RESUMEN
OBJECTIVE: To investigate the enzymatic activity of hepatic lipase (HL) in postmenopausal women (PMW) and reproductive age women (RAW); and to evaluate the relationship between this enzyme and the atherogenic intermediate density lipoproteins (IDL) and low density lipoproteins (LDL), and antiatherogenic high density lipoproteins (HDL) and its subfractions (HDL2 and HDL3). DESIGN: We studied 55 PMW receiving no hormonal treatment in a cross-sectional study in comparison with a control group of 55 RAW, matched by body mass index. Follicle-stimulating hormone was > 40 mUI/ml in PMW and 3-12 mUI/ml in RAW. PMW presented at least 1 year of natural menopause and no more than 10 years of amenorrhea with E2 serum concentration < 15 pg/ml. RESULTS: HL activity was significantly higher in PMW versus RAW (14.0 +/- 1.4 vs. 10.9 +/- 0.4 micromol of fatty acids/ml of postheparin plasma, respectively, mean +/- SEM, p < 0.001). In PMW, IDL cholesterol showed a positive correlation with LDL cholesterol (r = 0.28, p < 0.05), and HDL2 cholesterol was inversely correlated with HL activity (r = 0.31, p < 0.05). HL was positively correlated with plasma concentration of LDL cholesterol in both groups (r = 0.27, p < 0.05). The higher values of HL activity and IDL cholesterol were independent of age. CONCLUSIONS: Higher HL activity is associated with a more atherogenic profile in PMW.
Asunto(s)
Arteriosclerosis/sangre , Lipasa/sangre , Lipoproteínas LDL/sangre , Lipoproteínas/sangre , Hígado/enzimología , Posmenopausia/sangre , Índice de Masa Corporal , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , VLDL-Colesterol/sangre , Estudios Transversales , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Lipoproteínas IDLRESUMEN
A rapid laboratory diagnosis of Clostridium difficile-associated diarrhea (CDAD) is important in patient management and in the administration of appropriate therapeutic modalities. The VIDAS(R) C. difficile Toxin A II (CDA 2) assay (bioMerieux, Inc., Hazelwood, MO) was compared with the cell culture cytotoxicity assay (CCA) for the rapid detection of C. difficile in stool from patients in whom C. difficile infection was suspected. Thirty-eight consecutively collected CCA-positive stool specimens, and 33 CCA-negative stool specimens were tested by the CDA 2 assay. Where appropriate, discordant specimens were repeated and/or tested by isolation utilizing cycloserine-cefoxitin-fructose agar (CCFA). Among 12 discordant stool specimens, 7 were VIDAS(R)-/cytotoxicity+, 2 were VIDAS(R) equivocal (E)/cytotoxicity+, 2 were VIDAS(R) E/cytotoxicity-, and 1 was VIDAS(R)+/cytotoxicity-. One VIDAS(R) E/cytotoxicity+ lacked sufficient stool to be repeated. From the single VIDAS(R)+/cytotoxicity- specimen, C. sordelli was isolated. Specimens that were equivocal by VIDAS(R), were omitted from incorporation into this study's test parameters. The sensitivity, specificity, positive and negative predictive values for the CDA 2 assay were 80.6, 96.8, 96.7, and 81.1%, respectively. The specimens which yielded false negative VIDAS(R) results had low levels of toxin based on endpoint titrations using the cytotoxicity assay. Although the CDA 2 assay displayed a reduced sensitivity compared with the CCA, the automated assay is rapid (results promulgated within 2 h), with computer generated readings obviating visual interpretations. Recognition of the CDA 2 assay's limitations is important to addressing this test's clinical utility.
Asunto(s)
Toxinas Bacterianas/análisis , Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/diagnóstico , Diarrea/diagnóstico , Heces/microbiología , Células Cultivadas , Clostridioides difficile/inmunología , Enterotoxinas , Heces/química , Técnica del Anticuerpo Fluorescente/métodos , Humanos , Técnicas para Inmunoenzimas/métodos , Sensibilidad y EspecificidadRESUMEN
Mast cell hyperplasia can be causally related with chronic inflammation and liver fibrosis. Their survival and proliferation is dependent upon locally produced growth factors, the major one being the stem cell factor (SCF). Glucocorticoids can decrease mastocytosis, down-regulating the mast cell production of pro-inflammatory factors or inhibiting the expression of SCF in stroma. We compared dexamethasone effect on SCF expression in co-cultures of mast cells with NIH/3T3 fibroblasts or with primary cultures of activated hepatic stellate cells. Dexamethasone abrogated the NIH/3T3 stroma capacity to sustain mast cell proliferation, but not of hepatic stellate cells, at the post-transcriptional level. Mast cells reverted completely dexamethasone effect on hepatic stellate cells, increasing their SCF synthesis and transport. In both models, dexamethasone inhibited the mast cell spreading on the stroma, which was thus not required for mast cell survival and proliferation. Liver pathologies associated with mast cell hyperplasia are not expected to be sensitive to glucocorticoid treatments.
Asunto(s)
Antiinflamatorios/farmacología , Dexametasona/farmacología , Regulación hacia Abajo/efectos de los fármacos , Mastocitos/efectos de los fármacos , Factor de Células Madre/efectos de los fármacos , Células 3T3/efectos de los fármacos , Células 3T3/metabolismo , Animales , Técnicas de Cocultivo , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/fisiología , Granuloma/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Mastocitos/metabolismo , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Factor de Células Madre/metabolismoRESUMEN
The cDNA encoding the Schistosoma mansoni dolichol phosphate mannose synthase was completely sequenced, displaying the highest homology with Cricetulus griseus and Saccharomyces pombe genes. The Schistosome enzyme had a K(m) of 0.127 microM, a value that is within the range of those reported for several other species. Thin-layer chromatography of the radiolabelled schistosome lipid intermediate showed it was identical to dolichol-phosphate (C80-C105). Expression of dolichol phosphate mannose synthase of S. mansoni (SmDPMS) was analysed by Northern blot and quantified by semi-quantitative RT-PCR with cDNA from mature and immature male and female worms. Northern blot analysis revealed a single 1-kb band. Both approaches confirmed a higher level of expression in mature female worms, as compared to immature and male worms.
Asunto(s)
Fosfatos de Dolicol/metabolismo , Manosiltransferasas/metabolismo , Schistosoma mansoni/enzimología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Northern Blotting , Cromatografía en Capa Delgada , Cartilla de ADN/química , Femenino , Biblioteca de Genes , Masculino , Manosiltransferasas/genética , Datos de Secuencia Molecular , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de AminoácidoRESUMEN
Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined by the WHO. Furthermore, malaria (caused by various Plasmodium species) can be considered a neglected disease in certain countries and with regard to availability and affordability of the antimalarials. Living organisms, especially plants, provide an innumerable number of molecules with potential for the treatment of many serious diseases. The current review attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs. In part I, a general description of the diseases, the current state of therapy and need for new therapeuticals, assay methods and strategies applied in the search for new plant derived natural products against these diseases and an overview on natural products of terpenoid origin with antiprotozoal potential were given. The present part II compiles the current knowledge on natural products with antiprotozoal activity that are derived from the shikimate pathway (lignans, coumarins, caffeic acid derivatives), quinones of various structural classes, compounds formed via the polyketide pathways (flavonoids and related compounds, chromenes and related benzopyrans and benzofurans, xanthones, acetogenins from Annonaceae and polyacetylenes) as well as the diverse classes of alkaloids. In total, both parts compile the literature on almost 900 different plant-derived natural products and their activity data, taken from over 800 references. These data, as the result of enormous efforts of numerous research groups world-wide, illustrate that plant secondary metabolites represent an immensely rich source of chemical diversity with an extremely high potential to yield a wealth of lead structures towards new therapies for NTDs. Only a small percentage, however, of the roughly 200,000 plant species on earth have been studied chemically and only a small percentage of these plants or their constituents has been investigated for antiprotozoal activity. The repository of plant-derived natural products hence deserves to be investigated even more intensely than it has been up to present.
Asunto(s)
Antiprotozoarios/uso terapéutico , Productos Biológicos/uso terapéutico , Enfermedades Desatendidas/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Plantas Medicinales/química , Infecciones por Protozoos/tratamiento farmacológico , Animales , Antiprotozoarios/química , Antiprotozoarios/metabolismo , Productos Biológicos/química , Productos Biológicos/metabolismo , Humanos , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Plantas Medicinales/metabolismoRESUMEN
Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.
Asunto(s)
Antiprotozoarios/uso terapéutico , Productos Biológicos/uso terapéutico , Enfermedades Desatendidas/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Plantas Medicinales/química , Plantas Medicinales/metabolismo , Infecciones por Protozoos/tratamiento farmacológico , Animales , Antiprotozoarios/química , Antiprotozoarios/metabolismo , Productos Biológicos/química , Productos Biológicos/metabolismo , Humanos , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/metabolismoAsunto(s)
Anticuerpos , Estradiol , Estro/efectos de los fármacos , Progesterona , Animales , Líquidos Corporales , Gonadotropina Coriónica/farmacología , Dietilestilbestrol/farmacología , Femenino , Hormona Luteinizante/metabolismo , Ovulación , Embarazo , Seudoembarazo , Ratas , Útero/fisiología , Frotis VaginalAsunto(s)
Hemoproteínas/biosíntesis , Hemoproteínas/química , Schistosoma mansoni/metabolismo , Animales , Cristalización , Femenino , Hemo/análisis , Hemo/metabolismo , Hemoproteínas/análisis , Concentración de Iones de Hidrógeno , Masculino , Pigmentos Biológicos/análisis , Pigmentos Biológicos/biosíntesis , Pigmentos Biológicos/química , Schistosoma mansoni/química , Caracteres Sexuales , Solubilidad , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Considering the limited and toxic therapeutic arsenal available for visceral leishmaniasis (VL), the drug repositioning approach could represent a promising tool to the introduction of alternative therapies. Histamine H1-receptor antagonists are drugs belonging to different therapeutic classes, including antiallergics and anxyolitics. In this work, we described for the first time the activity of H1-antagonists against L. (L.) infantum and their potential effectiveness in an experimental hamster model. The evaluation against promastigotes demonstrated that chlorpheniramine, cinnarizine, hydroxyzine, ketotifen, loratadine, quetiapine and risperidone exerted a leishmanicidal effect against promastigotes, with IC50 values in the range of 13-84µM. The antihistaminic drug cinnarizine demonstrated effectiveness against the intracellular amastigotes, with an IC50 value of 21µM. The mammalian cytotoxicity was investigated in NCTC cells, resulting in IC50 values in the range of 57-229µM. Cinnarizine was in vivo studied as a free formulation and entrapped into phosphatidylserine-liposomes. The free drug was administered for eight consecutive days at 50mg/kg by intraperitoneal route (i.p.) and at 100mg/kg by oral route to L. infantum-infected hamsters, but showed lack of effectiveness in both regimens, as detected by real time PCR. The liposomal formulation was administered by i.p. route at 3mg/kg for eight days and reduced the parasite burden to 54% in liver when compared to untreated group; no improvement was observed in the spleen of infected hamsters. Cinnarizine is the first antihistaminic drug with antileishmanial activity and could be used as scaffold for drug design studies for VL.
Asunto(s)
Receptores Histamínicos H1 , Loratadina , Leishmania , Leishmaniasis VisceralRESUMEN
Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.
Asunto(s)
Plantas Medicinales/metabolismo , Plantas Medicinales/química , Infecciones por Protozoos/tratamiento farmacológico , Productos Biológicos/metabolismo , Productos Biológicos/uso terapéutico , Productos Biológicos/química , Humanos , Extractos Vegetales/metabolismo , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Animales , Fitoterapia , Antiprotozoarios/metabolismo , Antiprotozoarios/uso terapéutico , Antiprotozoarios/químicaRESUMEN
Leishmaniasis and Chagas disease afflict the poorest countries in the world. The Brazilian flora represents a rich source for the screening of potential antiparasitic compounds. In this work, we tested the total alkaloid and ethanol extracts of nine different plants from Brazilian families which produce isoquinoline alkaloids, to determine their in vitro antiparasitic effect against L. chagasi and T. cruzi parasites. Promastigotes of L. chagasi were shown to be susceptible only to the total alkaloid extracts of A. crassiflora (EC50 value = 24.89 microg/ml), A. coriacea (EC50 value = 41.60 microg/ml), C. ovalifolia (EC50 value = 63.88 microg/ml) and G. australis (EC50 value = 37.88 microg/ml). Except for the G. australis total alkaloids, all the three extracts presented a considerable activity when tested against intracellular amastigotes. The most effective alkaloid extracts were those from A. crassiflora and C. ovalifolia, which reduced the number of infected macrophages at 25 microg/ml by 86.1% and 89.8%, respectively. Among the 18 tested extracts, 16 showed anti-Trypanosoma activity. Eight extracts (A. crassiflora, A. coriacea, C. ovalifolia, D. furfuracea, D. lanceolata, S. guianensis, X. emarginata and G. australis) were the most effective against the trypomastigotes, killing approximately 100% of the parasites at the maximal concentration of 100 microg/ml. Cytotoxicity against mammalian cells was evaluated for all extracts, but potential ones showed little or no cytotoxicity and a considerable antiparasitic effect, including D. furfuracea, D. lanceolata, G. australis, S. guianensis and X. emarginata. Plants are a rich source of natural compounds, and a powerful tool for the development of new arsenals for the therapy of protozoan diseases.
Asunto(s)
Antiprotozoarios/farmacología , Leishmania/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Plantas Medicinales , Trypanosoma cruzi/efectos de los fármacos , Alcaloides , Animales , Antiprotozoarios/administración & dosificación , Antiprotozoarios/uso terapéutico , Femenino , Isoquinolinas , Macrófagos Peritoneales/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Parasitaria , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Hojas de la PlantaRESUMEN
The occurrence of a receptor for human LDL was investigated in the tegument of adult Schistosoma mansoni employing several approaches. Binding of LDL to SDS-PAGE fractionated tegument proteins was measured directly on nitro-cellulose membranes and visualised by an anti-human LDL antibody. Proteins with an Mr of 60, 35 and 14 kDa were evidenced. Affinity chromatography of 125I-labelled tegument proteins on a LDL-Sepharose column, revealed the same pattern of proteins observed in the immunoblot experiments. Finally, the binding of human LDL to the intact tegument was measured by microcalorimetry. Binding was shown to be an exothermic reaction, releasing approximately 2500 kcal/mol, it was saturable, and reproducibly displayed a biphasic curve suggesting that binding of LDL to S. mansoni might occur through a two step process, initiated by a nonspecific hydrophobic interaction followed by a specific high affinity ligand-receptor reaction. Pre-treatment of the tegument with trypsin reduced the binding of LDL to the tegument. Furthermore, albumin, which is an abundant lipid carrier protein in the serum and thus a potential ligand, failed to release any measurable heat when incubated with the tegument.
Asunto(s)
Proteínas del Helminto/metabolismo , Lipoproteínas LDL/metabolismo , Schistosoma mansoni/crecimiento & desarrollo , Schistosoma mansoni/metabolismo , Animales , Calorimetría , Cricetinae , Interacciones Huésped-Parásitos , Humanos , Ligandos , Unión Proteica , Receptores de LDL/metabolismoRESUMEN
The formation of mannolipid through catalysis by mannosyl transferase of adult females of Schistosoma mansoni was found to be 2-3-fold higher than male worms. In contrast, mannosyl transferase in immature females generated approximately the same amount of mannolipid as male worms, immature or not. Exogenous dolichol phosphate added to homogenates of male worms produced a stoichiometric increase in mannolipid formation. Saturating amounts of dolichol phosphate generated similar mannosyl transferase activities in male and female homogenates, showing that in S. mansoni, dolichol phosphate is the lipid intermediate in the glycosylation reaction and that this mannolipid is a rate-limiting substrate. Thin layer chromatography revealed that the mannolipid was identical in male and female worms. Adult males incubated with 14C-acetate synthesised several apolar compounds, one of which displayed a Rf identical to that of the mannolipid. When exposed to 14C-acetate treated males in vitro, untreated females were able to incorporate a compound, which partitioned in the same way as the mannolipid. The increased mannosyl transferase-dependent mannolipid formation in adult females may reflect a higher energy demand by these parasites, which is probably associated with oogenesis.
Asunto(s)
Fosfatos de Dolicol/metabolismo , Manosiltransferasas/metabolismo , Schistosoma mansoni/enzimología , Animales , Cricetinae , Femenino , Cinética , Masculino , MesocricetusRESUMEN
Leishmaniasis is an endemic tropical disease in South America, with few therapeutic approaches. Snake venoms are complex protein mixtures with biological actions that could be used as tools for drug development. Here we show that Bothrops moojeni crude venom presented a killing effect in vitro against Leishmania spp. promastigotes, but not with amastigotes, as determined by a viability assay using the mitochondrial oxidative function. Purification of active fractions from crude venom was performed by molecular exclusion and ion exchange chromatography. Anti-Leishmania and l-amino acid oxidase (L-AAO, EC.1.4.3.2.) activities co-eluted in the same fractions. The molecular weight of the active enzyme was estimated to be 140 kDa by molecular exclusion chromatography, and 69 kDa by SDS--PAGE, with a 4.8 isoelectric point. Using substrate subtraction and catalase for scavenging, the action of L-AAO was demonstrated to be hydrogen-peroxide-dependent.
Asunto(s)
Aminoácido Oxidorreductasas/metabolismo , Aminoácido Oxidorreductasas/farmacología , Antiprotozoarios/farmacología , Bothrops , Venenos de Crotálidos/farmacología , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Leishmania/efectos de los fármacos , Aminoácido Oxidorreductasas/aislamiento & purificación , Animales , Antiprotozoarios/aislamiento & purificación , Venenos de Crotálidos/química , Técnicas In Vitro , L-Aminoácido OxidasaRESUMEN
Complementary DNA, encoding the mitochondrial enzyme NADH-ubiquinone oxidoreductase subunit 5 (SmND5) of the human parasite Schistosoma mansoni was isolated by screening a S. mansoni cDNA library with a human androgen receptor (hAR) cDNA probe. The complete nucleotide and deduced aminoacid sequences of SmND5 were determined. Southern blot analysis revealed the occurrence of a single copy gene for SmND5 and by means of RT-PCR, it was shown that sex- and stage-specific expression of SmND5 occurred. In order to establish a functional relationship between the mitochondrial enzyme and the androgen receptor, the effects of testosterone were compared to those of classical respiratory chain inhibitors, using adult schistosome and beef heart submitochondrial particles. Physiological concentrations of testosterone were able to inhibit the maintenance of proton gradient across the mitochondrial membranes, as well as ATP synthesis. The steroid was found to be cytotoxic to the larvae, but not to adult schistosomes. A model is proposed to explain the observed in vivo testosterone-related differences in worm burdens, in experimental chronic infections.
Asunto(s)
Mitocondrias Cardíacas/metabolismo , NADH NADPH Oxidorreductasas/química , NADH NADPH Oxidorreductasas/genética , Schistosoma mansoni/enzimología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Abejas/enzimología , Caenorhabditis elegans/enzimología , Bovinos , Clonación Molecular , Secuencia de Consenso , ADN Complementario , Complejo I de Transporte de Electrón , Biblioteca de Genes , Humanos , Mitocondrias Cardíacas/efectos de los fármacos , Datos de Secuencia Molecular , NADH NADPH Oxidorreductasas/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Receptores Androgénicos/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Schistosoma mansoni/genética , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Partículas Submitocóndricas/efectos de los fármacos , Partículas Submitocóndricas/metabolismo , Testosterona/farmacologíaRESUMEN
El hipotiroidismo aumenta su frecuencia con la edad. Las formas asintómaticas podrían ser detectadas mediante las determinaciones de Thyroid Stimulating Hormone (TSH) bajo el Test de THR (Thyroid Releasing Hormone) en los primeros estadios. La incidencia del hipotiroidismo subclínico (SCH) en la etapa del cimaterio no es bien conocida. El objetivo de este trabajo es realizar mediante la determinación de TSH, un "Screening" del Hipotiroidismo Subclínico (SCH) En 209 pacientes se determinaron valores de TSH, T3, T4 y anticuerpos antitiroideos y además se realizó ultrasonografía tiroidea