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1.
Eur J Nutr ; 63(1): 209-220, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37804448

RESUMO

PURPOSE: Previously reported associations of protein-rich foods with stroke subtypes have prompted interest in the assessment of individual amino acids. We examined the associations of dietary amino acids with risks of ischaemic and haemorrhagic stroke in the EPIC study. METHODS: We analysed data from 356,142 participants from seven European countries. Dietary intakes of 19 individual amino acids were assessed using validated country-specific dietary questionnaires, calibrated using additional 24-h dietary recalls. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischaemic and haemorrhagic stroke in relation to the intake of each amino acid. The role of blood pressure as a potential mechanism was assessed in 267,642 (75%) participants. RESULTS: After a median follow-up of 12.9 years, 4295 participants had an ischaemic stroke and 1375 participants had a haemorrhagic stroke. After correction for multiple testing, a higher intake of proline (as a percent of total protein) was associated with a 12% lower risk of ischaemic stroke (HR per 1 SD higher intake 0.88; 95% CI 0.82, 0.94). The association persisted after mutual adjustment for all other amino acids, systolic and diastolic blood pressure. The inverse associations of isoleucine, leucine, valine, phenylalanine, threonine, tryptophan, glutamic acid, serine and tyrosine with ischaemic stroke were each attenuated with adjustment for proline intake. For haemorrhagic stroke, no statistically significant associations were observed in the continuous analyses after correcting for multiple testing. CONCLUSION: Higher proline intake may be associated with a lower risk of ischaemic stroke, independent of other dietary amino acids and blood pressure.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/epidemiologia , Estudos Prospectivos , Aminoácidos , Prolina , Fatores de Risco
2.
Cureus ; 15(5): e38948, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37309331

RESUMO

Systemic glucocorticoid therapy is used worldwide by one to three percent of the general population and 0.5-1.8% on long-term oral glucocorticoid use. It is widely used in conditions such as inflammation, autoimmune diseases, and cancer to inhibit inflammatory responses. One of the possible undesirable side effects of exogenous corticosteroid treatment is adrenal suppression upon discontinuation of the medication and adrenal insufficiency after utilizing the supraphysiologic doses for more than one month. To prevent patients from the unwanted signs and symptoms of adrenal insufficiency, including fatigue, gastrointestinal upset, anorexia/weight loss, etc., better management of the quantity and frequency of exogenous corticosteroid use, as well as better education before starting its use, is needed. For patients actively on exogenous corticosteroids, a close follow-up must be in place to avoid adrenal suppression after the eventual discontinuation of their use. This review article summarizes the important studies to date on this subject, especially oral glucocorticoid use, and analyzes risks such as dose, duration of exposure, and comorbidities of adrenal insufficiency associated with oral glucocorticoid use. We comprehensively include information on those with primary adrenal insufficiency and pediatric patients, hoping to provide better insight and clinical reference.

3.
Cancers (Basel) ; 14(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36428592

RESUMO

Resistin is a polypeptide implicated in inflammatory processes, and as such could be linked to colorectal carcinogenesis. In case-control studies, higher resistin levels have been found in colorectal cancer (CRC) patients compared to healthy individuals. However, evidence for the association between pre-diagnostic resistin and CRC risk is scarce. We investigated pre-diagnostic resistin concentrations and CRC risk within the European Prospective Investigation into Cancer and Nutrition using a nested case-control study among 1293 incident CRC-diagnosed cases and 1293 incidence density-matched controls. Conditional logistic regression models controlled for matching factors (age, sex, study center, fasting status, and women-related factors in women) and potential confounders (education, dietary and lifestyle factors, body mass index (BMI), BMI-adjusted waist circumference residuals) were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for CRC. Higher circulating resistin concentrations were not associated with CRC (RR per doubling resistin, 1.11; 95% CI 0.94-1.30; p = 0.22). There were also no associations with CRC subgroups defined by tumor subsite or sex. However, resistin was marginally associated with a higher CRC risk among participants followed-up maximally two years, but not among those followed-up after more than two years. We observed no substantial correlation between baseline circulating resistin concentrations and adiposity measures (BMI, waist circumference), adipokines (adiponectin, leptin), or metabolic and inflammatory biomarkers (C-reactive protein, C-peptide, high-density lipoprotein cholesterol, reactive oxygen metabolites) among controls. In this large-scale prospective cohort, there was little evidence of an association between baseline circulating resistin concentrations and CRC risk in European men and women.

4.
Nutrients ; 14(16)2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36014812

RESUMO

Three metabolite patterns have previously shown prospective inverse associations with the risk of aggressive prostate cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC). Here, we investigated dietary and lifestyle correlates of these three prostate cancer-related metabolite patterns, which included: 64 phosphatidylcholines and three hydroxysphingomyelins (Pattern 1), acylcarnitines C18:1 and C18:2, glutamate, ornithine, and taurine (Pattern 2), and 8 lysophosphatidylcholines (Pattern 3). In a two-stage cross-sectional discovery (n = 2524) and validation (n = 518) design containing 3042 men free of cancer in EPIC, we estimated the associations of 24 dietary and lifestyle variables with each pattern and the contributing individual metabolites. Associations statistically significant after both correction for multiple testing (False Discovery Rate = 0.05) in the discovery set and at p < 0.05 in the validation set were considered robust. Intakes of alcohol, total fish products, and its subsets total fish and lean fish were positively associated with Pattern 1. Body mass index (BMI) was positively associated with Pattern 2, which appeared to be driven by a strong positive BMI-glutamate association. Finally, both BMI and fatty fish were inversely associated with Pattern 3. In conclusion, these results indicate associations of fish and its subtypes, alcohol, and BMI with metabolite patterns that are inversely associated with risk of aggressive prostate cancer.


Assuntos
Dieta , Neoplasias da Próstata , Animais , Índice de Massa Corporal , Estudos Transversais , Dieta/efeitos adversos , Peixes , Glutamatos , Humanos , Masculino , Estudos Prospectivos , Neoplasias da Próstata/etiologia , Fatores de Risco
5.
Int J Cancer ; 148(11): 2759-2773, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33554339

RESUMO

Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Infecções por Helicobacter/epidemiologia , Fumar/epidemiologia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Austrália/etnologia , Europa (Continente)/etnologia , Feminino , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fumar/efeitos adversos , Neoplasias Gástricas/etiologia
6.
Emergencias (Sant Vicenç dels Horts) ; 32(4): 242-252, ago. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-190941

RESUMO

OBJETIVO: EL objetivo principal fue describir el perfil clínico y la mortalidad a los 30 días de diferentes categorías diagnósticas en los casos de COVID-19 atendidos en un servicio de urgencias (SU). MÉTODO: Análisis secundario del registro COVID-19_URG-HCSC. Se seleccionaron los casos sospechosos de COVID-19 atendidos en un SU de Madrid desde el 28 de febrero hasta el 31 de marzo de 2020. La muestra se dividió: 1) sospecha con PCR no realizada (S/PCR NR); 2) sospecha con PCR negativa (S/PCR-); 3) sospecha con PCR positiva (S/PCR+); 4) alta sospecha con PCR negativa o no realizada (AS/PCR- o NR); y 5) alta sospecha con PCR positiva (AS/PCR+). Se recogieron variables clínicas, radiológicas y microbiológicas del episodio de urgencias. La variable de resultado principal fue la mortalidad por cualquier causa a los 30 días. Las variables secundarias fueron el ingreso y la gravedad del episodio. RESULTADOS: Se incluyeron 1.993 pacientes; 17,2% S/PCR NR, 11,4% S/PCR-, 22,1% S/PCR+, 11,7% AS/PCR- o NR y 37,6% AS/PCR+. Se hallaron diferencias estadísticamente significativas respecto a las variables demográficas, comorbilidad, clínicas, radiográficas, analíticas y terapéuticas y de resultados a corto plazo en función las categorías diagnósticas. La mortalidad global a los 30 días fue de un 11,5%, 56,5% casos fueron hospitalizados y 19,6% casos sufrieron un episodio grave. Las categorías de AS y de S/PCR+ tuvieron un incremento del riesgo ajustado de mortalidad a los 30 días y de sufrir un episodio grave durante el ingreso hospitalario respecto a S/PCR-. En relación al ingreso, solo las categorías de AS tuvieron un incremento del riesgo ajustado de hospitalización respecto a la categoría de S/PCR-. CONCLUSIONES: Existen diferentes categorías diagnósticas de la enfermedad COVID-19 en función del perfil clínico y microbiológico que tienen correlato con el pronóstico a 30 días


OBJECTIVE: The primary objective was to describe the clinical characteristics and 30-day mortality rates in emergency department patients with coronavirus disease 2019 (COVID-19) in different diagnostic groupings. METHODS: Secondary analysis of the COVID-19 registry compiled by the emergency department of Hospital Clínico San Carlos in Madrid, Spain. We selected suspected COVID-19 cases treated in the emergency department between February 28 and March 31, 2020. The cases were grouped as follows: 1) suspected, no polymerase chain reaction (PCR) test (S/no-PCR); 2) suspected, negative PCR (S/PCR-); 3) suspected, positive PCR (S/PCR+); 4) highly suspected, no PCR, or negative PCR (HS/no or PCR-); and 5) highly suspected, positive PCR (HS/PCR+). We collected clinical, radiologic, and microbiologic data related to the emergency visit. The main outcome was 30-day all-cause mortality. Secondary outcomes were hospitalization and clinical severity of the episode. RESULTS: A total of 1993 cases (90.9%) were included as follows: S/no-PCR, 17.2%; S/PCR-, 11.4%; S/PCR+, 22.1%; HS/no PCR or PCR-, 11.7%; and HS/PCR+, 37.6%. Short-term outcomes differed significantly in the different groups according to demographic characteristics; comorbidity and clinical, radiographic, analytical, and therapeutic variables. Thirty-day mortality was 11.5% (56.5% in hospitalized cases and 19.6% in cases classified as severe). The 2 HS categories and the S/PCR+ category had a greater adjusted risk for 30-day mortality and for having a clinically severe episode during hospitalization in comparison with S/PCR- cases. Only the 2 HS categories showed greater risk for hospitalization than the S/PCR- cases


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Serviços Médicos de Emergência/estatística & dados numéricos , Ficha Clínica , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Reação em Cadeia da Polimerase
7.
Eur Geriatr Med ; 11(5): 829-841, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32671732

RESUMO

PURPOSE: To determine the differences by age-dependent categories in the clinical profile, presentation, management, and short-term outcomes of patients with laboratory-confirmed COVID-19 admitted to a Spanish Emergency Department (ED). METHODS: Secondary analysis of COVID-19_URG-HCSC registry. We included all consecutive patients with laboratory-confirmed COVID-19 admitted to the ED of the University Hospital Clinico San Carlos (Madrid, Spain). The population was divided into six age groups. Demographic, baseline and acute clinical data, and in-hospital and 30-day outcomes were collected. RESULTS: 1379 confirmed COVID-19 cases (mean age 62 (SD 18) years old; 53.5% male) were included (18.1% < 45 years; 17.8% 45-54 years; 17.9% 55-64 years; 17.2% 65-74 years; 17.0% 75-84 years; and 11.9% ≥ 85 years). A statistically significant association was found between demographic, comorbidity, clinical, radiographic, analytical, and therapeutic variables and short-term results according to age-dependent categories. There were less COVID-specific symptoms and more atypical symptoms among older people. Age was a prognostic factor for hospital admission (aOR = 1.04; 95% CI 1.02-1.05) and in-hospital (aOR = 1.08; 95% CI 1.05-1.10) and 30-day mortality (aOR = 1.07; 95% CI 1.04-1.09), and was associated with not being admitted to intensive care (aOR = 0.95; 95% CI 0.93-0.98). CONCLUSIONS: Older age is associated with less COVID-specific symptoms and more atypical symptoms, and poor short-term outcomes. Age has independent prognostic value and may help in shared decision-making in patients with confirmed COVID-19 infection.


Assuntos
Infecções por Coronavirus , Hospitalização/estatística & dados numéricos , Pandemias , Pneumonia Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Estudos Retrospectivos , SARS-CoV-2 , Espanha
8.
Emergencias ; 32(4): 242-252, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32692001

RESUMO

OBJECTIVES: The primary objective was to describe the clinical characteristics and 30-day mortality rates in emergency department patients with coronavirus disease 2019 (COVID-19) in different diagnostic groupings. MATERIAL AND METHODS: Secondary analysis of the COVID-19 registry compiled by the emergency department of Hospital Clínico San Carlos in Madrid, Spain. We selected suspected COVID-19 cases treated in the emergency department between February 28 and March 31, 2020. The cases were grouped as follows: 1) suspected, no polymerase chain reaction (PCR) test (S/no-PCR); 2) suspected, negative PCR (S/PCR-); 3) suspected, positive PCR (S/PCR+); 4) highly suspected, no PCR, or negative PCR (HS/no or PCR-); and 5) highly suspected, positive PCR (HS/PCR+). We collected clinical, radiologic, and microbiologic data related to the emergency visit. The main outcome was 30-day all-cause mortality. Secondary outcomes were hospitalization and clinical severity of the episode. RESULTS: A total of 1993 cases (90.9%) were included as follows: S/no-PCR, 17.2%; S/PCR-, 11.4%; S/PCR+, 22.1%; HS/no PCR or PCR-, 11.7%; and HS/PCR+, 37.6%. Short-term outcomes differed significantly in the different groups according to demographic characteristics; comorbidity and clinical, radiographic, analytical, and therapeutic variables. Thirty-day mortality was 11.5% (56.5% in hospitalized cases and 19.6% in cases classified as severe). The 2 HS categories and the S/PCR+ category had a greater adjusted risk for 30-day mortality and for having a clinically severe episode during hospitalization in comparison with S/PCR- cases. Only the 2 HS categories showed greater risk for hospitalization than the S/PCR- cases. CONCLUSION: COVID-19 diagnostic groups differ according to clinical and laboratory characteristics, and the differences are associated with the 30-day prognosis.


OBJETIVO: El objetivo principal fue describir el perfil clínico y la mortalidad a los 30 días de diferentes categorías diagnósticas en los casos de COVID-19 atendidos en un servicio de urgencias (SU). METODO: Análisis secundario del registro COVID-19_URG-HCSC. Se seleccionaron los casos sospechosos de COVID-19 atendidos en un SU de Madrid desde el 28 de febrero hasta el 31 de marzo de 2020. La muestra se dividió: 1) sospecha con PCR no realizada (S/PCR NR); 2) sospecha con PCR negativa (S/PCR­); 3) sospecha con PCR positiva (S/ PCR+); 4) alta sospecha con PCR negativa o no realizada (AS/PCR­ o NR); y 5) alta sospecha con PCR positiva (AS/ PCR+). Se recogieron variables clínicas, radiológicas y microbiológicas del episodio de urgencias. La variable de resultado principal fue la mortalidad por cualquier causa a los 30 días. Las variables secundarias fueron el ingreso y la gravedad del episodio. RESULTADOS: Se incluyeron 1.993 pacientes; 17,2% S/PCR NR, 11,4% S/PCR­, 22,1% S/PCR+, 11,7% AS/PCR­ o NR y 37,6% AS/PCR+. Se hallaron diferencias estadísticamente significativas respecto a las variables demográficas, comorbilidad, clínicas, radiográficas, analíticas y terapéuticas y de resultados a corto plazo en función las categorías diagnósticas. La mortalidad global a los 30 días fue de un 11,5%, 56,5% casos fueron hospitalizados y 19,6% casos sufrieron un episodio grave. Las categorías de AS y de S/PCR+ tuvieron un incremento del riesgo ajustado de mortalidad a los 30 días y de sufrir un episodio grave durante el ingreso hospitalario respecto a S/PCR­. En relación al ingreso, solo las categorías de AS tuvieron un incremento del riesgo ajustado de hospitalización respecto a la categoría de S/PCR­. CONCLUSIONES: Existen diferentes categorías diagnósticas de la enfermedad COVID-19 en función del perfil clínico y microbiológico que tienen correlato con el pronóstico a 30 días.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Adulto , COVID-19 , Causas de Morte , Comorbidade , Intervalos de Confiança , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Grupos Diagnósticos Relacionados , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Reação em Cadeia da Polimerase/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , SARS-CoV-2 , Espanha/epidemiologia , Avaliação de Sintomas , Fatores de Tempo , Resultado do Tratamento
9.
Int Urol Nephrol ; 46(6): 1161-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24265040

RESUMO

PURPOSE: Estimated glomerular filtration rate (GFR) is a useful tool for the detection of chronic kidney disease (CKD). Several methods have been proposed, but findings can vary in specific groups such as patients with diabetes, elderly and high and low body mass index and, also, with the stage of CKD. The objective of this study was comparing the accuracy of the currently used equations for estimating GFR with that of the gold standard technetium-(99m)-diethylene triamine pentaacetic acid (99mTc-DTPA). METHODS: We performed a cross-sectional study of 129 patients with all five CKD stages. GFR was estimated using the following: 24-h urine creatinine clearance, Cockcroft-Gault equation, MDRD equation, CKD-EPI equation, Hoek's cystatin C equation, and isotopic 99mTc-DTPA (as gold standard). We evaluated agreement in the whole study population and according to age, sex, weight, and diabetes. RESULTS: All methods had good agreement. The best agreement was observed with the cystatin C [intraclass coefficient correlation (ICC) 95 % confidence interval (95 % CI), 0.87 (0.82-0.91)], followed by CKD-EPI [ICC 0.83 (0.77-0.88)]. Twenty-four-hour urine creatinine clearance showed the worst agreement in patients older than 65 years [ICC 0.70 (0.56-0.79)]. The Cockcroft-Gault equation showed the worst agreement in younger than 65 years [ICC 0.64 (0.42-0.79)]. The best agreement for classification in the correct CKD stage was with the cystatin C equation [κ = 0.80 (0.74-0.87)]. GFR was overestimated with all methods in CKD stages 4 and 5. CONCLUSIONS: The methods used in clinical practice are adequate for classification of CKD. Cystatin C is the most accurate method, followed by CKD-EPI. The Cockcroft-Gault equation is not accurate in young patients. Twenty-four-hour urine creatinine clearance loses accuracy in patients aged older than 65 years.


Assuntos
Algoritmos , Creatinina/urina , Cistatina C/sangue , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/fisiopatologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Estudos Transversais , Diabetes Mellitus/sangue , Diabetes Mellitus/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urina , Fatores Sexuais , Pentetato de Tecnécio Tc 99m
11.
Endocrinol. nutr. (Ed. impr.) ; 60(10): 590-598, dic. 2013. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-118144

RESUMO

Tanto el crecimiento como la función de la glándula tiroides son regulados por la tirotropina (TSH), la cual ejerce su función a través de su receptor (TSHR). El TSHR es el antígeno clave en varias alteraciones tiroideas, entre las que se incluyen el hipertiroidismo y el hipotiroidismo, o en algunos tumores. Actualmente, se disponen de diversas estrategias terapéuticas para muchos de estos trastornos, como son los fármacos antitiroideos o la administración de radioyodo. Desgraciadamente, estas terapias no están exentas de efectos secundarios. Además, el tratamiento de las complicaciones derivadas de la enfermedad de Graves, como la oftalmopatía tiroidea, resulta muchas veces difícil e insatisfactorio. Los recientes avances en investigación básica, tanto en modelos in vitro como in vivo, sugieren que los análogos de la TSH podrían emplearse en el diagnóstico y en el tratamiento en algunas de las enfermedades tiroideas. La llegada de los métodos de cribado de alto rendimiento ha proporcionado un grupo de análogos de la TSH, también llamados pequeñas-moléculas, que son fármacos con características potencialmente prometedoras. Estas pequeñas-moléculas son sustancias con bajo peso molecular que pueden poseer actividad agonista, antagonista y, en algunos casos, agonista inversa sobre el TSHR. En esta revisión nos centraremos en los avances actuales en el desarrollo de los análogos de la TSH y su posible aplicación clínica. Los rápidos avances en este campo podrían propiciar que en los próximos años se desarrollen ensayos clínicos con pequeñas-moléculas relacionadas con el TSHR para pacientes con enfermedad de Graves, cáncer de tiroides y osteoporosis de origen tiroideo (AU)


The thyroid-stimulating hormone (TSH) receptor (TSHR) is a major regulator of thyroid function and growth, and is the key antigen in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Various effective treatment strategies are currently available for many of these clinical conditions such as antithyroid drugs or radioiodine therapy, but they are not devoid of side effects. In addition, treatment of complications of Graves’ disease such as Graves’ ophthalmopathy is often difficult and unsatisfactory using current methods. Recent advances in basic research on both in vitro and in vivo models have suggested that TSH analogs could be used for diagnosis and treatment of some of the thyroid diseases. The advent of high-throughput screening methods has resulted in a group of TSH analogs called small molecules, which have the potential to be developed as promising drugs. Small molecules are low molecular weight compounds with agonist, antagonist and, in some cases, inverse agonist activity on TSHR. This short review will focus on current advances in development of TSH analogs and their potential clinical applications. Rapid advances in this field may lead to the conduct of clinical trials of small molecules related to TSHR for the management of Graves’ disease, thyroid cancer, and thyroid-related osteoporosis in the coming years (AU)


Assuntos
Humanos , Doenças da Glândula Tireoide/fisiopatologia , Receptores da Tireotropina/análise , Testes de Função Tireóidea , Hormônios Tireóideos/análise , Neoplasias da Glândula Tireoide/patologia , Doença de Graves/fisiopatologia
12.
Endocrinol Nutr ; 60(10): 590-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23538281

RESUMO

The thyroid-stimulating hormone (TSH) receptor (TSHR) is a major regulator of thyroid function and growth, and is the key antigen in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Various effective treatment strategies are currently available for many of these clinical conditions such as antithyroid drugs or radioiodine therapy, but they are not devoid of side effects. In addition, treatment of complications of Graves' disease such as Graves' ophthalmopathy is often difficult and unsatisfactory using current methods. Recent advances in basic research on both in vitro and in vivo models have suggested that TSH analogs could be used for diagnosis and treatment of some of the thyroid diseases. The advent of high-throughput screening methods has resulted in a group of TSH analogs called small molecules, which have the potential to be developed as promising drugs. Small molecules are low molecular weight compounds with agonist, antagonist and, in some cases, inverse agonist activity on TSHR. This short review will focus on current advances in development of TSH analogs and their potential clinical applications. Rapid advances in this field may lead to the conduct of clinical trials of small molecules related to TSHR for the management of Graves' disease, thyroid cancer, and thyroid-related osteoporosis in the coming years.


Assuntos
Receptores da Tireotropina/análise , Doenças da Glândula Tireoide/tratamento farmacológico , Doença de Graves/tratamento farmacológico , Humanos , Neoplasias da Glândula Tireoide/tratamento farmacológico
13.
Hepatology ; 46(3): 885-97, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17654698

RESUMO

UNLABELLED: The transcription of the gene (CYP7A1) encoding cholesterol 7alpha-hydroxylase, a key enzyme in cholesterol homeostasis, is repressed by bile acids via multiple mechanisms involving members of the nuclear receptor superfamily. Here, we describe a regulatory mechanism that can be exploited for modulating bile acid synthesis. By dissecting the mechanisms of CYP7A1 transcription, we found that bile acids stimulate the sequential recruitment of the histone deacetylases (HDACs) 7, 3, and 1, and of the corepressor SMRTalpha (silencing mediator of retinoid and thyroid receptors-alpha) and the nuclear corepressor. Bile acids, but not the farnesoid X receptor-selective agonist GW4064, increase the nuclear concentration of HDAC7, which promotes the assembly of a repressive complex that ultimately represses CYP7A1 transcription. Interestingly, despite its high basal expression level, small heterodimer partner (SHP) is associated with the CYP7A1 promoter only at a later stage of bile acid repression. Gene silencing with small interfering RNA confirms that HDAC7 is the key factor required for the repression of CYP7A1 transcription, whereas knockdown of SHP does not prevent the down-regulation of CYP7A1. Administration of the HDAC inhibitors valproic acid or trichostatin A to genetically hypercholesterolemic mice increases Cyp7a1 messenger RNA and bile acid synthesis and consequently markedly reduces total plasma and low-density lipoprotein cholesterol. CONCLUSION: By using a combination of molecular, cellular, and animal models, our study highlights the importance of HDACs in the feedback regulation of CYP7A1 transcription and identifies these enzymes as potential targets to modulate bile acid synthesis and for the treatment of hypercholesterolemia.


Assuntos
Ácidos e Sais Biliares/biossíntese , Colesterol 7-alfa-Hidroxilase/genética , Regulação da Expressão Gênica , Histona Desacetilases/metabolismo , Animais , Ácidos e Sais Biliares/genética , Ácidos e Sais Biliares/farmacologia , Núcleo Celular/enzimologia , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Retroalimentação Fisiológica , Histona Acetiltransferases/análise , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Histona Desacetilases/análise , Histona Desacetilases/genética , Humanos , Isoxazóis/farmacologia , Lipoproteínas LDL/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Correpressor 2 de Receptor Nuclear , Regiões Promotoras Genéticas , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologia , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Transcrição Gênica/genética
15.
San José; Ambientico; set. 2005. 4 p. ilus.(Ambientico).
Monografia | Desastres | ID: des-17568

RESUMO

Coordinado por el Instituto Metereológico Nacional (IMN) y la Oficina Nacional de Implementación Conjunta, ambos adscritos al Ministerio de Ambiente Energía y Minas (MINAE), este programa desarrolla los temas de interés para el país, que van desde el diagnóstico, incluyendo los inventarios de emisiones de gases de efecto invernadero y los estudios de vulnerabilidad e impactos del cambio climático, hasta la realización de análisis de opciones de mitigación y adaptación que lleven a políticas y medidas integradoras de un plan de acción de cambio climático.


Assuntos
Mudança Climática , Estratégias de Saúde , Costa Rica
16.
SITUA ; 9(17): 67-72, sept. 2000-feb. 2001.
Artigo em Espanhol | LILACS, LIPECS | ID: lil-295140

RESUMO

El estudio de los componentes fenólicos de la oenothera rosea y multicaulis pretende aportar a las investigaciones realizadas respecto a estas especies, que validen científicamente sus propiedades farmacológicas. El fin de esta investigación implica el estudio de los componentes fenólicos a través del tratamiento del extracto hidroalcohólico con acetato de etilo. Las pruebas fitoquímicas desarrolladas permiten determinar que los componentes mayoritarios presentes en ambas especies son los flavonoides. El monitoreo de la cromatografía de columna se ha realizado con la cormatografía de capa fina utilizando como eluyente AcOEt; HCO2H; AcOH; H2O, revelado con FeCl3 al 1 por ciento, se observan manchas en la cromatoplaca de color verde para Oenothera multicaulis y azul para Oenothera rosea. El método espectroscópico ultravioleta visible con reactivos de desplazamiento para elucidar la estructura del flavonoide aislado por cromatografía (fracción 12) reporta para Oenothera rosea la presencia de un flavonoide glicosídico denominado Quercetrina, mientras que Oenothera multicaulis no reporta resultados cuantitativos por espectroscopía. Finalmente los resultados determinan que los compuestos fenólicos en lo que respecta a flavonoides no son parecidos en ambas especies.


Assuntos
Oenothera biennis , Cromatografia
18.
In. Castillo Godoy, Delia, coord. Memoria : Primer encuentro constructivo centroamericano "Genero y cultura en desastres". Guatemala, Centro de Coordinación para la Prevención de los Desastres Naturales en América Central (CEPREDENAC);Guatemala. Comité Nacional de Emergencia (CONE);Guatemala. Instituto Nacional de Sismología, Vulcanología, Meteorología e Hidrología (INSIVUMEH);Suecia. Agencia Sueca de Desarrollo Internacional (ASDI), 1997. p.74-80.
Monografia em Es | Desastres | ID: des-9178
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