Biomedical subjects

R Lira

Publications and source records attributed to R Lira.

At least 19 recordsLinked to original sources

PubMed2005

Informant consensus factor and antibacterial activity of the medicinal plants used by the people of San Rafael Coxcatlán, Puebla, México.

Using ethnobotanical techniques, the medicinal flora used by the inhabitants of San Rafael Coxcatlán, Puebla was determined. During the field work, two types of interviews were applied (free listing and semi-structured) to 60 informants, who supplied consistent information concerning the use of 46 species of medicinal plants. Further analysis showed 13 categories of different medicinal use. An informant consensus factor was calculated and 16 species were selected due to their utilization in the treatment of diseases of possible bacterial origin. Of these 16 plants, sequential extractions were made with hexane, ethyl acetate and methanol. The obtained extracts were used to assess their antibacterial activity against 14 bacterial strains; 75% of the plants presented antibacterial activity. The medicinal species Jatropha neopauciflora Pax (Euphorbiaceae) and Juliania adstringens (Schldl.) Schldl. (Julianiaceae) were those that showed the biggest activity. Moreover, these species also had the highest informant consensus factor values.

Anti-Bacterial Agents↗

PubMed2005

Composition and antibacterial activity of essential oil of Lantana achyranthifolia Desf. (Verbenaceae).

The essential oil of the aerial parts of Lantana achyranthifolia Desf. (Verbenaceae) was examined by GC and GC-MS. Eighteen constituents were identified. Carvacrol, 1,8-cineole, isocaryophyllene, beta-bisabolene and alpha-bisabolol were found to be the major components. The oil exhibited antibacterial activity against fourteen Gram-positive and Gram-negative bacteria.

Anti-Bacterial Agents↗

PubMed2003

Ethnobotany and antibacterial activity of some plants used in traditional medicine of Zapotitlán de las Salinas, Puebla (México).

The village of Zapotitlán de las Salinas is situated in the Valley of Tehuacán-Cuicatlán, Puebla, Mexico. Plant species used by the local inhabitants to treat gastrointestinal diseases were identified using ethnobotanical, ethnographic and taxonomic methods. Out of 119 interviews, 44 plant species were registered, of which the following are the most frequently used (listed in descending order): Lippia graveolens H.B. et K. (Verbenaceae), Lantana achyranthifolia Desf. (Verbenaceae), Turnera diffusa (Willd.) ex Schult. (Turneraceae), Lippia oaxacana Rob. et Greenm. (Verbenaceae), Gymnolaena oaxacana (Greenm.) Rydb. (Asteraceae), Cordia curassavica (Jacq.) Roem. et Schult. (Boraginaceae), Lantana camara L. (Verbenaceae) and Acalypha hederacea Torrey (Euphorbiaceae). From these plants, hexane, chloroform and ethanol extracts were prepared in order to assess their antibacterial activity against 14 bacterial strains causing the most common gastrointestinal diseases in Mexican population. All hexane extracts showed antibacterial activity against Gram-positive and Gram-negative bacteria. There is a correlation between the frequency of mention (of plant use) and the antibacterial activity. In conclusion, the knowledge of plants most frequently used for gastrointestinal infections in Zapotitlán de las Salinas is supported by scientific rationale.

Anti-Bacterial Agents↗

PubMed2001

Toward a novel metal-based chemotherapy against tropical diseases. 6. Synthesis and characterization of new copper(II) and gold(I) clotrimazole and ketoconazole complexes and evaluation of their activity against Trypanosoma cruzi.

The complexes [Cu(CTZ)(4)]Cl(2).2H(2)O (1), [Cu(CTZ)Cl(2)](2) (2), [Cu(KTZ)(3)Cl(2)] (3), and [Cu(KTZ)Cl(2)](2).2H(2)O (4) were prepared by reaction of CuCl(2) with CTZ and KTZ (where CTZ = 1-[[(2-chlorophenyl)diphenyl]methyl]-1H-imidazole and KTZ = cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine), respectively, in acetonitrile at different ligand to metal molar ratios. Gold complexes [Au(PPh(3))(CTZ)]PF(6) (5) and [Au(PPh(3))(KTZ)]PF(6).H(2)O (6) were synthesized by reaction of AuClPPh(3), with KPF(6) and CTZ or KTZ in acetonitrile. All the new compounds were characterized by NMR spectroscopy and microanalytical methods, and for the paramagnetic species EPR spectroscopy and DC magnetic susceptibility measurements were also employed. The solid-state structure of 1 has been determined by X-ray crystallography. 1 crystallizes in the triclinic space group P(-)1, with a = 12.773(2) A, b = 15.326(4) A, c = 11.641(2) A, V = 1957.4(7) A(3), Z = 1, and D(calcd) = 1.284 g/cm(3). The structure refinement converged at R1 = 0.0731 and wR2 = 0.1962. Complex 1 displayed a square-planar structure typical for tetrakis(imidazole)copper(II) complexes. The new compounds were tested for in vitro activity against cultures of epimastigotes of Trypanosoma cruzi, the causative agent of Chagas disease. At concentrations equivalent to 10(-6) M of total CTZ or KTZ (in DMSO) all the complexes exhibited significantly higher growth inhibitory activity than their respective parental compounds.

Algorithms↗

PubMed2001

Structure-activity studies of antitumor agent irofulven (hydroxymethylacylfulvene) and analogues.

Many analogues of the antitumor agent irofulven have been readily prepared by replacing the allylic hydroxyl with a variety of nucleophiles. Analogues of acylfulvene (the precursor to irofulven) were also prepared by Michael reaction with acrolein. The toxicity of the analogues was determined, as well as preclinical antitumor activity. Several analogues exhibited good activity in mouse xenografts. Structural requirements for activity are discussed.

Animals↗

PubMed2001

Leishmaniasis recidivans recurrence after 43 years: a clinical and immunologic report after successful treatment.

We describe a patient with very late recurring leishmaniasis recidivans from whom lesional biopsy samples were obtained during and after topical steroid treatment that demonstrated the ability of the host to contain the parasite in the absence of therapy. Combination therapy with intralesional sodium stibogluconate and oral itraconazole was successful and immunologic data suggest that both CD4(+) and CD8(+) T cell subsets had roles in this disease process.

Animals↗

PubMed2001

Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: a potential route to chemotherapy.

We have investigated the effects in vitro of a series of bisphosphonates on the proliferation of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum. The results show that nitrogen-containing bisphosphonates of the type used in bone resorption therapy have significant activity against parasites, with the aromatic species having in some cases nanomolar or low-micromolar IC(50) activity values against parasite replication (e.g. o-risedronate, IC(50) = 220 nM for T. brucei rhodesiense; risedronate, IC(50) = 490 nM for T. gondii). In T. cruzi, the nitrogen-containing bisphosphonate risedronate is shown to inhibit sterol biosynthesis at a pre-squalene level, most likely by inhibiting farnesylpyrophosphate synthase. Bisphosphonates therefore appear to have potential in treating parasitic protozoan diseases.

Animals↗

PubMed2001

Mechanism of action of anti-proliferative lysophospholipid analogues against the protozoan parasite Trypanosoma cruzi: potentiation of in vitro activity by the sterol biosynthesis inhibitor ketoconazole.

We investigated the mechanism of action of metabolically stable lysophospholipid analogues (LPAs), with potent anti-tumour and anti-protozoal activity against Trypanosoma cruzi, the causative agent of Chagas' disease. Against the axenically grown epimastigote form of the parasite, the IC(50)s after 120 h for ET-18-OCH(3), miltefosine and ilmofosine were 3, 1 and 3 microM, respectively; at higher concentrations immediate lytic effects were observed. Eradication of the intracellular amastigote, grown inside Vero cells, was achieved at 0.1, 0.1 and 1 microM for ET-18-OCH(3), miltefosine and ilmofosine, respectively. Analysis of the lipid composition of epimastigotes exposed to LPAs at their IC(50) for 120 h showed that the ratio of phosphatidyl-choline (PC) to phosphatidylethanolamine (PE) changed from 1.5 in control cells to c. 0.67 in those treated with the analogues. A significant increase in the content of phosphatidylserine was also observed in treated cells. Intact epimastigotes efficiently incorporated radioactivity from L-[methyl-(14)C]methionine into PC, but not from [methyl-(14)C]choline. ET-18-OCH(3) inhibited the incorporation of L-[methyl-(14)C]methionine into PC with an IC(50) of 2 microM, suggesting that inhibition of the de novo synthesis through the Greenberg's pathway was a primary effect underlying the selective anti-parasitic activity of this compound. Antiproliferative synergism was observed as a consequence of combined treatment of epimastigotes with ET-18-OCH(3) and ketoconazole, a sterol biosynthesis inhibitor, probably due to the fact that a secondary effect of the latter is also a blockade of PC synthesis at the level of PE-PC-N-methyl-transferase.

Animals↗

PubMed2001

'Yes, you can!'.

Explore the source record for details and available documents.

Asthma↗

PubMed2001

Sporotrichosis in patient with AIDS: report of a case and review.

Although sporotrichosis is not an AIDS-defining infection, reports of sporotrichosis in individuals infected with HIV are increasing. We report an unusual case of this co-infection in a man with progressive deep cutaneous ulcerations with numerous pleomorphic yeast cells of Sporothrix schenckii. In addition a review of the literature on this subject was carried out and commented upon.

Journal Article↗

PubMed2000

A natural model of Leishmania major infection reveals a prolonged "silent" phase of parasite amplification in the skin before the onset of lesion formation and immunity.

A model of Leishmania major infection in C57BL/6 mice has been established that combines two main features of natural transmission: low dose (100 metacyclic promastigotes) and inoculation into a dermal site (the ear dermis). The evolution of the dermal lesion could be dissociated into two distinct phases. The initial "silent" phase, lasting 4-5 wk, favored establishment of the peak load of parasites in the dermis in the absence of lesion formation or any overt histopathologic changes in the site. The second phase corresponds to the development of a lesion associated with an acute infiltration of neutrophils, macrophages, and eosinophils into the dermis and was coincident with the killing of parasites in the site. The onset of immunity/pathology was correlated with the appearance of cells staining for IL-12p40 and IFN-gamma in the epidermal compartment, and an expansion of T cells capable of producing IFN-gamma in the draining lymph node. Parasite growth was not enhanced over the first 4.5 wk in anti-CD4-treated mice, SCID mice, or C57BL/6 mice deficient in IL-12p40, IFN-gamma, CD40 ligand, or inducible NO synthase. These mice all failed to ultimately control infection in the site, but in some cases (anti-CD4 treated, IL-12p40-/-, CD40 ligand-/-, and SCID) high dermal parasite loads were associated with little or no pathology. These results extend to a natural infection model a role for Th1 cells in both acquired resistance and lesion formation, and document the remarkable avoidance of this response during a prolonged phase of parasite amplification in the skin.

Animals↗

PubMed2000

Sesquiterpenes from the basidiomycete Omphalotus illudens.

A new sesquiterpene, omphadiol (4), has been isolated from cultures of Omphalotus illudens. Several known compounds, including illudosin (1), were also obtained. Structures were determined using MS, NMR, and X-ray techniques.

Basidiomycota↗

PubMed2000

In vitro antiproliferative effects and mechanism of action of the new triazole derivative UR-9825 against the protozoan parasite Trypanosoma (Schizotrypanum) cruzi.

We describe the in vitro antiproliferative effects of the new triazole derivative UR-9825 against the protozoan parasite Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas' disease in Latin America. The compound was found to be extremely active against the cultured (epimastigote) form of the parasite, equivalent to that present in the reduviid vector, with a MIC of 30 nM, a concentration 33-fold lower than that required with the reference compound ketoconazole. At that MIC, growth arrest coincided with depletion of the parasite's 4,14-desmethyl endogenous sterols (ergosterol, 24-ethylcholesta-5,7,22-trien-3b-ol, and precursors) and their replacement by methylated sterols (lanosterol, 24-methylenedihydrolanosterol, and obtusifoliol), as revealed by high-resolution gas chromatography coupled with mass spectrometry. This indicated that the primary mechanism of action of UR-9825 was inhibition of the parasite's sterol C14alpha demethylase, as seen with other azole derivatives. The phospholipid composition of growth-arrested epimastigotes was also altered, when compared to controls, with a significant increase in the content of phosphatidylethanolamine and phosphatidylserine and a concomitant reduction of the content of phosphatidylcholine. The clinically relevant intracellular amastigote form, grown in cultured Vero cells at 37 degrees C, was even more sensitive to UR-9825, with a MIC of 10 nM, comparable to that for ketoconazole. The results showed that UR-9825 is among the most potent azole derivatives tested against this parasite and support in vivo studies with this compound.

Animals↗

PubMed2000

Evolution of lesion formation, parasitic load, immune response, and reservoir potential in C57BL/6 mice following high- and low-dose challenge with Leishmania major.

A model of cutaneous leishmaniasis using 10(2) Leishmania major metacyclic promastigotes inoculated into the footpads of genetically resistant C57BL/6 mice was studied in order to more accurately reproduce the evolution of lesion formation and the kinetics of parasite growth and immune response as they might occur in naturally exposed reservoirs and in human hosts. In contrast to the more conventional experimental model employing 10(6) metacyclic promastigotes, in which the rapid development of footpad lesions was associated with an increasing number of amastigotes in the site, the low-dose model revealed a remarkably "silent" phase of parasite growth, lasting approximately 6 weeks, during which peak parasitic loads were established in the absence of any overt pathology. Footpad swelling was observed after 6 weeks, coincident with the onset of parasite clearance and with production of high levels of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) in draining lymph nodes. Low-dose challenge of IL-12- and IFN-gamma-depleted or -deficient mice provided strong evidence that the induction or expression of cellular immunity is essentially absent during the first 6 to 8 weeks of intracellular growth, since the concentration of amastigotes in the site was not enhanced compared to that for wild-type animals during this time. By monitoring the ability of infected mice to transmit parasites to vector sand flies, it was observed that following low-dose challenge, footpads without apparent lesions provided an efficient source of parasites for exposed flies and that the low-dose challenge actually extended the duration of parasite transmissibility during the course of infection.

Animals↗

PubMed1999

Evidence that the high incidence of treatment failures in Indian kala-azar is due to the emergence of antimony-resistant strains of Leishmania donovani.

The possibility that the high frequency of treatment failures in Indian kala-azar might be due to infection with antimony-resistant strains of Leishmania donovani has not been experimentally addressed. L. donovani isolates were obtained from splenic aspiration smears of 24 patients in Bihar, India, who either did not respond (15) or did respond (9) to 1 or more full courses of treatment with sodium antimony gluconate (SAG). A strong correlation (P<.001) between clinical response and SAG sensitivity in vitro was observed only when strains were assayed as intracellular amastigotes: responsive isolates ED50=2.4+/-2.6, ED90=6.4+/-7.8 microgram SAG/mL; unresponsive isolates ED50=7.4+/-3.7 microgram SAG/mL, ED90=29.1+/-11.1 SAG/mL. No correlation with clinical response was found by use of extracellular promastigotes (ED50=48+/-22 vs. 52+/-29 microgram/mL). The emergence of antimony-resistant L. donovani strains appears to be a cause of treatment failures in India.

Adolescent↗

PubMed1998

Leishmania tropica: the identification and purification of metacyclic promastigotes and use in establishing mouse and hamster models of cutaneous and visceral disease.

Few experimental studies on Leishmania tropica have been undertaken despite the importance of this parasite as the cause of cutaneous leishmaniasis, and now visceral disease, in the Old World. In part, this is due to the absence of convenient animals models, especially mice, for L. tropica infections. An anti-lipophosphoglycan (LPG) monoclonal antibody XCIV 1H2-A8 (T11), specific for L. tropica, was found to distinguish between culture-derived procyclic and metacyclic promastigotes. The antibody was used to negatively select for nonagglutinated metacyclic forms in stationary cultures, and the exceptional virulence of the purified metacyclics was verified by their infectivity for mouse macrophages in vitro and by their ability to produce cutaneous lesions in footpads of BALB/c mice. The lesions produced by three cutaneous isolates of L. tropica were nonulcerative and nonprogressive. Nonetheless, the lesions failed to heal, and high numbers of parasites could be recovered from footpads and draining lymph nodes up to 9 months after infection. Infections using L. tropica metacyclics purified from cutaneous, visceral and viscerotropic (Desert Storm) isolates of L. tropica were compared in both mouse and hamster models. Differences in disease progression were found that may reflect the parasite tissue tropism and virulence displayed by these strains in their human hosts. These findings suggest a role for parasite-related determinants in the clinical spectrum of disease.

Agglutination Tests↗

PubMed1997

Leishmania mexicana: binding of promastigotes to type I collagen.

During leishmania infection, parasites are inoculated to the human host through the bite of a sandfly vector into the dermis, where they first interact with tissue components, cells and extracellular matrix molecules. Since collagen is the most abundant component of the skin matrix, we investigated whether there is a specific interaction of Leishmania mexicana promastigotes with this host component. Promastigotes were able to attach to collagen fibrils and move through the matrix of mouse skin sections and to penetrate easily into a type I collagen gel. Denatured type I collagen coated beads (Cytodex 3) readily bound to the parasite surface. The interaction of promastigotes with type I collagen was dose dependent and saturable and was competitively and specifically inhibited with increasing concentrations of gelatin. Biotin-labeled parasite surface molecules were able to associate with both denatured collagen from microcarriers and native type I collagen from bovine kidney. It is suggested that the presence of parasite cell membrane receptors to collagen may confer a specific tropism for the skin, where collagen is the most abundant component of the matrix.

Animals↗

PubMed1989

Differential response of adherent and unanchored melanoma cells to bromodeoxyuridine evidenced by specific lectin-binding protein changes.

The possible differential response of adherent and nonadherent cells of the same tumor type to pyrimidine analogues has been investigated. We show that bromodeoxyuridine (BUdR) increases interactions of attached cells with their substrate without markedly affecting the cell adhesion properties of the same cells when these are not anchored. However, evidence for an adhesion-independent response of both cell types to BUdR has been obtained with lectin binding assays using 125I-labelled Lens culinaris agglutinin (LCA). This revealed a greatly increased binding of LCA to a large glycoconjugate in all cultures exposed to the halogenated pyrimidine. Attachment-dependent effects of BUdR were manifested in flattened cells by a greater LCA-binding to a 240-kDa protein and by increased interaction of 125I-labelled wheat-germ agglutinin (WGA) with a 200-kDa protein and a large glycoconjugate sharply defined in electrophoresis. Although both tumor cell aggregates and anchored cells exhibit detectable responses to pyrimidine analogues such as BUdR, the corresponding effects are thus manifested unequally in cells with different adhesion properties.

Animals↗