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V Muñoz

Publications and source records attributed to V Muñoz.

At least 73 records · Page 4Linked to original sources

Intrinsic secondary structure propensities of the amino acids, using statistical phi-psi matrices: comparison with experimental scales.

Today there are several different experimental scales for the intrinsic alpha-helix as well as beta-strand propensities of the 20 amino acids obtained from the thermodynamic analysis of various model systems. These scales do not compare well with those extracted from statistical analysis of three-dimensional structure databases. Possible explanations for this could be the limited size of the databases used, the definitions of intrinsic propensities, or the theoretical approach. Here we report a statistical determination of alpha-helix and beta-strand propensities derived from the analysis of a database of 279 three-dimensional structures. Contrary to what has been generally done, we have considered a particular residue as in alpha-helix or beta-strand conformation by looking only at its dihedral angles (phi-psi matrices). Neither the identity nor the conformation of the surrounding residues in the amino acid sequence has been taken into consideration. Pseudoenergy empirical scales have been calculated from the statistical propensities. These scales agree very well with the experimental ones in relative and absolute terms. Moreover, its correlation with the average of the experimental scales for alpha-helix or beta-strand is as good as the correlations of the individual experimental scales with the average. These results show that by using a large enough database and a proper definition for the secondary structure propensities, it is possible to obtain a scale as good as any of experimental origin. Interestingly the phi-psi analysis of the Ramachandran plot suggests that the amino acids could have different beta-strand propensities in different subregions of the beta-strand area.

Amino Acids↗

Leishmanicidal and trypanocidal activities of Bolivian medicinal plants.

Cutaneous and mucocutaneous leishmaniasis are endemic diseases in South America, especially in the subandean areas of the humid lowlands of Bolivia. Fourteen plants used topically in folk medicine to treat cutaneous leishmaniasis were collected in the tropical regions of colonization and in the rain forest occupied by Chimane Indians. Three of four plants used by the Chimane Indians exhibited an in vitro activity against three species of Leishmania. Two of ten plants used by the colonists showed an in vitro activity. We have also included results obtained with extracts from 53 Bolivian medicinal plants used for other diseases and from 43 plants collected with basis of chemotaxonomic criteria from all parts of Bolivia. All extracts were also screened in vitro against three strains of Trypanosoma cruzi (Trypanosomatidae), the causative agent of Chagas' disease.

Animals↗

Elucidating the folding problem of helical peptides using empirical parameters.

Using an empirical analysis of experimental data we have estimated a set of energy contributions which accounts for the stability of isolated alpha-helices. With this database and an algorithm based on statistical mechanics, we describe the average helical behaviour in solution of 323 peptides and the helicity per residue of those peptides analyzed by nuclear magnetic resonance. Moreover the algorithm successfully detects the alpha-helical tendency, in solution, of a peptide corresponding to a beta-strand of ubiquitin.

Algorithms↗

Antileishmanial activity of a tetralone isolated from Ampelocera edentula, a Bolivian plant used as a treatment for cutaneous leishmaniasis.

The stem bark of Ampelocera edentula Kuhlm. (Ulmaceae) is used by the Chimanes Indians from Bolivia for the treatment of cutaneous leishmaniasis caused by the protozoan Leishmania braziliensis. A chloroform extract of the stem barks was found to be active against extracellular forms of Leishmania ssp. and Trypanosoma cruzi at 50 micrograms/ml. Bioassay-guided fractionation of this extract allowed us to isolate one active compound. Its structure was elucidated by spectral and chemical studies as 4-hydroxy-1-tetralone. BALB/c mice infected with L. amazonensis (PH8) or L. venezuelensis were treated one day after the parasitic infection with 4-hydroxy-1-tetralone (25 mg/kg/day) or with reference drug, Glucantime (56 mg Sbv/kg/day) for 14 days. Lesion development was the criteria used to evaluate the disease severity. 4-Hydroxy-1-tetralone was slightly less effective than the reference drug against L. amazonensis or L. venezuelensis. Single treatment near the site of infection, 14 days after infection with L. amazonensis, with 4-hydroxy-1-tetralone (50 mg/kg) was more effective than Glucantime (112 mg/kg). This study is, to our knowledge, the first to show the activity of a tetralone for the experimental treatment of New World cutaneous leishmaniasis.

Animals↗

Isolation of bis-indole alkaloids with antileishmanial and antibacterial activities from Peschiera van heurkii (syn. Tabernaemontana van heurkii).

Extracts from leaves and stem bark of Peschiera van heurkii (Muell. Arg.) L. Allorge (syn. Tabernaemontana van heurkii Muell. Arg., Apocynaceae) have been assayed for antileishmanial and antibacterial activities. The activities were concentrated in the alkaloid fractions which yielded 20 indole and bisindole alkaloids. The strongest leishmanicidal and antibacterial activities were observed with the dimeric alkaloids conodurine (1), N-demethylconodurine (= gabunine) (2), and conoduramine (3). Weak toxicity towards macrophage host cells and strong activity against the intracellular amastigote form of Leishmania were observed for compounds 1 and 2. In vivo, 1 was less active than glucantime (= N-methylglucamine antimonate), the drug of reference, while 2 was devoid of activity at 100 mg/kg.

Alkaloids↗

Inspiratory muscle training in chronic airflow limitation: comparison of two different training loads with a threshold device.

The usefulness of inspiratory muscle training (IMT) in chronic airflow limitation (CAL) patients is a controversial issue, mainly due to differences in the training load. To further evaluate this aspect, we studied the effect of the magnitude of the load using a threshold pressure trainer. Ten CAL patients (5 males, 5 females) 67 +/- 2 yrs (mean +/- SEM) and forced expiratory volume in one second (FEV1) 36 +/- 2% pred, were trained for 30 min a day using a load of 30% of their maximal inspiratory mouth pressure (PImax) (Group 1). Another 10 CAL patients (5 males, 5 females), 73 +/- 2 yrs and FEV1 37 +/- 2% pred), were trained using only 12% of their PImax (Group 2). Training was assessed by PImax, inspiratory muscle power output (IMPO), sustainable inspiratory pressure (SIP), maximal inspiratory flow rate (VImax), pattern of breathing during loaded breathing, Mahler's dyspnoea score, and the 6 min walking distance (6MWD). After 5 weeks of training, Group 1 exhibited significant increments in: PImax (34 +/- 11%); IMPO (92 +/- 16%); SIP (36 +/- 9%); and VImax (34 +/- 13%). Dyspnoea was also reduced, and the 6MWD increased by 48 +/- 22 m. We observed no significant changes in Group 2. During loaded breathing, Group 1 showed a significant increment in tidal volume (VT) and mean inspiratory flow (VT/TI), and a reduction in inspiratory time (TI). In Group 2, VT and VT/TI also increased significantly, but the breathing frequency increased with a reduction of expiratory time.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Laparoscopic lumboaortic retroperitoneal lymphadenectomy in testicular neoplasm].

Lumboaortic lymphadenectomy is a therapeutic alternative for patients with nonseminomatous testis tumors and its principal untoward effect is the loss of ejaculation. The anatomic knowledge of lymph node metastasis allows lower limit definition of aortic dissection, maintaining the diagnostic sensitivity and ejaculation. We report three patients with nonseminomatous testis tumors subjected to a reduced video-laparoscopic lumboaortic lymphadenectomy. An adequate amount of tissue was obtained in all and lymph node metastasis found in two. No complications occurred and patients were discharged 48 hours later. It is concluded that this technique is an alternative staging technique with low morbidity that allows a rapid patient discharge.

Adult↗

2-substituted quinoline alkaloids as potential antileishmanial drugs.

Ten 2-substituted quinoline alkaloids isolated from a plant used for treatment of New World cutaneous leishmaniasis have antileishmanial in vitro activities against the extracellular forms of Leishmania spp. BALB/c mice infected with Leishmania amazonensis PH8 or H-142 or Leishmania venezuelensis were treated 1 day after the parasitic infection with a quinoline alkaloid (100 mg/kg of body weight per day) or with reference drug N-methylglucamine antimonate (Glucantime) (56 mg of pentavalent antimony [Sbv] per kg per day) for 14 days. Lesion development was the criterium used to assess disease severity. Two three-carbon chain quinolines [2-n-propylquinoline and 2-(1',2'-trans-epoxypropyl)quinoline (chimanine D)] were more potent than N-methylglucamine antimonate against L. amazonensis PH8, and five quinoline alkaloids [2-(3,4-methylenedioxyphenylethyl)quinoline, cusparine, 2-(3,4-dimethoxyphenylethyl)quinoline, 2-(E)-prop-1'-enylquinoline (chimanine B), and skimmianine] were as effective as the reference drug. Single treatment near the site of infection, 14 days after infection with L. amazonensis, with 2-n-propylquinoline or chimanine B reduced the severity of lesions but less notably than N-methylglucamine antimonate. 2-n-Propylquinoline exhibited significant activity against the virulent strain L. venezuelensis. The active products did not show any apparent toxicities during the experiment. This study is, to our knowledge, the first to show the activity of 2-substituted quinoline alkaloids for experimental treatment of New World cutaneous leishmaniasis. Further investigations of these compounds might yet prove helpful for the development of new antileishmanial drugs.

Alkaloids↗

Inhibition by N-methyl-D-aspartic acid (NMDA) receptor antagonist of lordosis behavior induced by estrogen followed by progesterone or luteinizing hormone-releasing hormone (LHRH) in the rat.

The effects of glutamate receptor antagonists on sexual receptivity induced by progesterone and LHRH were examined in ovariectomized, estradiol-primed rats (OVX-EB). Enhancement of lordosis/mounts quotient (L/M) by progesterone (0.5 mg) or LH-RH (150 ng; third ventricle, IVT) in OVX-EB rats was significantly decreased by IVT injection of (+) 2-amino-7-phosphonoheptanoic acid a competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist. On the contrary, there were no changes in L/M quotient after IVT injection of 6,7-dinitroquinoxaline-2,3,dione at two dose levels, a Non-NMDA receptor antagonist. The NMDA antagonist did not modify lordosis behavior in OVX-EB rats. The results indicate that the NMDA type of glutamate receptors appears to mediate progesterone and LHRH facilitatory actions and suggest that glutamatergic synapses may be involved in lordosis-facilitating neural mechanisms.

2-Amino-5-phosphonovalerate↗

Biological and chemical studies of Pera benensis, a Bolivian plant used in folk medicine as a treatment of cutaneous leishmaniasis.

The stem barks of Pera benensis are employed by the Chimane Indians in the Bolivian Amazonia as treatment of cutaneous leishmaniasis caused by the protozoan Leishmania braziliensis. The chloroform extracts containing quinones were found active against the promastigote forms of Leishmania and the epimastigote forms of Trypanosoma cruzi at 10 micrograms ml-1. The activity guided fractionation of the extract by chromatography afforded active compounds. Their structures were elucidated, by spectral and chemical studies, as known naphthoquinones, plumbagin, 3,3'-biplumbagin, 8-8'-biplumbagin, and triterpene, lupeol. The activity in vitro of each compound was evaluated against 5 strains of Leishmania (promastigote), 6 strains of Trypanosoma cruzi (epimastigote) and the intracellular form (amastigote) of Leishmania amazonensis. The baseline drugs used were Glucantime and pentamidine (Leishmania spp.), nifurtimox and benznidazole (T. cruzi). Plumbagin was the most active compound in vitro. This study has demonstrated that Pera benensis, a medicinal plant used in folk medicine, is an efficient treatment of cutaneous leishmaniasis.

Animals↗

Effect of natural naphthoquinones in BALB/c mice infected with Leishmania amazonensis and L. venezuelensis.

Plumbagin, 3,3'-biplumbagin and 8,8'-biplumbagin are naphthoquinones isolated by activity-directed fractionation from a Bolivian plant, Pera benensis, used in folk medicine as treatment of cutaneous leishmaniasis caused by Leishmania braziliensis. BALB/c mice were infected with L. mexicana or L. venezuelensis and treated 24 h after the parasitic infection with plumbagin (5 or 2.5 mg/kg/day), 3,3'-biplumbagin, 8,8'-biplumbagin (25 mg/kg/d) or Glucantime (200 mg/kg/d). Lesion development was the criteria employed to evaluate the inhibitory effect. The bis-naphthoquinones were less potent than Glucantime against L. amazonensis and L. venezuelensis. Plubagin and Glucantime delayed the development of L. amazonensis and L. venezuelensis. Assays of a single local treatment on foot-pad infection two weeks after the parasitic inoculation with L. amazonensis showed that 8,8'-biplumbagin (50 mg/kg/d) was as potent as Glucantime (400 mg/kg/d).

Animals↗

[Active antihelminitic alkaloids: active in vitro against Leishmanic Tropica the protozoa involved in leishmaniasis].

Leishmaniasis caused by protozoan Leishmania ssp., is an endemic parasitic disease in Central and South America. The chemotherapeutic agents against Leishmania ssp. (pentavalent antimony compounds, pentamidine and amphothericine B) are toxic and expensive products. Basing on the Bolivian folk medicine, we tried to find new active principles. Fourteen isoquinoline alkaloids, especially bisbenzylisoquinoline alkaloids extracted from Annonaceae, Berberidaceae, Hernandiaceae and Menispermaceae, demonstrate highly effective activity against this protozoan. Among them gyrocarpine, daphnandrine and obaberine seem to be of particular interest. The therapeutic effect was studied by biological assays on culture forms in vitro three strains of Leishmania, L. donovani, L. braziliensis (cutaneous and mucocutaneous leishmaniasis), L. mexicana amazonensis (cutaneous) and L. donovani (visceral leishmaniasis).

Alkaloids↗

[ Active trypanocidal alkaloids, bisbenzylisoquinoles ii. active in vitro against trypanosoma cruzi the agent responsible for trypanosomiasis, south america].

Chagas disease caused by the protozoan Trypanosoma cruzi is an endemic parasitic disease in Central and South America. The chemotherapeutic agents against Trypanosoma cruzi (imidazol compounds, lampit and benznidazol) are not very convenient products. Since it is known that protozoan Trypanosoma are close to Leishmania we studied the action of 14 bisbenzylisoquinoline alkaloids, in vitro, on three strains of T. cruzi (Tulahuen, C8C11, and 1979 CL1). As in the case of Leishmania, gyrocarpine, daphnandrine and obaberine showed an interesting activity and we judge them to be worthy of in vivo assays.

Alkaloids↗

Effect of topically applied adrenergic blockers on fertility.

The contraceptive properties of two adrenergically active drugs, propranolol and reserpine, were measured in vivo and in vitro. Propranolol became effective as a spermicide for human sperm at a concentration of about 2 x 10(-3) M and for rat sperm at 2 x 10(-2) M. Reserpine was also more effective on human than rat sperm and about 20 times less effective than propranolol. Both propranolol and reserpine prevented implantation when instilled into the uteri of rats. The anti-implantation effect persisted for up to 5 days after instillation of propranolol. When freely breeding rats eventually became pregnant after daily vaginal instillation of propranolol, the number of uterine implantations decreased as the concentration of vaginally instilled propranolol increased. The implantations tended to be toward the fundal end of the uteri, away from the source of propranolol, thus indicating a topical rather than a systemic anti-implantation effect.

Animals↗