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1.
Actas Dermosifiliogr ; 107(9): 740-750, 2016 Nov.
Artículo en Inglés, Español | MEDLINE | ID: mdl-27436804

RESUMEN

A wide range of treatments is now available for nonmelanoma skin cancer, including 5-fluorouracil, ingenol mebutate, imiquimod, diclofenac, photodynamic therapy, methotrexate, cetuximab, vismodegib, and radiotherapy. All are associated with high clinical and histologic response rates. However, some tumors do not respond due to resistance, which may be primary or acquired. Study of the resistance processes is a broad area of research that aims to increase our understanding of the nature of each tumor and the biologic features that make it resistant, as well as to facilitate the design of new therapies directed against these tumors. In this second article, having covered the topical treatments of nonmelanoma skin cancer, we review resistance to other nonsurgical treatments, such as monoclonal antibodies against basal and squamous cell carcinomas, intralesional chemotherapy, photodynamic therapy, and radiotherapy.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma/tratamiento farmacológico , Resistencia a Antineoplásicos , Fotoquimioterapia , Neoplasias Cutáneas/tratamiento farmacológico , Anilidas/administración & dosificación , Anilidas/farmacología , Anilidas/uso terapéutico , Células Presentadoras de Antígenos/efectos de los fármacos , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/farmacología , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Carcinoma/genética , Carcinoma/radioterapia , Cetuximab/administración & dosificación , Cetuximab/farmacología , Cetuximab/uso terapéutico , Ensayos Clínicos como Asunto , Terapia Combinada , Resistencia a Antineoplásicos/fisiología , Receptores ErbB/antagonistas & inhibidores , Humanos , Inyecciones Intralesiones , Queratoacantoma/tratamiento farmacológico , Metaanálisis como Asunto , Metotrexato/administración & dosificación , Metotrexato/farmacología , Metotrexato/uso terapéutico , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/fisiología , Células Madre Neoplásicas/efectos de los fármacos , Receptor Patched-1/antagonistas & inhibidores , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Piridinas/administración & dosificación , Piridinas/farmacología , Piridinas/uso terapéutico , Tolerancia a Radiación/genética , Tolerancia a Radiación/fisiología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/radioterapia
2.
Int J Cosmet Sci ; 37(1): 41-55, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25256953

RESUMEN

BACKGROUND: The search of substances that minimize cutaneous ageing has increased in the last few years. Previous studies have described the regenerative properties of the secretion of the mollusc Cryptomphalus aspersa (C. aspersa) when applied topically. OBJECTIVE: We evaluate the in vitro effects of a new product derived from the eggs of C. aspersa, IFC-CAF, on cell proliferation, migration, distribution of cytoskeletal proteins, production of extracellular components as well as its ability to prevent cutaneous ageing because of intrinsic or extrinsic factors (exposure to UVB) by determination of ageing markers. METHODS: We have used the human keratinocyte cell line (HaCaT cells), primary dermal fibroblasts (HDF) and senescent dermal fibroblasts (SHDF). The effects of the compound on cell proliferation and on the cell cycle were determined by the MTT colorimetric assay, estimation of total protein and/or trypan blue test and by flow cytometry, respectively. We also studied cell migration using the wound-healing migration assay, whereas ELISA assays, Western Blot and immunofluorescence microscopy were carried out to test the expression of proteins related to cytoskeleton, extracellular matrix and with ageing. RESULTS: We have found that IFC-CAF does not promote proliferation but induces migration of HaCaT, HDF and SHDF in a time- and dose-dependent manner; a better organization of cytoskeletal proteins (F-actin and vimentin) and promotes the production of extracellular components (fibronectin, collagen 1 and MMPs) and the adhesion to cell-substrate vinculin protein. IFC-CAF also prevents cutaneous ageing. The treatment decreases the expression of the ageing-related markers b-Gal, p53 and p16INK4 in SDDF cells, and improves cell survival after UVB irradiation and nuclear repair in HaCaT cells. CONCLUSION: IFC-CAF has regenerative properties and protects against ageing factors being, therefore, a potential therapeutic agent for treating or preventing skin ageing.


Asunto(s)
Movimiento Celular , Queratinocitos/citología , Moluscos/química , Óvulo/química , Envejecimiento de la Piel , Piel/citología , Animales , Fibroblastos/citología , Técnicas In Vitro
4.
J Healthc Qual Res ; 38(4): 214-223, 2023.
Artículo en Español | MEDLINE | ID: mdl-36868998

RESUMEN

INTRODUCTION: Health workers are at high risk of becoming infected with COVID-19. The objective of the study was to evaluate the risks and improve the biological and radiological safety measures for taking chest X-rays in patients with COVID-19 in a Social Security hospital in Utcubamba (Peru). MATERIAL AND METHODS: Quasi-experimental intervention study type before and after without a control group, carried out between May and September 2020. A process map and an analysis of failure modes and effects (FMEA) of radiological care were prepared. The gravity (G), occurrence (O), and detectability (D) values ??were found and the risk priority number (RPN) was calculated for each failure mode (FM). FM with RPN ≥ 100 and G ≥ 7 were prioritized. Improvement actions were implemented based on the recommendations of recognized institutions and the O and D values ??were re-evaluated. RESULTS: The process map consisted of 6 threads and 30 steps. 54 FM were identified, 37 of whom had RPN ≥ 100 and 48 had G ≥ 7. Most of the errors occurred during the examination 50% (27). After entering the recommendations, 23 FM had RPN ≥ 100. CONCLUSIONS: Although none of the measures applied through the FMEA made the failure mode impossible, they made it more detectable and less frequent and reduced the RPN for each failure mode; however, a periodic update of the process is necessary.


Asunto(s)
COVID-19 , Humanos , Rayos X , COVID-19/epidemiología , Medición de Riesgo , Radiografía , Pacientes
5.
J Appl Microbiol ; 109(6): 2079-86, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20846331

RESUMEN

AIMS: To evaluate the capability of the exopolysaccharides (EPS) produced by lactobacilli and bifidobacteria from human and dairy origin to antagonize the cytotoxic effect of bacterial toxins. METHODS AND RESULTS: The cytotoxicity of Bacillus cereus extracellular factors on Caco-2 colonocytes in the presence/absence of the EPS was determined by measuring the integrity of the tissue monolayer and the damage to the cell membrane (extracellular lactate dehydrogenase activity). Additionally, the protective effect of EPS against the haemolytic activity of the streptolysin-O was evaluated on rabbit erythrocytes. The EPS produced by Bifidobacterium animalis ssp. lactis A1 and IPLA-R1, Bifidobacterium longum NB667 and Lactobacillus rhamnosus GG were able to counteract the toxic effect of bacterial toxins on the eukaryotic cells at 1mg ml(-1) EPS concentration. The EPS A1 was the most effective in counteracting the effect of B. cereus toxins on colonocytes, even at lower doses (0·5mg ml(-1) ), whereas EPS NB667 elicited the highest haemolysis reduction on erythrocytes. CONCLUSIONS: The production of EPS by lactobacilli and bifidobacteria could antagonize the toxicity of bacterial pathogens, this effect being EPS and biological marker dependent. SIGNIFICANCE AND IMPACT OF THE STUDY: This work allows gaining insight about the mechanisms that probiotics could exert to improve the host health.


Asunto(s)
Toxinas Bacterianas/farmacología , Bifidobacterium/metabolismo , Lactobacillus/metabolismo , Polisacáridos Bacterianos/metabolismo , Animales , Células CACO-2 , Membrana Celular/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Eritrocitos/microbiología , Hemólisis , Humanos , Conejos
6.
JDR Clin Trans Res ; 5(3): 278-283, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31560579

RESUMEN

INTRODUCTION: Oral health mirrors systemic health; yet, few clinics worldwide provide dental care as part of primary medical care, nor are dental records commonly integrated with medical records. OBJECTIVES: To determine the degree to which misreporting of underlying health conditions poses problems for dental clinicians, we assessed misreporting of 2 common medical health conditions-hypertension and diabetes-at the time of dental examination and assessment. METHODS: Using comparative chart analysis, we analyzed medical records of a diverse group of patients previously seen at the University of Texas Physician outpatient practice and then treated at the University of Texas Health Science Center at Houston School of Dentistry. Electronic health records of patients aged ≥18 y were extracted from 2 databases: Allscripts (University of Texas Physician) and axiUm (University of Texas Health Science Center at Houston). We identified 1,013 patients with the commonly occurring conditions of diabetes, hypertension, or both, with nonintegrated records contained in Allscripts and axiUm. We identified the percentage of those patients previously diagnosed with diabetes and/or hypertension by their physicians who failed to report these conditions to their dental clinicians. RESULTS: Of those patients with diabetes, 15.1% misreported their diabetes condition to their dental clinicians, while 29.0% of patients with hypertension also misreported. There was no relationship between sex and misreporting of hypertension or diabetes, but age significantly affected reporting of hypertension, with misreporting decreasing with age. CONCLUSIONS: Because these conditions affect treatment planning in the dental clinic, misreporting of underlying medical conditions can have negative outcomes for dental patients. We conclude that policies that support the integration of medical and dental records would meaningfully increase the quality of health care delivered to patients, particularly those dental patients with underlying medical conditions. KNOWLEDGE TRANSFER STATEMENT: Our study illustrates an urgent need for policy innovation within a currently fragmented health care delivery system. Dental clinicians rely on the accuracy of health information provided by patients, which we found was misreported in ~15% to 30% of dental patient records. An integrated health care system can close these misreporting gaps. Policies that support the integration of medical and dental records can improve the quality of health care delivered, particularly for dental patients with underlying medical conditions.


Asunto(s)
Prestación Integrada de Atención de Salud , Registros Electrónicos de Salud , Instituciones de Salud , Humanos , Atención al Paciente , Atención Primaria de Salud
7.
J Dairy Sci ; 92(9): 4158-68, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19700676

RESUMEN

This work reports on the physicochemical characterization of 21 exopolysaccharides (EPS) produced by Lactobacillus and Bifidobacterium strains isolated from human intestinal microbiota, as well as the growth and metabolic activity of the EPS-producing strains in milk. The strains belong to the species Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus vaginalis, Bifidobacterium animalis, Bifidobacterium longum, and Bifidobacterium pseudocatenulatum. The molar mass distribution of EPS fractions showed 2 peaks of different sizes, which is a feature shared with some EPS from bacteria of food origin. In general, we detected an association between the EPS size distribution and the EPS-producing species, although because of the low numbers of human bacterial EPS tested, we could not conclusively establish a correlation. The main monosaccharide components of the EPS under study were glucose, galactose, and rhamnose, which are the same as those found in food polymers; however, the rhamnose and glucose ratios was generally higher than the galactose ratio in our human bacterial EPS. All EPS-producing strains were able to grow and acidify milk; most lactobacilli produced lactic acid as the main metabolite. The lactic acid-to-acetic acid ratio in bifidobacteria was 0.7, close to the theoretical ratio, indicating that the EPS-producing strains did not produce an excessive amount of acetic acid, which could adversely affect the sensory properties of fermented milks. With respect to their viscosity-intensifying ability, L. plantarum H2 and L. rhamnosus E41 and E43R were able to increase the viscosity of stirred, fermented milks to a similar extent as the EPS-producing Streptococcus thermophilus strain used as a positive control. Therefore, these human EPS-producing bacteria could be used as adjuncts in mixed cultures for the formulation of functional foods if probiotic characteristics could be demonstrated. This is the first article reporting the physicochemical characteristics of EPS isolated from human intestinal microbiota.


Asunto(s)
Bifidobacterium/metabolismo , Lactobacillus/metabolismo , Leche/microbiología , Polisacáridos Bacterianos/metabolismo , Ácido Acético/metabolismo , Animales , Bifidobacterium/crecimiento & desarrollo , Fermentación , Humanos , Concentración de Iones de Hidrógeno , Intestinos/microbiología , Ácido Láctico/metabolismo , Lactobacillus/crecimiento & desarrollo , Lactosa/metabolismo , Leche/química
8.
Front Microbiol ; 10: 1046, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31191465

RESUMEN

The intake of fermented foods is gaining increasing interest due to their health-promoting benefits. Among them, fermented dairy foods have been associated with obesity prevention, and reduction of the risk of metabolic disorders and immune-related pathologies. Fermented foods could lead to these health benefits by providing the consumer with both easily metabolizable nutrients and beneficial microorganisms. Our aim was to evaluate the relationship between the consumption of fermented dairy products and the intestinal microbiota, serum lipid profile, and the pro-oxidant/inflammatory status. 130 healthy adults were evaluated. Dietary fermented food intake was assessed by an annual food frequency questionnaire (FFQ), including 26 fermented dairy products. Levels of the major phylogenetic types of the intestinal microbiota were determined by qPCR, and concentration of fecal short chain fatty acids were assessed by gas chromatography. Serum glucose and lipid profile, as well as serum malondialdehyde (MDA), C-reactive protein (CRP), and leptin levels were determined by standardized protocols. Among fermented dairy foods, natural yogurt, sweetened yogurt and matured/semi-matured cheese were the most consumed. While natural yogurt consumers showed increased fecal levels of Akkermansia with respect to non-consumers, sweetened yogurt intake was associated to lower levels of Bacteroides. Serum levels of CRP were also significantly reduced in yogurt consumers. Our results underline the interest in exploring the potential effects of the different yogurt types and the role the microbiota may play in such effects.

9.
Benef Microbes ; 10(2): 179-188, 2019 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-30574803

RESUMEN

In vitro models are frequently used in probiotic research. However, such models often fail to predict in vivo functionality and efficacy. This fact complicates the screening process for selecting the most suitable strains, prior to accomplish expensive animal studies and clinical intervention trials. Therefore, additional sensitive, discriminating and cost-effective models are needed to conduct preliminary assays before undertaking human intervention studies definitely proving efficacy. With this purpose in mind, we explored the potential of axenic Drosophila melanogaster populations as well as of these axenic flies treated with probiotic microbial strains as a model to test the effects of probiotics on a subset of developmental and behavioural traits. An axenic D. melanogaster progeny from the wild-type Canton S strain was obtained and its eggs were further developed until pupae eclosion occurred in growth medium containing either of two probiotic strains: Bifidobacterium animalis subsp. lactis Bb12 or Lactobacillus rhamnosus GG. Whereas B. animalis Bb12 colonised the flies, the capacity of L. rhamnosus LGG to colonise was considerably lower in our experimental conditions. Regarding the influence of microbial load on the flies' development, the axenic condition caused a decrease in egg survival, and lowered adults' average weight with respect to wild-type flies. Both probiotics were able to counteract these effects. An earlier emergence of adults was observed from eggs treated with L. rhamnosus GG in comparison to the other fly populations. The axenic condition did not influence negative geotaxis behaviour in Drosophila; however, flies mono-associated with B. animalis Bb12 moved faster than wild-type. Our results suggest that the use of axenic/probiotic-treated D. melanogaster populations may be an affordable model for preliminary testing of the effects of probiotics on developmental or behavioural aspects.


Asunto(s)
Drosophila melanogaster/crecimiento & desarrollo , Evaluación Preclínica de Medicamentos/métodos , Modelos Animales , Probióticos/administración & dosificación , Animales , Bifidobacterium animalis/crecimiento & desarrollo , Peso Corporal , Femenino , Vida Libre de Gérmenes , Lacticaseibacillus rhamnosus/crecimiento & desarrollo , Masculino , Análisis de Supervivencia , Resultado del Tratamiento
10.
J Geophys Res Space Phys ; 124(9): 7413-7424, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35860291

RESUMEN

Pluto energies of a few kiloelectron volts and suprathermal ions with tens of kiloelectron volts and above. We measure this population using the Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) instrument on board the New Horizons spacecraft that flew by Pluto in 2015. Even though the measured ions have gyroradii larger than the size of Pluto and the cross section of its magnetosphere, we find that the boundary of the magnetosphere is depleting the energetic ion intensities by about an order of magnitude close to Pluto. The intensity is increasing exponentially with distance to Pluto and reaches nominal levels of the interplanetary medium at about 190R P distance. Inside the wake of Pluto, we observe oscillations of the ion intensities with a periodicity of about 0.2 hr. We show that these can be quantitatively explained by the electric field of an ultralow-frequency wave and discuss possible physical drivers for such a field. We find no evidence for the presence of plutogenic ions in the considered energy range.

11.
J Microbiol Methods ; 152: 210-216, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30006229

RESUMEN

Several in vitro screening tests have been used for selecting probiotic strains; however they often show low predictive value and only a limited number of strains have demonstrated functionality in vivo. The most used in vitro tests represent a very simplified version of the gut environment, especially since they do not consider the accompanying microbiota. Therefore, there is a need to develop sensitive and discriminating in vitro models including the microbiota. Here we developed an in vitro model to discriminate among microbiotas/fecal waters from different population groups. To this end samples were obtained from seven healthy adults, five IBD-patients, ten full-term and ten preterm newborns. Fecal microbiotas were purified and their impact, as well as that of the fecal waters, on HT29 cells was continuously monitored for 22 h using a real-time cell analyzer (RTCA). The composition of the purified microbiotas was assessed by 16S rRNA gene profiling and qPCR and the levels of short chain fatty acids (SCFA) determined by gas chromatography. The microbiota fractions and SCFA concentrations obtained from IBD-patients, full-term and preterm babies, showed clear differences with regard to those of the control group (healthy adults). Moreover, the purified intestinal microbiotas and fecal waters also differed from the control group in the response induced on the HT29 cells assay developed. In short, we have developed a real-time, impedance-based in vitro model for assessing the functional response induced by purified microbiotas and fecal waters upon intestinal epithelial cells. The capability of the assay for discriminating the functional responses induced, by microbiotas or fecal waters from different human groups, promises to be of help on the search for compounds/strains to restore the functionality of the microbiota-host's interaction.


Asunto(s)
Heces/microbiología , Microbioma Gastrointestinal/fisiología , Células HT29/microbiología , Interacciones Microbiota-Huesped/fisiología , Grupos de Población , Adulto , Bacterias/clasificación , Bacterias/genética , Cromatografía de Gases , Células Epiteliales , Ácidos Grasos Volátiles/análisis , Microbioma Gastrointestinal/genética , Humanos , Técnicas In Vitro , Recién Nacido , Intestinos , Persona de Mediana Edad , Probióticos , ARN Ribosómico 16S/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
12.
Rev Chilena Infectol ; 24(4): 270-5, 2007 Aug.
Artículo en Español | MEDLINE | ID: mdl-17728913

RESUMEN

Dental caries is a transmissible infectious disease in which Streptococcus mutans is a principal protagonist. Although it is widely believed that pregnancy is harmful to teeth, the effect of pregnancy on the development of caries is not clear. Considering this situation, the aim of the present study was to evaluate the levels of infection and to differentiate bacterial species with cariogenic potential in pregnant women from the Araucania region in Chile, by bacteriological and molecular analysis. In this work, we evaluated 51 pregnant women aged 15 to 40 years. The results show that 100% of women are infected by mutans streptococci Group, and 70.6% exhibited high levels of infection (> 500.000 cfu/mL). The molecular analysis shows that Streptococcus mutans and Streptococcus sobrinus frequencies were 92.1% and 1.9%, respectively. In conclusion, our data suggest that pregnant women are a high risk group for caries development.


Asunto(s)
Caries Dental/microbiología , Complicaciones Infecciosas del Embarazo/microbiología , Streptococcus mutans/genética , Streptococcus sobrinus/genética , Adolescente , Adulto , Chile , Índice CPO , Femenino , Humanos , Embarazo , Factores de Riesgo , Streptococcus mutans/aislamiento & purificación , Streptococcus sobrinus/aislamiento & purificación
13.
J Expo Sci Environ Epidemiol ; 26(3): 257-62, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-25993025

RESUMEN

Sufficient epidemiologic evidence has established an etiologic link between bladder cancer risk and occupational exposure as a painter to organic solvents. Currently, it remains to be established whether gene-specific promoter methylation contributes to bladder cancer development, including by enhancing chromosome breakage or loss. We investigated the effect of chronic exposure to organic solvents and paints on DNA methylation profiles in the promoter regions of four genes (GSTP1, p16(INK4a), APC and CDH1) and micronucleus (MN) frequency in exfoliated urothelial cells from voided urine from Colombian male non-smoking car painters and age-matched unexposed individuals. The exposed group had a higher percentage of individuals with >2 MNs/2000 cells compared with the unexposed group (P=0.04). Gene-specific analysis showed a significantly higher percentage of individuals with methylated GSTP1, p16(INK4a) and APC in the exposed group. Poisson regression analysis indicated that exposed individuals with methylated GSTP1 and p16(INK4a) promoters were more than twofold more likely to have an increase in MN frequency as compared with the reference. Finally, among exposed individuals with GSTP1 and p16(INK4a) methylated promoters, those with a greater age had a higher RR of increased MN frequency compared with younger exposed individuals with methylated promoters. These results support the conclusion that gene-specific promoter methylation may increase MN frequency in a dependent or independent interaction with occupational exposure to organic solvents.


Asunto(s)
Metilación de ADN , Pruebas de Micronúcleos , Exposición Profesional , Pintura/toxicidad , Regiones Promotoras Genéticas , Solventes/toxicidad , Urotelio/efectos de los fármacos , Humanos , Masculino , Urotelio/citología
14.
Food Funct ; 6(8): 2424-39, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26068710

RESUMEN

The human intestinal tract is home to a complex microbial community called microbiota. This gut microbiota, whilst playing essential roles in the maintenance of the health of the host, is exposed to the impact of external factors such as the use of medication or dietary patterns. Alterations in the composition and/or function of the microbiota have been described in several disease states, underlining the role of the gut microbiota in keeping the health status. Among the different dietary compounds, polyphenols constitute a very interesting group as some of them have been found to possess important biological activities, including antioxidant, anticarcinogenic or antimicrobial activities. The term polyphenol comprises thousands of molecules presenting a phenol ring and are widely distributed in plant foods. The bioactivity of these compounds is highly dependent on their intestinal absorption and often they are ingested as non-absorbable precursors that are transformed into bioactive forms by specific microorganisms in the intestine. Some of these microorganisms have been identified and the enzymatic steps involved have been elucidated. However, little is known about the impact of these ingested polyphenols upon the human gut microbiota. The heterogeneity of the polyphenol compounds and their food sources, as well as their coexistence with other bioactive compounds within a normal diet, together with the complexity of the human gut microbiota make difficult the understanding of the interactions between dietary polyphenols and gut microbes. This is, however, an important area of research which promises to expand our knowledge on the food functionality area through understanding the microbiota-food component interaction.


Asunto(s)
Microbioma Gastrointestinal , Tracto Gastrointestinal/metabolismo , Fenoles/metabolismo , Dieta , Tracto Gastrointestinal/microbiología , Salud , Humanos
15.
Mol Biochem Parasitol ; 78(1-2): 127-36, 1996 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8813683

RESUMEN

In Trypanosoma cruzi a cell surface enzyme with trans-sialidase (TS) activity has been implicated as an important factor in establishing infection. The enzyme is encoded by genes belonging to a large super-family which on the basis of sequence has been subdivided into 4 groups. TS mediates the transfer of sialic acid residues from host glycoconjugates to acceptor molecules on the parasite surface. To study the organisation of the TS genes we isolated several distinct cosmids from a library constructed with DNA from the T. cruzi X10.6 clone. In these cosmids, the TS genes (group I) were present either as single copies or as a direct tandem repeat. A common feature of the cosmids was the presence of a related group III gene located 10-12kb downstream of the TS gene(s) and arranged in the same orientation. In several of the cosmids we also identified a mucin-like glycoprotein gene located between the group I and group III genes. The mucin-like genes are part of a large polymorphic family and contour clamped homogeneous electric field electrophoresis (CHEFE) analysis showed that they were linked to members of the TS super-family at multiple sites in the X10.6 genome. Screening of a second cosmid library made with DNA from the CL-Brener clone confirmed this multiple linkage suggesting that it is a common feature of the species. This genetic organisation may have important functional significance since the mucin-like glycoproteins are the major cell surface acceptors of sialic acid.


Asunto(s)
Genes Protozoarios , Glicoproteínas/genética , Mucinas/genética , Neuraminidasa/genética , Proteínas Protozoarias/genética , Trypanosoma cruzi/enzimología , Trypanosoma cruzi/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Secuencia Conservada , Cósmidos , Cartilla de ADN/genética , Ligamiento Genético , Genoma de Protozoos , Datos de Secuencia Molecular , Polimorfismo Genético , Mapeo Restrictivo , Homología de Secuencia de Aminoácido
16.
J Med Chem ; 36(1): 81-6, 1993 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-8421292

RESUMEN

A novel class of ligands, phenylenediamine-thiol-thioether (PhAT), was synthesized, and their 99mTc complexes were evaluated for potential use as a functional brain imaging agent. The ligands reacted with Na99mTcO4 and SnCl2 to form single, stable, neutral, and lipophilic 99mTc complexes. Several of these complexes showed significant brain uptake and retention in rats. In particular, the S-ethyl, allyl, and propargyl derivatives had high initial brain uptake (0.88, 0.99, and 0.82% dose/g at 5 min, respectively) and good retention (0.71, 0.75, and 0.67% dose/g at 30 min). The structure-activity relationship of alkyl, alkenyl, and alkynyl thioether derivatives is reported.


Asunto(s)
Encéfalo/metabolismo , Fenilendiaminas/síntesis química , Sulfuros/síntesis química , Tecnecio/metabolismo , Animales , Encéfalo/diagnóstico por imagen , Cromatografía Líquida de Alta Presión , Femenino , Ligandos , Fenilendiaminas/química , Fenilendiaminas/farmacocinética , Cintigrafía , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Sulfuros/química , Sulfuros/farmacocinética , Distribución Tisular
17.
Environ Health Perspect ; 107(6): 501-5, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10339452

RESUMEN

Exposure to pesticides remains a major environmental health problem. Health risk from such exposure needs to be more precisely understood. We conducted three different cytogenetic assays to elucidate the biological effects of exposure to mixed pesticides in 20 Costa Rica farmers (all nonsmokers) compared with 20 matched controls. The farmers were also exposed to dibromochloropropane during the early employment years, and most of them experienced sterility/fertility problems. Our data show that the farmers had consistently higher frequencies of chromosome aberrations, as determined by the standard chromosome aberration assay, and significantly abnormal DNA repair responses (p < 0.05), as determined by the challenge assay, but no statistically significant differences in the tandem-probe fluorescence in situ hybridization (FISH) assay (p > 0.05). Genotype analysis indicates that farmers with certain "unfavorable" versions of polymorphic metabolizing genes (cytochrome P4502E1, the glutathione S-transferases mu and theta, and the paraoxonase genes) had significantly more biological effects, as determined by all three cytogenetic assays, than both the farmers with the "favorable" alleles and the matched controls. A unique observation is that, in individuals who had inherited any of the mentioned "unfavorable" alleles, farmers were consistently underrepresented. In conclusion, the Costa Rican farmers were exposed to genotoxic agents, most likely pesticides, which expressed the induction of biological and adverse health effects. The farmers who had inherited "unfavorable" metabolizing alleles were more susceptible to genotoxic effects than those with "favorable" alleles. Our genotype data suggest that the well-recognized "healthy worker effect" may be influenced by unrecognized occupational selection pressure against genetically susceptible individuals.


Asunto(s)
Enfermedades de los Trabajadores Agrícolas/inducido químicamente , Enfermedades de los Trabajadores Agrícolas/genética , Mutágenos/toxicidad , Plaguicidas/toxicidad , Adulto , Alelos , Aberraciones Cromosómicas/genética , Costa Rica , Reparación del ADN/efectos de los fármacos , Genotipo , Humanos , Hibridación Fluorescente in Situ , Masculino , Pruebas de Mutagenicidad , Polimorfismo de Longitud del Fragmento de Restricción
18.
Acta Trop ; 63(4): 195-207, 1997 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9088434

RESUMEN

A malaria study area in the Philippines is described. It consists of the municipality of Morong, Bataan on the Island of Luzon. In January 1992, the population was 19454 in 106 villages located on a narrow coastal plain, or in valleys of streams running from the mountainous interior. This is an area of low level but persistent seasonal transmission of malaria with approximately one thousand cases reported each year, mainly from February to July. In spite of the low level of malaria, it is apparently quite stable. The study site has been used to investigate parameters leading to stable malaria. Hypotheses tested were that there was substantial under reporting of cases; that there was strain specific immunity stabilising the incidence of malaria and that malaria transmission in this area is highly localised in small regions with a high enough malaria prevalence to account for the year to year stability. The study plan included cross sectional surveys of parasite prevalence and seropositivity, longitudinal surveys, passive case detection, entomological surveys, anthropological surveys to assess knowledge of malaria and documentation of the health-seeking behaviour of the population.


Asunto(s)
Malaria/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Estudios Transversales , Demografía , Notificación de Enfermedades , Accesibilidad a los Servicios de Salud , Humanos , Inmunidad Activa , Lactante , Recién Nacido , Estudios Longitudinales , Malaria/inmunología , Malaria/transmisión , Persona de Mediana Edad , Filipinas/epidemiología , Prevalencia , Estaciones del Año , Estudios Seroepidemiológicos
19.
Acta Trop ; 63(4): 209-20, 1997 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9088435

RESUMEN

The vectorial importance of known and potential vectors in Morong, Bataan, Philippines was assessed based on human and animal baited collections of adult mosquitoes and on larval collections. Anopheles flavirostris, the principal vector in the Philippines, was the most abundant among human landing catches, followed by An. maculatus sensu lato (s.l.). Both showed similar seasonal abundance with a peak during the early drier part of the year, which coincided with the peak in malaria cases. Both An. flavirostris and An. maculatus s.l. fed throughout the night with the broad peak of capture from 00:00 to 04:00 and from 22:00 to 00:00, respectively. The two species had similar parous rates (0.76 and 0.72, respectively) giving an average life span equivalent to four feeding cycles. Neither vector was abundant with average human landing rates on collectors of 0.6 and 0.4 mosquitoes per person per night, respectively over the study period. An. maculatus s.l. showed a stronger preference for outdoor feeding compared to An. flavirostris. An. maculatus s.l. was markedly zoophilic with a biting rate on water buffalo 50 times the human landing rate. An. flavirostris was less zoophilic with a corresponding ratio of 7.5. It was concluded that in this area, An. flavirostris is the principal vector. The combination of localised transmission, late night biting pattern and localised breeding sites of An. flavirostris suggest that the use of bed nets and environmental management are relevant control measures that can be implemented through community participation.


Asunto(s)
Mordeduras y Picaduras de Insectos/epidemiología , Insectos Vectores/clasificación , Malaria/transmisión , Animales , Anopheles/clasificación , Anopheles/fisiología , Búfalos , Ritmo Circadiano , Demografía , Humanos , Control de Insectos , Insectos Vectores/fisiología , Malaria/epidemiología , Estaciones del Año
20.
Acta Trop ; 63(4): 241-56, 1997 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9088437

RESUMEN

Field epidemiological studies were conducted to examine factors affecting endemicity in an area with a low prevalence of malaria. Two annual cross sectional surveys were done to estimate parasite prevalence rates at two periods in time, to determine the distribution of the parasitemic population and to describe the serological status of the population. A longitudinal study of a sample of infected people was used to measure reinfection rates and antibody dynamics. A 2 year passive case detection was done to estimate the number and distribution of people with symptomatic infections. Malaria was found in all age groups, with marked clustering of cases. Active and passive case detection and serological surveys all gave a similar pattern of malaria distribution: generally low prevalence with small foci of relatively high endemicity. The infection frequencies were generally similar in all age groups, measured by both active and passive case detection. There was a high frequency of P. falciparum gametocytemic infections in the asymptomatic cases found through active case detection. Twenty to 39 year old males had the highest frequency of infection by active case detection, and 10-19 year old males by passive case detection. These two groups were also more likely to be gametocyte positive than their female counterparts, suggesting that in this community, this portion of the population acts as the main reservoir of infection.


Asunto(s)
Malaria/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Animales , Anticuerpos Antiprotozoarios/análisis , Niño , Preescolar , Estudios Transversales , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Malaria/inmunología , Malaria Falciparum/epidemiología , Masculino , Persona de Mediana Edad , Filipinas/epidemiología , Plasmodium/aislamiento & purificación , Prevalencia , Recurrencia , Estudios Seroepidemiológicos , Factores Sexuales
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