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1.
Pharmacol Res ; 203: 107183, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38631619

RESUMO

INTRODUCTION: Data on positive rechallenge in idiosyncratic drug-induced liver injury (DILI) are scarce. We aim to analyse the clinical presentation, outcome and drugs associated with positive rechallenge in two DILI registries. METHODS: Cases from the Spanish and Latin American DILI registries were included. Demographics, clinical characteristics and outcome of cases with positive rechallenge according to CIOMS/RUCAM and current definitions were analysed. RESULTS: Of 1418 patients with idiosyncratic DILI, 58 cases had positive rechallenge (4.1%). Patients with positive rechallenge had shorter duration of therapy (p=0.001) and latency (p=0.003). In patients with rechallenge, aspartate transaminase levels were increased (p=0.026) and showed a prolonged time to recovery (p=0.020), albeit no differences were seen in terms of fatal outcomes. The main drug implicated in rechallenge was amoxicillin-clavulanate (17%). The majority of re-exposure events were unintentional (71%). Using both existing definitions of positive rechallenge, there were four cases which exclusively fulfilled the current criteria and five which only meet the historical definition. All cases of positive rechallenge, irrespective of the pattern of damage, fulfilled the criteria of either alanine transaminase (ALT) ≥3 times the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) ≥2 times ULN. CONCLUSIONS: Episodes of rechallenge were characterised by shorter duration of therapy and latency, and longer time to resolution, but did not show an increased incidence of fatal outcome. Based on our findings, ALT ≥3 times ULN and/or ALP ≥2 times ULN, regardless of the pattern of damage, is proposed as a new definition of rechallenge in DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Sistema de Registros , Humanos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos Prospectivos , Espanha/epidemiologia , Aspartato Aminotransferases/sangue , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos
2.
Occup Med (Lond) ; 73(3): 128-132, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-36719103

RESUMO

BACKGROUND: Antibody (Ab) tests for SARS-CoV-2 virus allows for the estimation of incidence, level of exposure and duration of immunity acquired by a previous infection. In health workers, the hospital setting might convey a greater risk of infection. AIMS: To describe the frequency of immunoglobulin G (IgG) Abs (IgG-Abs) to the SARS-CoV-2 virus among workers at a third-level university hospital in Colombia. METHODS: In this cross-sectional study, we included medical and non-medical personnel with at least one real-time polymerase chain reaction (RT-PCR)/antigen test between March 2020 and March 2021. In April 2021, an IgG-Ab test against SARS-CoV-2 was conducted for all participants and replicated 2 weeks later in a random sample (10%). The frequency of IgG-Abs is presented based on status (positive/negative) and time elapsed since RT-PCR/antigen test (<3 months, 3-6 months, >6 months). RESULTS: We included 1021 workers (80% women, median age 34 years (interquartile range 28-42), 73% medical personnel, 23% with previous positive RT-PCR/antigen). The overall seroprevalence was 35% (95% CI 31.6-37.4, 35% in medical and 33% in non-medical personnel). For those with a previous positive RT-PCR/antigen test, the seroprevalence was 90% (<3 months), 82% (3-6 months) and 48% (>6 months). In participants with a previous negative RT-PCR/antigen test, the seroprevalence was 17% (<3 months), 21% (3-6 months) and 29% (>6 months). CONCLUSIONS: High IgG-Ab positivity was found in hospital personnel, regardless of work activities. The prevalence of detectable Abs differed by previous RT-PCR/antigen status and time elapsed since the diagnostic test.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Feminino , Adulto , Masculino , COVID-19/epidemiologia , Colômbia/epidemiologia , Estudos Soroepidemiológicos , Estudos Transversais , Imunoglobulina G , Pessoal de Saúde , Recursos Humanos em Hospital , Hospitais
3.
Entropy (Basel) ; 25(2)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36832572

RESUMO

Survival probability measures the probability that a system taken out of equilibrium has not yet transitioned from its initial state. Inspired by the generalized entropies used to analyze nonergodic states, we introduce a generalized version of the survival probability and discuss how it can assist in studies of the structure of eigenstates and ergodicity.

4.
J Eur Acad Dermatol Venereol ; 35(4): 844-883, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32976663

RESUMO

Dermatophyte infections are the most common fungal infections in humans; among them, tinea capitis (TC) - the most contagious fungal infection - is caused by anthropophilic, zoophilic and geophilic dermatophytes. The purpose of this systematic review was to determine the different aetiological variants involved in TC and the overall epidemiology of the causes of this infection in the last two decades. We searched the MEDLINE (PubMed) and Embase databases for articles published from July 2000 to August 2019 using the following search terms: 'Tinea capitis', 'Africa', 'America', 'Asia', 'Europe', 'Oceania', and the names of the countries on each continent. The flow of information through the different phases in this systematic review was depicted using a PRISMA flow diagram, which mapped the number of records identified, included and excluded, and the reasons for exclusion. Our findings indicate that the frequency of different aetiologic agents of TC in the reported studies varied globally, from 0.4-87.7% in Africa, 0.2-74.0% in North America, 0.0-91.2% in Eastern Asia, 0.0-69.0% in Eastern Europe and 2.9-86.4% in Oceania. Microsporum canis is the most frequent reported zoophilic agent worldwide, while Trichophyton violaceum and Trichophyton tonsurans are the predominant anthropophilic agents. Over time, the frequency of these latter fungal infections has increased globally, and these fungi have become the major species globally. Anthropophilic transmission - the most prevalent type of transmission - could be explained by two factors: (i) the socioeconomic status of affected countries and population groups with associated risk factors and (ii) movement of populations importing new causes of infection to areas where they had not been encountered previously. We observed that intercontinental migration and travel; globalization; environmental, climatic and ecological changes; and accelerated evolution of health technologies may influence the observed epidemiological changes and, consequently, contributed to the variations in the global status of TC.


Assuntos
Tinha do Couro Cabeludo , Arthrodermataceae , Ásia , Europa (Continente) , Europa Oriental , Humanos , Microsporum , Tinha do Couro Cabeludo/epidemiologia , Trichophyton
5.
J Helminthol ; 93(2): 187-194, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29386074

RESUMO

In the Pampa region of Argentina, farming activities have been performed since the beginning of the 20th century, but in the 1990s, land-use patterns rapidly changed towards intensive agriculture and poultry breeding. This study compares the helminth community of Akodon azarae (Rodentia) among three habitats with different land use in pampean agroecosystems: poultry farms, mono-cultivated fields and abandoned fields (not used for 35 years), under the prediction that there will be greater helminth richness and diversity in mice from abandoned fields compared to those from the other habitats. Nevertheless, the highest abundance of A. azarae occurred on poultry farms, the habitat most disturbed by human activity, while cultivated fields showed the lowest. Helminth richness and diversity were significantly higher on poultry farms than in the other habitats, due to the presence of Trichuris laevitestis, Protospirura numidica criceticola and cysts of Taenia taeniaeformis. We suggest that the helminth fauna of A. azarae can survive on poultry farms despite disturbance from farming activities, because rodents can move and get shelter within farm perimeter fences, where dense and high vegetation grows. This farm area could offer good conditions for geohelminth development, while chicken sheds could attract insects that are intermediate hosts of helminths with indirect life cycles. On the contrary, agrochemicals applied in cultivated fields would negatively influence helminth diversity and composition, by decreasing host populations (arthropods and rodents) and affecting free larval stages of geohelminths.


Assuntos
Agricultura , Ecossistema , Helmintos/isolamento & purificação , Roedores/parasitologia , Sigmodontinae/parasitologia , Animais , Argentina , Fazendas , Estágios do Ciclo de Vida , Aves Domésticas , Doenças dos Roedores/parasitologia , Estações do Ano , Taenia , Trichuris
6.
Lupus ; 27(14): 2181-2189, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30282560

RESUMO

The importance of the immunomodulatory effects of vitamin D has recently been associated with autoimmune and chronic inflammatory diseases. Vitamin D deficiency has been linked to the development of autoimmune conditions. Antiphospholipid syndrome is an autoimmune disease characterized by thrombotic events and obstetric complications in patients with antiphospholipid antibodies. Current data show that patients with antiphospholipid syndrome have a high prevalence of vitamin D deficiency even without classic risk factors. Several studies have suggested vitamin D may have anti-thrombotic functions. In antiphospholipid syndrome, low vitamin D serum levels have been associated with thrombotic manifestations, suggesting a possible protective role of vitamin D in antiphospholipid syndrome. This literature review presents current evidence on the haemostatic functions of vitamin D and their possible relationship with the clinical manifestations of antiphospholipid syndrome.


Assuntos
Síndrome Antifosfolipídica/complicações , Deficiência de Vitamina D/complicações , Vitamina D/metabolismo , Anticorpos Antifosfolipídeos/sangue , Anticoagulantes/uso terapêutico , Feminino , Humanos , Gravidez , Complicações Hematológicas na Gravidez/etiologia , Trombose/tratamento farmacológico , Trombose/etiologia , Deficiência de Vitamina D/tratamento farmacológico
7.
Lupus ; 27(9): 1542-1546, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29732937

RESUMO

We studied the epidemiologic triad-related factors influencing human papilloma virus (HPV) persistence in Mexican women with systemic lupus erythematosus (SLE). Patients aged ≥18 years with SLE (American College of Rheumatology criteria), with and without HPV persistence, were selected. Groups were analyzed by (1) host: clinical disease characteristics; (2) agent: (I) infectious (prevalence, incidence, HPV genotype and co-infections (≥2 HPV genotypes or mycoplasmas)), (II) chemical (contraceptives and immunosuppressive drugs) and (III) physical (vitamin D deficiency) and (3) environment. A total of 121 SLE patients were selected over a two-year period. (1) Host: mean age 45.8 years and disease duration 12.7 years. (2) Agent: (I) infectious. HPV infection prevalence in the second sample was 26.4%, high-risk HPV genotypes 21.5% and co-infections 7.4%. HPV infection incidence was 13.2%, persistence 13.2% and clearance 15.7%. (II) Chemical: use of oral hormonal contraceptives 5% and immunosuppressive treatment 97.5%. (III) Physical: Vitamin D levels were similar in both groups. (3) Environment: (I) natural. A total of 60.6% of patients were residents of Puebla City. (II) Social: The mean education level was 10.9. Poverty levels were: III degree 52.4%, IV degree 28% and II degree 17%. (III) Cultural behavioral: Onset of sexual life was 20.5 years, 10% had ≥3 sexual partners and 51.2% were postmenopausal. In conclusion, no factor of the epidemiologic triad was associated with HPV infection prevalence.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Infecções por Papillomavirus/epidemiologia , Adulto , Idoso , Estudos de Coortes , Meio Ambiente , Feminino , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Adulto Jovem
8.
Philos Trans A Math Phys Eng Sci ; 375(2108)2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29084885

RESUMO

A main feature of a chaotic quantum system is a rigid spectrum where the levels do not cross. We discuss how the presence of level repulsion in lattice many-body quantum systems can be detected from the analysis of their time evolution instead of their energy spectra. This approach is advantageous to experiments that deal with dynamics, but have limited or no direct access to spectroscopy. Dynamical manifestations of avoided crossings occur at long times. They correspond to a drop, referred to as correlation hole, below the asymptotic value of the survival probability and to a bulge above the saturation point of the von Neumann entanglement entropy and the Shannon information entropy. By contrast, the evolution of these quantities at shorter times reflects the level of delocalization of the initial state, but not necessarily a rigid spectrum. The correlation hole is a general indicator of the integrable-chaos transition in disordered and clean models and as such can be used to detect the transition to the many-body localized phase in disordered interacting systems.This article is part of the themed issue 'Breakdown of ergodicity in quantum systems: from solids to synthetic matter'.

9.
Ultrastruct Pathol ; 41(3): 258-263, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28524812

RESUMO

A case of a 47-year-old male with a sacral spine mass was investigated by histology, immunohistochemistry (IHC), and electron microscopy (EM). The light microscopy of the first core biopsy revealed scant cellularity with spindle and round cells with eosinophilic cytoplasm within a fibromyxoid background. Immunostaining with pancytokeratin, cytokeratin 19, and S100 was nonspecific. Another biopsy was attempted to obtain a more definitive diagnosis. Light microscopy of the second core had scant cellular material. However, the tissue was specifically requested for ultrastructural evaluation and revealed features diagnostic of chordoma. After definitive diagnosis, radical resection of the mass was performed. This case illustrates how EM was instrumental in the definitive diagnosis before radical resection in a case that was not clear by hematoxylin and eosin (H&E) and IHC alone.


Assuntos
Cordoma/ultraestrutura , Microscopia Eletrônica , Sacro/ultraestrutura , Biomarcadores Tumorais/análise , Biópsia/métodos , Cordoma/diagnóstico , Cordoma/patologia , Humanos , Imuno-Histoquímica/métodos , Masculino , Microscopia Eletrônica/métodos , Pessoa de Meia-Idade
10.
J Physiol ; 594(5): 1247-64, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26926316

RESUMO

Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean P(aO2) levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery during the last third of gestation. The ratio of oxygen (from 2.7 ± 0.2 to 3.8 ± 0.8; P < 0.05) and of glucose (from 2.3 ± 0.1 to 3.3 ± 0.6; P < 0.05) delivery to the fetal carotid, relative to the fetal femoral circulation, increased during and shortly after the period of chronic hypoxia. In contrast, oxygen and glucose delivery remained unchanged from baseline in normoxic fetuses. Fetal plasma urate concentration increased significantly during chronic hypoxia but not during normoxia (Δ: 4.8 ± 1.6 vs. 0.5 ± 1.4 µmol l(-1), P<0.05). The data support the hypotheses tested and show persisting redistribution of substrate delivery away from peripheral and towards essential circulations in the chronically hypoxic fetus, associated with increases in xanthine oxidase-derived reactive oxygen species.


Assuntos
Gasometria/métodos , Coração Fetal/fisiopatologia , Hipóxia Fetal/fisiopatologia , Testes de Função Cardíaca/métodos , Tecnologia de Sensoriamento Remoto/métodos , Animais , Gasometria/instrumentação , Circulação Coronária , Feminino , Testes de Função Cardíaca/instrumentação , Circulação Placentária , Gravidez , Tecnologia de Sensoriamento Remoto/instrumentação , Ovinos
11.
Br J Dermatol ; 174(3): 499-504, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26471781

RESUMO

Endogenous molecules that exhibit fluorescence hold the potential to serve as reporters of tissue structure, activity and physiology. Fluorescence excitation spectroscopy is one means to measure and express tissue's innate fluorescence. This review focuses on the application of endogenous fluorescence ultraviolet excitation spectroscopy to dermatology.


Assuntos
Dermatopatias/diagnóstico , Proliferação de Células , Epiderme/patologia , Humanos , Envelhecimento da Pele/patologia , Espectrometria de Fluorescência/métodos
12.
Br J Dermatol ; 174(5): 1086-91, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26783740

RESUMO

BACKGROUND: Fluorescence excitation provides the ability to interrogate innate molecules whose radiation emission correlates with specific functional states of tissue. OBJECTIVES: The present study demonstrates the effectiveness of a novel ultraviolet (UV) fluorescence excitation photography system in its ability to image rapidly proliferating epidermal skin lesions by capturing endogenous fluorescence emissions attributed to tryptophan. METHODS: A clinical prototype UV fluorescence excitation photography system was used to acquire images of endogenous fluorescence ascribed to tryptophan. RESULTS: Twelve human subjects and 11 ex vivo samples with various skin lesions consistently exhibited increased endogenous fluorescence at 340-nm wavelength upon excitation at 295 nm in rapid epidermal proliferations, including psoriasis, actinic keratoses and basal cell carcinoma, compared with surrounding normal skin. In contrast, nonproliferating lesions showed decreased fluorescence. CONCLUSIONS: This simple but robust point-and-shoot imaging system may offer a clinically useful, noncontact, noninvasive device for the diagnosis and detection of skin disease. As opposed to structural imaging modalities, fluorescence excitation imaging at 295/340-nm wavelengths offers high-sensitivity, wide-field functional imaging of cellular proliferation without the need for externally applied dyes or lengthy image processing. Furthermore, the image is instantly available and does not require interpretation or reconstruction.


Assuntos
Epiderme/patologia , Dermatopatias/patologia , Proliferação de Células , Humanos , Fotografação/métodos , Espectrometria de Fluorescência/métodos
13.
Crit Rev Food Sci Nutr ; 56(1): 82-91, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-24628089

RESUMO

Pregnancy is a complex period of human growth, development, and imprinting. Nutrition and metabolism play a crucial role for the health and well-being of both mother and fetus, as well as for the long-term health of the offspring. Nevertheless, several biological and physiological mechanisms related to nutritive requirements together with their transfer and utilization across the placenta are still poorly understood. In February 2009, the Child Health Foundation invited leading experts of this field to a workshop to critically review and discuss current knowledge, with the aim to highlight priorities for future research. This paper summarizes our main conclusions with regards to maternal preconceptional body mass index, gestational weight gain, placental and fetal requirements in relation to adverse pregnancy and long-term outcomes of the fetus (nutritional programming). We conclude that there is an urgent need to develop further human investigations aimed at better understanding of the basis of biochemical mechanisms and pathophysiological events related to maternal-fetal nutrition and offspring health. An improved knowledge would help to optimize nutritional recommendations for pregnancy.


Assuntos
Saúde Global , Transtornos da Nutrição do Lactente/prevenção & controle , Fenômenos Fisiológicos da Nutrição Materna , Modelos Biológicos , Política Nutricional , Cooperação do Paciente , Complicações na Gravidez/prevenção & controle , Adulto , Desenvolvimento Infantil , Feminino , Desenvolvimento Fetal , Humanos , Transtornos da Nutrição do Lactente/epidemiologia , Recém-Nascido , Estado Nutricional , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Risco , Aumento de Peso
14.
Neurologia ; 31(4): 223-30, 2016 May.
Artigo em Espanhol | MEDLINE | ID: mdl-26315759

RESUMO

INTRODUCTION: Parkinson disease is a neurodegenerative condition involving motor, cognitive, and linguistic deficits. It is important to know why all these different deficits co-occur in the affected people. This paper aims to clarify whether these comorbid deficits result from the selective impairment of a computational primitive, namely, a context-sensitive computational ability according to Chomsky's Hierarchy (a well-established research tool in comparative neuroscience). PATIENTS AND METHODS: A total of 15 medicated subjects with Parkinson disease and 15 controls were selected. They were matched in age and education. A battery of tasks was designed to test 3 different domains (motor capacities, cognition, and language) and 2 different computational abilities (context-free and context-sensitive operations). RESULTS: Significant differences between groups were observed only regarding the linguistic task involving context-sensitive computations (correferences). CONCLUSIONS: The observed deficits in our patients with Parkinson disease cannot be explained in terms of the selective impairment of one only unspecific, low-level computational process. At the same time, differences between patients and controls are expected to be greater if the former are not medicated. Moreover, we should pursue in the search of (this kind of) computational primitives than can be selectively impaired in people with Parkinson disease, because they may help to achieve an earlier diagnosis of this condition.


Assuntos
Doença de Parkinson/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cognição , Feminino , Humanos , Testes de Linguagem , Masculino , Pessoa de Meia-Idade , Destreza Motora , Testes Neuropsicológicos , Doença de Parkinson/psicologia , Desempenho Psicomotor
15.
Asian-Australas J Anim Sci ; 29(5): 666-73, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26954168

RESUMO

Two experiments were conducted to evaluate the effects of the level of corn dry distillers grains with solubles (CDDGS) supplementation on growing performance, blood metabolites, digestion characteristics and ruminal fermentation patterns in steers grazing dormant forage. In Exp. 1, of growth performance, 120 steers (204±5 kg initial body weight [BW]) were distributed randomly into 3 groups (each of 40 steers), which were provided with the following levels of CDDGS supplement: 0%, 0.25%, or 0.50% BW. All groups of steers were grazed for 30 days in each of 3 grazing periods (March, April, and May). Approximately 1,000 ha of the land was divided with electric fencing into 3 equally sized pastures (333 ha in size). Blood samples were collected monthly from 20 steers in each grazing group for analysis of glucose (G), urea-nitrogen (UN) and non-esterified fatty acids. Final BW, average daily gain (ADG) and supplement conversion (CDDGS-C) increased with increasing levels of CDDGS supplementation (p<0.05).The CDDGS supplementation also increased the plasma G and UN concentrations (p<0.05). In Exp. 2, of digestive metabolism, 9 ruminally cannulated steers (BW = 350±3 kg) were distributed, following a completely randomized design, into groups of three in each pasture. The ruminally cannulated steers were provided the same levels of CDDGS supplementation as in the growing performance study (0%, 0.25%, and 0.50% BW), and they grazed along with the other 40 steers throughout the grazing periods. The dry matter intake, crude protein intake, neutral detergent fiber intake (NDFI), apparent digestibility of dry matter (ADDM), crude protein (ADCP) and neutral detergent fiber (ADNDF) increased with increasing levels of CDDGS supplementation (p<0.05). The ruminal degradation rates of CP (kdCP), NDF (kdNDF) and passage rate (kp) also increased with increasing levels of CDDGS supplementation (p<0.05). Ruminal ammonia nitrogen (NH3-N) and propionate concentrations also increased with increasing levels of CDDGS supplementation (p<0.05). However, acetate concentrations decreased with increasing levels of CDDGS supplementation (p<0.05). Liquid dilution rate increased with increasing levels of CDDGS supplementation but ruminal liquid volume decreased (p<0.05). On the basis of these findings, we can conclude that CDDGS supplementation enhanced the productive performance of cattle grazing native rangeland without negatively affecting forage intake, glucose and urea-nitrogen blood concentrations, ruminal degradation and ruminal fermentation patterns.

16.
Pharmacogenomics J ; 15(4): 322-5, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25403996

RESUMO

Psoriasis is a prevalent autoimmune disease of the skin that causes significant psychological and physical disability. Tumor necrosis factor (TNF)-blocking agents have proven to be highly efficacious in the management of moderate-to-severe psoriasis. However, a significant percentage of patients do not respond to this treatment. Recently, variation at the PDE3A-SLCO1C1 (phosphodiesterase 3A-SoLute Carrier Organic anion transporter family member 1C1) locus has been robustly associated with anti-TNF response in rheumatoid arthritis. Using a cohort of 130 psoriasis patients treated with anti-TNF therapy, we sought to analyze the association of this locus with treatment response in psoriasis. We found a highly significant association between PDE3A-SLCO1C1 and the clinical response to TNF blockers (P=0.0031). Importantly, the allele that was previously associated with the lack of response to rheumatoid arthritis (G allele, single-nucleotide polymorphism rs3794271) was associated with a higher anti-TNF efficacy in psoriasis. The results of this study are an important step in the characterization of the pharmacogenetic profile associated with anti-TNF response in psoriasis.


Assuntos
Antirreumáticos/uso terapêutico , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/genética , Transportadores de Ânions Orgânicos/genética , Psoríase/tratamento farmacológico , Psoríase/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Alelos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Estudos de Coortes , Determinação de Ponto Final , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento
17.
Haemophilia ; 21(1): e12-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25359594

RESUMO

Swimming is beneficial for persons with haemophilia (PWH) providing good maintenance of the cardiovascular and musculoskeletal system and improving many psychological characteristics. In the Desafío del Caribe Project, young PWH from Venezuela and Mexico took part in an open water competition in the Gulf of Mexico under a multidisciplinary team supervision. Eight severe haemophilia A, two moderate haemophilia A, one severe haemophilia B and two moderate haemophilia B subjects were included. Haematological, musculoskeletal and psychological evaluations were carried out before and during training for the competition. Training program included physical exercise routines and swimming practices that alternated between pools and open water. Swimmers had coverage with factor concentrates before pool and open water trainings. In physiatric evaluations, the Hemophilia Joint Health Score (HJHS) was used. The objective of the psychology area was to analyse self-esteem, precompetition anxiety, coping mechanisms and relaxation levels. The need of factor prophylaxis before intense trainings was confirmed. In the musculoskeletal system a decrease of elbow pain as well as an increase of muscle strength in the ankles were observed. In the psychological area significant differences between the first and second test in self-esteem levels, cognitive anxiety and group cohesion were found. PWH must be provided with orientation and encouragement to practice swimming regularly. High competition exercise must be supervised by a multidisciplinary team which must evaluate the pros and cons of the activity to make relevant recommendations.


Assuntos
Hemofilia A/fisiopatologia , Hemofilia A/psicologia , Hemofilia B/fisiopatologia , Hemofilia B/psicologia , Natação , Adolescente , Testes Hematológicos , Hemofilia A/sangue , Hemofilia B/sangue , Humanos , Exame Físico , Autoimagem , Adulto Jovem
18.
Pharmacol Res ; 101: 94-101, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26215469

RESUMO

Hypoxia induces several responses at cardiovascular, pulmonary and reproductive levels, which may lead to chronic diseases. This is relevant in human populations exposed to high altitude (HA), in either chronic continuous (permanent inhabitants) or intermittent fashion (HA workers, tourists and mountaineers). In Chile, it is estimated that 1.000.000 people live at highlands and more than 55.000 work in HA shifts. Initial responses to hypoxia are compensatory and induce activation of cardioprotective mechanisms, such as those seen under intermittent hypobaric (IH) hypoxia, events that could mediate preconditioning. However, whenever hypoxia is prolonged, the chronic activation of cellular responses induces long-lasting modifications that may result in acclimatization or produce maladaptive changes with increase in cardiovascular risk. HA exposure during pregnancy induces hypoxia and oxidative stress, which in turn may promote cellular responses and epigenetic modifications resulting in severe impairment in growth and development. Sadly, this condition is accompanied with an increased fetal and neonatal morbi-mortality. Further, developmental hypoxia may program cardio-pulmonary circulations later in postnatal life, ending in vascular structural and functional alterations with augmented risk on pulmonary and cardiovascular failure. Additionally, permanent HA inhabitants have augmented risk and prevalence of chronic hypoxic pulmonary hypertension, right ventricular hypertrophy and cardiopulmonary remodeling. Similar responses are seen in adults that are intermittently exposed to chronic hypoxia (CH) such as shift workers in HA areas. The mechanisms involved determining the immediate, short and long-lasting effects are still unclear. For several years, the study of the responses to hypoxic insults and pharmacological targets has been the motivation of our group. This review describes some of the mechanisms underlying hypoxic responses and potential therapeutic approaches with antioxidants such as melatonin, ascorbate, omega 3 (Ω3) or compounds that increase the nitric oxide (NO) bioavailability.


Assuntos
Doença da Altitude/tratamento farmacológico , Aclimatação , Adulto , Doença da Altitude/complicações , Doença da Altitude/fisiopatologia , Animais , Antioxidantes/uso terapêutico , Fenômenos Fisiológicos Cardiovasculares , Chile , Doença Crônica , Feminino , Humanos , Recém-Nascido , Masculino , Óxido Nítrico/metabolismo , Estresse Oxidativo , Gravidez , Complicações na Gravidez/fisiopatologia , Reprodução
19.
Transpl Infect Dis ; 16(4): 642-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24984587

RESUMO

Emphysematous pyelonephritis (EPN) is an acute, severe necrotizing infection of the renal parenchyma and perirenal tissue, which results in the presence of gas within the renal parenchyma, collecting system, or perinephric tissue. EPN of renal allograft is rare, with only 23 cases reported in Western literature. Here, we report a patient treated successfully with surgery. We also review the literature, focusing on old and new suggested classification systems for EPN.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Escherichia coli/patologia , Transplante de Rim/efeitos adversos , Pielonefrite/terapia , Idoso , Drenagem , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Humanos , Pielonefrite/microbiologia
20.
Rheumatol Int ; 34(10): 1419-25, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24615021

RESUMO

The aim of this study was to evaluate bone mass changes after 1 year of four different types of pharmacological intervention. Ninety-seven prostate cancer patients treated with androgen deprivation therapy, and severe osteopenia or osteoporosis were retrospectively studied. Patients were divided in four groups. Group 1: 28 patients treated with denosumab, Group 2: 24 patients treated with alendronate, Group 3: 24 patients with no antiresorptive treatment and Group 4: 21 patients previously treated with alendronate and switched to denosumab. Dual X-ray absorptiometry was performed at baseline and after 1 year. Bone mass changes at the L2-L4 lumbar spine, femoral neck and total hip were evaluated. No differences were found at baseline. After 1 year, men receiving denosumab or alendronate (Group 1 and 2) showed a significant bone mass increase at the lumbar spine (+2.4 and +5.0 %, respectively), while no significant changes were observed in Group 3 and 4. At the femoral neck, Group 1 and 2 patients showed a significant bone mass increase (+3.7 and +3.6 %, respectively), while no significant changes were observed in Group 3 and 4. At the total hip, we observed a significant bone mass increase in Group 1 (+2.9 %) and a significant bone mass loss in Group 3 patients (-1.9 %). No significant changes were observed in Group 2 and 4. Denosumab increased significantly bone mass in all three dual X-ray absorptiometry standard sites, while alendronate did not at total hip. No benefit was observed in men previously treated with alendronate who switched to denosumab treatment.


Assuntos
Alendronato/uso terapêutico , Antagonistas de Androgênios/efeitos adversos , Anilidas/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Leuprolida/efeitos adversos , Nitrilas/efeitos adversos , Osteoporose/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Compostos de Tosil/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Doenças Ósseas Metabólicas/induzido quimicamente , Doenças Ósseas Metabólicas/diagnóstico por imagem , Denosumab , Colo do Fêmur/diagnóstico por imagem , Humanos , Leuprolida/uso terapêutico , Vértebras Lombares/diagnóstico por imagem , Masculino , Nitrilas/uso terapêutico , Osteoporose/induzido quimicamente , Osteoporose/diagnóstico por imagem , Neoplasias da Próstata/patologia , Radiografia , Compostos de Tosil/uso terapêutico
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