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1.
Medicine (Baltimore) ; 99(50): e22867, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327227

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has emerged as a major health problem worldwide; according to statistics, 10% to 25% of patients with NAFLD can progress to nonalcoholic steatohepatitis (NASH). A link between the composition and metabolites of intestinal microbiota and the development of NAFLD is becoming clearer. It is believed that microbiota factors are driving forces of hepatic steatosis and inflammation. The formulated food that contains prebiotics and dietary fiber may improve NAFLD by altering the intestinal flora and its metabolites. METHODS: The study plan to recruit adult patients (18-75 years, n = 120) with NAFLD, range of alanine aminotransferase is 1.5 to 5 times upper limit of normal (ULN) or liver biopsy is confirmed as NASH. Participants will be randomly allocated into 2 groups: formulated food (n = 80) and a placebo group (n = 40) for 24 weeks. Both groups will receive lifestyle and nutritional advice. The primary endpoint is a decrease in MRS-PDFF by more than 30% from baseline at 24 weeks. The secondary endpoints include the change of anthropometric, liver function, glycolipid metabolism, and systemic inflammation at 4, 12, and 24 weeks. In addition, we consider the changes in intestinal microbiota as an exploration to assess the abundance and diversity at 24 weeks. Weeks 24 to 36 are the follow-up period of drug withdrawal. DISCUSSION: This clinical trial will provide evidence of efficacy and safety of formulated food as a potential new therapeutic agent for NAFLD patients. TRIAL REGISTRATION: The trial is registered in the China Clinical Trial Center (ChiCTR1800016178).


Assuntos
Alimentos Formulados/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Adulto , Idoso , Alanina Transaminase/análise , Bactérias/metabolismo , Estudos de Casos e Controles , China/epidemiologia , Fígado Gorduroso/dietoterapia , Fígado Gorduroso/microbiologia , Feminino , Seguimentos , Alimentos Formulados/microbiologia , Alimentos Formulados/provisão & distribução , Humanos , Inflamação/dietoterapia , Inflamação/microbiologia , Metabolismo dos Lipídeos/fisiologia , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Hepatopatia Gordurosa não Alcoólica/patologia , Segurança , Resultado do Tratamento
2.
Transplantation ; 104(9): 1929-1942, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32769628

RESUMO

BACKGROUND: Liver graft viability assessment has long been considered a limit of hypothermic oxygenated machine perfusion (HOPE). Aim of this study was assessing correlations of easily available perfusate parameters (PP) (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, glucose, lactate, and pH) with graft features and outcome. METHODS: In the period October 2018-February 2020, perfusate samples were obtained every 30 minutes during 50 dual-HOPE (D-HOPE) procedures. Correlations of PP with graft factors, 90-day graft loss, early allograft dysfunction (EAD), L-GrAFT score, acute kidney injury, and comprehensive complication index were analyzed using Pearson coefficient, receiver-operating characteristics analysis and by univariable and multivariable regression. RESULTS: Median D-HOPE time was 122 minutes. All parameters were normalized to liver weight. Only macrovesicular steatosis (MaS) significantly impacted PP levels and slope. Grafts with ≥30% MaS exhibited significantly different PP values and slope. Graft loss and EAD rate were 2% (n = 1) and 26% (n = 13). All PP except lactate correlated with EAD, 90-minute alanine aminotransferase showing the highest area under the receiver-operating characteristics curve (0.84). However, at multivariable analysis, the only factor independently associated with EAD was MaS (odds ratio, 5.44; confidence interval, 1.05-28.21; P = 0.04). Ninety minutes lactate dehydrogenase had the strongest correlation with L-GrAFT (R = 0.70; P < 0.001). PP correlated poorly with comprehensive complication index and grades 2-3 acute kidney injury rate. CONCLUSIONS: PP were predictive of graft function after transplant, but their association with graft survival and clinical outcomes requires further evaluation. MaS influenced levels of PP and was the only independent predictor of EAD.


Assuntos
Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Doadores de Tecidos , Alanina Transaminase/análise , Aspartato Aminotransferases/análise , Temperatura Baixa , Feminino , Sobrevivência de Enxerto , Humanos , Concentração de Íons de Hidrogênio , L-Lactato Desidrogenase/análise , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Eur. j. anat ; 24(4): 257-261, jul. 2020.
Artigo em Inglês | IBECS | ID: ibc-193956

RESUMO

The electromagnetic radiation from the mobile phone is a subject of recent study because of the enormous increase in mobile phone use through-out the world. The objective of this experiment was therefore to investigate the biochemical and histopathological effects of mobile phone radiation on male Swiss albino mice’s liver. Male mice were categorized into three groups in this research: control group (A), exposed group for 40 minutes (B) and exposed group for 60 minutes (C). Experimental groups were exposed to radiation per day for 60 days from 4G connected mobile phones. The control group received no radiation. At the end of the radiation exposure, biochemical (alanine transaminase (ALT) and aspartate transaminase (AST)) and histological tests were performed. The results indicated that there was significant (P < 0.05) increase in mean values of ALT and AST in both radiation-exposed groups of mice if com-pared to the control group. Histopathologically marked infiltration of mononuclear cellular aggregates were present surrounding the bile duct and hepatic artery in the liver of 60-minute-exposure group, whereas in 40-minute-exposure group con-gestion was observed in the portal vein and the central vein of the liver. The findings revealed and evidenced that mobile phone radiation has harmful effects on enzyme activity and liver tis


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Assuntos
Animais , Masculino , Camundongos , Fígado/efeitos da radiação , Fígado/patologia , Telefone Celular , Radiação Eletromagnética , Exposição à Radiação/efeitos adversos , Alanina Transaminase/efeitos da radiação , Modelos Animais , Alanina Transaminase/análise , Aspartato Aminotransferases/efeitos da radiação
4.
Int. j. morphol ; 38(3): 558-564, June 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1098287

RESUMO

Chronic hepatotoxicity is a debilitating and frequently life-threatening disease resulting in progressive liver failure. The toxic chemical, thioacetamide (TAA) is used to evaluate hepatoprotective agents, and the polyphenolic compound, resveratrol was proposed as a novel treatment for diseases with hyperactivation of the mammalian target of rapamycin (mTOR) cell signaling pathway. This analysis sought to investigate the potential protective effect of resveratrol against liver injury induced by TAA via the inhibition of hepatic mTOR. Model group rats received several injections of TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed at week 10 and the protective group was pretreated with resveratrol (20 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment. Harvested liver tissues were examined using light microscopy and liver homogenates were assayed for biomarkers of inflammation and assessed the levels of mTOR protein in all animal groups. In addition, blood samples were assayed for biomarkers of liver injury enzyme. TAA substantially damaged the hepatic tissue of the model group such as infiltration of inflammatory cells, vacuolated cytoplasm, dark pyknotic nuclei, and dilated congested blood vessel that were effectively protected by resveratrol. Resveratrol also significantly (p<0.05) inhibited TAA-induced mTOR, high sensitivity c-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in harvested liver homogenates and blood samples. Thus, we conclude that resveratrol effectively protects against TAA-induced hepatotoxicity in rats, possibly due to the inhibition of mTOR and inflammation.


La hepatotoxicidad crónica es una enfermedad debilitante y potencialmente mortal que produce insuficiencia hepática progresiva. La toxicidad del químico de la tioacetamida (TAA) se utiliza para evaluar los agentes hepatoprotectores y el compuesto polifenólico, resveratrol, se propuso como un nuevo tratamiento para enfermedades con hiperactivación de la vía de señalización celular mTOR (mammalian Target of Rapamycin). Aquí buscamos investigar el posible efecto protector del resveratrol contra la lesión hepática inducida por TAA a través de la inhibición de la vía de señalización mTOR en hepatocitos. Las ratas del grupo modelo recibieron varias inyecciones de TAA (200 mg / kg; dos veces por semana durante 8 semanas) antes de ser sacrificadas en la semana 10 y el grupo protector se trató previamente con resveratrol (20 mg / kg) diariamente durante dos semanas antes de las inyecciones de TAA y continuó recibiendo ambos agentes hasta el final del experimento. Se examinaron los tejidos hepáticos recolectados usando microscopía óptica y se analizaron los homogeneizados hepáticos para detectar biomarcadores de inflamación y se evaluaron los niveles de proteína mTOR en todos los grupos de animales. Además, se analizaron muestras de sangre para detectar biomarcadores de la enzima de lesión hepática. TAA dañó sustancialmente el tejido hepático del grupo modelo, con infiltración de células inflamatorias, citoplasma vacuolado, núcleos picnóticos oscuros y vasos sanguíneos congestionados dilatados que estaban efectivamente protegidos por el resveratrol. El resveratrol también inhibió significativamente (p <0.05) mTOR, proteína C-reactiva (hs-CRP), factor de necrosis tumoral alfa (TNF-α), interleucina-6 (IL-6), alanina aminotransferasa (ALT ) y aspartato aminotransferasa (AST) en las muestras de sangre y de hígados recolectados. En conclusión, el resveratrol protege eficazmente contra la hepatotoxicidad inducida por TAA en ratas, posiblemente debido a la inhibición de mTOR y de la inflamación.


Assuntos
Animais , Masculino , Camundongos , Tioacetamida/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Resveratrol/administração & dosagem , Aspartato Aminotransferases/análise , Proteína C-Reativa/análise , Fator de Necrose Tumoral alfa/análise , Alanina Transaminase/análise , Modelos Animais de Doenças
5.
Zhonghua Gan Zang Bing Za Zhi ; 28(4): 332-337, 2020 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-32403886

RESUMO

Objective: To observe the histopathological manifestations of liver biopsy in patients with hepatic sinusoidal obstruction syndrome (HSOS) induced by pyrrolizidine alkaloid (PA). Methods: Patients diagnosed with PA-HSOS from 2012 to 2017 were selected, and the general conditions, liver function indexes, medication history, liver biopsy time, histopathological slides of liver biopsy, and follow-up data of clinical prognosis after 6 months of onset were collected. Clinical staging with clinical data was used to observe the histopathological manifestations of patients at different clinical stages. Wilcoxon rank-sum test, unpaired t-test and univariate linear regression analysis were used for data analysis. Results: A total of 16 cases were collected. Alanine transaminase and aspartate transaminase was 59.25 U/L and 25.50 U/L, 108 U/L and 45 U/L, respectively, after 6 months of onset and follow-up, and the differences were statistically significant. Moreover, total bile acids and albumin was 35 µmol/L and 36.15 µmol/L, and 32.45 g/L and 31 g/L, respectively, and the differences were not statistically significant. PA-HSOS pathological development process was divided into early, middle and late stages. In the early stage, the central lobular sinusoidal endothelium integrity was impaired and the entry of erythrocytes had interspersed thin reticular fibers and perisinusoidal space. In the middle stage (hemorrhagic zone), erythrocytes, reticular fibers and collagen fibers were lysed, densely collapsed and deposited. The cavity of the bloodstream was hyperemic and dilated, and the cavity was covered with sinus endothelial cells. The hepatic plate regenerated around the hemorrhagic zone and some of the hepatic sinuses were decompensated. In the late stage, deposited collagen in the hemorrhagic zone had formed a large fibrous scar, and most of the dilated cavity in the bloodstream was covered with vascular endothelium. The marginal zone hepatic cells were regenerated in two rows and gradually inserted into the fibrous septum. Different hepatic lobular lesions obtained from the same patients liver biopsy tissues were changed at different stages. Hepatic lobule injury proportion with severe internal bleeding in liver biopsy tissue had no relation with the prognosis of patients. Conclusion: In the early stage of PA-HSOS, erythrocytes in the central zone of lobules enter the perisinusoidal space through the damaged sinus endothelium, which is manifested as hepatic plate hemorrhagic necrosis. In the middle and late stage, liver plate regeneration and vascular remodeling occurred, so most of the patients' clinical course was self-limited. Pathological staging and liver biopsy time have an apparent correlation, but the prognosis of patients cannot be judged based on the extent of hemorrhage and injury of biopsy samples.


Assuntos
Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/patologia , Fígado/patologia , Alcaloides de Pirrolizidina/efeitos adversos , Alanina Transaminase/análise , Aspartato Aminotransferases/análise , Biópsia , Humanos
6.
Clin Chem Lab Med ; 58(7): 1095-1099, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32301746

RESUMO

Objectives The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to date, the epidemic has gradually spread to 209 countries worldwide with more than 1.5 million infected people and 100,000 deaths. Amplification of viral RNA by rRT-PCR serves as the gold standard for confirmation of infection, yet it needs a long turnaround time (3-4 h to generate results) and shows false-negative rates as large as 15%-20%. In addition, the need of certified laboratories, expensive equipment and trained personnel led many countries to limit the rRT-PCR tests only to individuals with pronounced respiratory syndrome symptoms. Thus, there is a need for alternative, less expensive and more accessible tests. Methods We analyzed the plasma levels of white blood cells (WBCs), platelets, C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), alkaline phosphatase and lactate dehydrogenase (LDH) of 207 patients who, after being admitted to the emergency room of the San Raffaele Hospital (Milan, Italy) with COVID-19 symptoms, were rRT-PCR tested. Of them, 105 tested positive, whereas 102 tested negative. Results Statistically significant differences were observed for WBC, CRP, AST, ALT and LDH. Empirical thresholds for AST and LDH allowed the identification of 70% of either COVID-19-positive or -negative patients on the basis of routine blood test results. Conclusions Combining appropriate cutoffs for certain hematological parameters could help in identifying false-positive/negative rRT-PCR tests. Blood test analysis might be used as an alternative to rRT-PCR for identifying COVID-19-positive patients in those countries which suffer from a large shortage of rRT-PCR reagents and/or specialized laboratory.


Assuntos
Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Testes Hematológicos/métodos , Pneumonia Viral/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/análise , Alanina Transaminase/sangue , Fosfatase Alcalina/análise , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/análise , Aspartato Aminotransferases/sangue , Betacoronavirus/patogenicidade , Plaquetas , Proteína C-Reativa/análise , Infecções por Coronavirus/sangue , Feminino , Humanos , Itália , L-Lactato Desidrogenase/análise , L-Lactato Desidrogenase/sangue , Laboratórios , Leucócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , RNA Viral , Reação em Cadeia da Polimerase em Tempo Real/métodos , Estudos Retrospectivos , gama-Glutamiltransferase/análise , gama-Glutamiltransferase/sangue
7.
Int. j. morphol ; 38(2): 278-288, abr. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1056435

RESUMO

This experiment was designed to study the effects of oral administration of artemether which is the most rapid-acting class of antimalarial drugs and the possible protective effect of vitamin E taken with it on the liver of albino rats. A total of twenty-four adult male albino rats were used in this study and were divided into four groups. Group one served as a control and rats in group two exposed to oral intake of artemether daily for fifteen days. The third and fourth groups treated with artemether plus low and high doses of vitamin E respectively. At the end of the experiment, the rats were sacrificed, and the livers were obtained and processed for histological, biochemical and statistical studies. Histological study of the hepatocytes of rats exposed to artemether showed nearly complete disintegration of most cellular contents except few numbers of mitochondria and rough endoplasmic reticulum. Also, the cytoplasm of these cells had few lysosomes, many vacuoles and irregular nuclei with abnormal distribution of chromatin and were shown. The hepatic sinusoids were dilated and filled with blood and vacuoles and bile ductules were abnormal in its structure. Treatment with low and high doses of vitamin E in concomitant with artemether ameliorated the hepatic histopathological lesions and its parenchyma attained nearly normal structure. As far as biochemical changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rats treated with artemether were significantly elevated as compared to the control. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were significantly increased in the liver in rats treated with artemether. However, vitamin E ameliorated the rise in ALT and AST with decreased MDA concentration and levels of SOD as compared to the corresponding artemether group values. Results of the present suggest that artemether has a harmful and stressful effect on hepatic tissue and the treatment with vitamin E may alleviate this toxicity.


Este experimento fue diseñado para estudiar los efectos de la administración oral de arteméter, la clase de medicamentos antipalúdicos de acción rápida, y el posible efecto protector de la vitamina E en el hígado de ratas albinas. Se utilizaron un total de 24 ratas albinas machos adultas y se dividieron en cuatro grupos. El grupo uno sirvió como control y las ratas en el grupo dos recibieron la dosis oral de arteméter diariamente durante 15 días. Los grupos tres y cuatro fueron tratados con arteméter, más dosis bajas y altas de vitamina E, respectivamente. Al final del experimento, se sacrificaron las ratas y se obtuvieron y procesaron los hígados para estudios histológicos, bioquímicos y estadísticos. El estudio histológico de los hepatocitos de ratas expuestas a arteméter mostró una desintegración casi completa de la mayoría de los contenidos celulares, excepto algunos mitocondrias y retículo endoplásmico rugoso. Además, el citoplasma de estas células tenía pocos lisosomas, muchas vacuolas y núcleos irregulares con distribución anormal de cromatina. Los sinusoides hepáticos estaban dilatados y llenos de sangre y vacuolas, y los conductos biliares tenían una estructura anormal. El tratamiento con dosis bajas y altas de vitamina E en forma concomitante con arteméter mejoró las lesiones histopatológicas hepáticas y su parénquima alcanzó una estructura casi normal. En cuanto a los cambios bioquímicos, la alanina aminotransferasa (ALT) y la aspartato aminotransferasa (AST) en ratas tratadas con arteméter se elevaron significativamente en comparación con el control. Los niveles de superóxido dismutasa (SOD) y malondialdehído (MDA) aumentaron significativamente en el hígado en ratas tratadas con arteméter. Sin embargo, la vitamina E mejoró el aumento de ALT y AST con una disminución de la concentración de MDA y los niveles de SOD en comparación con los valores correspondientes del grupo de arteméter. Los resultados del presente estudio sugieren que el arteméter tiene un efecto dañino y estresante sobre el tejido hepático y el tratamiento con vitamina E puede aliviar esta toxicidad.


Assuntos
Animais , Masculino , Ratos , Vitamina E/farmacologia , Artemisininas/toxicidade , Doença Hepática Crônica Induzida por Substâncias e Drogas/enzimologia , Aspartato Aminotransferases/análise , Vitamina E/administração & dosagem , Microscopia Eletrônica de Transmissão , Alanina Transaminase/análise , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Antimaláricos/toxicidade
8.
Arq. bras. med. vet. zootec. (Online) ; 72(2): 371-378, Mar./Apr. 2020. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1128217

RESUMO

The aim of this study was to evaluate the metabolic, inflammatory, and hepatic aspects, as well as the milk yield in heifers submitted to protocol for induction of lactation compared to primiparous cows. Sixty Holstein heifers were selected and enrolled into two groups: Control (n= 30), pregnant heifers and Induction heifers (n= 30), non-pregnant femeales, submitted to a lactation induction protocol. Blood samples were collected at: pre-lactation period (weeks -3, -2 and -1) and post-lactation period (weeks 1, 2 and 3), aiming to evaluate glucose, non-esterified fatty acids, paraoxonase-1, albumin, ALT, GGT and cortisol. The protocol efficiently induced lactation in all the heifers, which produced 74.54% of the total production of milk from primiparous cows. In the pre-lactation period, induced animals presented higher concentrations of non-esterified fatty acids than the Control heifers, and the opposite was observed in the post lactation period. In both moments albumin and ALT were lower in the Induction group, and paraoxonase-1 activity and GGT concentrations were higher, compared to the Control. Thus, lactation induction protocol is efficient to initiate milk production in dairy heifers with no considerable changes in energetic, metabolic and hepatic profile when compared to heifers in physiological lactation.(AU)


O objetivo deste estudo foi avaliar os perfis metabólico, inflamatório, hepático e a produção de leite de novilhas induzidas à lactação comparadas a primíparas. Sessenta novilhas da raça Holandês foram selecionadas e alocadas em grupos: controle (n=30), novilhas prenhas, e indução (n=30), novilhas vazias submetidas a um protocolo de indução de lactação. As amostras de sangue foram coletadas nas semanas -3, -2 e -1 (pré-lactação) e nas semanas 1, 2 e 3 (pós-início de lactação) para avaliação de glicose, ácidos graxos não esterificados, paraoxonase-1, albumina, ALT, GGT e cortisol. O protocolo induziu eficientemente a lactação em todas as novilhas, que produziram 74,54% da produção total de leite do controle. No período pré-lactação, o grupo indução apresentou maiores concentrações de ácidos graxos não esterificados que o controle, e o oposto foi observado pós-lactação. Em ambos os momentos, albumina e ALT foram menores no grupo indução, e a atividade da paraoxonase-1 e as concentrações de GGT foram maiores, em comparação ao controle. Assim, o protocolo de indução de lactação foi eficiente para iniciar a produção de leite em novilhas induzidas, além de terem sido observadas alterações nos perfis energético, metabólico e hepático em comparação a novilhas em lactação fisiológica.(AU)


Assuntos
Animais , Feminino , Bovinos , Lactação/fisiologia , Hidrocortisona/análise , Alanina Transaminase/análise , Albuminas/análise , Ácidos Graxos não Esterificados/análise , gama-Glutamiltransferase/análise , Leite
9.
Lancet Gastroenterol Hepatol ; 5(4): 362-373, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32027858

RESUMO

BACKGROUND: The burden of non-alcoholic fatty liver disease (NAFLD) is increasing globally, and a major priority is to identify patients with non-alcoholic steatohepatitis (NASH) who are at greater risk of progression to cirrhosis, and who will be candidates for clinical trials and emerging new pharmacotherapies. We aimed to develop a score to identify patients with NASH, elevated NAFLD activity score (NAS≥4), and advanced fibrosis (stage 2 or higher [F≥2]). METHODS: This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov, number NCT01985009. FINDINGS: Between March 20, 2014, and Jan 17, 2017, 350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0·80, 95% CI 0·76-0·85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0·74-0·95, 0·85; 95% CI 0·83-0·87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0·35 for sensitivity of 0·90 or greater and 0·67 for specificity of 0·90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0·83 (84/101) and a negative predictive value (NPV) of 0·85 (93/110). In the external validation cohorts, PPV ranged from 0·33 to 0·81 and NPV from 0·73 to 1·0. INTERPRETATION: The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease. FUNDING: Echosens and UK National Institute for Health Research.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Fibrose/patologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Adulto , Alanina Transaminase/análise , Aspartato Aminotransferases/análise , Biópsia , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Inglaterra/epidemiologia , Feminino , Fibrose/classificação , França/epidemiologia , Humanos , Fígado/metabolismo , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Turquia/epidemiologia , Estados Unidos/epidemiologia
10.
Medicine (Baltimore) ; 99(7): e18882, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049787

RESUMO

RATIONALE: Procalcitonin (PCT) is used as a biomarker for identifying the occurrence of sepsis. Previous studies have reported high levels of PCT with acetaminophen intoxication without evidence of infection. Here, we report two patients with acetaminophen intoxication with high levels of PCT without showing any symptoms of bacterial infection. PATIENT CONCERNS: This case study examined two unrelated patients with acetaminophen intoxication admitted to emergency at different times. The first patient was admitted to the emergency department after ingesting approximately 8000 mg (153.8 mg/kg) of acetaminophen. On admission, C-reactive protein (CRP), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were normal. PCT and acetaminophen levels were 31.89 ng/mL and below 0.5 µg/mL, respectively. The second patient was admitted to the emergency department 8 h after ingesting ∼23,600 mg (280.6 mg/kg) of acetaminophen. By the second day of admission, GOT and GPT increased to 2508 and 1473 IU/L, respectively. PCT was 45.66 ng/mL with acetaminophen level at 116.9 µg/mL. Both patients were clear of symptoms associated with bacterial infection. DIAGNOSIS: Acetaminophen intoxication. INTERVENTIONS: N-acetylcysteine was given intravenously to both patients for 20 h per protocol. OUTCOMES: Both patients were discharged without complications. LESSONS: Observations suggests that elevated levels of PCT in patients intoxicated with acetaminophen may be associated with involvement of other organs impacted by cytokine stimuli from sterile inflammation resulting from hepatic damage rather than PCT secretion directly caused by hepatic cell damage.


Assuntos
Acetaminofen/toxicidade , Acetilcisteína/administração & dosagem , Overdose de Drogas/tratamento farmacológico , Pró-Calcitonina/metabolismo , Acetilcisteína/uso terapêutico , Alanina Transaminase/análise , Aspartato Aminotransferases/análise , Proteína C-Reativa/análise , Overdose de Drogas/diagnóstico , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
12.
Int. j. morphol ; 38(1): 83-90, Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1056402

RESUMO

We sought to determine whether the combined polyphenolic compounds, resveratrol and quercetin can substantially protect against modulation of hepatic biomarkers of apoptosis and survival, p53-Bax axis and B-cell lymphoma 2 (Bcl-2) in an animal model of acetaminophen-induced acute liver injury via the association of oxidative stress and interleukin-11 (IL-11). The model group of rats received a single dose of acetaminophen (2 g/kg), whereas the protective group of rats was pre-treated for 7 days with combined doses of resveratrol (30 mg/kg) and quercetin (50 mg/kg) before being given a single dose of acetaminophen. All rats were then sacrificed 24 hours post acetaminophen ingestion. Acetaminophen overdose induced acute liver injury as demonstrated by profound liver parenchymal damage and increased levels of the liver injury enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Acetaminophen significantly (p<0.05) modulated malondialdehyde (MDA), p53, apoptosis regulator Bax, Bcl-2, IL-11, interleukin-6 (IL-6), ALT, AST, superoxide dismutase (SOD), and glutathione peroxidase (GPx), which were significantly protected by resveratrol plus quercetin. We further demonstrated a significant (p<0.01) correlation between IL-11 scoring and the levels of p53, Bax, Bcl-2, and MDA. Thus, resveratrol plus quercetin effectively protect against acetaminophen-induced apoptosis, which is associated with the inhibition of oxidative stress and IL-11.


En el estudio se intentó determinar si los compuestos polifenólicos combinados, el resveratrol y la quercetina pueden proteger sustancialmente contra la modulación de los biomarcadores hepáticos de apoptosis y supervivencia, el eje p53-Bax y el linfoma de células B 2 (Bcl-2) en un modelo animal de lesión hepática aguda inducida por acetaminofén, a través de la asociación del estrés oxidativo y la interleucina-11 (IL-11). El grupo modelo de ratas recibió una dosis única de acetaminofén (2 g / kg), mientras que el grupo protector de ratas fue tratado durante 7 días con dosis combinadas de resveratrol (30 mg / kg) y quercetina (50 mg / kg) antes de recibir una dosis única de acetaminofén. Todas los animales fueron sacrificados 24 horas después de la ingestión de acetaminofén. La sobredosis de acetaminofén indujo una lesión hepática aguda, como se observó en el daño profundo del parénquima hepático y el aumento de los niveles de las enzimas en la lesión hepática, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). Acetaminofén moduló significativamente (p <0.05) malondialdehído (MDA), p53, regulador de apoptosis Bax, Bcl2, IL-11, interleucina-6 (IL-6), ALT, AST, superóxido dismutasa (SOD) y glutatión peroxidasa ( GPx), los que se encontraron significativamente protegidos por el resveratrol y quercetina. Además se determinó una correlación significativa (p <0.01) entre la puntuación de IL-11 y los niveles de p53, Bax, Bcl-2 y MDA. En conclusión, el resveratrol más la quercetina protegen de manera efectiva contra la apoptosis inducida por acetaminofén, asociada con la inhibición del estrés oxidativo y la IL-11.


Assuntos
Animais , Ratos , Quercetina/administração & dosagem , Apoptose/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Resveratrol/administração & dosagem , Acetaminofen/toxicidade , Antioxidantes/administração & dosagem , Quercetina/farmacologia , Aspartato Aminotransferases/análise , Biomarcadores , Interleucina-1 , Estresse Oxidativo , Alanina Transaminase/análise , Modelos Animais de Doenças , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Resveratrol/farmacologia , Antioxidantes/farmacologia
13.
Med Sci Monit ; 26: e916459, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31958336

RESUMO

BACKGROUND Serum uric acid (SUA) and alanine aminotransferase (ALT) levels are increased in patients with metabolic syndrome. This study aimed to investigate the association between the combined levels of SUA and ALT and the risk of metabolic syndrome in residents ≥60 years of age in Northeastern China. MATERIAL AND METHODS A population study included nine communities in Shenyang, Northeast China, and 3,998 participants (1,434 men and 2,564 women) who were ≥60 years old. SUA and ALT measurements (levels 1-3) and clinical parameters were recorded. Metabolic syndrome was diagnosed according to the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). The association between the combined SUA and ALT levels and metabolic syndrome was determined by multivariate logistic regression analysis in tertiles that included Groups 1-9. RESULTS The prevalence of metabolic syndrome was 43.2% (men), and 61.9% (women), and the prevalence and odds ratio (OR) values increased with increasing SUA and ALT levels. The OR values of metabolic syndrome in the ALT Groups 2-3 were 1.329 (95% CI, 1.137-1.554) and 2.362 (95% CI, 2.006-2.781), and in the SUA Groups 2-3 the OR values were 1.718 (95% CI, 1.466-2.015) and 2.743 (95% CI, 2.310-3.256). The OR of the combined increase in SUA and ALT and metabolic syndrome in Groups 1-9 ranged from 1.494-5.889 (all, p<0.05). CONCLUSIONS Increased combined SUA and ALT was more significantly associated with metabolic syndrome than an increase in SUA or ALT alone.


Assuntos
Alanina Transaminase/análise , Síndrome Metabólica/metabolismo , Ácido Úrico/análise , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , China/epidemiologia , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Ácido Úrico/sangue
14.
Eur Heart J Acute Cardiovasc Care ; 9(2): 128-137, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30525871

RESUMO

BACKGROUND: Current guidelines recommend emergency surgical correction in patients with post infarction ventricular septal rupture (PIVSR), but patients with multiorgan failure are commonly managed conservatively because of high surgical risk. We assessed characteristics and outcomes of operated PIVSR patients with or without the use of short-term ventricular assist devices (ST-VADs). We also assessed the impact of a ST-VAD on the performance of surgery. METHODS: We retrospectively analysed all consecutive patients with PIVSR between January 2004 and May 2017. Baseline clinical characteristics, use of ST-VAD and performance of surgery during admission were assessed. The main outcome measured was in-hospital mortality. RESULTS: A total of 28 patients were included. Mean age was 69.2 years. Most patients (20/28, 71.4%) underwent surgical repair. ST-VADs were used in 11/28 patients (39.3%). This percentage progressively increased across the study period, from 22.2% (2/9) in 2004-2011 to 58.3% (7/12) in 2015-2017 (p=0.091). Patients undergoing ST-VAD use had poorer INTERMACS status, higher values of creatinine, lactate and alanine aminotransferase and lower left ventricular ejection fraction as compared with operated patients without support. In-hospital mortality did not differ according to the use of ST-VADs in operated patients (27.3% without ST-VAD vs. 22.2% with ST-VAD, p=0.604). All five patients undergoing early preoperative venoarterial extracorporeal membrane oxygenator support and delayed surgery survived at hospital discharge. CONCLUSIONS: ST-VAD use increased in patients with PIVSR. Despite a higher risk profile in operated patients undergoing ST-VAD use, mortality was not significantly different in these patients. Early preoperative venoarterial extracorporeal membrane oxygenation should be considered for very high risk PIVSR patients.


Assuntos
Coração Auxiliar/efeitos adversos , Infarto do Miocárdio/complicações , Assistência Perioperatória/métodos , Choque Cardiogênico/etiologia , Ruptura do Septo Ventricular/complicações , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/análise , Estudos de Casos e Controles , Creatinina/sangue , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Mortalidade Hospitalar/tendências , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/complicações , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Fatores de Risco , Volume Sistólico/fisiologia , Resultado do Tratamento , Função Ventricular Esquerda/fisiologia , Ruptura do Septo Ventricular/cirurgia
15.
Intern Emerg Med ; 15(2): 337-339, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31734856

RESUMO

BACKGROUND: Liver dysfunction has been widely reported in connection with anorexia nervosa (AN) but the pathogenesis of these alterations has never been fully understood despite reported theories about the presence of insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). The aim of this study is to investigate if hypertransaminasemia in AN is linked to IR and NAFLD. METHODS: Anthropometric data and laboratory exams of 34 patients and 34 controls were analyzed, including alanine-aminotransferase, aspartate-aminotransferase and homeostatic model assessment of insulin resistance (HOMA-IR) index. All subjects also underwent magnetic resonance imaging (MRI), ultrasonography (US), and transient elastography (TE). RESULTS: Evidence of increased alanine aminotransferase in AN patients was confirmed in our sample together with a lower HOMA-IR index compared to controls. Positive results in US appeared in 16 patients vs none in controls (p = 0.0007); patients with liver parenchyma abnormalities in US were not different than normal-US patients in any of the studied variables. Only one patient showed non-alcoholic fatty liver disease in MRI while abnormal TE was found in four patients and never in controls. CONCLUSIONS: Liver damage suggested by increased serum liver enzymes cannot be due to liver steatosis but potentially to a different liver disease (not identified by MRI) or to an early liver fibrosis not associated with an insulin-resistant status.


Assuntos
Anorexia Nervosa/complicações , Fígado Gorduroso/etiologia , Fígado/anormalidades , Alanina Transaminase/análise , Alanina Transaminase/sangue , Anorexia Nervosa/fisiopatologia , Antropometria/métodos , Fígado Gorduroso/sangue , Humanos , Resistência à Insulina/fisiologia , Fígado/fisiopatologia , Ultrassonografia/métodos
16.
BMC Res Notes ; 12(1): 802, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831048

RESUMO

OBJECTIVE: The association between unbalanced iron indices and the conditions of schizophrenia are not well understood. Liver dysfunction which has been linked to iron metabolism might be a contributing factor. This case-control study evaluated serum iron indices and liver function in treatment-naïve schizophrenia patients and those already on treatment at the Psychiatric Department of the Komfo Anokye Teaching Hospital (KATH), Kumasi-Ghana. RESULTS: The mean age of the respondents was 39.6 ± 0.8 years. Increased levels of serum iron, TS, AST, ALT and AST:ALT ratio and lower levels of UIBC, TIBC, Transferrin, and log Ferritin:AST ratio levels were observed among the treatment-naïve group compared to the control. The treatment-naïve and treatment groups showed significantly higher serum AST:ALT ratio, and lower log10ferrtin:AST ratio than the healthy controls. There was a significant correlation between log10ferritin and AST, and log10ferritin and GGT in both treatments (r = 0.343; p = 0.003, and r = 0.502; p = 0.001 respectively) and treatment-naïve groups (r = 0.348; p = 0.002, and r = 0.614; p < 0.001 respectively). Percentage transferrin saturation correlated significantly with GGT only, in the treatment-naïve group (r = 0.667; p < 0.001), and ALT and GGT in the treatment group (r = 0.252; p = 0.030 and r = 0.646; p = 0.014 respectively).


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Ferritinas/sangue , Sobrecarga de Ferro/sangue , Ferro/sangue , Esquizofrenia/complicações , Adulto , Alanina Transaminase/análise , Aspartato Aminotransferases/análise , Estudos de Casos e Controles , Feminino , Ferritinas/análise , Gana , Humanos , Sobrecarga de Ferro/complicações , Fígado/metabolismo , Testes de Função Hepática , Masculino , Esquizofrenia/sangue , Transferrina/química , Transferrina/metabolismo
17.
Genet Test Mol Biomarkers ; 23(12): 865-870, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31821094

RESUMO

Background: The association between liver enzymes and the future development of atrial fibrillation (AF) from observational studies is unclear. We, therefore, performed a meta-analysis to systematically evaluate the relationship between liver enzymes and AF risk. Methods: We searched the PubMed and Embase databases for observational cohort studies assessing the association between liver enzymes and AF risk. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Results: Five prospective studies with 282,615 participants and 7062 AF events were included. The pooled fully adjusted RRs (95% CIs) for AF were 1.10 (1.06-1.14) per 1-standard deviation change in log baseline level of gamma glutamyltransferase (GGT). No positive association was found between alanine aminotransferase (ALT, RR 1.04, 95% CI 0.90-1.20, p = 0.607) or aspartate aminotransferase (AST, RR 1.05, 95% CI 0.96-1.15, p = 0.268) and the risk of AF. Conclusions: The baseline GGT level is positively associated with the AF risk in a log-linear manner. We found no significant association between ALT or AST and the risk of AF. However, further well-designed prospective studies are needed to confirm these findings and elucidate the pathophysiological mechanisms.


Assuntos
Fibrilação Atrial/etiologia , Fígado/enzimologia , Medição de Risco/métodos , gama-Glutamiltransferase/análise , Alanina Transaminase/análise , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/análise , Aspartato Aminotransferases/metabolismo , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , gama-Glutamiltransferase/metabolismo
18.
Acta Cir Bras ; 34(10): e201901003, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851211

RESUMO

PURPOSE: To evaluate that Connexin (Cx43) plays a role in lesions after hepatic ischemia/reperfusion (IR) injury. METHODS: We use Cx43 deficient model (heterozygotes mice) and compared to a wild group. The groups underwent 1 hour ischemia and 24 hours reperfusion. The heterozygote genotype was confirmed by PCR. We analyzed the hepatic enzymes (AST, ALT, GGT) and histology. RESULTS: The mice with Cx43 deficiency showed an ALT mean value of 4166 vs. 307 in the control group (p<0.001); AST mean value of 7231 vs. 471 in the control group (p<0.001); GGT mean value of 9.4 vs. 1.7 in the control group (p=0.001); histology showed necrosis and inflammation in the knockout group. CONCLUSIONS: This research demonstrated that the deficiency of Cx43 worses the prognosis for liver injury. The topic is a promising target for therapeutics advancements in liver diseases and procedures.


Assuntos
Conexina 43/deficiência , Modelos Animais de Doenças , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/metabolismo , Alanina Transaminase/análise , Animais , Aspartato Aminotransferases/análise , Conexina 43/análise , Técnicas de Genotipagem , Fígado/patologia , Camundongos Knockout , Necrose , Reação em Cadeia da Polimerase , Valores de Referência , Traumatismo por Reperfusão/patologia , Fatores de Tempo , gama-Glutamiltransferase/análise
19.
J Emerg Med ; 57(6): e181-e183, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31767218

RESUMO

BACKGROUND: Haff disease is a rare syndrome of rhabdomyolysis thought to be caused by a heat-stable toxin associated with the consumption of seafood from fresh or brackish water. CASE REPORT: We present the case of a patient with Haff disease who presented to the emergency department with nausea/vomiting, diarrhea, and myalgias after a seafood buffet. Initially, he was treated with i.v. fluids and antiemetics for presumed gastroenteritis, but his symptoms did not improve. He was found to have elevated aspartate aminotransferase and alanine aminotransferase, normal point-of-care ultrasound, urinalysis with large blood and no red blood cells, and an elevated creatine phosphokinase (CPK). He was admitted to the hospital to receive ongoing fluid resuscitation for rhabdomyolysis presumed to be from fish. Liver enzymes and CPK downtrended, and patient was discharged on hospital day 3. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Undiagnosed Haff disease has important clinical implications, including multi-organ failure and death. Always maintain a high level of suspicion for Haff disease in patients with symptoms suggestive of gastroenteritis, but complicated by minor liver function test elevations and dipstick positivity for heme, without significant numbers of red blood cells per high-power field, in the setting of recent seafood ingestion.


Assuntos
Enzimas/análise , Fígado/enzimologia , Rabdomiólise/sangue , Adulto , Alanina Transaminase/análise , Alanina Transaminase/sangue , Aspartato Aminotransferases/análise , Aspartato Aminotransferases/sangue , Creatina Quinase/análise , Creatina Quinase/sangue , Diarreia/etiologia , Serviço Hospitalar de Emergência/organização & administração , Enzimas/sangue , Humanos , Fígado/fisiopatologia , Masculino , Rabdomiólise/complicações , Rabdomiólise/fisiopatologia , Águas Salinas/efeitos adversos , Alimentos Marinhos/efeitos adversos , Vômito/etiologia
20.
Exp Parasitol ; 207: 107772, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610183

RESUMO

Cyclosporiasis is an emerging worldwide infection caused by an obligate intracellular protozoan parasite, Cyclospora cayetanensis. In immunocompetent patients, it is mainly manifested by self-limited diarrhea, which is persistent and may be fatal in immunocompromised patients. The standard treatment for cyclosporiasis is a combination of two antibiotics, trimethoprim and sulfamethoxazole. Gastrointestinal, haematologic and renal side effects were reported with this combination. Moreover, sulfa allergy, foetal anomalies and recurrence were recorded with no alternative drug treatment option. In this study, silver nanoparticles were chemically synthesized to be evaluated for the first time for their anti-cyclospora effects in both immunocompetent and immunosuppressed experimental mice in comparison to the standard treatment. The effect of silver nanoparticles was assessed through studying stool oocyst load, oocyst viability, ultrastructural changes in oocysts, and estimation of serum gamma interferon. Toxic effect of the therapeutic agents was evaluated by measuring liver enzymes, urea and creatinine in mouse sera. Results showed that silver nanoparticles had promising anti-cyclospora potentials. The animals that received these nanoparticles showed a statistically significant decrease in the oocyst burden and number of viable oocysts in stool and a statistically significant increase in serum gamma interferon in comparison to the corresponding group receiving the standard treatment and to the infected non-treated control group. Scanning electron microscopic examination revealed mutilated oocysts with irregularities, poring and perforations. Biochemical results showed no evidence of toxicity of silver nanoparticles, as the sera of the mice showed a statistically non-significant decrease in liver enzymes in immunocompetent subgroups, and a statistically significant decrease in immunosuppressed subgroups. Furthermore, a statistically non-significant decrease in urea and creatinine was recorded in all subgroups. Thus, silver nanoparticles proved their effectiveness against Cyclospora infection, and this will draw the attention to its use as an alternative to the standard therapy.


Assuntos
Coccidiostáticos/uso terapêutico , Cyclospora/efeitos dos fármacos , Ciclosporíase/tratamento farmacológico , Nanopartículas Metálicas/uso terapêutico , Alanina Transaminase/análise , Animais , Aspartato Aminotransferases/análise , Coccidiostáticos/farmacologia , Coccidiostáticos/toxicidade , Creatinina/sangue , Ciclofosfamida/imunologia , Cyclospora/isolamento & purificação , Cyclospora/ultraestrutura , Diarreia/tratamento farmacológico , Diarreia/parasitologia , Fezes/parasitologia , Humanos , Imunocompetência , Hospedeiro Imunocomprometido , Imunossupressores/imunologia , Interferon gama/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Nanopartículas Metálicas/toxicidade , Camundongos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Oocistos/isolamento & purificação , Oocistos/ultraestrutura , Prata , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Ureia/sangue
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