Relation between hepatitis B carrier status and antibody against synthetic Plasmodium falciparum erythrocyte surface (pf155 - RESA) antigen

A survey on Plasmodium infection was carried out in gold mine camps located in the Brazilian Amazon. Antibody against P. falciparum ring-infected erythrocyte surface antigen (RESA) was quantified by an enzyme-immunoassay in order to assess P. falciparum exposure. Hepatitis B, a common infection in this area, was also investigated by serologic markers. Among 520 sampled subjects, 517 (99.4%) admitted previous symptomatic malaria, 106 (20.4%) had positive thick smears for malaria, 82.9% had HBV markers, and 7.1% were HBsAg positive. Anti-RESA titers was significantly lower in HBV carriers than in people with resolved HBV infection suggesting that the anti-RESA immune response could be supressed by HBV carrier status. Moreover, immunedeficient responses to both infections may take place in some subjects causing concomitant lower anti-RESA response and incapacity to clear HBV.     

Biology of Amblyomma aureolatum (Pallas, 1772) (Acari: Ixodidae) on some laboratory hosts in Brazil

The ixodid Amblyomma aureolatum is suspected to play a role in the epidemiology of wild life-cycle hemoparasites, which frequently infect dogs in rural and hunting areas in Brazil. Little is known about its bionomics. The objective of the present study was to evaluate some bionomic aspects of A. aureolatum ticks in Brazil. One engorged female, collected from a dog (Canis familiaris) in S?o Sebasti?o das Aguas Claras, State of Minas Gerais, was used to establish a colony in the laboratory. Subsequently its parasitic stage progeny were fed on domestic dogs and laboratory animals. The free-living stages were incubated at 27 degrees C +/- 2 degrees C and minimum 70% relative humidity in a BOD incubator. The egg incubation period ranged from 31 to 34 days; the parasitic period of larvae ranged from 4 to 6 days and ecdysis to nymphs occurred from day 19 up to day 22. The parasitic period of nymphs ranged from 5 to 8 days and the period of ecdysis to adults from 31 to 33 days. The parasitic period of adults ranged from 11 to 15 days, the pre-oviposition period from 6 to 12 days, and the oviposition period from 9 to 38 days. The total duration of the life cycle ranged from 116 to 168 days.     

Involvement of monoaminergic system in the antidepressant-like effect of the hydroalcoholic extract of Siphocampylus verticillatus

The antidepressant-like effect of the hydroalcoholic extract obtained from aerial parts of Siphocampylus verticillatus, a Brazilian medicinal plant, was investigated in two models of depression in mice and against synaptosomal uptake of serotonin, noradrenaline and dopamine. The immobility times in the forced swimming test (FST) and in the tail suspension test (TST) were significantly reduced by the extract (dose range 100-1000 mg/kg, i.p.), without accompanying changes in ambulation when assessed in an open-field. In addition when given orally the extract was also effective in reducing the immobility time in the TST. The efficacy of extract in the TST was comparable to that of the tricyclic antidepressant imipramine (15 mg/kg, i.p.) and with fluoxetine (32 mg/kg, i.p.). The anti-immobility effect of the extract (600 mg/kg, i.p.) assessed in the TST was not affected by pre-treatment with naloxone (1 mg/kg, i.p., a non-selective opioid receptor antagonist) or L-arginine (750 mg/kg, i.p., a nitric oxide precursor). In contrast, the extract (600 mg/kg, i.p.) antidepressant-like effect was significantly reduced by pre-treatment of animals with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis), sulpiride (50 mg/kg, i.p., a selective D2 receptor antagonist), prazosin (62.5 microg/kg, i.p., an alpha1 adrenoreceptor antagonist) or by guanosine 5'-monophosphate (GMP, 250 mg/kg, i.p., a nucleotide known to block some actions elicited by NMDA). The biochemical data show that the extract of S. verticillatus inhibited in a graded manner the uptake of monoamines. However, at the IC50 level, the extract was approximately 3.2 to 3.4-fold more potent and also more efficacious in inhibiting the synaptosomal uptake of noradrenaline and serotonin than dopamine. Taken together these data demonstrate that the extract of S. verticillatus elicited a significant antidepressant-like effect, when assessed in the TST and FST in mice. Its action seems to involve an interaction with adrenergic, dopaminergic, glutamatergic and serotonergic systems.     

Joint determination by Brownian dynamics and fluorescence quenching of the in-depth location profile of biomolecules in membranes

The in-depth molar distribution function of fluorophores is revealed by a new methodology for fluorescence quenching data analysis in membranes. Brownian dynamics simulation was used to study the in-depth location profile of quenchers. A Lorentzian profile was reached. Since the Stern-Volmer equation is valid at every depth in the membrane for low quencher concentrations, the molar distribution of the fluorophore (also regarded as a Lorentzian) can be achieved. The average location and the broadness of the fluorophore distribution can be calculated. The importance of the knowledge of the location width is demonstrated and discussed, since this parameter reveals important conclusions on structural features of the interaction of membranes with probes and biomolecules (e.g., conformational freedom in proteins), as well as photophysical properties (e.g., differential fluorophore quantum yields). Subsequent use of this methodology by the reader does not, necessarily, involve the performance of simulations and is not limited to the use of Lorentzian function distributions.     

2-styrylchromones as novel inhibitors of xanthine oxidase. A structure-activity study

The purpose of this study was the evaluation of the xanthine oxidase (XO) inhibition produced by some synthetic 2-styrylchromones. Ten polyhydroxylated derivatives with several substitution patterns were synthesised, and these and a positive control, allopurinol, were tested for their effects on XO activity by measuring the formation of uric acid from xanthine. The synthesised 2-styrylchromones inhibited xanthine oxidase in a concentration-dependent and non-competitive manner. Some IC50 values found were as low as 0.55 microM, which, by comparison with the IC50 found for allopurinol (5.43 microM), indicates promising new inhibitors. Those 2-styrylchromones found to be potent XO inhibitors should be further evaluated as potential agents for the treatment of pathologies related to the enzyme's activity, as is the case of gout, ischaemia/reperfusion damage, hypertension, hepatitis and cancer.     

Microarray synthesis through multiple-use PCR primer design

A substantial percentage of the expense in constructing full-genome spotted microarrays comes from the cost of synthesizing the PCR primers to amplify the desired DNA. We propose a computationally-based method to substantially reduce this cost. Historically, PCR primers are designed so that each primer occurs uniquely in the genome. This condition is unnecessarily strong for selective amplification, since only the primer pair associated with each amplification need be unique. We demonstrate that careful design in a genome-level amplification project permits us to save the cost of several thousand primers over conventional approaches.     

Spectroscopic evidence for a preferential location of lidocaine inside phospholipid bilayers

We examined the effect of uncharged lidocaine on the structure and dynamics of egg phosphatidylcholine (EPC) membranes at pH 10.5 in order to assess the location of this local anesthetic in the bilayer. Changes in the organization of small unilamellar vesicles were monitored either by electron paramagnetic resonance (EPR)-in the spectra of doxyl derivatives of stearic acid methyl esters labeled at different positions in the acyl chain (5-, 7-, 12- and 16-MeSL)-or by fluorescence, with pyrene fatty-acid (4-, 6-, 10- and 16-Py) probes. The largest effects were observed with labels located at the upper positions of the fatty-acid acyl-chain. Dynamic information was obtained by 1H-NMR. Lidocaine protons presented shorter longitudinal relaxation times (T(1)) values due to their binding, and consequent immobilization to the membrane. In the presence of lidocaine the mobility of all glycerol protons of EPC decreased, while the choline protons revealed a higher degree of mobility, indicating a reduced participation in lipid-lipid interactions. Two-dimensional Nuclear Overhauser Effect experiments detected contacts between aromatic lidocaine protons and the phospholipid-choline methyl group. Fourier-transform infrared spectroscopy spectra revealed that lidocaine changes the access of water to the glycerol region of the bilayer. A "transient site" model for lidocaine preferential location in EPC bilayers is proposed. The model is based on the consideration that insertion of the bulky aromatic ring of the anesthetic into the glycerol backbone region causes a decrease in the mobility of that EPC region (T(1) data) and an increased mobility of the acyl chains (EPR and fluorescence data).     

Calculation of hydrodynamic properties of small nucleic acids from their atomic structure

Hydrodynamic properties (translational diffusion, sedimentation coefficients and correlation times) of short B-DNA oligonucleotides are calculated from the atomic-level structure using a bead modeling procedure in which each non-hydrogen atom is represented by a bead. Using available experimental data of hydrodynamic properties for several oligonucleotides, the best fit for the hydrodynamic radius of the atoms is found to be ~2.8 Å. Using this value, the predictions for the properties corresponding to translational motion and end-over-end rotation are accurate to within a few percent error. Analysis of NMR correlation times requires accounting for the internal flexibility of the double helix, and allows an estimation of ~0.85 for the Lipari–Szabo generalized order parameter. Also, the degree of hydration can be determined from hydrodynamics, with a result of ~0.3 g (water)/g (DNA). These numerical results are quite similar to those found for globular proteins. If the hydrodynamic model for the short DNA is simply a cylindrical rod, the predictions for overall translation and rotation are slightly worse, but the NMR correlation times and the degree of hydration, which depend more on the cross-sectional structure, are more severely affected.