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1.
Int J Mol Sci ; 25(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38542065

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant liver ailment attributed to factors like obesity and diabetes. While ongoing research explores treatments for NAFLD, further investigation is imperative to address this escalating health concern. NAFLD manifests as hepatic steatosis, precipitating insulin resistance and metabolic syndrome. This study aims to validate the regenerative potential of chimeric fibroblast growth factor 21 (FGF21) and Hepatocyte Growth Factor Receptor (HGFR) in NAFLD-afflicted liver cells. AML12, a murine hepatocyte cell line, was utilized to gauge the regenerative effects of chimeric FGF21/HGFR expression. Polysaccharide accumulation was affirmed through Periodic acid-Schiff (PAS) staining, while LDL uptake was microscopically observed with labeled LDL. The expression of FGF21/HGFR and NAFLD markers was analyzed by mRNA analysis with RT-PCR, which showed a decreased expression in acetyl-CoA carboxylase 1 (ACC1) and sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) with increased expression of hepatocellular growth factor (HGF), hepatocellular nuclear factor 4 alpha (HNF4A), and albumin (ALB). These findings affirm the hepato-regenerative properties of chimeric FGF21/HGFR within AML12 cells, opening novel avenues for therapeutic exploration in NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Fígado/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo
2.
BMC Ophthalmol ; 23(1): 513, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38110856

RESUMO

BACKGROUND: To review cases of branch retinal vein occlusion (BRVO) secondary to rhegmatogenous retinal detachment (RRD) and its surgical management and presume their mechanism. METHODS: Medical records of patients who underwent surgery for RRD between 2015 and 2019 at a single tertiary care center were retrospectively reviewed. New BRVO secondary to RRD or its surgical procedure was diagnosed based on the fundus examination and its clinical course. RESULTS: A total of 734 RRD surgeries were performed for five years, and six cases of new BRVOs were noticed in the first year after surgery (incidence was 0.68%: six cases of BRVO / 734 cases of surgical RRD); five cases occurred after vitrectomy, and one occurred after scleral buckling. In three cases, retinal veins were presumed to already be partially occluded related due to a kink of the retinal vein seen before surgery. In the other three cases, the retinal veins were presumed to have incurred damage during vitrectomy. CONCLUSION: In the present cohort, RRD or its related procedures caused BRVO within a year of surgery at an incidence of 0.68%. The proposed mechanisms are kinks of the retinal vein on the detached retina and damage to the retinal vein during vitrectomy.


Assuntos
Descolamento Retiniano , Oclusão da Veia Retiniana , Humanos , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Descolamento Retiniano/cirurgia , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/cirurgia , Estudos Retrospectivos , Recurvamento da Esclera/efeitos adversos , Fundo de Olho , Vitrectomia/métodos , Resultado do Tratamento
3.
Int J Med Sci ; 19(11): 1631-1637, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36237990

RESUMO

Background: Diaphragm movement is well correlated with inspired volume of the lung. Dexmedetomidine (DEX) has less effect on respiratory functions than other sedatives. The objective of this study was to investigate diaphragmatic movement using ultrasound (US) during DEX infusion for sedation in spontaneously breathing patients undergoing unilateral upper limb surgery. Methods: A total of 33 consecutive patients were enrolled in this study. Patients were sedated using DEX with ipsilateral axillary brachial nerve plexus block. Diaphragmatic activity was evaluated using diaphragmatic thickening at end-inspiration (TEI), diaphragmatic thickening at end-expiration (TEE), and diaphragmatic thickening fraction (DTF) measured by diaphragmatic US at three time-points; T0, baseline; T1, after DEX sedation; and T2, after DEX recovery. Supplementary oxygen was applied with a simple mask at 5 L/min. Peripheral oxygen saturation (SpO2), end tidal CO2 (EtCO2), and respiratory rate (RR) were recorded. Results: TEI and TEE showed no significant changes during the study period (P = 0.394 and P = 0.205, respectively). DTF was maintained at both T0 and T1 (P = 1.000). At recovery after DEX infusion discontinued, DTF was increased by 3.85%, although such increase was not statistically significant (T0 vs. T2, P = 0.525). SpO2 remained above 99% and EtCO2 remained below 36 mmHg. Desaturation episodes were not observed during the study period. Conclusions: Results of this study showed that DEX sedation did not affect the diaphragmatic movement in situation of decreased RR induced by DEX. This finding implies that DEX-induced sedation does not result in clinically significant respiratory depression.


Assuntos
Dexmedetomidina , Dióxido de Carbono , Dexmedetomidina/farmacologia , Diafragma/diagnóstico por imagem , Humanos , Hipnóticos e Sedativos , Oxigênio , Ultrassonografia
4.
J Pharmacol Exp Ther ; 369(3): 318-327, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30894456

RESUMO

Tegoprazan, a novel potassium-competitive acid blocker (P-CAB), is a next-generation therapeutics developed for the treatment of acid-related gastrointestinal diseases such as gastroesophageal reflux disease (GERD) and peptic ulcers. In the present study, the in vitro and in vivo pharmacological properties of tegoprazan were compared with those of esomeprazole, a representative proton pump inhibitor. In vitro enzyme assays were performed using ion-leaky vesicles containing gastric H+/K+-ATPases isolated from pigs. The in vivo efficacies of tegoprazan were evaluated in rat models of GERD and peptic ulcer. Tegoprazan inhibited the activity of porcine H+/K+-ATPase with an IC50 value of 0.53 µM in a reversible manner, whereas esomeprazole showed weak and irreversible inhibition with an IC50 value of 42.52 µM. In a GERD model, tegoprazan showed dose-dependent efficacy in inhibiting esophageal injury and gastric acid secretion with an ED50 of 2.0 mg/kg, which was 15-fold more potent than that of esomeprazole. In peptic ulcer models, tegoprazan exhibited superior antiulcer activity compared with esomeprazole. The ED50 of tegoprazan in the naproxen-, ethanol-, and water-immersion restraint stress-induced peptic ulcer models were 0.1, 1.4, and 0.1 mg/kg, respectively. In the acetic acid-induced peptic ulcer model, the curative ratio of tegoprazan at 10 mg/kg was higher than that of esomeprazole at 30 mg/kg (44.2% vs. 32.7%, respectively), after 5 days of repeated oral administration. Thus, tegoprazan is a novel P-CAB that shows potent and reversible inhibition of gastric H+/K+-ATPase and may provide stronger efficacy compared with previous proton pump inhibitors.


Assuntos
Derivados de Benzeno/farmacologia , Ácido Gástrico/metabolismo , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/metabolismo , Imidazóis/farmacologia , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/metabolismo , Potássio/metabolismo , Animais , Derivados de Benzeno/uso terapêutico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esomeprazol/farmacologia , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Imidazóis/uso terapêutico , Ratos , Estômago/efeitos dos fármacos , Estômago/enzimologia , Distribuição Tecidual
5.
Prep Biochem Biotechnol ; 47(6): 539-546, 2017 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-27136080

RESUMO

A fibrinolytic metalloprotease with in vitro fibrinolytic effects was purified from the edible mushroom Pleurotus ferulae using several chromatography steps including anion and ion exchange, gel filtration, and fast protein liquid chromatography columns. The molecular mass of the enzyme was estimated to be 20.0 kDa, as determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fibrin zymography. The protease was active at 50°C, and pH 4.0, 5.0, and 8.0. The fibrinolytic activity of the enzyme was inhibited by ethyleneglycol-bis-(2-aminoethyl)-N,N,N',N' tetraacetic acid and strongly inhibited by two metal ions, Cu and Mg. In vitro assays evaluating fibrinolytic activity on a fibrin plate, fibrin turbidity, and thrombolytic activity on fibrin clots using human fibrinogen and human thrombin revealed that the enzyme could hydrolyze fibrin polymers directly and inhibit the formation of fibrin clots. In activated partial thromboplastin time (APTT) and prothrombin time assays, the enzyme strongly prolonged the APTT, which detects an activity of intrinsic and common pathways. The enzyme showed strong in vivo protective effect against mortality/paralysis from epinephrine plus collagen-induced acute thromboembolism in in vivo model. Our findings suggest that the enzyme may have a potential for treatment and prevention of thrombosis-relative diseases.


Assuntos
Fibrinolíticos/isolamento & purificação , Carpóforos/enzimologia , Metaloproteases/isolamento & purificação , Pleurotus/enzimologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Fibrinolíticos/metabolismo , Fibrinolíticos/uso terapêutico , Carpóforos/metabolismo , Humanos , Masculino , Metaloproteases/metabolismo , Metaloproteases/uso terapêutico , Camundongos Endogâmicos ICR , Pleurotus/metabolismo , Tromboembolia/sangue , Tromboembolia/tratamento farmacológico
6.
J Biochem Mol Toxicol ; 30(3): 111-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26418808

RESUMO

Undaria pinnatifida is a well-known traditional Korean food with a variety of biological activities. Carrageenan (carr) is commonly used to induce paw edema in animal models. This study was designed to elucidate the processes underlying the anti-inflammatory effect of fucoxanthin isolated from the sporophyll of U. pinnatifida in carr-induced paw edema in ICR mice. Fucoxanthin significantly decreased carr-induced increased nitric oxide levels in the plasma of mice with carr-induced paw edema. Fucoxanthin protected catalase (CAT) and superoxide dismutase (SOD) activity against disruption in mice with carr-induced paw edema. In addition, fucoxanthin repressed carr-induced activation of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor kappa B, as well as carr-induced phosphorylation of mitogen-activated protein kinase, extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and protein kinase B/Akt. These results suggest that fucoxanthin may have therapeutic potential as a treatment for patients with inflammatory diseases.


Assuntos
Modelos Animais de Doenças , Inflamação/prevenção & controle , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Xantofilas/farmacologia , Animais , Catalase/metabolismo , Ciclo-Oxigenase 2/metabolismo , Edema/prevenção & controle , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação , Superóxido Dismutase/metabolismo
7.
Acta Radiol ; 57(11): 1372-1379, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25585852

RESUMO

Background There has been no comparison study to assess the diagnostic efficacy of additional anterior cruciate ligament (ACL) views in three-dimensional (3D) volume isotropic turbo spin-echo acquisition (VISTA) and two-dimensional (2D) fast spin-echo (FSE) T2-weighted (T2W) images for the diagnosis of ACL tear. Purpose To compare the diagnostic performances of additional ACL views on VISTA with those on the 2D FSE T2W images. Material and Methods This retrospective study included 78 patients who were suspected to have ACL injury and underwent both 2D TSE T2W magnetic resonance imaging (MRI) and 3D VISTA MRI of the knee between November 2012 and March 2013. The diagnostic performance of each oblique sagittal and coronal view and the combined images was evaluated for sensitivity, specificity, and accuracy for diagnosing an ACL tear. The arthroscopically and clinically confirmed diagnoses were used as the reference standard. The values were statistically analyzed using the McNemar test. Results The inter-observer agreement between two readers of the additional ACL views on 3D VISTA and 2D FSE T2W images were substantial on 2D FSE images and nearly concurred on the VISTA image. When considering both views of the oblique sagittal and coronal images, the inter-observer agreement between readers nearly concurred. There were no statistically significant differences in the sensitivity, specificity, and accuracy between 2D FSE images and VISTA images. Conclusion The performance of the additional ACL view on 3D VISTA MRI is comparable to that of 2D FSE T2W MRI in the diagnosis of ACL tear though the image quality of the 3D VISTA MRI is not equal to that of 2D FSE MRI.


Assuntos
Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Imageamento Tridimensional/métodos , Articulação do Joelho/diagnóstico por imagem , Posicionamento do Paciente/métodos , Adolescente , Adulto , Idoso , Anisotropia , Feminino , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Marcadores de Spin , Adulto Jovem
8.
Helicobacter ; 20(6): 424-30, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25752487

RESUMO

BACKGROUND: The eradication rate of Helicobacter pylori (H. pylori) infection might be affected by the degree of inflammation of gastric mucosa represented by the endoscopic stage of peptic ulcer disease (PUD). The aims of this study were to evaluate the eradication rates of H. pylori infection according to the endoscopic stage of PUD and to document whether early eradication in the active stage could yield a higher eradication rate in patients with peptic ulcer bleeding (PUB). MATERIALS AND METHODS: A total of 1,177 patients with PUD (380 gastric ulcer, 710 duodenal ulcer, and 87 combined ulcer) who received proton-pump inhibitor (PPI)-based triple therapy were included, and the eradication rates were compared by ulcer stage. Univariate and multivariate analyses were conducted to identify factors influencing eradication rate. In PUB, the eradication rates between the early eradication group (≤7 days) and the late eradication group (>7 days) were compared. RESULTS: The eradication rates according to endoscopic stage were significantly different in gastric ulcer (active vs healing vs scarring; 84.8% vs 82.7% vs 70.6%, p = .014, respectively), but there were no significant differences in duodenal ulcer (active vs healing vs scarring; 87.6% vs 80.9%% vs 80.9% p = .169, respectively). In multivariate analyses, active ulcer as well as age younger than 50 was a significantly independent predictor of successful eradication (Odds ratio; 2.799, 95% CI; 1.659-4.723, p = .0001). The eradication rate of the early eradication group was significantly higher than the late eradication group in PUB (89.2% vs 71.9%, 95% CI; 1.265-8.269, p = .011). CONCLUSIONS: There was a significant difference in the eradication rate according to the endoscopic stage of gastric ulcer. Active ulcer was an independent predictor of successful eradication. Furthermore, early H. pylori eradication should be considered in patients with PUB to yield a higher eradication rate.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/patologia , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/patologia , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
9.
J Biochem Mol Toxicol ; 29(5): 240-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25651404

RESUMO

We investigated in vitro and in vivo fibrinolytic and antithrombotic activity of spirulan and analyzed its partial biochemical properties. Spirulan, a sulfated polysaccharide from the blue-green alga Arthrospira platensis, exhibits antithrombotic potency. Spirulan showed a strong fibrin zymogram lysis band corresponding to its molecular mass. It specifically cleaved Aα and Bß, the major chains of fibrinogen. Spirulan directly decreased the activity of thrombin and factor X activated (FXa), procoagulant proteins. In vitro assays using human fibrin and mouse blood clots showed fibrinolytic and hemolytic activities of spirulan. Spirulan (2 mg/kg) showed antithrombotic effects in the ferric chloride (FeCl3 )-induced carotid arterial thrombus model and collagen and epinephrine-induced pulmonary thromboembolism mouse model. These results may be attributable to the prevention of thrombus formation and partial lysis of thrombus. Therefore, we suggest that spirulan may be a potential antithrombotic agent for thrombosis-related diseases.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Fibrina/antagonistas & inibidores , Fibrinolíticos/farmacologia , Polissacarídeos/farmacologia , Trombose/tratamento farmacológico , Animais , Cianobactérias/química , Fibrinogênio/antagonistas & inibidores , Fibrinolíticos/química , Humanos , Camundongos , Polissacarídeos/química , Trombose/patologia
10.
Int J Med Sci ; 12(11): 891-904, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26640409

RESUMO

OBJECTIVES: A newly developed angiotensin II receptor blocker, fimasartan, is effective in lowering blood pressure through its action on the renin-angiotensin system. Renal interstitial fibrosis, believed to be due to oxidative injury, is an end-stage process in the progression of chronic kidney disease. Nuclear factor erythroid 2-related factor 2 (Nrf2) is known to regulate cellular oxidative stress and induce expression of antioxidant genes. In this study we investigated the role of Nrf2 in fimasartan-mediated antioxidant effects in mice with renal fibrosis induced by unilateral ureteral obstruction (UUO). MATERIALS AND METHODS: UUO was induced surgically in mice, followed by either no treatment with fimasartan or the intraperitoneal administration of fimasartan (3 mg/kg/day). On day 7, we evaluated the changes in the renin-angiotensin system (RAS) and the expression of Nrf2 and its downstream antioxidant genes, as well as renal inflammation, apoptosis, and fibrosis in the obstructed kidneys. The effect of fimasartan on the Nrf2 pathway was also investigated in HK-2 cells stimulated by tumor necrosis factor-α. RESULTS: The mice with surgically induced UUO showed increased renal inflammation and fibrosis as evidenced by histopathologic findings and total collagen content in the kidney. These effects were attenuated in the obstructed kidneys of the fimasartan-treated mice. Fimasartan treatment inhibited RAS activation and the expression of Nox1, Nox2, and Nox4. In contrast, fimasartan upregulated the renal expression of Nrf2 and its downstream signaling molecules (such as NQO1; HO-1; GSTa2 and GSTm3). Furthermore, it increased the expression of antioxidant enzymes, including CuSOD, MnSOD, and catalase. The fimasartan-treated mice had significantly less apoptosis on TUNEL staining, with decreased levels of pro-apoptotic protein and increased levels of anti-apoptotic protein. In the HK-2 cells, fimasartan treatment inhibited RAS activation, decreased expression of mitogen-activated protein kinases (MAPKs), and upregulated the Nrf2 pathway. CONCLUSIONS: These results suggest that fimasartan has beneficial effects in reducing renal oxidative stress, inflammation, and fibrosis. Possible mechanisms to explain these effects are inhibition of RAS and MAPKs and upregulation of Nrf2 signaling, with subsequent induction of antioxidant pathways.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Rim/patologia , Fator 2 Relacionado a NF-E2/fisiologia , Nefrite/prevenção & controle , Pirimidinas/uso terapêutico , Tetrazóis/uso terapêutico , Animais , Apoptose , Fibrose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistema Renina-Angiotensina/efeitos dos fármacos , Transdução de Sinais , Sístole/efeitos dos fármacos , Obstrução Ureteral
11.
Neurochem Res ; 39(1): 84-96, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24214023

RESUMO

Celastrol, a potent natural triterpene and one of the most promising medicinal molecules, is known to possess a broad range of biological activity. Rotenone, a pesticide and complex I inhibitor, is commonly used to produce experimental models of Parkinson's disease both in vivo and in vitro. The present study was designed to examine the effects of celastrol on cell injury induced by rotenone in the human dopaminergic cells and to elucidate the possible mechanistic clues in its neuroprotective action. We demonstrate that celastrol protects SH-SY5Y cells from rotenone-induced cellular injury and apoptotic cell death. Celastrol also prevented the increased generation of reactive oxygen species and mitochondrial membrane potential (ΔΨm) loss induced by rotenone. Similarly, celastrol treatment inhibited cytochrome c release, Bax/Bcl-2 ratio changes, and caspase-9/3 activation. Celastrol specifically inhibited rotenone-evoked p38 mitogen-activated protein kinase activation in SH-SY5Y cells. These data suggest that celastrol may serve as a potent agent for prevention of neurotoxin-induced neurodegeneration through multiple mechanisms and thus has therapeutic potential for the treatment of neurodegenerative diseases.


Assuntos
Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/fisiopatologia , Rotenona/toxicidade , Triterpenos/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Triterpenos Pentacíclicos , Rotenona/antagonistas & inibidores
12.
Neurochem Res ; 39(4): 707-18, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24549762

RESUMO

Dendropanax morbifera Leveille (Araliaceae) is well known in Korean traditional medicine for a variety of diseases. Rotenone is a commonly used neurotoxin to produce in vivo and in vitro Parkinson's disease models. This study was designed to elucidate the processes underlying neuroprotection of rutin, a bioflavonoid isolated from D. morbifera Leveille in cellular models of rotenone-induced toxicity. We found that rutin significantly decreased rotenone-induced generation of reactive oxygen species levels in SH-SY5Y cells. Rutin protected the increased level of intracellular Ca(2+) and depleted level of mitochondrial membrane potential (ΔΨm) induced by rotenone. Furthermore, it prevented the decreased ratio of Bax/Bcl-2 caused by rotenone treatment. Additionally, rutin protected SH-SY5Y cells from rotenone-induced caspase-9 and caspase-3 activation and apoptotic cell death. We also observed that rutin repressed rotenone-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinase phosphorylation. These results suggest that rutin may have therapeutic potential for the treatment of neurodegenerative diseases associated with oxidative stress.


Assuntos
Neurônios Dopaminérgicos/enzimologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Rotenona/toxicidade , Rutina/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Araliaceae , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Inibidores de Proteínas Quinases/isolamento & purificação , Rotenona/antagonistas & inibidores , Rutina/isolamento & purificação , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
BMC Endocr Disord ; 14: 24, 2014 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-24606630

RESUMO

BACKGROUND: The purpose of this study was to evaluate the association between blood manganese levels and the prevalence of chronic diseases in the Korean population. METHODS: This was a cross-sectional study based on the Korean National Health and Nutrition Examination Survey (KNAHNES). The study included 3996 participants 20 years of age or older whose blood manganese levels had been measured. The participants were also evaluated for the presence of five chronic diseases: diabetes, renal dysfunction, hypertension, ischemic heart disease, and stroke. RESULTS: Blood manganese levels were significantly lower in the diabetes group compared with the non-diabetes group (1.26 ± 0.02 vs. 1.35 ± 0.01 µg/dL; p = 0.001) and the renal dysfunction group compared with those with normal renal function (1.28 ± 0.03 vs. 1.35 ± 0.01 µg/dL; p = 0.04). There was no significant association between blood manganese levels and the presence of ischemic heart disease or stroke. A multivariate logistic regression analysis adjusted for age, sex, and body mass index was performed; the odds ratio was 0.652 (95% CI: 0.46-0.92) for diabetes and 0.589 (95% CI: 0.39-0.88) for renal dysfunction when comparing the higher quartiles (Q2-4) with the lowest quartile (Q1) of blood manganese level. The prevalence of diabetes was 7.6% in Q1 and 5.3% in Q2-4 (p = 0.02). Similarly, the prevalence of renal dysfunction was 6.8% in Q1, compared with 4.6% in Q2-4 (p = 0.02). CONCLUSION: The prevalence of diabetes and renal dysfunction increased in participants with low blood manganese levels, suggesting that blood manganese may play a role in glucose homeostasis and renal function.

14.
Clin Exp Nephrol ; 18(5): 726-34, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24276216

RESUMO

BACKGROUND: The objective of this study was to evaluate the associations of blood lead and cadmium levels with estimated glomerular filtration rate (eGFR) and proteinuria in Korean adults. METHODS: This was a cross-sectional study based on the Korea Nation Health and Nutrition Examination Survey (KNHANES) to analyze the association of blood lead and cadmium levels with renal dysfunction and urine protein excretion. We defined renal dysfunction as eGFR < 60 ml/min/1.73 m(2), as measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and proteinuria as positive urine dip-stick result. RESULTS: Blood lead and cadmium levels were significantly increased in the renal dysfunction group compared with the normal renal function group. Lead levels were significantly higher in the proteinuria group than in the group with no proteinuria. There were no differences in cadmium levels according to the amount of proteinuria. Multivariate logistic regression analysis adjusted for age and sex demonstrated higher lead and cadmium levels in the renal dysfunction group than in the group with normal renal function [odds ratio (OR) 1.344, 95 % confidence interval (CI) 1.157-1.162, P < 0.05; OR 1.467, 95 % CI 1.077-1.999, P < 0.05, respectively]. For proteinuria, the fully adjusted ORs comparing the highest versus the lowest lead and cadmium quartiles were 1.22 (95 % CI 1.00-1.50) and 0.51 (95 % CI 0.24-1.08), respectively, showing no significance. For reduced eGFR, the fully adjusted ORs comparing the highest versus the lowest lead and cadmium quartiles were 1.23 (95 % CI 0.98-1.53) and 1.93 (95 % CI 1.39-2.67), respectively, showing the significant association between lead and cadmium levels and renal function. The risk of having reduced eGFR for individuals in the highest quartiles of both lead and cadmium levels in blood was greater than for those in the highest quartile of blood level of lead or cadmium only. CONCLUSION: The CKD-EPI equation showed that blood lead and cadmium levels were associated with renal dysfunction in the Korean adult population. This finding has significant implications for environmental institutional strategies regarding heavy metal exposure.


Assuntos
Cádmio/toxicidade , Taxa de Filtração Glomerular/efeitos dos fármacos , Chumbo/toxicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Cádmio/sangue , Estudos Transversais , Feminino , Humanos , Chumbo/sangue , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , República da Coreia , Adulto Jovem
15.
BMC Nephrol ; 15: 96, 2014 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-24957046

RESUMO

BACKGROUND: Although percutaneous renal biopsy remains an essential tool in the diagnosis and treatment of renal diseases, in recent times the traditional procedure of nephrologists has been performed by non-nephrologists rather than nephrologists at many institutions. The present study assessed the safety and adequacy of tissue yield during percutaneous renal biopsy according to practitioners and techniques based on ultrasound. METHODS: This study included 658 native renal biopsies performed from 2005 to 2010 at a single centre. The biopsies were performed by nephrologists or expert ultrasound radiologists using the ultrasound-marked blind or real-time ultrasound-guided techniques. RESULTS: A total of 271 ultrasound-marked blind biopsies were performed by nephrologists, 170 real-time ultrasound-guided biopsies were performed by nephrologists, and 217 real-time ultrasound-guided biopsies were performed by radiologists during the study period. No differences in post-biopsy complications such as haematoma, need for transfusion and intervention, gross haematuria, pain, or infection were observed among groups. Glomerular numbers of renal specimens from biopsies performed by nephrologists without reference to any technique were higher than those obtained from real-time ultrasound-guided biopsies performed by expert ultrasound radiologists. CONCLUSIONS: Percutaneous renal biopsy performed by nephrologists was not inferior to that performed by expert ultrasound radiologists as related to specimen yield and post-biopsy complications.


Assuntos
Competência Clínica/estatística & dados numéricos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Hematúria/etiologia , Rim/patologia , Dor/etiologia , Adulto , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/estatística & dados numéricos , Feminino , Hematúria/diagnóstico , Hematúria/prevenção & controle , Humanos , Rim/diagnóstico por imagem , Masculino , Nefrologia/estatística & dados numéricos , Dor/diagnóstico , Dor/prevenção & controle , Radiografia , Radiologia/estatística & dados numéricos , Reprodutibilidade dos Testes , República da Coreia , Estudos Retrospectivos , Sensibilidade e Especificidade
16.
J Korean Med Sci ; 29(2): 230-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24550650

RESUMO

This study investigated whether tempol, an anti-oxidant, protects against renal injury by modulating phosphatidylinositol 3-kinase (PI3K)-Akt-Forkhead homeobox O (FoxO) signaling. Mice received unilateral ureteral obstruction (UUO) surgery with or without administration of tempol. We evaluated renal damage, oxidative stress and the expression of PI3K, Akt, FoxO3a and their target molecules including manganese superoxide dismutase (MnSOD), catalase, Bax, and Bcl-2 on day 3 and day 7 after UUO. Tubulointerstitial fibrosis, collagen deposition, α-smooth muscle actin-positive area, and F4/80-positive macrophage infiltration were significantly lower in tempol-treated mice compared with control mice. The expression of PI3K, phosphorylated Akt, and phosphorylated FoxO3a markedly decreased in tempol-treated mice compared with control mice. Tempol prominently increased the expressions of MnSOD and catalase, and decreased the production of hydrogen peroxide and lipid peroxidation in the obstructed kidneys. Significantly less apoptosis, a lower ratio of Bax to Bcl-2 expression and fewer apoptotic cells in TUNEL staining, and decreased expression of transforming growth factor-ß1 were observed in the obstructed kidneys from tempol-treated mice compared with those from control mice. Tempol attenuates oxidative stress, inflammation, and fibrosis in the obstructed kidneys of UUO mice, and the modulation of PI3K-Akt-FoxO3a signaling may be involved in this pathogenesis.


Assuntos
Óxidos N-Cíclicos/farmacologia , Fatores de Transcrição Forkhead/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Obstrução Ureteral/metabolismo , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Colágeno/metabolismo , Óxidos N-Cíclicos/uso terapêutico , Fibrose , Proteína Forkhead Box O3 , Peróxido de Hidrogênio/metabolismo , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Nefropatias/patologia , Peroxidação de Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Índice de Gravidade de Doença , Marcadores de Spin , Superóxido Dismutase/metabolismo , Obstrução Ureteral/complicações , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/patologia
17.
Int J Med Sci ; 10(11): 1430-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24046514

RESUMO

OBJECTIVE: In this study, we investigated the predictive capacity of the brachial-ankle aortic pulse wave velocity (baPWV), a marker of arterial stiffness, for the decline in renal function and for cardiovascular events in the early stages of chronic kidney disease (CKD). METHOD: Two hundred forty-one patients who underwent a comprehensive check-up were included and were divided into two groups according to their estimated glomerular filtration rates (eGFR): patients with CKD categories G2, G3a and G3b (30 ≤ eGFR < 90 ml/min/1.73m(2), eGFR < 90 group; n=117) and those with eGFR ≥ 90 ml/min/1.73 m(2) (eGFR ≥ 90 group; n=124). The change in renal function, the eGFR change, was determined by the slope of eGFR against time. We analysed whether baPWV was associated with eGFR change or predicted cardiovascular events. RESULTS: baPWV was independently associated with eGFR change in a multivariate analysis of the total patients (ß=-0.011, p=0.011) and remained significantly associated with eGFR change in a subgroup analysis of the eGFR < 90 group (ß=-0.015, p=0.035). baPWV was independently associated with cardiovascular events (odds ratio=1.002, p=0.048) in the eGFR < 90 group, but not in the eGFR ≥ 90 group. The receiver operative characteristic curve analysis showed that 1,568 cm/sec was the cut-off value of baPWV for predicting CV events in the eGFR < 90 group (area under curve=0.691, p=0.03) CONCLUSIONS: In patients with early stages of CKD, baPWV was independently associated with the decline in renal function and short-term cardiovascular events.


Assuntos
Insuficiência Renal Crônica/fisiopatologia , Adulto , Índice Tornozelo-Braço , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso
18.
Hepatogastroenterology ; 60(127): 1592-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24634927

RESUMO

BACKGROUND/AIMS: The clinical course of acute viral hepatitis A (AHA) is highly variable. Serum alphafetoprotein (AFP) level is often elevated in various types of acute liver injuries, indicating active liver regeneration. This study was aimed to investigate the clinical significance of serum AFP level in the aspect of the early recovery in AHA. METHODOLOGY: A total of 238 patients with AHA, confirmed by IgM anti-hepatitis A virus, were included. The patients were classified according to serum AFP level. Multivariate analysis by Cox proportional hazards model using dichotomized clinical variables was performed to identify the independent predictors for early recovery (ALT normalization within 2 weeks). RESULTS: The median age (range) was 30 (17-50) years and male dominant (62%, 147/238). Compared to low AFP group, high AFP group (>10 ng/mL) had significantly lower platelet counts (p <0.0001), lower albumin (p =0.003), lower AST (p <0.001), lower ALT (p = 0.001), higher total bilirubin level (p <0.0001) on univariate analysis. On Cox regression analysis, high AFP level (>10 ng/mL) was the only independent predictor for early recovery (Hazard ratio (HR); 2.392, 95% CI; 1.564-3.659, p = 0.0001). CONCLUSIONS: High serum AFP level (>10 ng/mL) may indicate the already-started recovery through active liver regeneration or the early recovery within 2 weeks in AHA.


Assuntos
Hepatite A/sangue , alfa-Fetoproteínas/análise , Doença Aguda , Adolescente , Adulto , Feminino , Hepatite A/diagnóstico , Hepatite A/fisiopatologia , Anticorpos Anti-Hepatite A/sangue , Humanos , Estimativa de Kaplan-Meier , Regeneração Hepática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Regulação para Cima , Adulto Jovem
19.
Acta Neurochir (Wien) ; 155(11): 2171-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24043415

RESUMO

BACKGROUND: The predictors of graft infection after cranioplasty (GIC) following decompressive craniectomy are not well established. Knowledge of the risk factors for GIC will allow development of preventive measures designed to reduce infection rates. Therefore, the objective of this study was to identify risk factors for the development of GIC. METHODS: A total of 85 patients underwent reconstructive cranioplasty after decompressive craniectomy between January 2009 and July 2011 and had a follow-up period of > 1 year; charts were reviewed retrospectively. Although autograft was used whenever possible, artificial bone was used for cranioplasty. GIC was defined as infection requiring removal of the bone graft. RESULTS: GIC occurred in six patients (7.05 %). GIC was not related to the indications for craniectomy, the interval of cranioplasty, graft material, or the size of the bone defect (p = 0.433, p = 0.206, p = 0.665, and p = 0.999, respectively). The GIC rate was significantly related to previous temporalis muscle resection, preoperative subgaleal fluid collection, operative times > 120 min, and postoperative wound disruptions (p = 0.001, p < 0.001, p = 0.035, and p = 0.016, respectively). Multiple logistic regression showed that the presence of a subgaleal fluid collection before cranioplasty significantly increased the risk of GIC (OR: 38.53; 95 % CI: 2.77-535.6; p = 0.006). CONCLUSIONS: The results of this study suggest that long operative times (> 120 min), craniectomy with temporalis muscle resection, the presence of preoperative subgaleal fluid collection, and postoperative wound disruption may be risk factors for graft infection after cranioplasty. Surgical techniques should be developed to reduce operative time and to avoid temporalis muscle resection when possible. In addition, meticulous dural closure aimed at reducing the formation of subgaleal fluid collection is important for the prevention of graft infections after cranioplasty.


Assuntos
Transplante Ósseo/efeitos adversos , Craniectomia Descompressiva/efeitos adversos , Procedimentos de Cirurgia Plástica/efeitos adversos , Crânio/cirurgia , Retalhos Cirúrgicos , Infecção da Ferida Cirúrgica/etiologia , Adulto , Idoso , Transplante Ósseo/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
20.
Eur J Med Res ; 28(1): 64, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36732838

RESUMO

BACKGROUND: Atelectasis can occur in many clinical practices. One way to prevent this complication is through the alveolar recruitment maneuver (ARM). However, hemodynamic compromise can accompany ARM. This study aims to predict ARM-induced hypotension using a non-invasive method. METHODS: 94 American Society of Anesthesiologists physical status I-II patients aged 19 to 75 with scheduled spinal surgery were enrolled. After anesthesia, we performed a stepwise ARM. Data on perfusion index, mean arterial pressure, heart rate, pleth variability index, cardiac index, and stroke volume variation was collected before induction of anesthesia (T0), just before ARM (T1), at the start of ARM (T2), 0.5 min (T3), 1 min (T4), 1.5 min (T5, end of ARM), and 2 min after the beginning of ARM (T6). Hypotension was defined as when the mean arterial pressure at T5 decreased by 20% or more compared to the baseline. The primary endpoint is that the perfusion index measuring before induction of anesthesia, which reflects the patients' own vascular tone, was correlated with hypotension during ARM. RESULTS: Seventy-five patients (79.8%) patients developed hypotension during ARM. The pre-induction persufion index (Pi) (95% confidence interval) was 1.7(1.4-3.1) in the non-hypotension group and 3.4(2.4-3.9) in the hypotension group. (p < 0.004) The hypotension group showed considerably higher Pi than the non-hypotension group before induction. The decrease of Pi (%) [IQR] in the non-hypotensive group (52.8% [33.3-74.7]) was more significant than in the hypotensive group. (36% [17.6-53.7]) (p < 0.05) The area under the receiver operating characteristic curve of Pi for predicting hypotension during ARM was 0.718 (95% CI 0.615-0.806; p = 0.004), and the threshold value of the Pi was 2.4. CONCLUSION: A higher perfusion index value measuring before induction of anesthesia can be used to predict the development of hypotension during ARM. Prophylactic management of the following hypotension during ARM could be considered in high baseline Pi patients.


Assuntos
Raquianestesia , Hipotensão , Humanos , Hipotensão/induzido quimicamente , Hemodinâmica , Frequência Cardíaca , Estudos Prospectivos
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