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Biomedical subjects

V Muñoz

Publications and source records attributed to V Muñoz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Medicinal plants uses of the Tacana, an Amazonian Bolivian ethnic group.

We present the results of an ethnopharmacological investigation of a Bolivian lowland ethnic group, the Tacana. The Tacana have a long tradition of exchange with highland communities. Though facing rapid acculturation, highlighted by the loss of the Tacana language among the younger generations, the knowledge and uses of medicinal plants are still alive. Of the approximately 450 different plant species collected during this survey, 33% had medicinal uses. We present an overview of the traditional Tacana ethnomedicine and pharmacopoeia.

Bolivia↗
PubMed2000

A search for natural bioactive compounds in Bolivia through a multidisciplinary approach. Part III. Evaluation Of the antimalarial activity of plants used by Alteños Indians.

A total of 40 plant extracts traditionally used by the Alteños Indians, a native community living between the Andean block and the tropical valleys of Bolivia, were screened for antimalarial activity in vitro on Plasmodium falciparum chloroquine resistant (Indo) strain, and in vivo on rodent malaria Plasmodium vinckei petteri. Eleven extracts displayed good or moderate activity in vivo, and ten extracts good or very good antimalarial activity in vitro. Results of the screening are discussed here, in relation with the traditional use of plants.

Antimalarials↗
PubMed2000

Organ doses, detriment and genetic risk from interventional vascular procedures in Málaga (Spain).

Nowadays, the radiological risk from simple X-ray procedures is well known. The purpose of this work has been to estimate the population risk from digital angiographic and interventional procedures and to compare it with the one from simple procedures in the same population. The population risk has been estimated according to the following quantities: genetically significant dose, somatic significant dose, collective effective dose, annual per caput effective dose and detriment. These have been estimated from dose area product and organ dose. Organ dose values were estimated with the Eff-Dose software. A population of 605410 people were included in the study. In 1996, 1312 patients were to digital interventional vascular procedures in Malaga, and 159 of them were selected in this research project to obtain the dose area product and organ dose. The results obtained for the quantities evaluated are: genetically significant dose, 4.1 microGy; somatic significant dose, 0.9 mSv; collective effective dose, 11.65 person-Sv: annual per caput effective dose, 0.02 mSv and detriment, 0.65 radiogenic cancers per year. These procedures supply a high radiation dose, so they should have a greater contribution to population dose and risk than simple examinations. However, our results indicate just the opposite.

Adolescent↗
PubMed2000

Fast kinetics and mechanisms in protein folding.

This review describes how kinetic experiments using techniques with dramatically improved time resolution have contributed to understanding mechanisms in protein folding. Optical triggering with nanosecond laser pulses has made it possible to study the fastest-folding proteins as well as fundamental processes in folding for the first time. These include formation of alpha-helices, beta-sheets, and contacts between residues distant in sequence, as well as overall collapse of the polypeptide chain. Improvements in the time resolution of mixing experiments and the use of dynamic nuclear magnetic resonance methods have also allowed kinetic studies of proteins that fold too fast (greater than approximately 10(3) s-1) to be observed by conventional methods. Simple statistical mechanical models have been extremely useful in interpreting the experimental results. One of the surprises is that models originally developed for explaining the fast kinetics of secondary structure formation in isolated peptides are also successful in calculating folding rates of single domain proteins from their native three-dimensional structure.

Animals↗
PubMed2000

Effectiveness and pitfalls of initial highly active antiretroviral therapy in HIV-infected patients in routine clinical practice.

OBJECTIVE: To assess the long-term effectiveness of and factors associated with response to protease inhibitors (PIs) in a cohort of treatment-naive HIV-infected patients. DESIGN AND SETTING: Prospective study in a tertiary care centre. SUBJECTS: A total of 207 treatment-naive patients starting PIs from March 1996 to May 1998. MAIN OUTCOME MEASURES: Clinical, virological and immunological outcomes, and adherence to therapy after 12 months. RESULTS: Baseline median CD4 cell count and viral load were 160 cells/mm3 and 5 log10 copies/ml, respectively. After 48 weeks, 168 patients (81%) reached plasma HIV-RNA levels below 400 copies/ml, and the mean increase in CD4 cell count was 196 cells/mm3. Clinical events were observed in 29 patients (14%) after a median time of 100 days on therapy, yet mortality was extremely low (0.9%). By multivariate analysis, adherence over 90% [relative risk (RR), 16.66; 95% confidence interval (CI), 5.26-50; P=0.00001] and AIDS diagnosis at baseline (RR 0.35; 95% CI, 0.14-0.90; P=0.02) were the strongest predictors for virological suppression. An immunological recovery over 100 cells/mm3 was significantly associated with an initial virological response (RR 2.94; 95% CI, 1.31-6.66; P=0.009) and adherence over 90% (RR 3.44; 95% CI, 1.61-7.69; P=0.005). There were high rates of change with the first PI (40%), mostly due to adverse events (51%), but it did not compromise long-term effectiveness. CONCLUSIONS: Initial PI treatment in the clinical setting is able to reach equally good outcomes as those found in controlled trials. Changes in therapy due to toxicity do not compromise a successful outcome, which clearly depends on an adequate adherence to therapy.

Adolescent↗
PubMed1999

A simple model for calculating the kinetics of protein folding from three-dimensional structures.

An elementary statistical mechanical model was used to calculate the folding rates for 22 proteins from their known three-dimensional structures. In this model, residues come into contact only after all of the intervening chain is in the native conformation. An additional simplifying assumption is that native structure grows from localized regions that then fuse to form the complete native molecule. The free energy function for this model contains just two contributions-conformational entropy of the backbone and the energy of the inter-residue contacts. The matrix of inter-residue interactions is obtained from the atomic coordinates of the three-dimensional structure. For the 18 proteins that exhibit two-state equilibrium and kinetic behavior, profiles of the free energy versus the number of native peptide bonds show two deep minima, corresponding to the native and denatured states. For four proteins known to exhibit intermediates in folding, the free energy profiles show additional deep minima. The calculated rates of folding the two-state proteins, obtained by solving a diffusion equation for motion on the free energy profiles, reproduce the experimentally determined values surprisingly well. The success of these calculations suggests that folding speed is largely determined by the distribution and strength of contacts in the native structure. We also calculated the effect of mutations on the folding kinetics of chymotrypsin inhibitor 2, the most intensively studied two-state protein, with some success.

Models, Statistical↗
PubMed1999

Antiprotozoal activity of aporphine alkaloids isolated from Unonopsis buchtienii (Annonaceae).

On a preliminary screening, substantial leishmanicidal activity was observed for the petroleum ether and alkaloidal extracts of the stem bark of Unonopsis buchtienii, the alkaloids and sterols isolated from these were studied. Of the alkaloids, liriodenine exhibited the highest activity against Leishmania major and L donovani (IC100 = 3.12 micrograms/mL). On the other hand, O-methylmoschatoline and the petroleum ether extract without alkaloids showed an interesting in vitro activity against Trypanosoma brucei with an IC100 of 6.25 micrograms/mL. The highest cytotoxic activities were found with the petroleum ether extracts without alkaloids and with all alkaloids isolated (IC50 < 9 micrograms/mL for Vero cell line).

Alkaloids↗
PubMed1999

Acute cholestatic hepatitis by cytomegalovirus in an immunocompetent patient resolved with ganciclovir.

We report a case of acute cholestatic hepatitis in an immunocompetent young male with cytomegalovirus (CMV) primoinfection episode. The severity of the clinical symptoms led to a high-dose treatment with parenteral ganciclovir, with an immediate response and total resolution of symptoms. Therapeutic options are discussed, particularly the use of ganciclovir, even in immunocompetent patients when the severity of the symptoms could demand it.

Acute Disease↗
PubMed1999

[Cytomegalovirus granulomatous hepatitis in an immunocompetent patient].

A case of granulomatous hepatitis induced by cytomegalovirus in a 34-year-old immunocompetent male with no other history of interest is presented. The clinical severity of the picture with progressive cholestasis, evening fever peaks and the development of echographic signs of portal hypertension led to treatment with high doses of intravenous ganciclovir. Rapid clinical improvement was observed with normalization of the analytical parameters after 15 days of treatment. The pathologic, clinical and therapeutic aspects of the liver infection by cytomegalovirus in an immunocompetent patient are discussed.

Acute Disease↗
PubMed1998

A statistical mechanical model for beta-hairpin kinetics.

Understanding the mechanism of protein secondary structure formation is an essential part of the protein-folding puzzle. Here, we describe a simple statistical mechanical model for the formation of a beta-hairpin, the minimal structural element of the antiparallel beta-pleated sheet. The model accurately describes the thermodynamic and kinetic behavior of a 16-residue, beta-hairpin-forming peptide, successfully explaining its two-state behavior and apparent negative activation energy for folding. The model classifies structures according to their backbone conformation, defined by 15 pairs of dihedral angles, and is further simplified by considering only the 120 structures with contiguous stretches of native pairs of backbone dihedral angles. This single sequence approximation is tested by comparison with a more complete model that includes the 2(15) possible conformations and 15 x 2(15) possible kinetic transitions. Finally, we use the model to predict the equilibrium unfolding curves and kinetics for several variants of the beta-hairpin peptide.

Animals↗
PubMed1998

Position dependence of non-polar amino acid intrinsic helical propensities.

Until now and based on the success of the helix/coil transition theory it has been assumed that the alpha-helical propensities of the amino acids are position independent. This has been critical to derive the set of theoretical parameters for the 20 natural amino acids. Here, we have analyzed the behavior of several non-polar residues, Val, Ile, Leu, Met and Gly at the N-cap, at each position of the first helical turn and at a central helical position of a 16-residue peptide model system that starts with eight consecutive alanine residues. We have interpreted the results from these experiments with the model of the helix/coil transition (AGADIR), that indicates that the intrinsic helical propensity is position dependent. Gly, Val and Ile are more favorable at the first turn than in the middle of the alpha-helix, while for Leu and Met we observe the opposite behavior. The differences between the observed helical propensities are as large as 1.0 kcal/mol in some cases. Molecular modeling calculations using the ECEPP/2 force-field equipped with a hydration potential show that this effect can be explained by the combination of three factors: (a) the side-chains in the first helix turn are more solvent-exposed; (b) they have fewer intramolecular van der Waals' contacts; and (c) they posses higher configurational entropy than that in the central position of an alpha-helix. The position-dependent results of the calculations are in reasonable agreement with the experimental estimates and with the intrinsic propensities of the amino acids derived from the statistical analysis of the protein structure database.

Algorithms↗
PubMed1998

A novel antiprotozoal aminosteroid from Saracha punctata.

A new aminosteroid, 3beta-amino-22,26-epiminocholest-5-ene named sarachine (1), and two known flavonoids, eriodictyol (2) and 7-O-beta-D-glucopyranosyl-eriodictyol (3), were isolated from the leaves of Saracha punctata. The alkaloid was found to inhibit the growth of Leishmania braziliensis promastigotes (100% at 25 microM) and of Trypanosoma cruzi epimastigotes in culture (50% at 25 microM) and showed a strong in vitro antiplasmodial activity with an IC50 of 25 nM.

Animals↗
PubMed1997

Folding dynamics and mechanism of beta-hairpin formation.

Protein chains coil into alpha-helices and beta-sheet structures. Knowing the timescales and mechanism of formation of these basic structural elements is essential for understanding how proteins fold. For the past 40 years, alpha-helix formation has been extensively investigated in synthetic and natural peptides, including by nanosecond kinetic studies. In contrast, the mechanism of formation of beta structures has not been studied experimentally. The minimal beta-structure element is the beta-hairpin, which is also the basic component of antiparallel beta-sheets. Here we use a nanosecond laser temperature-jump apparatus to study the kinetics of folding a beta-hairpin consisting of 16 amino-acid residues. Folding of the hairpin occurs in 6 micros at room temperature, which is about 30 times slower than the rate of alpha-helix formation. We have developed a simple statistical mechanical model that provides a structural explanation for this result. Our analysis also shows that folding of a beta-hairpin captures much of the basic physics of protein folding, including stabilization by hydrogen bonding and hydrophobic interactions, two-state behaviour, and a funnel-like, partially rugged energy landscape.

Kinetics↗