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BACKGROUND: Elderly living kidney donors (LKDs) are becoming increasingly important in countries with a high prevalence of living-donor kidney transplants and an aging society. This study explored the features of elderly LKDs, focusing on their subsequent outcomes. METHODS: This single-center, retrospective, observational study included eligible LKDs who donated their kidneys between April 2008 and July 2022. LKDs were categorized into an elderly (≥70 years at donation) or a non-elderly group (<70 years). We examined pre-operative characteristics and post-operative outcomes, such as kidney function, complications, development of end-stage kidney disease (ESKD), and mortality. RESULTS: Of the 188 LKDs observed for a median of 5.7 years, 31 were in the elderly group (16.5%) and 157 (83.5%) were in the non-elderly group (mean age 72.5 ± 2.7 and 58.2 ± 7.3 years, respectively). No significant differences were observed in hospital stay length or peri-operative complications between groups. Both groups experienced a similar decline in post-donation estimated glomerular filtration rate (eGFR)-approximately 37%. In the elderly group, four LKDs died, and one progressed to ESKD. In the non-elderly group, two LKDs died, and none progressed to ESKD. The cause of death was not strongly suspected to be associated with the donation. CONCLUSIONS: eGFR was maintained even in elderly LKDs post-donation. Prioritizing LKDs' safety is paramount; however, donations from elderly people would be acceptable, considering their life expectancy. This can expand the pool of living kidney donors and address the growing demand for kidney transplants.
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Transplante de Rim , Doadores Vivos , Humanos , Estudos Retrospectivos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Japão/epidemiologia , Fatores Etários , Taxa de Filtração Glomerular , Nefrectomia/efeitos adversos , Falência Renal Crônica/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , População do Leste AsiáticoRESUMO
Splenectomy is a risk factor for serious pneumococcal disease like overwhelming post-splenectomy infection (OPSI). In healthy individuals with small spleen, fulminant pneumococcal infection similar to OPSI has been reported. Furthermore, it is reported that small spleen was associated with severe pneumococcal infection patients treated in an intensive care unit. However, the association between the small spleen and pneumococcal pneumonia was not investigated enough. We retrospectively analyzed patients with pneumococcal pneumonia who underwent computed tomography examination with measurement of the splenic volume at Harasanshin Hospital between 2004 and 2019. Data on their background characteristics, laboratory findings, and clinical courses were collected. 413 patients were included in the final analysis. The splenic volume was significantly lower in the moderate (P < 0.001), severe (P < 0.00005), and extremely severe (P < 0.001) pneumonia groups compared with the mild pneumonia group. Furthermore, the splenic volume was significantly lower in patients died within 30 days of pneumonia treatment (median of 73.49 versus 110.77 cm3, P < 0.005) or during hospitalization (median of 71.69 versus 111.01 cm3, P < 0.0005). Splenic volume <40 cm3 was significantly associated with mortality within 30 days and total hospital mortality as a risk factor in univariate analysis. Splenic volume <40 cm3 was an independent risk factor for mortality within 30 days (odds ratio: 5.0, 95% confidence interval: 1.2-21.1, P < 0.05) and total hospital mortality (odds ratio: 7.4, 95% confidence interval: 1.8-30.6, P < 0.01) in multivariate logistic regression analysis. These results suggest that small spleen is a risk factor for severity and mortality of pneumococcal pneumonia.
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Infecções Pneumocócicas , Pneumonia Pneumocócica , Humanos , Pneumonia Pneumocócica/diagnóstico por imagem , Estudos Retrospectivos , Índice de Gravidade de Doença , Baço/diagnóstico por imagem , EsplenectomiaRESUMO
Cytomegalovirus (CMV) is a common infectious pathogen in kidney transplant patients. Here, we present a case of CMV esophagitis with antigenemia, that developed within 3 days of kidney transplantation, a timeline generally considered to be too early for development of a CMV infection. Intense immunosuppressive therapy for desensitization in ABO-incompatibility or in the presence of donor-specific antibody can increase the risk for significant opportunistic infection immediately after or even before transplantation.
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Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Infecções por Citomegalovirus/diagnóstico , Esofagite/etiologia , Transplante de Rim/efeitos adversos , Esofagite/patologia , Esofagite/virologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The accumulation of intramyocellular lipid (IMCL) is recognized as an important determinant of insulin resistance, and is increased by a high-fat diet (HFD). However, the effects of HFD on IMCL and insulin sensitivity are highly variable. The aim of this study was to identify the genes in muscle that are related to this inter-individual variation. Fifty healthy men were recruited for this study. Before and after HFD for 3 days, IMCL levels in the tibialis anterior were measured by (1)H magnetic resonance spectroscopy, and peripheral insulin sensitivity was evaluated by glucose infusion rate (GIR) during the euglycemic-hyperinsulinemic clamp. Subjects who showed a large increase in IMCL and a large decrease in GIR by HFD were classified as high responders (HRs), and subjects who showed a small increase in IMCL and a small decrease in GIR were classified as low responders (LRs). In five subjects from each group, the gene expression profile of the vastus lateralis muscle was analyzed by DNA microarray analysis. Before HFD, gene expression profiles related to lipid metabolism were comparable between the two groups. Gene Set Enrichment Analysis demonstrated that five gene sets related to lipid metabolism were upregulated by HFD in the HR group but not in the LR group. Changes in gene expression patterns were confirmed by qRT-PCR using more samples (LR, n = 9; HR, n = 11). These results suggest that IMCL accumulation/impaired insulin sensitivity after HFD is closely associated with changes in the expression of genes related to lipid metabolism in muscle.
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Dieta Hiperlipídica , Resistência à Insulina/genética , Metabolismo dos Lipídeos/genética , Fibras Musculares Esqueléticas/metabolismo , Adulto , Variações do Número de Cópias de DNA/efeitos dos fármacos , DNA Mitocondrial/genética , Gorduras na Dieta/administração & dosagem , Perfilação da Expressão Gênica , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Adulto JovemRESUMO
Introduction: Gastrointestinal complications are common after solid organ transplantation. New-onset inflammatory bowel disease (IBD) after transplantation (de novo) is a major differential diagnosis of diarrhea after liver transplantation (LT) because of its high incidence in the field. However, the incidence of IBD after kidney transplantation (KT) remains unknown. Methods: This case series comprised six de novo IBD patients who had undergone KT at our hospital from April 1998 to December 2020. In this period, 232 KT recipients were identified. Participants were analyzed based on their colonoscopy diagnoses. Detailed clinical information regarding both KT- and IBD-related symptoms or outcomes was obtained, and we calculated the incidence of de novo IBD from the date of KT. Results: Of the 232 recipients in the median observation period of 6.1 (interquartile range: 2.6, 10.8) years, six recipients (one with Crohn's disease and five with ulcerative colitis) were diagnosed with de novo IBD. The incidence of de novo IBD after KT was 355.8/100,000 person-years (95% confidence interval, 159.8-791.9 per 100,000 person-years). Bloody stools and diarrhea did not always occur, with bloody stools occurring in three and diarrhea in 2 patients at the time of diagnosis. No recipient developed graft failure or extraintestinal complications (e.g., IBD-related nephritis or arthritis). Conclusion: Despite a small sample size, this study's results indicate that the incidence of de novo IBD after KT may be similar to that after LT and higher than that in the general population. Larger studies are required to validate these preliminary findings.
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Under the strict quarantine policy imposed to combat the COVID-19 (coronavirus disease 2019) pandemic in Japan, the prevalence of respiratory infections by viruses other than SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been largely unknown. However, such information on viral circulation is important in order to develop better management policies that are based on scientific data. Here, we retrospectively investigated respiratory virus infections in individuals who visited a community hospital with respiratory symptoms between June of 2020 and September of 2021 with the use of the BioFire FilmArray Respiratory Panel 2.1. Virus was detected in 65 out of a total of 328 subjects, with SARS-CoV-2 (67.7%), rhino/enterovirus (18.5%), and parainfluenza virus 3 (7.7%) accounting for most of the infections. No influenza virus or respiratory syncytial virus (RSV) infections were detected. The monthly cases of rhino/enterovirus infection were highest from winter to spring, with this temporal pattern differing from that of SARS-CoV-2. SARS-CoV-2 was detected more frequently (P < 0.001) in subjects with cough (31/104 cases, 29.8%) than in those without cough (13/224 cases, 5.8%), suggesting that cough might contribute to the prediction of COVID-19. Our findings also suggest that testing for rhino/enterovirus and parainfluenza virus 3, in addition to SARS-CoV-2, may be important for the rigorous diagnosis of respiratory virus infections. IMPORTANCE Influenza virus, RSV, adenovirus, and rhino/enterovirus were the major respiratory viruses before COVID-19 pandemic. Circulating respiratory viruses may have been affected by our strong quarantine policy during the COVID-19 pandemic. We checked the circulating respiratory viruses from our outpatients by using a multiplex PCR kit that had recently been released. SARS-CoV-2 was the most frequently detected virus, and it was followed by rhino/enterovirus and parainfluenza virus 3. No influenza virus or RSV infections were detected during our study period, suggesting that influenza virus and RSV became almost extinct. COVID-19 cases frequently experienced cough, and this frequency was statistically significantly higher than that observed in the cases without SARS-CoV-2 detection. The cough can be an indicator of COVID-19.
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A 73-year-old man receiving hemodialysis and antiplatelets was admitted with a mild case of COVID-19. Heparin was added, and iliopsoas hemorrhage developed. He was successfully treated by interventional radiology. A 76-year-old man receiving hemodialysis and antiplatelets was admitted with mild COVID-19. Heparin was added, and iliacus hemorrhage developed. Despite heparin discontinuation, he died of worsening pneumonia. A 74-year-old man undergoing hemodialysis was admitted with severe COVID-19. Gastrointestinal bleeding developed during continuous hemodiafiltration with heparin. Upon switching to nafamostat and increasing the dose, iliopsoas hemorrhage developed. Despite interventional radiology, he died of infectious complications. Attention to hemorrhagic complications is therefore needed in patients with COVID-19.
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COVID-19 , Idoso , Anticoagulantes/efeitos adversos , COVID-19/complicações , Hemorragia/tratamento farmacológico , Heparina/uso terapêutico , Humanos , Masculino , Diálise Renal/efeitos adversosRESUMO
Hypouricemia in kidney transplant (KT) recipients is rare since they usually have subnormal kidney function which raises serum uric acid level. Recently, interests in pathogenesis of hypouricemia have been increasing due to the understanding of the role of uric acid transporter in renal hypouricemia (RHUC). We herein report the case of RHUC consequently developed in a KT recipient from a living donor with RHUC diagnosed by the detailed urinary and genetic test. A 73-year-old Japanese man underwent KT, and the donor was his wife who had hypouricemia [serum uric acid (S-UA) 0.6 mg/dL]. Nine months after KT, the recipient's S-UA was low (1.5 mg/dL) with serum creatinine (S-Cr) of 1.56 mg/dL, and fractional excretion of UA (FEUA) was high (59.7%; normal < 10%), indicating RHUC. Regarding the donor's information, S-Cr, S-UA, and FEUA were 0.95 mg/dL, 1.0 mg/dL, and 54.5%, respectively. To investigate further on the pathogenesis of RHUC in both the recipient and the donor, we performed genetic tests. The donor had a homozygous mutation of W258X in the SLC22A12 gene and the recipient had a wild type of W258X. Finally, we reviewed the previous literature on RHUC among KT recipients and discussed the strategy of follow-up for these patients.
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Transplante de Rim , Transportadores de Ânions Orgânicos , Idoso , Feminino , Humanos , Rim , Transplante de Rim/efeitos adversos , Doadores Vivos , Masculino , Transportadores de Ânions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Erros Inatos do Transporte Tubular Renal , Ácido Úrico , Cálculos UrináriosRESUMO
OBJECTIVE: We evaluated the impact of chronic kidney disease (CKD) on the presence and severity of aortic stenosis (AS) in patients at high risk for coronary artery disease (CAD). METHODS: One hundred and twenty consecutive patients who underwent invasive coronary angiography were enrolled. Aortic valve area (AVA) was calculated by the continuity equation using transthoracic echocardiography, and was normalized by body surface area (AVA index). RESULTS: Among all 120 patients, 78% had CAD, 55% had CKD (stage 3: 81%; stage 4: 19%), and 34% had AS (AVA < 2.0 cm²). Patients with AS were older, more often female, and had a higher frequency of CKD than those without AS, but the prevalence of CAD and most other coexisting conventional risk factors was similar between patients with and without AS. Multivariate linear regression analysis indicated that only CKD and CAD were independent determinants of AVA index with standardized coefficients of -0.37 and -0.28, respectively. When patients were divided into 3 groups (group 1: absence of CKD and CAD, n = 16; group 2: presence of either CKD or CAD, n = 51; and group 3: presence of both CKD and CAD, n = 53), group 3 had the smallest AVA index (1.19 ± 0.30*# cm²/m², *p < 0.05 vs. group 1: 1.65 ± 0.32 cm²/m², and #p < 0.05 vs. group 2: 1.43 ± 0.29* cm²/m²) and the highest peak velocity across the aortic valve (1.53 ± 0.41*# m/sec; *p < 0.05 vs. group 1: 1.28 ± 0.29 m/sec, and #p < 0.05 vs. group 2: 1.35 ± 0.27 m/sec). CONCLUSION: CKD, even pre-stage 5 CKD, has a more powerful impact on the presence and severity of AS than other conventional risk factors for atherosclerosis in patients at high risk for CAD.
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Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/epidemiologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Ecocardiografia/estatística & dados numéricos , Falência Renal Crônica/diagnóstico por imagem , Falência Renal Crônica/epidemiologia , Idoso , Comorbidade , Feminino , Humanos , Japão/epidemiologia , Masculino , Prevalência , Medição de Risco , Fatores de RiscoRESUMO
This study was conducted to determine the correlation between reproductive hormones and musth in a male African elephant. Changes in circulating luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and immunoreactive (ir-) inhibin and the degree of musth were evaluated for 4 years. LH increased 4 weeks before musth began. The highest concentrations of testosterone and ir-inhibin were observed from April to October. There were positive correlations among testosterone, ir-inhibin and musth behavior. These findings suggested that the surge-like LH in the pre-musth period might stimulate secretion of testosterone and ir-inhibin and thus initiate the musth behavior. This study also suggested that the high LH level before musth might be a useful biomarker for the beginning of the musth season.
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Elefantes/sangue , Elefantes/fisiologia , Hormônio Luteinizante/sangue , Animais , Hormônio Foliculoestimulante/sangue , Inibinas/sangue , Masculino , Testosterona/sangue , Fatores de TempoRESUMO
Reproduction of captive elephants in zoos has shown a low fecundity and requires improvement. One of the reasons for low fecundity is ovarian dysfunction in many female elephants. To investigate whether prolactin has a correlation with ovarian function in female elephants, the serum concentrations of prolactin, progesterone and estradiol-17beta in four African female elephants (one cycling female and three non-cycling female elephants) were measured. Cyclic patterns of prolactin and estradiol-17beta were observed in the cycling female elephant, which tended to be high during the follicular phase and low during the luteal phase. On the other hand, a cyclic pattern of prolactin was not observed in the non-cycling female elephants. One of the three non-cycling females (Mako) had developed breasts and showed significantly higher average levels of prolactin than the other female elephants. These results suggested that high concentrations of circulating estradiol-17beta during the follicular phase stimulated prolactin secretion. They also suggested that hyperprolactinemia in Mako was one of the causes of the developed mammary glands and ovarian dysfunction.
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Elefantes/fisiologia , Ovário/fisiologia , Prolactina/metabolismo , Animais , Estradiol/sangue , Ciclo Estral/sangue , Ciclo Estral/fisiologia , Feminino , Glândulas Mamárias Animais/anatomia & histologia , Glândulas Mamárias Animais/fisiologia , Progesterona/sangue , Prolactina/sangue , Radioimunoensaio , OvinosRESUMO
Vitamin A and its derivatives contribute to many physiological processes, including vision, neural differentiation, and reproduction. Vitamin A deficiency causes early cessation of spermatogenesis, characterized by a marked depletion of germ cells. However, there has been no clear understanding about the role of chronic intake of vitamin A excess (VAE) in spermatogenesis. The objective of this study was to investigate whether chronic intake of VAE diet causes arrest of spermatogenesis. To examine the effects of VAE on spermatogenesis, we used ICR male mice fed with control (AIN-93G purified diet: 4 IU/g) diet or VAE (modified AIN-93G diet with VAE: 1,000 IU/g) diet for 7 weeks (from 3 to 10 weeks of age). At 10 weeks of age, the retinol concentration in the testes of VAE mice was significantly higher than that of control mice. Testicular cross sections from control mice contained a normal array of germ cells, while the seminiferous tubules from VAE mice exhibited varying degrees of testicular degeneration. Daily sperm production in VAE testes was dramatically decreased compared to that in control testes. Sperm viability, motility, and morphology were also impaired in VAE mice. Furthermore, we examined the effects of VAE on the expression of genes involved in retinoid signaling and spermatogenesis to determine the underlying molecular mechanisms. Therefore, we are the first to present results describing the long-term dietary intake of VAE impairs spermatogenesis using a mouse model.
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Exposição Dietética/efeitos adversos , Hipervitaminose A/etiologia , Hipervitaminose A/fisiopatologia , Espermatogênese/efeitos dos fármacos , Vitamina A/administração & dosagem , Vitamina A/efeitos adversos , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Hipervitaminose A/metabolismo , Masculino , Camundongos Endogâmicos ICR , Gravidez , Retinoides , Transdução de Sinais/genética , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatogênese/genética , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Fatores de Tempo , Vitamina A/metabolismoRESUMO
BACKGROUND: It has been reported that 20% of lung cancer patients have renal impairment caused by chronic kidney disease (CKD). Since docetaxel is predominantly excreted by the hepatobiliary system, it is administered to non-small cell lung cancer (NSCLC) patients with renal impairment. However, few clinical data are available on the toxicity and efficacy of docetaxel for patients with nondialysis renal impairment. Furthermore, some cases of tubular nephrotoxicity caused by docetaxel in NSCLC patients have been reported. Therefore, a retrospective cohort study was conducted to assess the influence of nondialysis CKD on the toxicity and efficacy of docetaxel in NSCLC patients. METHODS: NSCLC patients who received docetaxel were assessed for renal function, occurrence of adverse events and treatment efficacy. RESULTS: A total of 34 NSCLC patients who received docetaxel were studied. Eight (23.5%) patients had nondialysis CKD stage 3b or higher, with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 . Although the differences were not statistically significant, the starting dose of docetaxel (mg/m2 ) was lower (60 mg/m2 ; 37.5% vs. 69.2%) in patients with an eGFR <45 than that in patients with an eGFR ≥45. No significant association was observed between pretreatment eGFR and hematological and nonhematological toxicities. No significant difference was observed in the disease control rate (62.5% vs. 65.4%, P = 1.000) or in the median overall survival (10.7 vs. 11.7, P = 0.735) between patients with an eGFR <45 and those with an eGFR ≥45. CONCLUSION: Docetaxel is a reasonable option for NSCLC patients with nondialysis CKD stage 3b or higher. Dose reduction of docetaxel is also a possibility for NSCLC patients with CKD stage 3b or higher.
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Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/uso terapêutico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Progressão da Doença , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Humanos , Japão , Estimativa de Kaplan-Meier , Testes de Função Renal , Masculino , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
To assess and compare the efficacy and safety of insulin glargine as intensive replacement of basal insulin in Japanese patients with type 1 (n = 72) and type 2 (n = 46) diabetes, we switched their intensive insulin regimen from NPH plus regular or rapid-acting insulin to glargine plus bolus insulin, which included regular and rapid-acting insulin, and recorded changes in glycemic control and frequency of hypoglycemia for 18 months. The dose titration of basal and bolus insulin was based on home self-monitored blood glucose measurements and monthly HbA(1C). Mean HbA(1C) level was improved significantly at 3 months after switching to glargine plus bolus insulin regimen and these effects continued for 18 months in both type 1 and type 2 diabetes patients (HbA(1C) level: type 1: baseline 8.9 +/- 2.6%, 18 months 7.8 +/- 1.5% (p<0.05), type 2: baseline 8.2 +/- 2.6%, 18 months 7.7 +/- 1.5%. Body weight was slightly but significantly increased at 18 months only in type 2 diabetes. Total daily bolus insulin doses were not changed but basal insulin could be increased significantly after switching regimens in both types diabetes compared with baseline. The frequency of mild to moderate hypoglycemia (self-assisted episodes, blood glucose <70 mg/dl) was marginally lower with glargine but not significantly. Self-monitored fasting blood glucose level was significantly improved after switching in type 2 diabetes. Patients with the worst HbA(1C) level at baseline exhibited more than 10% improvement in HbA(1C) level after switching both type 1 and type 2 diabetes. The HbA(1C) levels of the effectively treated patients were comparable to those of ineffectively treated ones at 6 months and the same improvement was seen at 18 months. Our results suggested that insulin glargine is more effective than NPH insulin as intensive replacement of basal insulin, particularly in those Japanese patients with difficult glycemic control with NPH insulin, equally in both type 1 and type 2 diabetes.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Isófana/uso terapêutico , Insulina/análogos & derivados , Adulto , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Insulina/uso terapêutico , Insulina Glargina , Insulina Isófana/efeitos adversos , Insulina de Ação Prolongada , Japão , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
We analyzed lipids in liver diseases by agarose gel electrophoresis, and differential staining and simultaneous analysis of the cholesterol (Chol) and triglyceride (TG) fractions. Liver diseases were classified into chronic hepatitis (CH), liver cirrhosis (LC), hepatocellular carcinoma (HCC), and metastatic liver cancer, and each fraction was compared among these diseases. Atypical patterns that were unclassifiable according to the WHO classification of hyperlipidemia phenotypes were classified, and their clinical importance was evaluated. With progression of the pathologic conditions of CH, LC, and HCC, the T-Chol level, each Chol fraction, and the TG fraction decreased while the LDL-TG fraction increased. Metastatic liver cancer showed a lower HDL-fraction level but higher levels of the other parameters than HCC. When the subjects were classified into survivors and patients who died, the HDL fraction level in HCC and metastatic liver cancer, and the LDL level in LC and metastatic liver cancer differed between survivors and patients who died. Phenotypes of hyperlipidemia also differed among diseases, and atypical patterns were frequently observed in patients who died. There were 6 atypical patterns, of which 4 (slow alpha HDL, abnormal LDL, Lp-X, and Lp-Y) were associated with liver diseases. Slow alpha HDL appeared during slight bile stagnation and was accompanied by increases in the apo E level and the HDL particle size. Abnormal LDL appeared with severe liver dysfunction; a TG peak appeared at the position of LDL, and the HDL and VLDL fractions were negligible. Lp-X was a Chol-rich band, occurring on the cathode side of LDL in the presence of marked bile stagnation such as that in obstructive jaundice, and was accompanied by appearance of abnormal LDL. Lp-Y was similar to Lp-X in terms of mobility and associated diseases but contained Chol and TG. Abnormal LDL, Lp-X, and Lp-Y were often observed in patients with poor outcomes. Lipid analysis in liver diseases by this method showed results reflecting the pathologic conditions and may be clinically useful.
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Lipoproteínas/metabolismo , Hepatopatias/fisiopatologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Colesterol/metabolismo , Hepatite Crônica/metabolismo , Hepatite Crônica/mortalidade , Humanos , Hiperlipidemias/metabolismo , Hepatopatias/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Triglicerídeos/metabolismoAssuntos
Encefalite/etiologia , Pneumonia por Mycoplasma/complicações , Criança , Eletroencefalografia , Encefalite/diagnóstico , Galactosilceramidas/imunologia , Glucocorticoides/administração & dosagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pneumonia por Mycoplasma/imunologia , Prednisolona/administração & dosagem , Fatores de Tempo , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
CONTEXT: Intramyocellular lipid (IMCL) accumulation is observed in both insulin-resistant subjects and insulin-sensitive endurance athletes (athlete's paradox). We hypothesized that the expression pattern of fatty acid transporters may influence oxidative capacity and determine the association between IMCL and insulin resistance. OBJECTIVE: The objective of the study was to investigate the muscle expression of fatty acid transporters and their function related to insulin sensitivity in IMCL-accumulated subjects. DESIGN AND SETTING: The study subjects were 36 nonobese healthy men. Their IMCL levels were measured by (1)H-magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by steady-state glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by quantitative RT-PCR. We compared the clinical phenotypes and the expression levels of genes involved in lipid metabolism in skeletal muscle between IMCL-accumulated high-GIR (H-GIR) subjects (n = 8) and low-GIR subjects (n = 9). The functions of candidate fatty acid transporters were determined by in vitro analyses. RESULTS: Compared with the low-GIR group, body fat was lower and maximum oxygen uptake was higher in the H-GIR group. Several lipid oxidation genes in muscle were up-regulated in the H-GIR group, and this was associated with increased expression of higher plasma membrane-associated fatty acid-binding protein (FABPpm) and decreased expression of fatty acid transport protein (FATP)-1. Overexpression of FABPpm in C2C12 myotubes increased fatty acid oxidation coupled with the elevated expression of genes related to fatty acid oxidation. These changes were not observed in FATP1-overexpressed myotubes. CONCLUSIONS: Differences in the gene expression of fatty acid transporters may, at least in part, affect insulin sensitivity in IMCL-accumulated nonobese men.
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Peso Corporal/fisiologia , Proteínas de Transporte de Ácido Graxo/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Resistência à Insulina/fisiologia , Músculo Esquelético/metabolismo , Animais , Células Cultivadas , Ácidos Graxos não Esterificados/metabolismo , Glucose/administração & dosagem , Técnica Clamp de Glucose , Humanos , Hiperinsulinismo/metabolismo , Metabolismo dos Lipídeos/fisiologia , Masculino , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/citologia , Oxirredução , Adulto JovemRESUMO
OBJECTIVE: Mounting evidence indicates that the gut microbiota are an important modifier of obesity and diabetes. However, so far there is no information on gut microbiota and "live gut bacteria" in the systemic circulation of Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Using a sensitive reverse transcription-quantitative PCR (RT-qPCR) method, we determined the composition of fecal gut microbiota in 50 Japanese patients with type 2 diabetes and 50 control subjects, and its association with various clinical parameters, including inflammatory markers. We also analyzed the presence of gut bacteria in blood samples. RESULTS: The counts of the Clostridium coccoides group, Atopobium cluster, and Prevotella (obligate anaerobes) were significantly lower (P < 0.05), while the counts of total Lactobacillus (facultative anaerobes) were significantly higher (P < 0.05) in fecal samples of diabetic patients than in those of control subjects. Especially, the counts of Lactobacillus reuteri and Lactobacillus plantarum subgroups were significantly higher (P < 0.05). Gut bacteria were detected in blood at a significantly higher rate in diabetic patients than in control subjects (28% vs. 4%, P < 0.01), and most of these bacteria were Gram-positive. CONCLUSIONS: This is the first report of gut dysbiosis in Japanese patients with type 2 diabetes as assessed by RT-qPCR. The high rate of gut bacteria in the circulation suggests translocation of bacteria from the gut to the bloodstream.
Assuntos
Bacteriemia/complicações , Sangue/microbiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/microbiologia , Disbiose/microbiologia , Intestinos/microbiologia , Adulto , Idoso , Bacteriemia/microbiologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Disbiose/sangue , Disbiose/etiologia , Fezes/microbiologia , Feminino , Humanos , Japão , Masculino , Microbiota/fisiologia , Pessoa de Meia-IdadeRESUMO
Telaprevir-based triple therapy is highly effective for chronic hepatitis C. However, concern has been expressed over the high frequency and severity of its dermatological side-effects compared with those associated with peginterferon (PEG-IFN) and ribavirin (RBV) therapy. Thus, here, we evaluated the dermatological adverse reactions of telaprevir-based triple therapy in Japanese multicenter phase III clinical trials in an attempt to characterize the dermatological side-effects and establish appropriate management plans. In these trials, 126 treatment-naïve patients and 141 treatment-failure patients were administrated telaprevir, PEG-IFN-α-2b and RBV for 12 weeks followed by PEG-IFN-α-2b and RBV for another 12 weeks (T12/PR24 group), and 63 treatment-naïve patients were administrated PEG-IFN-α-2b and RBV for 48 weeks (PR48 group). Dermatological adverse reactions developed in over 80% patients in both groups, and most of them were grade 1 or 2. In the T12/PR24 group, there were more grade 2 or grade 3 events, and the time to onset was earlier than that in the PR48 group. Most reactions could be managed with topical corticosteroids and oral antihistamines, and the rates of discontinuation due to dermatological reactions were not high even in the T12/PR24 group. In the T12/PR24 group, however, two cases of Stevens-Johnson syndrome and one case of drug rash with eosinophilia and systemic symptoms, which corresponds to drug-induced hypersensitivity syndrome in Japan, were reported. For appropriate treatments of individual dermatological adverse reactions, the judgment of discontinuation of antiviral drugs and treatment based on the severity are extremely important in this triple therapy.