RESUMEN
InP-In2O3 colloidal quantum dots (QDs) synthesized by a single-step chemical method without injection of hot precursors (one-pot) were investigated. Specifically, the effect of the tris(trimethylsilyl)phosphine, P(TMS)3, precursor concentration on the QDs properties was studied to effectively control the size and shape of the samples with a minimum size dispersion. The effect of the P(TMS)3 precursor concentration on the optical, structural, chemical surface, and electronic properties of InP-In2O3 QDs is discussed. The absorption spectra of InP-In2O3 colloids, obtained by both UV-Vis spectrophotometry and photoacoustic spectroscopy, showed a red-shift in the high-energy regime as the concentration of the P(TMS)3 increased. In addition, these results were used to determine the band-gap energy of the InP-In2O3 nanoparticles, which changed between 2.0 and 2.9 eV. This was confirmed by Photoluminescence spectroscopy, where a broad-band emission displayed from 2.0 to 2.9 eV is associated with the excitonic transition of the InP and In2O3 QDs. In2O3 and InP QDs with diameters ranging approximately from 8 to 10 nm and 6 to 9 nm were respectively found by HR-TEM. The formation of the InP and In2O3 phases was confirmed by X-ray Photoelectron Spectroscopy.
RESUMEN
PURPOSE: The aim of this phase II study was to evaluate the activity and safety of the combination of cisplatin and vinorelbine with thoracic radiotherapy in unresectable locally advanced stage III non-small cell lung cancer (NSCLC). The primary endpoint was the objective response rate (ORR). Secondary objectives included toxicity profile, progression-free survival (PFS), and overall survival (OS). MATERIALS AND METHODS: A total of 48 NSCLC patients were enrolled (median age 60 years, 52% stage IIIA and 48% stage IIIB, 52% adenocarcinoma). Patients received three cycles of chemotherapy every 21 days [intravenous cisplatin 80 mg/m2 and intravenous vinorelbine 25 mg/m2 on day 1 and oral vinorelbine on day 8 (60 mg/m2)] concurrent with radiotherapy (66 Gy, administered at 1.8 Gy per day, five consecutive days per week). RESULTS: ORR was 79.2% (72.9% showing partial response and 6.3% showing complete response). With a median follow-up of 20.7 months, median PFS was 12 months and median OS was 36 months. Grade 3/4 toxicities were: neutropenia (14.5%), anaemia (6.2%), vomiting (2%), and oesophagitis (4.2%). No toxic deaths were reported. CONCLUSION: This combined regimen shows efficacy and a manageable safety profile. PFS and OS outcomes are encouraging and warrant further research.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Neoplasias Pulmonares/terapia , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Caja Torácica/efectos de la radiación , España/epidemiología , Análisis de Supervivencia , Vinorelbina/administración & dosificación , Vinorelbina/efectos adversosRESUMEN
BACKGROUND: How to overcome the difficulty in diagnosing extrapulmonary and extraspinal osteoarticular tuberculosis? What is the most appropriate way to manage the patient? MATERIAL AND METHODS: Retrospective series of four cases of extrapulmonary and extraspinal osteoarticular tuberculosis (two patients with knee involvement, one patient with involvement of the carpus, and a fourth patient who presented with tenosynovitis of the anterior tibial tendon of the ankle). The time elapsed from the onset of the clinical picture to the diagnosis ranged between 7 months and 2 years. The definitive diagnosis resulted from the presence of caseating granulomas in the biopsy (3 cases), and the isolation of the bacillus in culture (3 cases) or with staining (one case). Only in one case was there lung involvement after the extrapulmonary presentation. One patient had spinal involvement in the form of epidural abscess months after the extraspinal presentation. All patients received chemotherapy. Surgery was performed in 3 of the 4 cases. The Martini assessment was used to evaluate the functional outcome. RESULTS: In all patients the lesion was cured, with two excellent and two poor functional outcomes. CONCLUSIONS: A high clinical suspicion index is needed to prevent a delayed diagnosis. Chemotherapy is the cornerstone of treatment. Surgery is indicated mainly as a diagnostic procedure, but partial resection of the lesion may be performed at the same time.
Asunto(s)
Tuberculosis Osteoarticular/diagnóstico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Noroviruses constitute an important cause of acute gastroenteritis, mainly in semi-closed populations such as hospitals, hotels and cruise ships. This study records the most important norovirus outbreak in the Dominican Republic in a single resort, with more than 800 people being affected in a 15-day period. Analysis of clinical and environmental samples demonstrated that norovirus was the aetiological agent responsible for the outbreak. Although enhanced hygiene and disinfection measures were achieved, the outbreak was only controlled after suspension of entry into the resort.
Asunto(s)
Infecciones por Caliciviridae/epidemiología , Brotes de Enfermedades , Gastroenteritis/epidemiología , Norovirus/aislamiento & purificación , Infecciones por Caliciviridae/virología , República Dominicana/epidemiología , Microbiología Ambiental , Gastroenteritis/virología , Colonias de Salud , Humanos , Control de Infecciones/métodos , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Colloidal suspensions of bimetallic Au/Pd nanoparticles were prepared by simultaneous reduction of the metal ions from their corresponding chloride salts with polymer (PVP) stabilizer. Thermal properties of water containing bimetallic nanoparticles with different nominal compositions (Au/Pd = 12/1, 5/1, 1/1, 1/5) were measured using the mode mismatched dual-beam thermal lens technique to determine the effect of particle composition on the thermal diffusivity of the nanofluids. The characteristic time constant of the transient thermal lens was estimated by fitting the experimental data to the theoretical expression for transient thermal lens. The thermal diffusivity of the nanofluids (water, containing Au/Pd bimetallic nanoparticles) is seen to be strongly dependent on the composition of the particles. The maximum diffusivity was achieved for the nanoparticles with highest Au/Pd molar ratio. A possible mechanism for such high thermal diffusivity of the nanofluids with bimetallic particles is given. UV-Vis spectroscopy, TEM and high-resolution electron microscopy (HREM) techniques were used to characterize the Au/Pd bimetallic nanoparticles.
Asunto(s)
Coloides/química , Oro/química , Microfluídica/métodos , Nanoestructuras/química , Nanoestructuras/ultraestructura , Nanotecnología/métodos , Paladio/química , Difusión , Calor , Ensayo de Materiales , Metales/química , Tamaño de la Partícula , Soluciones , Conductividad TérmicaRESUMEN
Licensed as well as candidate cholera vaccines available at the present requires the dose preparation (included buffer) at the moment of application. The aim of this work was to evaluate the presentation in oral tablets of an inactivated cholera vaccine to avoid that inconveniences during application. We have therefore compared inactivated cultures of Vibrio cholerae with tablets formulation vaccine. We obtained that antigenic activity (ELISA) and immunogenicity in animal model (ELISA and vibriocidal tests) of V. cholerae inactivated cell remained unaltered in the final tablet formulation. The results suggest that the oral tablet formulation could be a useful pharmaceutical form in order to produce a new and affordable cholera vaccine.
Asunto(s)
Vacunas contra el Cólera/administración & dosificación , Cólera/prevención & control , Administración Oral , Animales , Anticuerpos Antibacterianos/sangre , Vacunas contra el Cólera/inmunología , Recuento de Colonia Microbiana , Ensayo de Inmunoadsorción Enzimática , Modelos Animales , Conejos , Comprimidos , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Vibrio cholerae/inmunologíaRESUMEN
Genetically modified Vibrio cholerae strain 638 (biotype El Tor, serotype Ogawa) has previously been shown to be immunogenic in animal models and in human trials. Our objective in the work reported herein was to describe the process development methods for the production of the 638 attenuated cholera vaccine. Cell seed bank, culture of biomass, lyophilization and final formulation were processes were developed. The results show kinetics of culture that fulfils a logistical model. The microbiological properties, colonizing capability, immunogenicity and non-toxigenicity of the final product were indistinguishable from the properties of the working seed lot. We conclude that the non-reactogenic, immunogenic and protective strain 638 is robust and can withstand the fermentation processes required for large-scale production of a vaccine.
Asunto(s)
Vacunas contra el Cólera , Tecnología Farmacéutica , Vibrio cholerae/inmunología , Animales , Cólera/prevención & control , Toxina del Cólera/análisis , Vacunas contra el Cólera/efectos adversos , Vacunas contra el Cólera/inmunología , Industria Farmacéutica , Fermentación , Humanos , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Vibrio cholerae/genética , Vibrio cholerae/patogenicidad , Vibrio cholerae/fisiologíaRESUMEN
The antiinflammatory (per os and topic) and analgesic (per os) properties of the aerial part of Proustia pyrifolia a species in danger of extinction were investigated, and the major compounds of two of its active extracts were isolated. In addition, the evaluation of cytotoxicity in three tumoral cell lines and the acute toxicity of the crude methanol extract were also assayed, together with the antioxidant activity for the different extracts of this species. The results of the evaluation of the topic antiinflammatory activities induced by arachidonic acid, and phorbol 12-myristate 13-acetate of the different extracts showed that this species possesses active constituents that could diminish cyclo-oxygenase and lipoxygenases activities, the enzymes that allow the synthesis of proinflammatory endogenous substances as prostaglandin E(2) and leukotrienes, respectively. Our results corroborate the antiinflammatory and analgesic effects of Proustia pyrifolia, and could justify its use in folk medicine for the treatment of rheumatic and gout illnesses. From bio-active extracts beta-sitosterol, quercetin and dihydroquercetin were obtained, and these compounds could explain in part the antiinflammatory, analgesic and antioxidant activities of this species. The crude methanol extract did not present acute toxicity or cytotoxic activity, however only this extract exhibited antioxidant activity.
Asunto(s)
Analgésicos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Asteraceae/química , Animales , Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos , Antioxidantes/farmacología , Carragenina , Fenómenos Químicos , Química Física , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Edema/inducido químicamente , Edema/prevención & control , Femenino , Cobayas , Dosificación Letal Mediana , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Dimensión del Dolor/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Solventes , España , Células Tumorales Cultivadas , Xantina Oxidasa/antagonistas & inhibidoresRESUMEN
Seeking for new medicinal compounds in plants used in traditional medicine, which grow in Venezuela, we investigated the anti-inflammatory activity of the leaf hexane extract (HE) and several fractions obtained from sp. Bursera simaruba (L.) Sarg. (Indio desnudo) using carrageenan-induced paw edema inflammation. Oral administration of leaf HE as well I (91-100) fraction, and compounds VIII 25-26 and VIII 29, inhibited the carrageenan-induced paw edema with different capacity and time course, over a period of 7h. The anti-inflammatory effect was comparable to that of the reference drug phenylbutazone (80 mg/kg, p.o.). Included in fraction I (91-100), Vitamin E was identified as one of its components and compound VIII 29 was identified as a methyl-beta-peltatin A. The comparison of the anti-inflammatory activity of VIII 29 fraction with the corresponding standard of methyl-beta-peltatin A, suggest that this compound could be one of the active principles involved in the anti-inflammatory activity of Bursera simaruba (L.) Sarg. leave. Our results contribute to the pharmacological support of the use of Bursera simaruba (L.) Sarg. as anti-inflammatory in the ethnomedicinal practice.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Burseraceae , Edema/prevención & control , Fitoterapia , Extractos Vegetales/farmacología , Administración Oral , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/uso terapéutico , Carragenina , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Masculino , Medicina Tradicional , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , VenezuelaRESUMEN
La rotación mandibular terapéutica se lleva a cabo para modificar la dimensión vertical facial en caras extremas, cortas o largas. El síndrome de cara corta se beneficia de la rotación mandibular horaria llevada a cabo por aparatos ortopédicos que permiten la extrusión de molares. La rotación antihoraria es buscada en el síndrome de cara larga por medio de la extracción de molares o la cirugía de maxilares. Han sido revisados los procedimientos no quirúrgicos, analizando la estabilidad esquelética en grupos que presentaban estabilidad dentoclusal. El patrón esquelético vertical se muestra poco estable, incluso en este tipo de individuos. Asimismo, se ha estudiado una muestra de 15 pacientes de clase III y cara larga tratados con cirugía combinada de los maxilares y fijación semirrígida. Los resultados constatan que a los 3 años de finalizado el tratamiento se observa una cantidad de recidiva esqulética vertical superior que la sagital, aún en presencia de estabilidad dentaria
Asunto(s)
Humanos , Masculino , Adolescente , Femenino , Mandíbula/cirugía , Mandíbula/fisiología , Rotación , Somatotipos , Aparatos Activadores , Aparatos Ortodóncicos , Cefalometría , Extracción Dental , Cara , Anomalías Maxilomandibulares , Maloclusión Clase II de Angle/cirugía , Maloclusión Clase II de Angle/terapia , Maloclusión de Angle Clase III/cirugía , Maloclusión de Angle Clase III/terapia , Maloclusión/fisiopatología , Maloclusión/terapia , Mandíbula/crecimiento & desarrollo , Planificación de Atención al Paciente , Recurrencia , Técnicas de Fijación de Maxilares , Dimensión VerticalRESUMEN
Acaena splendens H. et A. has been used in Chilean folk medicine for the treatment of fever and inflammation. A description of the in vivo reduction of bacterial pyrogen-induced fever in rabbits and carrageenan-induced paw oedema in guinea pigs is presented. The methanol extract named ME-1, obtained after succesive extractions with petroleum ether and dichloromethane, showed a strong antipyretic action (45.7% of effect), though the antiinflammatory activity was only observed after submitting this extract to column fractionation, giving a crude mixture of flavonoids named C4 with both activities (55.7% and 98.9% of antiinflammatory and antipyretic effect respectively at a dose of 600 mg/kg). The bioassay-guided fractionation by column chromatography afforded the active fraction, which contained (-,-)-epicatechin, tiliroside, 7-O-acetyl-3-O-beta-D-glucosyl-kaempferol and 7-beta-D-glucosyloxy-5-hydroxy-chromone.
Asunto(s)
Quempferoles , Fenoles/farmacología , Extractos Vegetales/farmacología , Rosaceae , Analgésicos no Narcóticos/química , Analgésicos no Narcóticos/farmacología , Analgésicos no Narcóticos/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Benzopiranos/química , Benzopiranos/aislamiento & purificación , Carragenina/farmacología , Catequina/química , Catequina/aislamiento & purificación , Cromonas/química , Cromonas/aislamiento & purificación , Edema/inducido químicamente , Edema/tratamiento farmacológico , Femenino , Fiebre/tratamiento farmacológico , Flavonoides/química , Flavonoides/aislamiento & purificación , Glucósidos/química , Glucósidos/aislamiento & purificación , Cobayas , Miembro Posterior/efectos de los fármacos , Inflamación/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Masculino , Medicina Tradicional , Estructura Molecular , Naproxeno/farmacología , Fenoles/química , Fenoles/aislamiento & purificación , Fenoles/uso terapéutico , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , ConejosRESUMEN
As part of the studies to obtain an oral vaccine against cholera disease, the protective effect of serum from volunteers inoculated in a controlled trial with a candidate live attenuated vaccine of Vibrio cholerae O1, El Tor Ogawa (638; CTXφ mutant, hap::celA), was tested. It was confirmed that the serum, as well as the purified IgG and IgA from the volunteers had a protective effect in both of the animal models used, although the purified antibodies needed the presence of complement to be protective. These results emphasize the expectations about the protective potential of the candidate in challenge studies in humans to be conducted very soon.
Asunto(s)
Anticuerpos Antibacterianos/inmunología , Vacunas contra el Cólera/inmunología , Animales , Animales Recién Nacidos , Humanos , Inmunización Pasiva , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Conejos , Vacunas Atenuadas/inmunologíaRESUMEN
UNLABELLED: This work aimed to assess the utility of 99mTc-MIBI scintigraphy in the diagnosis and follow-up of lymphoma patients. Seventy-two patients with a previous diagnosis of lymphoma (41 with Hodgkin's and 31 with non-Hodgkin's disease) and a control group of 8 patients with palpable lymph nodes and a negative diagnosis of lymphoma based on the clinical examination, chest x-ray, lymphography, ultrasounds and biopsy were studied. Whole body scintigraphies were performed 20 min and 2 h after i.v. administration of 740 MBq of 99mTc-MIBI. The joint result of the already mentioned standard diagnostic tests was considered as the confirmation criterion. A sensitivity, specificity and accuracy of 96,2%, 100% and 97,4% respectively were obtained. Kappa coefficient was k = 0,94 +/- 0,11. CONCLUSION: Scintigraphy with 99mTc-MIBI is a useful tool for the diagnosis and follow-up of lymphomas regardless of their classification.
Asunto(s)
Enfermedad de Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/diagnóstico por imagen , Tecnecio Tc 99m Sestamibi , Adolescente , Adulto , Anciano , Enfermedad de Castleman/diagnóstico por imagen , Niño , Preescolar , Estudios de Evaluación como Asunto , Femenino , Estudios de Seguimiento , Humanos , Linfadenitis/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Cintigrafía , Sensibilidad y EspecificidadRESUMEN
The recent spread of El Tor cholera in Latin America highlights the need for a safe and economical vaccine. The main approach for developing live recombinant vaccines has been to disarm known pathogenic strains of cholera toxin leaving intact antigens involved in protection. These recombinant vaccine candidates do not cause severe diarrhea, but they are too reactogenic for wide scale usage. We describe here a test capable of determining the diarrheagenic potential of attenuated V. cholerae strains. The functional test consists in the simultaneous recording of net water movement, electrical potential difference and short-circuit current across the human intestine ex vivo. We found that human tissues incubated with supernatants from the attenuated 638, 413 and 251a V. cholerae strains caused no changes in the ion conductances and water absorption in ileal and colon tissues allowing them to be assayed in volunteers.
Asunto(s)
Vacunas contra el Cólera/toxicidad , Diarrea/inmunología , Mucosa Intestinal/microbiología , Vibrio cholerae/inmunología , Animales , Diarrea/metabolismo , Diarrea/microbiología , Modelos Animales de Enfermedad , Humanos , Íleon/inmunología , Íleon/metabolismo , Íleon/microbiología , Técnicas In Vitro , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Dosificación Letal Mediana , Ratones , Conejos , Vacunas Atenuadas/toxicidad , Vibrio cholerae/patogenicidadRESUMEN
Vibrio cholerae 638 (El Tor, Ogawa), a new CTXPhi-negative hemagglutinin/protease-defective strain that is a cholera vaccine candidate, was examined for safety and immunogenicity in healthy adult volunteers. In a double-blind placebo-controlled study, no significant adverse reactions were observed in volunteers ingesting strain 638. Four volunteers of 42 who ingested strain 638 and 1 of 14 who received placebo experienced loose stools. The strain strongly colonized the human small bowel, as evidenced by its isolation from the stools of 37 of 42 volunteers. V. cholerae 638, at doses ranging from 4 x 10(7) to 2 x 10(9) vibrios, elicited significant serum vibriocidal antibody and anti-Ogawa immunoglobulin A antibody secreting cell responses.
Asunto(s)
Toxina del Cólera/inmunología , Vacunas contra el Cólera/inmunología , Metaloendopeptidasas/inmunología , Vacunas Sintéticas/inmunología , Vibrio cholerae/inmunología , Adulto , Animales , Bacteriófagos/genética , Vacunas contra el Cólera/efectos adversos , Humanos , Masculino , Metaloendopeptidasas/genética , Mutagénesis , Conejos , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/genética , Vibrio cholerae/virologíaRESUMEN
Frontal analysis of aqueous phenol solutions in Amberlite XAD-4 columns was carried out at different experimental conditions. Operating variables such as the concentration, pH and ionic strength of the influent, the presence of competitor solutes, the fluid flow-rate and the column length were considered and their effects on the front profile, the phenol breakthrough volume and the equilibrium parameters were determined. The obtained results may explain some contradictory reported data concerning the recovery of hydrophilic compounds in solid phase extraction (SPE) systems using Amberlite XAD-2 or XAD-4 columns. Furthermore, it is demonstrated that the adsorption parameters derived from a frontal analysis in an XAD-4 column are directly transposable to columns of different sizes (at the analytical level). Therefore, the results of this study may also be used for prediction and/or design of a phenol SPE system adapted to a particular problem.
RESUMEN
We have generated murine monoclonal antibodies (MAb) against Vibrio cholerae mannose-sensitive hemagglutinin (MSHA) using conventional hybridoma procedures. Seven hybridomas were obtained and one characterized. Hybridoma 2F12/F1 secreted an antibody of the IgG3 type that reacted with a 17-kDa antigen corresponding to the product of the mshA gene. This MAb inhibited mannose-sensitive agglutination of chicken erythrocytes by EL tor and O139 vibrios. Vibrios expressing MSHA activity inhibited binding of the antibody secreted by 2F12/F1 to MSHA-coated microtiter plates.
Asunto(s)
Anticuerpos Antibacterianos/inmunología , Proteínas Bacterianas/inmunología , Proteínas Fimbrias , Hemaglutininas/inmunología , Vibrio cholerae/inmunología , Animales , Anticuerpos Monoclonales , Pollos , Ensayo de Inmunoadsorción Enzimática , Pruebas de Hemaglutinación , Hibridomas , Immunoblotting , Manosa/farmacología , Lectina de Unión a ManosaRESUMEN
Comparison of cholera toxin (CT) production directed by different gene constructs and S1 nuclease mapping revealed the presence of a ctxB-specific promoter within the ctxA coding sequence. Initiation of transcription in this region occurred in wild-type El Tor and classical biotype choleragenic vibrios. We propose that transcription from the ctxB-specific promoter and a stronger ribosomal binding site on the ctxB mRNA synergistically contribute to achieve the correct (5B:1A) subunit stoichiometry. Plasmid pB, a CT promoterless vector expressing only CTB, was used to detect promoter activity by restoration of A-subunit synthesis. Promoter activity expressed in vitro and in vivo was detected upstream of the zonula occludens toxin gene, suggesting that this factor could be produced in vivo to contribute to fluid accumulation. No promoter activity was detected in vitro and in vivo upstream from the accessory cholera enterotoxin gene.
Asunto(s)
Toxina del Cólera/genética , Regulación Bacteriana de la Expresión Génica , Regiones Promotoras Genéticas/genética , Vibrio cholerae/metabolismo , Secuencia de Bases , Eliminación de Gen , Datos de Secuencia MolecularRESUMEN
The recent spread of El Tor cholera to America augments the need for an effective, safe and economical vaccine. In the present paper we describe the construction of live attenuated V. Cholerae strains by specifically deleting the genes encoding cholera toxin and other putative toxins from the bacterial chromosome. To maximize the likelihood of exposing protective antigens relevant to currently circulating vibrios we selected for genetic manipulation recent epidemic V. cholerae isolates from Peru. The mutant strains did not produce cholera toxin in vitro and in vivo. Deletion of the virulence cassette was accompanied by marked attenuation in the infant mouse cholera model. A selected El Tor Ogawa candidate vaccine strain was refractory to acquisition of foreign genes by conjugation with toxigenic vibrios.