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1.
Asian Bioeth Rev ; : 1-17, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34804220

RESUMO

This questionnaire-based observational study was conducted in July 2020 with the aim of understanding the ethical and social issues faced by health care providers (HCPs) registered with the Japanese Society of Intensive Care Medicine in intensive care units (ICUs) during the coronavirus disease (COVID-19) pandemic. There were 200 questionnaire respondents, and we analyzed the responses of 189 members who had been involved in COVID-19 treatment in ICUs. The ethical and social issues that HCPs recognized during the pandemic were difficulties in the decision-making process with patients' families, limitations of life-sustaining treatment, lack of palliative care, and inadequate mental support for patients' families and HCPs. Regarding decision-making on issues of clinical ethics during the pandemic, more than half of the respondents thought they had failed to provide sufficient palliative care to patients and responded that they experienced moral distress. The free-text responses on moral distress revealed issues such as unusual treatment and care, restricted visits, challenging situations for HCPs, and psychological burden. Additionally, 38.1% of respondents experienced episodes of social prejudice or discrimination and 4.7% experienced a shortage of medical resources. Our study result shows that the moral distress of HCPs was caused by difficulties in patient-centered decision-making and insufficient medical care to patients and their families. These were caused mainly by a lack of communication due to the stronger implementation of infection control measures. We believe that it is important to address ethical and social issues during a pandemic in order to provide appropriate medical care and prevent burnout among HCPs. Supplementary Information: The online version contains supplementary material available at 10.1007/s41649-021-00194-y.

3.
Heart Vessels ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618188

RESUMO

Central venous catheters (CVCs) and pulmonary artery catheters (PACs) are widely used in intensive care and perioperative management. The detection and prevention of catheter-related thrombosis (CRT) are important because CRT is a complication of catheter use and can cause pulmonary embolism and bloodstream infection. Currently, there is no evidence for CRT in patients using both CVC and PAC. We conducted a single-center, prospective, observational study to identify the incidence, timing, and risk factors for CRT in patients undergoing cardiovascular surgery and using a combination of CVC and PAC through the right internal jugular vein (RIJV). Out of 50 patients, CRT was observed using ultrasonography in 39 patients (78%), and the median time of CRT formation was 1 day (interquartile range: 1-1.5) after catheter insertion. The mean duration of PAC placement was 3 days (interquartile range: 2-5), and the maximum diameter of CRT was 12 mm (interquartile range: 10-15). In short-axis images, CRT occupied more than half of the cross-sectional area of the RIJV in five patients (10%), and CRT completely occluded the RIJV in one patient (2%). Platelet count, duration of PAC placement, and intraoperative bleeding amount were found to be high-risk indicators of CRT. In conclusion, patients who underwent cardiovascular surgery and using both CVC and PAC had a high incidence of CRT. Avoiding unnecessary PAC placement and early removal of catheters in patients at high risk of developing CRT may prevent the development of CRT.

4.
J Alzheimers Dis ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34633321

RESUMO

BACKGROUND: The Iwaki Health Promotion Project (IHPP) is a community-based study for the prevention of lifestyle-related diseases and improvement of quality of life. OBJECTIVE: Between 2014 and 2017, a total of 4,442 Iwaki town residents from 19 to 93 years of age participated in annual surveys to clarify the natural course of age-related cognitive decline and mild cognitive impairment (MCI). METHODS: Modified OLD and SED-11Q questionnaires, MMSE, Logical Memory II, educational history, and APOE genotypes were examined at the first screening. MCI and dementia were diagnosed at the second examination by detailed neurological examination, CDR, and MRI, and followed for 3 years. Spline regression analyses based on a linear mixed model was adopted for statistical analysis. RESULTS: MMSE scores declined with age from 55 to 64 years. There was also interaction between levels of education and ages. At the second examination, 56 MCI and 5 dementia patients were identified. None of the MCI cases progressed to dementia during the 3 years. During follow-up examinations, 13 cases showed improved MMSE scores (0.95 point/year), 5 remained stable, and 7 deteriorated (-0.83 point/year). Five cases showed improved CDR-SOB scores (-0.28 point/year), 9 remained stable, and 6 deteriorated (0.3 point/year). CONCLUSION: IHPP revealed that age- and education-related cognitive decline began and advanced from 55 years of age. The prevalence of MCI and dementia was estimated to be 5.9%in the Iwaki town cohort over 60 yeas of age. About 30%of MCI cases showed progression of cognitive decline.

5.
Medicine (Baltimore) ; 100(30): e26660, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397692

RESUMO

ABSTRACT: Steroid pulse therapy is widely used to treat virus-associated acute encephalopathy, especially the cytokine storm type; however, its effectiveness remains unknown. We sought to investigate the effectiveness of early steroid pulse therapy for suspected acute encephalopathy in the presence of elevated aspartate aminotransferase (AST) levels.We enrolled children admitted to Hyogo Children's Hospital between 2003 and 2017 with convulsions or impaired consciousness accompanied by fever (temperature >38°C). The inclusion criteria were: refractory status epilepticus or prolonged neurological abnormality or hemiplegia at 6 hours from onset, and AST elevation >90 IU/L within 6 hours of onset. We excluded patients with a neurological history. We compared the prognosis between the groups with or without steroid pulse therapy within 24 hours. A good prognosis was defined as a Pediatric Cerebral Performance Category Scale (PCPC) score of 1-2 at the last evaluation, within 30 months of onset. Moreover, we analyzed the relationship between prognosis and time from onset to steroid pulse therapy.Fifteen patients with acute encephalopathy and 5 patients with febrile seizures were included in this study. Thirteen patients received steroid pulse therapy within 24 hours. There was no between-group difference in the proportion with a good prognosis. There was no significant correlation between PCPC and timing of steroid pulse therapy (rs = 0.253, P = .405). Even after excluding 2 patients with brainstem lesions, no significant correlation between PCPC and steroid pulse therapy timing (rs = 0.583, P = .060) was noted. However, the prognosis tended to be better in patients who received steroid pulse therapy earlier.Steroid pulse therapy within 24 hours did not improve the prognosis in children with suspected acute encephalopathy associated with elevated AST. Still, even earlier administration of treatment could prevent the possible neurological sequelae of this condition.


Assuntos
Encefalopatias/tratamento farmacológico , Pulsoterapia/normas , Esteroides/uso terapêutico , Fatores de Tempo , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Japão , Masculino , Prognóstico , Pulsoterapia/métodos , Pulsoterapia/estatística & dados numéricos
6.
J Diabetes Investig ; 12(10): 1759-1761, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34318628

RESUMO

Fruit intake may reduce the risk of type 2 diabetes by probably four factors: dietary fiber, phytochemicals (flavonoids), fructose, and chewing.

7.
J Diabetes Investig ; 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087060

RESUMO

AIMS/INTRODUCTION: This 6-month, single-center, prospective, open-labeled, randomized trial was designed to investigate whether physicians' diabetes self-management education using an education tool developed by the Japan Association of Diabetes Education and Care and a self-monitoring of blood glucose (SMBG) analyzer improves glycemic control in individuals with type 2 diabetes receiving insulin and SMBG. MATERIALS AND METHODS: Participants were randomized into intervention (I) and control (C) groups. Both groups received physicians' diabetes self-management education at each hospital visit, whereas the Japan Association of Diabetes Education and Care education tool and the SMBG readings analyzer was used in group I, but not group C. All participants filled out a diabetes treatment-related quality of life form and an original questionnaire on SMBG use with five questions (Q1-Q5) before and after the study period. RESULTS: A total of 76 individuals were recruited and randomized. Glycated hemoglobin (HbA1c) was significantly improved during the study period in group I, whereas no significant change was observed in group C. The change in HbA1c was greater in group I, although it did not reach statistical significance. The diabetes treatment-related quality of life total score was not changed in either group. Interestingly, the score of Q1 ("How important is SMBG to you?") in the SMBG questionnaire was unchanged in group I, whereas it was significantly decreased in group C. HbA1c change was independently associated with changes in insulin dose and SMBG Q1 score. CONCLUSION: Greater HbA1c-lowering by physicians' diabetes self-management education using the Japan Association of Diabetes Education and Care education tool and SMBG analyzer in individuals with type 2 diabetes receiving insulin and SMBG was suggested, but not confirmed.

8.
J Diabetes Investig ; 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022121

RESUMO

AIMS/INTRODUCTION: Differences in the glucose-lowering mechanisms of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been noted. Clarifying these differences could facilitate the choice of optimal drugs for individuals with type 2 diabetes and requires investigation in a clinical setting. MATERIALS AND METHODS: A single-arm, prospective, observational study was conducted to evaluate the effects of various GLP-1RAs on postprandial glucose excursion, secretions of insulin and glucagon as well as on the gastric emptying rate. Participants were subjected to meal tolerance tests before and 2 weeks and 12 weeks after GLP-1RA initiation. Effects on postprandial secretions of glucose-dependent insulinotropic polypeptide (GIP) and apolipoprotein B48 were also investigated. RESULTS: Eighteen subjects with type 2 diabetes received one of three GLP-1RAs, i.e., lixisenatide, n = 7; liraglutide, n = 6; or dulaglutide, n = 5. While 12-week administration of all of the GLP-1RAs significantly reduced HbA1c, only lixisenatide and liraglutide, but not dulaglutide, significantly reduced body weight. Postprandial glucose elevation was improved by all of the GLP-1RAs. Postprandial insulin levels were suppressed by lixisenatide, while insulin levels were enhanced by liraglutide. Postprandial glucagon levels were suppressed by lixisenatide. The gastric emptying rate was significantly delayed by lixisenatide, while liraglutide and dulaglutide had limited effects on gastric emptying. GIP secretion was suppressed by lixisenatide and liraglutide. Apolipoprotein B48 secretion was suppressed by all of the GLP-1RAs. CONCLUSIONS: All of the GLP-1RAs were found to improve HbA1c in a 12-week prospective observational study in Japanese individuals with type 2 diabetes. However, differences in the mechanisms of the glucose-lowering effects and body weight reduction were observed.

9.
J Diabetes Investig ; 12(9): 1545-1554, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33638884

RESUMO

AIMS/INTRODUCTION: We aimed to determine whether glucokinase is required for ß-cell mass expansion induced by high-starch diet (HSTD)-feeding, as has been shown in its high-fat diet-induced expansion. MATERIALS AND METHODS: Eight-week-old male wild-type (Gck+/+ ) or glucokinase haploinsufficient (Gck+/- ) mice were fed either a normal chow (NC) or an HSTD for 15 weeks. The bodyweight, glucose tolerance, insulin sensitivity, insulin secretion and ß-cell mass were assessed. RESULTS: Both HSTD-fed Gck+/+ and Gck+/- mice had significantly higher bodyweight than NC-fed mice. Insulin and oral glucose tolerance tests revealed that HSTD feeding did not affect insulin sensitivity nor glucose tolerance in either the Gck+/+ or Gck+/- mice. However, during the oral glucose tolerance test, the 15-min plasma insulin concentration after glucose loading was significantly higher in the HSTD group than that in the NC group for Gck+/+ , but not for Gck+/- mice. ß-Cell mass was significantly larger in HSTD-fed Gck+/+ mice than that in NC-fed Gck+/+ mice. In contrast, the ß-cell mass of the HSTD-fed Gck+/- mice was not different from that of the NC-fed Gck+/- mice. CONCLUSIONS: The results showed that HSTD feeding would increase pancreatic ß-cell mass and insulin secretion in Gck+/+ , but not Gck+/- mice. This observation implies that glucokinase in ß-cells would be required for the increase in ß-cell mass induced by HSTD feeding.

10.
Nat Commun ; 12(1): 966, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574227

RESUMO

Hydrogen atom transfer (HAT) hydrogenation has recently emerged as an indispensable method for the chemoselective reduction of unactivated alkenes. However, the hitherto reported systems basically require stoichiometric amounts of silanes and peroxides, which prevents wider applications, especially with respect to sustainability and safety concerns. Herein, we report a silane- and peroxide-free HAT hydrogenation using a combined cobalt/photoredox catalysis and ascorbic acid (vitamin C) as a sole stoichiometric reactant. A cobalt salophen complex is identified as the optimal cocatalyst for this environmentally benign HAT hydrogenation in aqueous media, which exhibits high functional-group tolerance. In addition to its applicability in the late-stage hydrogenation of amino-acid derivatives and drug molecules, this method offers unique advantage in direct transformation of unprotected sugar derivatives and allows the HAT hydrogenation of unprotected C-glycoside in higher yield compared to previously reported HAT hydrogenation protocols. The proposed mechanism is supported by experimental and theoretical studies.

12.
Endocr J ; 68(1): 31-43, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32879162

RESUMO

Recently, chronic hyponatremia, even mild, has shown to be associated with poor quality of life and high mortality. The mechanism by which hyponatremia contributes to those symptoms, however, remains to be elucidated. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a primary cause of hyponatremia. Appropriate animal models are crucial for investigating the pathophysiology of SIADH. A rat model of SIADH has been generally used and mouse models have been rarely used. In this study, we developed a mouse model of chronic SIADH in which stable and sustained hyponatremia occurred after 3-week continuous infusion of the vasopressin V2 receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP) and liquid diet feeding to produce chronic water loading. Weight gain in chronic SIADH mice at week 2 and 3 after starting dDAVP injection was similar to that of control mice, suggesting that the animals adapted to chronic hyponatremia and grew up normally. AQP2 expression in the kidney, which reflects the renal action of vasopressin, was decreased in dDAVP-infused water-loaded mice as compared with control mice that received the same dDAVP infusion but were fed pelleted chow. These results suggest that "vasopressin escape" occurred, which is an important process for limiting potentially fatal severe hyponatremia. Behavioral analyses using the contextual and cued fear conditioning test and T-maze test demonstrated cognitive impairment, especially working memory impairment, in chronic SIADH mice, which was partially restored after correcting hyponatremia. Our results suggest that vasopressin escape occurred in chronic SIADH mice and that chronic hyponatremia contributed to their memory impairment.

13.
J Alzheimers Dis ; 79(2): 573-584, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33337370

RESUMO

BACKGROUND: High sensitivity liquid chromatography mass spectrometry (LC-MS/MS) was recently introduced to measure amyloid-ß (Aß) species, allowing for a simultaneous assay that is superior to ELISA, which requires more assay steps with multiple antibodies. OBJECTIVE: We validated the Aß1-38, Aß1-40, Aß1-42, and Aß1-43 assay by LC-MS/MS and compared it with ELISA using cerebrospinal fluid (CSF) samples to investigate its feasibility for clinical application. METHODS: CSF samples from 120 subjects [8 Alzheimer's disease (AD) with dementia (ADD), 2 mild cognitive dementia due to Alzheimer's disease (ADMCI), 14 cognitively unimpaired (CU), and 96 neurological disease subjects] were analyzed. Aß species were separated using the Shimadzu Nexera X2 system and quantitated using a Qtrap 5500 LC-MS/MS system. Aß1-40 and Aß1-42 levels were validated using ELISA. RESULTS: CSF levels in CU were 666±249 pmol/L in Aß1-38, 2199±725 pmol/L in Aß1-40, 153.7±79.7 pmol/L in Aß1-42, and 9.78±4.58 pmol/L in Aß1-43. The ratio of the amounts of Aß1-38, Aß1-40, Aß1-42, and Aß1-43 was approximately 68:225:16:1. Linear regression analyses showed correlations among the respective Aß species. Both Aß1-40 and Aß1-42 values were strongly correlated with ELISA measurements. No significant differences were observed in Aß1-38 or Aß1-40 levels between AD and CU. Aß1-42 and Aß1-43 levels were significantly lower, whereas the Aß1-38/1-42, Aß1-38/1-43, and Aß1-40/Aß1-43 ratios were significantly higher in AD than in CU. The basic assay profiles of the respective Aß species were adequate for clinical usage. CONCLUSION: A quantitative LC-MS/MS assay of CSF Aß species is as reliable as specific ELISA for clinical evaluation of CSF biomarkers for AD.


Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Humanos
14.
Cytokine ; 137: 155324, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33032108

RESUMO

Patients with hemorrhagic shock and encephalopathy syndrome (HSES) have a high early mortality rate, which may be caused by a 'cytokine storm'. However, there is little information on how cytokines and chemokines change over time in these patients. We aimed to describe the characteristics of HSES by examining changes in serum biomarker levels over time. Six patients with HSES were included. We retrospectively evaluated their clinical course and imaging/laboratory data. We measured serum levels of multiple cytokines [interleukin 1ß (IL-1ß), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-gamma, and tumor necrosis factor alpha], chemokines (IL-8, monocyte chemoattractant protein-1, interferon-inducible protein-10), and growth and differentiation factor (GDF)-15. The highest cytokine and chemokine levels were noted in the first 24 h, and decreased thereafter. The GDF-15 level was markedly high. Cytokine, chemokine, and GDF-15 levels were significantly higher in patients with HSES than in controls in the first 24 h, except for IL-2 and IL-4. Patients with HSES have high inflammatory cytokine and chemokine levels, a high GDF-15 level in the first 24 h, and high lactate levels. Our study provides new insights on the pathophysiology of HSES, a detailed clinical picture of patients with HSES, and potential biomarkers.

15.
Biochem Biophys Res Commun ; 532(1): 47-53, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-32826056

RESUMO

Although diabetic polyneuropathy (DPN) is the commonest diabetic complication, its pathology remains to be clarified. As previous papers have suggested the neuroprotective effects of glucagon-like peptide-1 in DPN, the current study investigated the physiological indispensability of glucagon gene-derived peptides (GCGDPs) including glucagon-like peptide-1 in the peripheral nervous system (PNS). Neurological functions and neuropathological changes of GCGDP deficient (gcg-/-) mice were examined. The gcg-/- mice showed tactile allodynia and thermal hyperalgesia at 12-18 weeks old, followed by tactile and thermal hypoalgesia at 36 weeks old. Nerve conduction studies revealed a decrease in sensory nerve conduction velocity at 36 weeks old. Pathological findings showed a decrease in intraepidermal nerve fiber densities. Electron microscopy revealed a decrease in circularity and an increase in g-ratio of myelinated fibers and a decrease of unmyelinated fibers in the sural nerves of the gcg-/- mice. Effects of glucagon on neurite outgrowth were examined using an ex vivo culture of dorsal root ganglia. A supraphysiological concentration of glucagon promoted neurite outgrowth. In conclusion, the mice with deficiency of GCGDPs developed peripheral neuropathy with age. Furthermore, glucagon might have neuroprotective effects on the PNS of mice. GCGDPs might be involved in the pathology of DPN.


Assuntos
Neuropatias Diabéticas/etiologia , Peptídeos Semelhantes ao Glucagon/deficiência , Animais , Neuropatias Diabéticas/genética , Neuropatias Diabéticas/patologia , Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Glucagon/deficiência , Glucagon/genética , Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/deficiência , Peptídeo 1 Semelhante ao Glucagon/genética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeos Semelhantes ao Glucagon/genética , Peptídeos Semelhantes ao Glucagon/metabolismo , Hiperalgesia/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fibras Nervosas Mielinizadas/patologia , Condução Nervosa , Crescimento Neuronal , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Glucagon/genética , Receptores de Glucagon/metabolismo
16.
Metabol Open ; 5: 100024, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32812937

RESUMO

Purpose: Bile acids (BAs) have been shown to contribute to glucose and energy homeostasis. We have recently reported that miglitol, an alpha-glucosidase inhibitor, increases fecal BA excretion and ameliorate insulin resistance and obesity in mice. The aim of this study was to clarify the mechanisms by which miglitol affects BA metabolism. The expression of genes regulating BA metabolism, gut microbiome and short-chain fatty acids (SCFA) were examined. Procedures: NSY mice, representing an obese type 2 diabetic model, were fed with a high-fat diet with or without miglitol for 4 weeks. The expression of BA-related genes in the liver and the lower intestine were measured. Alterations in fecal microbiome, fecal SCFA along with plasma lipid levels were also evaluated. Major findings: Miglitol significantly increased fecal BA secretion and markedly upregulated the mRNA expression, protein levels and enzyme activity of hepatic cholesterol 7α-hydroxylase, a rate-limiting enzyme of BA synthesis. In the intestine, miglitol treatment significantly suppressed the mRNA expression of apical sodium-dependent bile acid transporter and ATP-binding cassette transporter G5 and G8. In fecal microbiome, the prevalence of prevotella was remarkably reduced and that of clostridium subcluster XIVa was increased by miglitol. Miglitol elevated formic and n-butyric acids along with total SCFA concentration in feces, while succinic acid was decreased. There was no change in plasma total cholesterol levels. Conclusions: Collectively, miglitol may affect BA metabolism via enhanced CYP7A1 activity resulting from at least in part the alterations in gut microbiome and SCFA production in obese diabetic mice.

17.
Seizure ; 80: 12-17, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32480278

RESUMO

PURPOSE: To evaluate barbiturate anaesthetic therapy using thiamylal for febrile refractory status epilepticus (fRSE) in children. METHODS: This was a review of a prospectively-collected database between April 2012-March 2016 for fRSE cases treated with thiamylal anaesthetic therapy in a single paediatric hospital in Japan. The sample comprised 23 children (median age, 23 months) with fRSE that underwent thiamylal anaesthetic therapy for convulsive seizures lasting longer than 60 min, sustained after intravenous administration of benzodiazepine and non-benzodiazepine anticonvulsants. The intervention comprised protocol-based thiamylal anaesthetic therapy with bolus administration. We measured the dose and time required to achieve the burst suppression pattern (BSP) on electroencephalography, seizure recurrence, death, neurological sequelae, and complications. RESULTS: All patients except one reached the BSP. The thiamylal median dose until reaching the BSP was 27.5 mg/kg, and the median time from thiamylal administration to reaching the BSP was 109.5 min. There was one case of immediate treatment failure and one of withdrawal seizure, but no breakthrough seizure. No deaths occurred during treatment, and neurological sequelae occurred in four cases (17%). Vasopressors were administered in all cases. Other complications included 11 cases of pneumonia and one of enterocolitis. CONCLUSION: We revealed the time and dose required to reach the BSP with thiamylal anaesthetic therapy using bolus administration in children. Our results suggested that reaching the BSP with bolus administration requires markedly less time than without bolus administration, rarely causes seizure recurrence in paediatric fRSE, and causes haemodynamic dysfunction and infections as often as observed without bolus administration.


Assuntos
Anestésicos , Estado Epiléptico , Anestésicos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Humanos , Lactente , Japão , Estado Epiléptico/tratamento farmacológico , Tiamilal/uso terapêutico
18.
J Diabetes Investig ; 11(6): 1434-1447, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32279428

RESUMO

AIMS/INTRODUCTION: Pancreatic islets are heterogenous. To clarify the relationship between islet heterogeneity and incretin action in the islets, we studied gene expression and metabolic profiles of non-large and enlarged islets of the Zucker fatty diabetes mellitus rat, an obese diabetes model, as well as incretin-induced insulin secretion (IIIS) in these islets. MATERIALS AND METHODS: Pancreatic islets of control (fa/+) and fatty (fa/fa) rats at 8 and 12 weeks-of-age were isolated. The islets of fa/fa rats at 12 weeks-of-age were separated into non-large islets (≤200 µm in diameter) and enlarged islets (>300 µm in diameter). Morphological analyses, insulin secretion experiments, transcriptome analysis, metabolome analysis and oxygen consumption analysis were carried out on these islets. RESULTS: The number of enlarged islets was increased with age in fatty rats, and IIIS was significantly reduced in the enlarged islets. Markers for ß-cell differentiation were markedly decreased in the enlarged islets, but those for cell proliferation were increased. Glycolysis was enhanced in the enlarged islets, whereas the tricarboxylic acid cycle was suppressed. The oxygen consumption rate under glucose stimulation was reduced in the enlarged islets. Production of glutamate, a key signal for IIIS, was decreased in the enlarged islets. CONCLUSIONS: The enlarged islets of Zucker fatty diabetes mellitus rats, which are defective for IIIS, show tumor cell-like metabolic features, including a dedifferentiated state, accelerated aerobic glycolysis and impaired mitochondrial function. The age-dependent increase in such islets could contribute to the pathophysiology of obese diabetes.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Incretinas/toxicidade , Secreção de Insulina/efeitos dos fármacos , Ilhotas Pancreáticas/patologia , Metaboloma/efeitos dos fármacos , Obesidade/fisiopatologia , Neoplasias Pancreáticas/patologia , Animais , Perfilação da Expressão Gênica , Ilhotas Pancreáticas/efeitos dos fármacos , Masculino , Neoplasias Pancreáticas/induzido quimicamente , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Ratos , Ratos Zucker
19.
J Neurol Sci ; 411: 116684, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32001378

RESUMO

OBJECTIVE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a syndrome characterized by biphasic seizures with impaired consciousness. AESD is rare outside Asia, and consecutive cohort studies are therefore scarce. Herein, we aimed to describe the detailed characteristics of AESD, including clinical course, electroencephalogram data, laboratory data, imaging findings, treatment, and outcomes. METHODS: We reviewed the clinical database and medical charts of 43 consecutive pediatric patients (<18 years old) who developed AESD between October 1, 2002, and September 30, 2019. RESULTS: We found that AESD occurred even though patients did not develop prolonged seizures. A comparison between the two groups (first seizure duration <30 min and first seizure duration ≥30 min) revealed three main findings: first, patients with AESD who had shorter seizures had better prognosis than those with prolonged seizures; second, patients with AESD who had shorter seizures tended to have earlier occurrence of a second seizure; and third, high signal intensity on diffusion-weighted magnetic resonance imaging was observed mainly in frontal areas, not diffusely, in patients with shorter seizures, and in a broader area in patients with prolonged seizures. CONCLUSIONS: Our description of the detailed clinical picture of AESD may add new insight into its pathophysiology.


Assuntos
Encefalopatias , Estado Epiléptico , Adolescente , Ásia , Criança , Estudos de Coortes , Imagem de Difusão por Ressonância Magnética , Humanos , Lactente , Convulsões/diagnóstico por imagem , Convulsões/epidemiologia
20.
Neurosci Lett ; 722: 134826, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32045623

RESUMO

Cerebrospinal fluid (CSF) total tau (t-tau) and tau protein phosphorylated at threonine 181 (p181tau) are established biomarkers for Alzheimer's disease (AD). Herein, we measured t-tau and p181tau to evaluate novel enzyme-linked immunosorbent assays (ELISAs) using 72 CSF samples including from patients with AD with dementia (ADD) and various neurodegenerative diseases. Our assay system showed good correlations with widely used ELISA systems for t-tau and p181tau and showed that serum and hemoglobin contamination in CSF samples did not decrease sensitivity. Significant increases in both t-tau and p181tau levels were observed in ADD. These findings suggested that our ELISAs were reliable assays for CSF t-tau and p181tau similar to commonly used ELISAs.


Assuntos
Doenças do Sistema Nervoso/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/metabolismo , Fosforilação/fisiologia , Adulto Jovem , Proteínas tau/metabolismo
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