulli equation to determine Young's modulus.

[Genotyping of the Plasmodium falciparum msp1 (block 2) and dhfr (codon 108) genes in field samples collected in four endemic Colombian localities].

Introduction: Plasmodium falciparum is a highly polymorphic parasite, which allows it to evade the host's immune response, spread drug resistance and favours transmission.

Objectives: To analyse the genetic diversity of P. falciparum populations in samples from four endemic localities in Colombia.