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1.
Clin Nutr ; 38(4): 1899-1904, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30007480

RESUMO

BACKGROUND & AIMS: Resting energy expenditure (REE) and respiratory quotient (RQ) as measured by indirect calorimetry (IC) may correlate with muscle mass and represent prognostic indicators in treating patients with liver cirrhosis. We aimed to assess the correlation of IC-measured REE and RQ with skeletal muscle mass (SM), mortality, and REE values as estimated by Harris-Benedict, European guidelines (EG), and Brazilian guidelines-DITEN (BG) equations in patients with liver cirrhosis. METHODS: In this prospectively designed study, REE was measured in 126 male patients with liver cirrhosis by IC and predicted by Harris-Benedict, EG (35 kcal/kg current weight), and BG (30 kcal/kg current weight) guidelines. Measurements were obtained at the time of admission to the study. Body composition was determined by whole-body dual-energy X-ray absorptiometry. The association between REE and 3-year survival was investigated. RESULTS: Cirrhosis etiology was classified as alcohol related (59.0%), viral (20.1%), cryptogenic (11.8%), or other (9.0%). Mean Child-Pugh and MELD indexes were 8.30 ± 2.0 and 14.38 ± 6.12, respectively. RQ showed a moderate correlation with SM (r = 0.64), while IC-measured REE was inversely associated with mortality (multivariate Cox Regression, HR = 0.88, 95% CI: 0.78; 1, p = 0.04). Among the predictive equations for REE, only Harris-Benedict yielded values close to the IC, with a positive Pearson correlation (r = 0.77), excellent accuracy (Cb = 0.98), and positive Lin's concordance correlation (CCC = 0.75). However, a large standard deviation was observed; HB-measured REE did not correlate with mortality. CONCLUSIONS: RQ and REE, as measured by IC, may be valuable tools for evaluating the severity of cirrhosis, by reflecting SM and predicting mortality, respectively. The predictive equations for REE included in this study cannot replace IC for this purpose. REGISTERED AT: www.clinicalTrials.gov (NCT02421848).


Assuntos
Metabolismo Energético/fisiologia , Cirrose Hepática , Adulto , Composição Corporal/fisiologia , Calorimetria Indireta , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
2.
Transplant Proc ; 50(10): 3650-3655, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30586839

RESUMO

BACKGROUND: Cardiovascular disease is a major contributing factor to long-term mortality after liver transplantation (LT). METHODS: This study evaluated the evolution of atherogenic risk in liver transplant recipients (LTRs). Thirty-six subjects were prospectively enrolled at 12 months and followed for 48 months after liver transplantation. Serum biomarkers of endothelial dysfunction (sICAM-1 and sVCAM-1), chronic inflammation (serum amyloid A), and oxidative stress (myeloperoxidase) were measured at 12 and 48 months after LT. Additionally, at 12 months all patients underwent a cardiac computed tomography (CT) scan and a coronary artery calcium score (CACS). RESULTS: The prevalence of risk factors of metabolic syndrome (MS) increased over the course of the study. The patients' sVCAM-1 and sICAM-1 increased from 1.82 ± 0.44 ng/mL to 9.10 ± 5.82 ng/mL (P < .001) and 0.23 ± 0.09 ng/mL to 2.7 ± 3.3 ng/mL, respectively from month 12 to 48. Serum myeloperoxidase increased from 0.09 ± 0.07 ng/mL to 3.46 ± 3.92 ng/mL (P < .001) over the course of the study. Serum amyloid A also increased from 21.4 ± 40.7 ng/mL at entry to 91.5 ± 143.6 ng/mL at end of study (P < .001). CONCLUSION: No association between these biomarkers and MS was noted. The cardiac CT revealed mild and moderate disease in 19% and 25% of the cohort, respectively. No association between serum biomarkers and CACS was noted. Serum biomarkers of atherogenic risk increase rapidly in LTRs and precede coronary plaques.


Assuntos
Aterosclerose/etiologia , Doenças Cardiovasculares/etiologia , Transplante de Fígado/efeitos adversos , Síndrome Metabólica/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Aterosclerose/epidemiologia , Biomarcadores/sangue , Cálcio/análise , Doenças Cardiovasculares/epidemiologia , Feminino , Seguimentos , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Peroxidase/sangue , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Prevalência , Estudos Prospectivos , Fatores de Risco , Proteína Amiloide A Sérica/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangue
3.
Transplant Proc ; 50(3): 754-757, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29661430

RESUMO

BACKGROUND: In the Model for End-Stage Liver Disease (MELD) system, patients with "MELD exceptions" points may have unfair privilege in the competition for liver grafts. Furthermore, organ distribution following identical ABO blood types may also result in unjust organ allocation. The aim of this study was to investigate access to liver transplantation in a tertiary Brazilian center, regarding "MELD exceptions" situations and among ABO-blood groups. METHODS: A total of 465 adult patients on the liver waitlist from August 2015 to August 2016 were followed up until August 2017. Patients were divided into groups according to ABO-blood type and presence of "exceptions points." RESULTS: No differences in outcomes were observed among ABO-blood groups. However, patients from B and AB blood types spent less time on the list than patients from A and O groups (median, 46, 176, 415, and 401 days, respectively; P = .03). "Exceptions points" were granted for 141 patients (30.1%), hepatocellular carcinoma being the most common reason (52.4%). Patients with "exceptions points" showed higher transplantation rate, lower mortality on the list, and lower delta-MELD than non-exceptions patients (56.7% vs 19.1% [P < .01]; 18.4% vs 38.5% [P < .01], and 2.0 ± 2.6 vs 6.9 ± 7.0 [P < .01], respectively). Patients with refractory ascites had a higher mortality rate than those with other "exceptions" or without (48%). CONCLUSIONS: The MELD system provides equal access to liver transplantation among ABO-blood types, despite shorter time on the waitlist for AB and B groups. The current MELD exception system provides advantages for candidates with "exception points," resulting in superior outcomes compared with those without exceptions.


Assuntos
Sistema ABO de Grupos Sanguíneos , Doença Hepática Terminal , Acessibilidade aos Serviços de Saúde/organização & administração , Transplante de Fígado , Seleção de Pacientes , Índice de Gravidade de Doença , Obtenção de Tecidos e Órgãos/organização & administração , Adulto , Idoso , Brasil , Doença Hepática Terminal/imunologia , Doença Hepática Terminal/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obtenção de Tecidos e Órgãos/métodos , Listas de Espera
4.
Transplant Proc ; 50(3): 758-761, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29661431

RESUMO

BACKGROUND: The Model for End-Stage Liver Disease (MELD) system reliably predicts mortality in cirrhotic patients. However, the etiology of liver disease and presence of portal vein thrombosis are not directly taken into account in MELD score. Its impact on the outcomes of patients on the waiting list is still unclear. The aim of this study was to investigate mortality and access to transplantation regarding etiology of liver disease and portal vein thrombosis (PVT). METHODS: A total of 465 adult patients on the liver waiting list from August 2015 to August 2016 were followed up until August 2017. Patients were divided into groups according to the etiology of liver disease and presence of PVT. RESULTS: The most frequent etiologies were hepatitis C (26.88%), alcoholic cirrhosis (26.02%) and cryptogenic cirrhosis (10.75%). Death while on the waiting list occurred in 168 patients (36.1%) and was more frequent in nonalcoholic steatohepatitis (NASH, 65.4%) and alcoholic cirrhosis (41.3%). A total of 142 (30.5%) patients underwent transplantation and viral, autoimmune, and biliary diseases showed higher proportion of transplantation (36.3%, 53.8%, and 34%, respectively; P < .01). Mean delta-MELD at the study endpoint was higher in patients with autoimmune hepatitis, biliary diseases, and NASH (8.3 ± 7.2, 8.3 ± 9.1, and 7.5 ± 9.1, respectively; P < .01). A total 77 patients (16.7%) presented PVT. There was no significant difference in outcomes between patients with and without PVT. CONCLUSIONS: Patients with NASH and alcoholic liver disease had higher mortality while on the waiting list, whereas patients with viral and autoimmune hepatitis had higher transplantation rate. Outcomes were not influenced by PVT.


Assuntos
Doença Hepática Terminal/mortalidade , Transplante de Fígado , Veia Porta , Índice de Gravidade de Doença , Trombose Venosa/mortalidade , Listas de Espera/mortalidade , Adulto , Brasil , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/cirurgia , Feminino , Hepatite C/complicações , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/congênito , Cirrose Hepática Alcoólica/complicações , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Trombose Venosa/etiologia
5.
Transplant Proc ; 50(3): 841-847, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29661450

RESUMO

BACKGROUND: The liver may be injured in situations where it is submitted to ischemia, such as partial hepatectomy and liver transplantation. In all cases, ischemia is followed by reperfusion and, although it is essential for the reestablishment of tissue function, reperfusion may cause greater damage than ischemia, an injury characterized as ischemia-reperfusion (I/R) damage. The aim of this work was to analyze the effect of ischemic preconditioning with the use of methylene blue (MB; 15 mg/kg) 5 or 15 minutes before I/R (IRMB5' and IRMB15', respectively) on the hepatic injury occurring after I/R. METHODS: Twenty-eight male Wistar rats were used, and liver samples submitted to partial ischemia (IR) or not (NI) were obtained from the same animal. The samples were divided into 7 groups. Data were analyzed statistically by means of the nonparametric Mann-Whitney test and Wilcoxon Matched test, with the level of significance set at 5% (P < .05). RESULTS: The rate of oxygen consumption by state 3 mitochondria was inhibited in all ischemic groups compared with the sham group (SH vs IR: P = .0052; SH vs IRMB5': P = .0006; SH vs IRMB15': P = .0048), which did not occur in the nonischemic contralateral portion of the same liver (SH vs NI: P = .7652; SH vs NIMB5': P = .059; SH vs NIMB15': P = .3153). The inhibition of the rate of oxygen consumption by state 3 mitochondria was maintained in the presence of MB (IR vs IRMB5': P = .4563; IR vs IRMB15': P = .9021). The respiratory control ratio was reduced in all ischemic groups compared with the sham group, owing to the inhibition of oxygen consumption in state 3 (SH vs IR: P = .0151; SH vs IRMB5': P = .005; SH vs IRMB15': P = .0007). CONCLUSIONS: Methylene blue had no effect on the mitochondrial respiratory parameters studied, but was able to reduce lipid peroxidation, preventing the production of reactive oxygen species (SH vs IRMB15': P = .0210).


Assuntos
Inibidores Enzimáticos/administração & dosagem , Precondicionamento Isquêmico/métodos , Fígado/irrigação sanguínea , Azul de Metileno/administração & dosagem , Traumatismo por Reperfusão/prevenção & controle , Animais , Isquemia/etiologia , Isquemia/fisiopatologia , Fígado/lesões , Fígado/cirurgia , Masculino , Mitocôndrias/fisiologia , Consumo de Oxigênio , Ratos , Ratos Wistar , Traumatismo por Reperfusão/etiologia
6.
Nutr Diabetes ; 7(3): e257, 2017 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-28319104

RESUMO

DM type 1 (T1D) incidence is increasing around 3% every year and represents risks for maternal and fetal health. The objective of this study was to explore the effects of diabetes on fetus liver cells in non-obese diabetic (NOD) mice. Hyperglycemic NOD (HNOD), normoglycemic NOD (NNOD) and BALB/c females were used for mating, and the fetus livers were collected at 19.5 gestation day (gd). HNOD group had reduced fetal weight (989.5±68.32 vs 1290±57.39 mg BALB/c, P<0.05) at 19.5 gd and higher glycemia (516.66±28.86 mg dl-1, P<0.001) at both 0.5 gd and 19.5 gd compared to other groups. The protein expression of albumin (ALB) was significantly reduced in HNOD group (0.9±0.2 vs 3.36±0.36 NNOD P<0.01, vs 14.1±0.49 BALB/c P<0.001). Reduced gene expression of ALB (1.34±0.12 vs 5.53±0.89 NNOD and 5.23±0.71 BALB/c, P<0.05), Hepatic Nuclear Factor-4 alpha (HNF-4α) (0.69±0.1 vs 3.66±0.36 NNOD, P<0.05) and miR-122 (0.27±0,10 vs 0.88±0.15 NNOD, P<0.05) was present in HNOD group. No difference for alpha-Fetoprotein (AFP) and gene expression was observed. In conclusion, our findings show the impacts of T1D on the expression of ALB, AFP, HNF-4α and miR-122 in fetus liver cells by using NNOD and HNOD mice.


Assuntos
Albuminas/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Albuminas/genética , Animais , Diabetes Mellitus Tipo 1/genética , Feminino , Feto , Expressão Gênica , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Masculino , Camundongos Endogâmicos NOD , MicroRNAs/genética , MicroRNAs/metabolismo
7.
Transplant Proc ; 49(2): 330-337, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28219594

RESUMO

OBJECTIVE: To measure the association between readmission after liver transplantation and corresponding adverse drug reactions. METHODS: A total of 48 patients undergoing liver transplantation were prospectively followed for 1 year. Of these, 23 were readmitted and evaluated by a pharmacist for causes of adverse drug reaction. The detection of adverse drug reactions was based on a combination of clinical interviews and physical and laboratory exams. Adverse reactions were defined in accordance with the Naranjo algorithm. RESULTS: A total of 67.6% of all readmissions were related to adverse drug reactions, with tacrolimus accounting for 80% of the drug reactions. The most common cause of readmission was infection (48.6%), followed by procedure-related reasons (29.7%). Of all patients requiring admission, 39.1% had Model for End-stage Liver Disease (MELD) scores below 21 at the time of transplantation, 17.4% had MELD scores between 21 and 29, and 43.5% had MELD scores above 29. Most (66.7%) of those readmitted more than twice had MELD scores above 29. CONCLUSION: Adverse drug reactions related to immunosuppressants frequently lead to readmission among liver transplant patients, and in our series tacrolimus was the most frequently associated drug.


Assuntos
Imunossupressores/efeitos adversos , Transplante de Fígado/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Doença Hepática Terminal/cirurgia , Feminino , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
8.
Nutr. Diabetes ; 7: e257, 2017.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib15387

RESUMO

DM type 1 (T1D) incidence is increasing around 3% every year and represents risks for maternal and fetal health. The objective of this study was to explore the effects of diabetes on fetus liver cells in non-obese diabetic (NOD) mice. Hyperglycemic NOD (HNOD), normoglycemic NOD (NNOD) and BALB/c females were used for mating, and the fetus livers were collected at 19.5 gestation day (gd). HNOD group had reduced fetal weight (989.5 +/- 68.32 vs 1290 +/- 57.39 mg BALB/c, P < 0.05) at 19.5 gd and higher glycemia (516.66 +/- 28.86 mg dl(-1), P < 0.001) at both 0.5 gd and 19.5 gd compared to other groups. The protein expression of albumin (ALB) was significantly reduced in HNOD group (0.9 +/- 0.2 vs 3.36 +/- 0.36 NNOD P < 0.01, vs 14.1 +/- 0.49 BALB/c P < 0.001). Reduced gene expression of ALB (1.34 +/- 0.12 vs 5.53 +/- 0.89 NNOD and 5.23 +/- 0.71 BALB/c, P < 0.05), Hepatic Nuclear Factor-4 alpha (HNF-4a) (0.69 +/- 0.1 vs 3.66 +/- 0.36 NNOD, P < 0.05) and miR-122 (0.27 +/- 0,10 vs 0.88 +/- 0.15 NNOD, P < 0.05) was present in HNOD group. No difference for alpha-Fetoprotein (AFP) and gene expression was observed. In conclusion, our findings show the impacts of T1D on the expression of ALB, AFP, HNF-4a and miR-122 in fetus liver cells by using NNOD and HNOD mice.

9.
Transplant Proc ; 48(2): 450-2, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27109976

RESUMO

BACKGROUND: The number of deceased organ donors has decreased slightly over the past 4 years. Although the pool of intestinal transplantation candidates is relatively small, donor allocation is challenging because of the inability to maintain the donor in a good condition and the complexities involved in making a suitable weight match between donors and recipients. Our goal was to analyze the epidemiologic profile of potential donors based on the organs offered by the regional Organ Procurement Organization from Hospital das Clinicas-USP (OPO/HC-USP) and attempt to estimate possible matches and program viability. METHODS: We retrospectively analyzed information from the OPO/HC-USP database regarding organs offered over the past 7 years as well as patients listed in our program. Data were collected regarding donor characteristics (eg, sex, age, race, body mass index, blood type, cause of death) and medical care details (eg, intensive care unit stay, use of vasopressor agents and antibiotics). RESULTS: In this time period, there were 18,103 brain death notifications in the state of São Paulo; 5,202 (35%) became viable donors, resulting in 5,201 (99%) effectively used livers and kidneys. Most potential donors were male, in their 40s, white, and had blood type O. Only 3 potential donors from OPO/HC-USP would have reached the established minimum criteria for intestinal donation over these 7 years.


Assuntos
Morte Encefálica , Intestinos/transplante , Doadores de Tecidos/provisão & distribuição , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Feminino , Hospitais , Humanos , Lactente , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral/estatística & dados numéricos , Estudos Retrospectivos , Adulto Jovem
10.
Transplant Proc ; 48(2): 497-8, 2016 03.
Artigo em Inglês | MEDLINE | ID: mdl-27109986

RESUMO

Anorectal dysfunction resulting in fecal incontinence or permanent colostomy is a current public health concern that strongly impairs patient quality of life. Present treatment options for this complex disease are expensive and usually ineffective. Anorectal transplantation is the logical treatment for fecal incontinence and permanent colostomy. This procedure has been clinically effective in a few cases reported in the medical literature. Furthermore, experiments in rats, pigs, and dogs have shown promising results, with functional recovery of the graft. In this article we describe the scientific evidence that anorectal transplantation may be an important option for treating anorectal dysfunction.


Assuntos
Colostomia , Incontinência Fecal/cirurgia , Reto/transplante , Animais , Cães , Humanos , Qualidade de Vida , Ratos , Recuperação de Função Fisiológica , Suínos
11.
Transpl Infect Dis ; 18(1): 137-40, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26671230

RESUMO

Leptospirosis has been rarely reported in solid organ transplant recipients. We report the first case to our knowledge of leptospirosis in a liver transplant recipient who developed jaundice and renal insufficiency. We describe his favorable clinical progression and discuss the possible mechanisms involved in the more benign disease course. We also review the previously published cases of leptospirosis in solid organ transplant recipients. Although this disease does not appear to present any particularities in this context, we highlight the importance of clinical suspicion in this setting, particularly after liver transplantation.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Antibacterianos/uso terapêutico , Leptospira/isolamento & purificação , Leptospirose/diagnóstico , Transplante de Fígado/efeitos adversos , Humanos , Icterícia/microbiologia , Leptospirose/microbiologia , Masculino , Pessoa de Meia-Idade
12.
Braz. j. med. biol. res ; 48(5): 408-414, 05/2015. graf
Artigo em Inglês | LILACS | ID: lil-744374

RESUMO

Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg-1·day-1 by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.


Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Transtorno Depressivo Maior/terapia , Custos de Cuidados de Saúde/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Diagnóstico Duplo (Psiquiatria) , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/economia , Inquéritos Epidemiológicos , Acessibilidade aos Serviços de Saúde/economia , Serviços de Saúde Mental/economia , Serviços de Saúde Mental/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/economia , Estados Unidos
13.
Braz J Med Biol Res ; 48(5): 408-14, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25714891

RESUMO

Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg(-1)·day(-1) by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.


Assuntos
Cirrose Hepática/tratamento farmacológico , Mitocôndrias Hepáticas/efeitos dos fármacos , Niacinamida/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/complicações , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Chaperonina 60/análise , Chaperonina 60/genética , Dieta Hiperlipídica/métodos , Dietilnitrosamina , Modelos Animais de Doenças , Colágenos Fibrilares/efeitos dos fármacos , Glutationa Transferase/análise , Glutationa Transferase/genética , Proteínas de Choque Térmico HSP90/análise , Proteínas de Choque Térmico HSP90/genética , Interleucina-10/análise , Interleucina-10/genética , Interleucina-6/análise , Interleucina-6/genética , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/genética , Mitocôndrias Hepáticas/metabolismo , Niacinamida/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Polarografia , RNA Mensageiro/isolamento & purificação , Ratos Sprague-Dawley , Sorafenibe , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-2/análise , Inibidor Tecidual de Metaloproteinase-2/genética , Fatores de Transcrição/análise , Fatores de Transcrição/genética
14.
Br J Surg ; 102(5): 558-62, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25692968

RESUMO

BACKGROUND: Although anorectal transplantation is a challenging procedure, it is a promising option for patients who have completely lost anorectal function or in whom it failed to develop, as in congenital malformations. The paucity of animal models with which to test functional outcomes was addressed in this study of anorectal manometry in rats. METHODS: Wistar rats were assigned randomly to four groups: orthotopic anorectal transplantation, heterotopic transplantation, sham operation, or normal control. Bodyweight and anal pressure were measured immediately before and after operation, and on postoperative days 7 and 14. ANOVA and Tukey's test were used to compare results for bodyweight, anal manometry and length of procedure. RESULTS: Immediately after the procedure, mean(s.d.) anal pressure in the orthotopic group (n = 13) dropped from 31·4(13·1) to 1·6(13·1) cmH2 O (P < 0·001 versus both sham operation (n = 13) and normal control (n = 15)), with partial recovery on postoperative day 7 (14·9(13·9) cmH2 O) (P = 0·009 versus normal control) and complete recovery on day 14 (23·7(12·2) cmH2 O). Heterotopic rats (n = 14) demonstrated partial functional recovery: mean(s.d.) anal pressure was 26·9(10·9) cmH2 O before operation and 8·6(6·8) cmH2 O on postoperative day 14 (P < 0·001 versus both sham and normal control). CONCLUSION: Orthotopic anorectal transplantation may result in better functional outcomes than heterotopic procedures. Surgical relevance Patients with a permanent colostomy have limited continence. Treatment options are available, but anorectal transplantation may offer hope. Some experimental studies have been conducted, but available data are currently insufficient to translate into a clinical option. This paper details functional outcomes in a rat model of anorectal autotransplantation. It represents a step in the translational research that may lead to restoration of anorectal function in patients who have lost or have failed to develop it.


Assuntos
Canal Anal/transplante , Reto/transplante , Canal Anal/fisiologia , Análise de Variância , Animais , Masculino , Manometria , Modelos Animais , Duração da Cirurgia , Pressão , Distribuição Aleatória , Ratos Wistar , Reto/fisiologia , Transplante Autólogo
15.
Transplant Proc ; 46(6): 1689-91, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25131013

RESUMO

BACKGROUND: Pancreas transplantation is a treatment for advanced type 1 diabetes and offers significant improvement in quality of life. Recent advances in surgical techniques and immunosuppression regimes lead to good outcomes. However, despite significant higher rates of multiorgan donors in Brazil, pancreas transplantation seems to have remained stable. This study aimed to investigate the acceptance rate of potential pancreas donors in the past 10 years in São Paulo State. METHODS: We retrospectively evaluated potential pancreas donors characteristics and its acceptance rate in São Paulo State in the past 10 years. We divided this period into 2 eras: 1st era from January 2003 to January 2008; and 2nd era from January 2008 to January 2013. Data were obtained from São Paulo's government official website. RESULTS: During the whole period, 5,005 deceased donors of all ages were available for pancreas transplantation. According to eras, we had 1,588 donors in the 1st and 3,417 in the 2nd era. In the 2nd era, donors >49 years old were significantly more common (P < .001). Blood test abnormalities, donor comorbidities, and high dosage of vasopressors also were significantly higher in the 2nd era. Rate of graft acceptance had a significant decrease in the 2nd era, from 46.4% to 25% (P < .05). CONCLUSIONS: Despite greater organ availability, pancreas transplantations performed in São Paulo State remained stable. Rate of graft acceptance is dramatically lower in more recent years.


Assuntos
Transplante de Pâncreas , Doadores de Tecidos , Adolescente , Adulto , Brasil , Criança , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Pâncreas/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde , Qualidade de Vida , Estudos Retrospectivos , Doadores de Tecidos/estatística & dados numéricos , Adulto Jovem
16.
Transplant Proc ; 46(6): 1839-41, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25131049

RESUMO

Intestinal failure is a multifaceted condition that may require high-complexity treatment and a multidisciplinary program, including home parenteral nutrition therapy (HPNT) and intestinal transplantation. In this article, we profile a Brazilian single-center experience with 128 cases of HTPN followed for the last 30 years and appraise the referral for potential intestinal and multivisceral transplantation.


Assuntos
Intestinos/transplante , Nutrição Parenteral no Domicílio/métodos , Cuidados Pós-Operatórios/métodos , Avaliação de Programas e Projetos de Saúde , Encaminhamento e Consulta , Adulto , Brasil , Feminino , Humanos , Masculino , Estudos Retrospectivos
17.
Transpl Infect Dis ; 16(3): 369-78, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24725123

RESUMO

INTRODUCTION: Acinetobacter baumannii is a leading agent of healthcare-associated infection. The objective of this study was to evaluate cases of colonization or infection with polymyxin-resistant A. baumannii (PRAB) in liver transplant recipients and to identify the risk factors for the acquisition of PRAB. METHODS: We evaluated all patients undergoing liver transplantation (LT) between January and November of 2011. The exclusion criterion was death within the first 72 h after transplant. Patients were screened for PRAB through weekly rectal and inguinal swabs during their stay in the intensive care unit (ICU) and at ICU discharge. Patients who came from other hospitals or had been treated in the emergency room for >72 h were screened at ICU admission. The minimum inhibitory concentrations (MICs) for polymyxins were determined by broth microdilution, and clonality was determined by pulsed-field gel electrophoresis. The stepwise logistic regression was used to identify risk factors related to acquisition of PRAB, and Cox forward regression used to identify risk factors for 60-day mortality. RESULTS: We evaluated 65 patients submitted to LT, among whom PRAB was isolated in 7, 4 of whom developed infection. The MICs for polymyxin E ranged from 16 to 128 mg/mL. All patients with PRAB required dialysis. The median time of polymyxin use before PRAB isolation was 21 days. These 4 included 1 case of primary bloodstream infection (BSI), which was treated with the carbapenem-polymyxin combination; 1 case of surgical site infection, which was treated with gentamicin, polymyxin, ampicillin-sulbactam, and tigecycline; and 2 cases of pneumonia, treated with the combination of carbapenem-polymyxin. In the case of BSI and in 1 of the cases of pneumonia, the treatment was considered successful. Mortality was 71% among the cases, compared with 33% among the non-cases. CONCLUSION: In the final model of the survival analysis, PRAB colonization or infection after LT was independently associated with mortality. One predominant clone was identified. The only risk factor identified in the multivariate analysis was polymyxin use. PRAB was an agent with high mortality, and the most important risk factor associated with colonization or infection for such bacterium was polymyxin use.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/uso terapêutico , Transplante de Fígado , Polimixinas/uso terapêutico , Portador Sadio , Estudos de Casos e Controles , Farmacorresistência Bacteriana , Quimioterapia Combinada , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade
18.
Tech Coloproctol ; 18(2): 129-35, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24057357

RESUMO

As many as 25 % of colorectal cancer (CRC) patients have liver metastases at presentation. However, the optimal strategy for resectable synchronous colorectal liver metastasis remains controversial. Despite the increasing use of laparoscopy in colorectal and liver resections, combined laparoscopic resection of the primary CRC and synchronous liver metastasis is rarely performed. The potential benefits of this approach are the possibility to perform a radical operation with small incisions, earlier recovery, and reduction in costs. The aim of this study was to review the literature on feasibility and short-term results of simultaneous laparoscopic resection. We conducted a systematic search of all articles published until February 2013. Search terms included: hepatectomy [Mesh], "liver resection," laparoscopy [Mesh], hand-assisted laparoscopy [Mesh], surgical procedures, minimally invasive [Mesh], colectomy [Mesh], colorectal neoplasms [Mesh], and "colorectal resections." No randomized trials are available. All data have been reported as case reports, case series, or case-control studies. Thirty-nine minimally invasive simultaneous resections were identified in 14 different articles. There were 9 (23 %) major hepatic resections. The most performed liver resection was left lateral sectionectomy in 26 (67 %) patients. Colorectal resections included low rectal resections with total mesorectal excision, right and left hemicolectomies, and anterior resections. Despite the lack of high-quality evidence, the laparoscopic combined procedure appeared to be feasible and safe, even with major hepatectomies. Good patient selection and refined surgical technique are the keys to successful simultaneous resection. Simultaneous left lateral sectionectomy associated with colorectal resection should be routinely proposed.


Assuntos
Neoplasias Colorretais/cirurgia , Laparoscopia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Colectomia/efeitos adversos , Neoplasias Colorretais/patologia , Conversão para Cirurgia Aberta , Hepatectomia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Fatores de Tempo
19.
Transplant Proc ; 45(3): 1133-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23622645

RESUMO

BACKGROUND: Intestinal/multivisceral transplantation (IT/MVT) is the gold standard treatment for patients with intestinal failure and complications related to total parenteral nutrition, gastrointestinal inoperable indolent tumors, or diffuse portal trombosis. Currently, the reported 1-year patient survival rate is around 80%, similar to other solid organ abdominal transplantations. Unfortunately, the patient survival decreases after the first year with the 5-year rate not close to 70% yet. Acute cellular rejection is the main cause of graft loss. Its early diagnosis may make it possible to improve survival of retransplantations. OBJECTIVE: To analyze the reported results published in the last 5 years by leading transplant centers to evaluate IT/MVT retransplantation results. METHODS: We performed a literature review using PubMed focusing on multivisceral and intestinal retransplantation in articles published between 2006 and 2012. In relation to the first transplantation, we analyzed demographics, imunosuppression, rejection, infection as well as graft and patient survival rates. RESULTS: Two centers reported results on intestinal and multivisceral retransplantations. Mazariegos et al reported their experience with 15 intestinal retransplantations in 14 pediatric recipients. Four patients died from posttransplant lymphoperliferative disease, severe acute cellular rejection, fungal sepsis, or bleeding from a pseudoaneurysm at a mean time of 5.7 months post-transplantation. Total parenteral nutrition was weaned at a median time of 32 days. Abu-Elmaged et al reported 47 cases with a 5-year survival of 47% for all retransplant modalities. Retransplantation with liver-contained visceral allograft achieved a 5-year survival rate of 61% compared with 16% for liver-free visceral grafts. CONCLUSION: Despite those huge improvements, some transplanted patients develop severe acute cellular rejection, culminating in graft loss and retransplantation. Repots on multivisceral and intestinal retransplantation outcomes suggest that it is a viable procedure with appropriate patient survival after primary graft loss.


Assuntos
Intestinos/transplante , Reoperação , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Lactente , Adulto Jovem
20.
Clin Transplant ; 26(6): E590-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23083337

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality worldwide. Chronic hepatitis B infection is associated with an increased risk of cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Our aim is to analyze, through a mathematical model, the potential impact of anti-HBV vaccine in the long-term (that is, decades after vaccination) number of LT. METHODS: The model simulated that the prevalence of HBV infection was 0.5% and that approximately 20% of all the liver transplantation carried out in the state of São Paulo are due to HBV infection. RESULTS: The theoretical model suggests that a vaccination program that would cover 80% of the target population would reach a maximum of about 14% reduction in the LT program. CONCLUSION: Increasing the vaccination coverage against HBV in the state of São Paulo would have a relatively low impact on the number of liver transplantation. In addition, this impact would take several decades to materialize due to the long incubation period of liver failure due to HBV.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Vacinas contra Hepatite B/administração & dosagem , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Transplante de Fígado/estatística & dados numéricos , Modelos Teóricos , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/virologia , Criança , Pré-Escolar , Hepatite B/complicações , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vírus da Hepatite B/patogenicidade , Humanos , Lactente , Recém-Nascido , Cirrose Hepática/prevenção & controle , Cirrose Hepática/virologia , Falência Hepática/cirurgia , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/virologia , Pessoa de Meia-Idade , Prevalência , Vacinação , Adulto Jovem
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