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1.
Korean J Transplant ; 36(4): 278-282, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36704806

RESUMO

Metastatic pulmonary calcification (MPC) is defined as calcium deposition in lung tissues. It is commonly seen in end-stage renal disease patients. However, MPC occurring in kidney transplant recipients (KTRs) is rare. We report a case of MPC in a 55-year-old female patient after successful kidney transplantation (KT). One year after KT, bisphosphonate and vitamin D were prescribed for osteoporosis. Then, 4.5 years after KT, we incidentally found multiple nodular lesions on chest X-ray (CXR) without any symptoms. Chest computed tomography showed multiple high-density nodules. A bone scan confirmed MPC in the right middle lobe and right lower lobe. A retrospective review of pretransplant blood chemistry revealed the following: serum calcium level, 11.2 mg/dL; phosphorus level, 3.2 mg/dL; intact parathyroid hormone level, lower than 2.5 pg/mL; and 24-hour urine calcium level, within normal limits (WNL). After KT, all of these parameters remained WNL. Therefore, hidden adynamic bone disease might have been aggravated by bisphosphonate and vitamin D supplementation, causing MPC. Both were discontinued. She was monitored by routine CXR, and MPC did not progress. Since MPC is commonly asymptomatic and difficult to diagnose in KTRs, caution is required when administering such medications. Patient should be followed up with routine CXR.

2.
Immunol Lett ; 228: 112-121, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33137380

RESUMO

Disease-modifying osteoarthritis (OA) therapy is not yet available. Several adjuvant therapies have demonstrated promising results in the treatment of OA. The present study aimed to investigate the therapeutic effects and underlying mechanisms of a combination of Lactobacillus acidophilus, vitamin B, and curcumin in the treatment of OA. Monosodium iodoacetate (MIA)-induced arthritis of the knee joint in rat was used as an animal model of human OA. The combination of L. acidophilus LA-1, vitamin B, and curcumin or a saline solution was given orally. Pain was measured according to the paw withdrawal latency, and paw withdrawal threshold. Cartilage destruction was analyzed using histomorphological techniques and the Mankin scoring system. Protein expression in the joint was examined using immunohistochemistry. The effects of the combination of L. acidophilus LA-1, vitamin B, and curcumin on mRNA levels in chondrocytes stimulated with interleukin (IL)-1ß were analyzed using real-time polymerase chain reaction. The combination of L. acidophilus, vitamin B, and curcumin effectively downregulated Th17 cells and the related cytokine IL-17, thereby maintained the Treg population, and increased the expression of the Treg-related cytokine IL-10 in human peripheral blood mononuclear cells. The OA animal model exhibited reduced pain and preservation of cartilage in response to the combination treatment. The expression levels of pro-inflammatory cytokines and the catabolic, matrix metalloproteinase-13 (MMP-13), were decreased, whereas the expression of the anabolic tissue inhibitors of metalloproteinases (TIMPs) were upregulated in response to the drug combination. The combination of L. acidophilus, vitamin B, and curcumin was beneficial in OA treatment, controlling the inflammatory response via regulation of the Th17/Treg population and reducing the expression of pro-inflammatory cytokines in human peripheral blood mononuclear cells. The combination treatment also preserved cartilage, suppressed osteoclastogenesis, and regulated the anabolic/catabolic imbalance. These findings indicate the therapeutic potential of combination use of L. acidophilus, vitamin B, and curcumin in patients with OA.


Assuntos
Antirreumáticos/farmacologia , Curcumina/farmacologia , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Articulações/efeitos dos fármacos , Lactobacillus acidophilus/fisiologia , Osteoartrite/tratamento farmacológico , Probióticos/farmacologia , Complexo Vitamínico B/farmacologia , Adulto , Animais , Células Cultivadas , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Humanos , Articulações/imunologia , Articulações/metabolismo , Articulações/patologia , Masculino , Camundongos Endogâmicos C57BL , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/metabolismo , Osteoartrite/imunologia , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteogênese/efeitos dos fármacos , Ratos Wistar , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th17/metabolismo
3.
J Korean Med Sci ; 35(19): e122, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32419395

RESUMO

Chaga mushrooms are widely used in folk remedies and in alternative medicine. Contrary to many beneficial effects, its adverse effect is rarely reported. We here report a case of end-stage renal disease after long-term taking Chaga mushroom. A 49-year-old Korean man with end stage renal disease (ESRD) was transferred to our hospital. Review of kidney biopsy finding was consistent with chronic tubulointerstitial nephritis with oxalate crystal deposits and drug history revealed long-term exposure to Chaga mushroom powder due to intractable atopic dermatitis. We suspected the association between Chaga mushroom and oxalate nephropathy, and measured the oxalate content of remained Chaga mushroom. The Chaga mushroom had extremely high oxalate content (14.2/100 g). Estimated daily oxalate intake of our case was 2 times for four years and 5 times for one year higher than that of usual diet. Chaga mushroom is a potential risk factor of chronic kidney disease considering high oxalate content. Nephrologist should consider oxalate nephropathy in ESRD patients exposed to Chaga mushrooms.


Assuntos
Inonotus/química , Falência Renal Crônica/diagnóstico , Humanos , Inonotus/metabolismo , Rim/patologia , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Oxalatos/química , Oxalatos/toxicidade , Fatores de Risco , Tomografia Computadorizada por Raios X , Calcificação Vascular/diagnóstico , Calcificação Vascular/diagnóstico por imagem
4.
Korean J Intern Med ; 35(2): 400-407, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31739654

RESUMO

BACKGROUND/AIMS: It is undetermined if herbal medicines (HM) containing aristolochic acid (AA)-containing have similar nephrotoxicity to AA itself. METHODS: We administered HM containing a high concentration of AA for 5 days (short-term study) or a low concentration of AA for 30 days (long-term study) to C57BL/6 mice; for comparison, same dose of AA compound was used as controls. RESULTS: The nephrotoxicity in the HM- and AA-treated mice was compared in terms of renal function, histopathology, oxidative stress, apoptotic cell death, and mitochondrial damage. Short-term HM treatment resulted in acute kidney injury (marked renal dysfunction, acute tubular necrosis, and neutrophil gelatinase-associated lipocalin [NGAL] expression) in which the severity of renal dysfunction and histopathology was comparable with that induced by the administration of AA alone. Long-term HM treatment resulted in features of chronic kidney disease (CKD, mild renal dysfunction and tubular atrophy and dilatation). No significant differences in these parameters were observed between the HM- and AA-treated mice. HM-induced oxidative stress (8-hydroxy-2'-deoxyguanosine and manganese- dependent superoxide dismutase expression) and apoptotic cell death (terminal deoxynucleotidyl transferase dUTP nick end labelling [TUNEL]-positive cells and active caspase-3 expression) were similar in HM- and AA-treated mice in the short-term and long-term studies. Mitochondrial injury, evaluated by electron microscopy, was also similar in HM- and AA-treated mice in the short-term and long-term studies. CONCLUSION: The nephrotoxic potential of HM containing AA was similar to that of AA itself.


Assuntos
Ácidos Aristolóquicos , Medicina Herbária , Animais , Apoptose , Ácidos Aristolóquicos/toxicidade , Rim , Camundongos , Camundongos Endogâmicos C57BL
5.
FASEB J ; 33(11): 12288-12298, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31431058

RESUMO

The major side effect of tacrolimus (Tac) is nephrotoxicity. We studied whether supplementation of coenzyme Q10, (CoQ10) a potent antioxidant, can reduce Tac-induced nephrotoxicity via improving mitochondrial function. In an in vitro study, CoQ10 reduced the production of Tac-induced mitochondrial reactive oxygen species and abolished the loss of mitochondrial membrane potential in proximal tubular cell line. Assessment of mitochondrial function revealed that CoQ10 decreased oxygen consumption and mitochondrial respiration rate increased by Tac, suggesting improvement of mitochondrial function to synthesize ATP with CoQ10 treatment. The effect of the CoQ10in vitro study was observed in an experimental model of chronic Tac-induced nephropathy. CoQ10 attenuated Tac-induced oxidative stress and was accompanied by function and histologic improvement. On electron microscopy, addition of CoQ10 increased not only the number but also the volume of mitochondria compared with Tac treatment only. Our data indicate that CoQ10 improves Tac-induced mitochondrial dysfunction in kidney. Supplementary CoQ10 treatment may be a promising approach to reduce Tac-induced nephrotoxicity.-Yu, J. H., Lim, S. W., Luo, K., Cui, S., Quan, Y., Shin, Y. J., Lee, K. E., Kim, H. L., Ko, E. J., Chung, B. H., Kim, J. H., Chung, S. J., Yang, C. W. Coenzyme Q10 alleviates tacrolimus-induced mitochondrial dysfunction in kidney.


Assuntos
Rim/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Tacrolimo/toxicidade , Ubiquinona/análogos & derivados , Apoptose/efeitos dos fármacos , Células Cultivadas , Humanos , Rim/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Ubiquinona/farmacologia
6.
Aging (Albany NY) ; 11(15): 5548-5569, 2019 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400753

RESUMO

The antioxidant function of Klotho is well-documented as a regulatory factor implicated in countering the aging process. This study investigated whether ginseng upregulates Klotho and its antiaging signaling in a setting of calcineurin inhibitor-induced oxidative stress. Although tacrolimus treatment reduced Klotho level in the serum and kidney, ginseng treatment was found to reverse the levels. Tacrolimus-induced oxidative stress was reduced by ginseng treatment, with functional and histological improvements. Effect of ginseng on Klotho-induced manganese superoxide dismutase signaling pathway during tacrolimus treatment in mice revealed that ginseng suppressed phosphatidylinositol 3-kinase/serine-threonine kinase Akt-mediated phosphorylation of forkhead box protein O3a and promoted the binding of forkhead box protein O3a to manganese superoxide dismutase promoter. In the mitochondria, ginseng reduced mitochondrial reactive oxygen species production, mitochondrial membrane potential, and oxygen consumption rate, whereas blocking phosphatidylinositol 3-kinase activity with LY294002 enhanced them. These findings together suggested that ginseng attenuated tacrolimus-induced oxidative stress via signaling between Klotho and the phosphatidylinositol 3-kinase/serine-threonine kinase Akt/forkhead box protein O3a-related antioxidant pathway.


Assuntos
Proteína Forkhead Box O3/metabolismo , Glucuronidase/metabolismo , Panax , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Superóxido Dismutase/metabolismo , Tacrolimo/efeitos adversos , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Antioxidantes/metabolismo , Inibidores de Calcineurina/efeitos adversos , Linhagem Celular , Modelos Animais de Doenças , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Proteínas Klotho , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fitoterapia , Insuficiência Renal Crônica/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/genética
7.
Sci Rep ; 9(1): 7995, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142763

RESUMO

We previously reported that oxidative stress induced by long-term tacrolimus treatment impairs mitochondrial function in pancreatic beta cells. In this study, we aimed to investigate the therapeutic potential of coenzyme Q10, which is known to be a powerful antioxidant, in mitochondrial dysfunction in tacrolimus-induced diabetic rats. In a rat model of tacrolimus-induced diabetes mellitus, coenzyme Q10 treatment improved pancreatic beta cell function. The administration of coenzyme Q10 improved insulin immunoreactivity within islets, which was accompanied by reductions in oxidative stress and apoptosis. Assessment of the mitochondrial ultrastructure by electron microscopy revealed that coenzyme Q10 treatment increased the size, number, and volume of mitochondria, as well as the number of insulin granules compared with that induced by tacrolimus treatment alone. An in vitro study using a pancreatic beta cell line showed that tacrolimus treatment increased apoptosis and the production of mitochondrial reactive oxygen species, while cotreatment with coenzyme Q10 effectively attenuated these alterations. At the subcellular level, tacrolimus-induced impairment of mitochondrial respiration was significantly improved by coenzyme Q10, as evidenced by the increased mitochondrial oxygen consumption and ATP production. Our data indicate that coenzyme Q10 plays an important role in reducing tacrolimus-induced oxidative stress and protects the mitochondria in pancreatic beta cells. These findings suggest that supplementation with coenzyme Q10 has beneficial effects in tacrolimus-induced diabetes mellitus.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Tacrolimo/efeitos adversos , Ubiquinona/análogos & derivados , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Ubiquinona/genética , Ubiquinona/farmacologia
8.
BMC Complement Altern Med ; 19(1): 54, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832648

RESUMO

BACKGROUND: We previously reported that tacrolimus (Tac) does not decrease T helper 17 cells (Th17) response in kidney transplantation. In this study, we evaluated whether Resveratrol (Resv) has immunosuppressive effects by decreasing Th17 responses in Tac-based immunosuppression. METHODS: We investigated the effects of Resv under Tac-treatment conditions, on CD4+ T cell differentiation to Th17 cells in peripheral blood mononuclear cells (PBMCs), and proliferation of CD4+ T cells co-cultured with human renal proximal tubular epithelial cells (HRPTEpiCs). The effects of Resv on Th17 cells were tested in the murine skin transplant model. RESULTS: In PBMCs, Tac did not but combination of Tac and Resv further suppressed Th17 immune response. In the co-culture study, combination of Resv to Tac significantly decreased HRPTEpiC-induced T cell proliferation compared to Tac alone. Resv treatment in the Jurkat cell induced the expression of AMP-activated protein kinase and suppressed the expression of mammalian target of rapamycin (mTOR), suggesting blocking Th17 pathway by Resv. In the murine skin transplant model, combination of Resv to Tac significantly prolonged skin graft survival accompanied by the suppression of Th17 cells, compared to either the Tac-alone or control groups. CONCLUSION: The results of our study suggest that Resv provides additional immunosuppressive effects to Tac by suppressing effector CD4+ T cells, especially Th17 cells, in the transplantation setting.


Assuntos
Imunossupressores/farmacologia , Resveratrol/farmacologia , Tacrolimo/farmacologia , Células Th17/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Adulto , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Transplante de Pele , Serina-Treonina Quinases TOR/metabolismo , Células Th17/imunologia , Células Th17/metabolismo
9.
Korean J Intern Med ; 34(5): 1078-1090, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29432674

RESUMO

BACKGROUND/AIMS: Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy. METHODS: Rats were treated daily with TAC (1.5mg/kg, subcutaneously) and SK (450 mg/kg, intravenously) for 4 weeks. The effects of SK on TAC-induced renal injury were assessed by measuring renal function, urine albumin excretion, histopathology, inflammatory cell infiltration, expression of profibrotic (transforming growth factor ß1 [TGF-ß1] and TGF-ß inducible gene-h3 [ßig-h3]) and proinflammatory cytokines, oxidative stress, and apoptotic cell death. RESULTS: Administration of SK preserved glomerular integrity (fractional mesangial area and Wilms tumor 1-positive glomeruli), attenuated tubulointerstitial fibrosis, and reduced the number of ectodermal dysplasia 1-positive cells, and this was paralleled by improved urine albumin excretion and renal dysfunction. At the molecular level, SK treatment suppressed expression of TGF-ß1/Smad2/3, ßig-h3, and proinflammatory cytokines. Oxidative stress and apoptotic cell death were significantly decreased with SK treatment, and apoptosis-related genes were regulated toward cell survival (active caspase-3 and the B-cell lymphoma-2/Bcl2-associated X [Bcl-2/Bax] ratio). CONCLUSION: SK protects against TAC-induced renal injury.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Tacrolimo , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Citocinas/metabolismo , Citoproteção , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/metabolismo , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
10.
Korean J Intern Med ; 34(2): 365-374, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29228766

RESUMO

BACKGROUND/AIMS: This study was performed to determine whether adding coenzyme Q10 (CoQ10) to metformin (MET) has a beneficial effect as a treatment for sirolimus (SRL)-induced diabetes mellitus (DM). METHODS: DM was induced in rats by daily treatment with SRL (0.3 mg/kg, subcutaneous) for 28 days, and animals were treated with CoQ10 (20 mg/kg, oral) and MET (250 mg/kg, oral) alone or in combination for the latter 14 days of SRL treatment. The effects of CoQ10 and MET on SRL-induced DM were assessed with the intraperitoneal glucose tolerance test (IPGTT) and by determining plasma insulin concentration and the homeostatic model assessment of insulin resistance (HOMA-R) index. We also evaluated the effect of CoQ10 on pancreatic islet size, apoptosis, oxidative stress, and mitochondria morphology. RESULTS: IPGTT revealed overt DM in SRL-treated rats. The addition of CoQ10 to MET further improved hyperglycemia, decreased HOMA-R index, and increased plasma insulin concentration compared with the SRL group than MET alone therapy. While SRL treatment induced smaller islets with decreased insulin staining intensity, the combination of CoQ10 and MET significantly improved insulin staining intensity, which was accompanied by a reduction in oxidative stress and apoptosis. In addition, co-treatment of CoQ10 and MET significantly increased the levels of antiperoxidative enzymes in the pancreas islet cells compared with MET. At the subcellular level, addition of CoQ10 to MET improved the average mitochondrial area and insulin granule number. CONCLUSION: Addition of CoQ10 to MET has a beneficial effect on SRL-induced DM compared to MET alone.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Ilhotas Pancreáticas/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Ubiquinona/análogos & derivados , Vitaminas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Ilhotas Pancreáticas/enzimologia , Masculino , Metformina/farmacologia , Metformina/uso terapêutico , Mitocôndrias/ultraestrutura , Distribuição Aleatória , Ratos Sprague-Dawley , Sirolimo , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico , Vitaminas/farmacologia
11.
Immunol Lett ; 203: 6-14, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30003932

RESUMO

Osteoarthritis (OA) is a chronic and degenerative disease that causes pain, cartilage deformation, and joint inflammation. Lactobacillus species have been used as dietary supplements to induce the production of antimicrobial and anti-inflammatory factors. The goal of this study was to determine whether Lactobacillus acidophilus ameliorates monosodium iodoacetate-induced OA. L. acidophilus showed anti-nociceptive properties and protected against cartilage destruction. It also downregulated the levels of proinflammatory cytokines and increased the levels of anti-inflammatory cytokines in the joints of OA rats. L. acidophilus additionally restored the balance between anabolic and catabolic factors in chondrocytes from OA patients. These results suggest that L. acidophilus can alleviate OA-associated pain and delay the progression of the disease by inhibiting proinflammatory cytokine production and reducing cartilage damage.


Assuntos
Cartilagem , Condrócitos , Lactobacillus acidophilus , Osteoartrite , Manejo da Dor , Dor , Animais , Cartilagem/imunologia , Cartilagem/patologia , Condrócitos/imunologia , Condrócitos/patologia , Ácido Iodoacético/toxicidade , Masculino , Osteoartrite/induzido quimicamente , Osteoartrite/imunologia , Osteoartrite/patologia , Osteoartrite/terapia , Dor/induzido quimicamente , Dor/imunologia , Dor/patologia , Ratos Wistar
12.
Korean J Intern Med ; 33(5): 961-969, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29551056

RESUMO

BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSION: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.


Assuntos
Ácidos Aristolóquicos , Medicamentos de Ervas Chinesas , Falência Renal Crônica , Idoso , Ácidos Aristolóquicos/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Falência Renal Crônica/induzido quimicamente , Masculino , República da Coreia/epidemiologia
13.
J Transl Med ; 16(1): 37, 2018 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-29466999

RESUMO

BACKGROUND: An altered gut microbiota balance is involved in the pathogenesis of inflammatory bowel disease (IBD), and several probiotic strains are used as dietary supplements to improve intestinal health. We evaluated the therapeutic effect of 12 probiotics in combination with prebiotics, rosavin, and zinc in the dextran sodium sulfate (DSS)-induced colitis mouse model. METHODS: The probiotic complex or the combination drug was administered orally to mice with DSS-induced colitis, and the body weight, disease activity index, colon length, and histopathological parameters were evaluated. Also, the combination drug was applied to HT-29 epithelial cells, and the expression of monocyte chemoattractant protein 1 (MCP-1) was evaluated by real-time polymerase chain reaction. RESULTS: Administration of the combination drug attenuated the severity of DSS-induced colitis. Moreover, the combination drug significantly reduced the levels of the proinflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, IL-1ß, and IL-17, and significantly increased the levels of Foxp3 and IL-10 in colon sections. Additionally, treatment with the combination drug reduced MCP-1 expression in HT-29 cells. Treatment with the combination drug decreased the levels of α-smooth muscle actin and type I collagen compared with vehicle treatment in mice with DSS-induced colitis. CONCLUSION: These results suggest that the combination of a probiotic complex with rosavin, zinc, and prebiotics exerts a therapeutic effect on IBD by modulating production of pro- and anti-inflammatory cytokines and the development of fibrosis.


Assuntos
Colite/tratamento farmacológico , Dissacarídeos/uso terapêutico , Inflamação/tratamento farmacológico , Intestinos/patologia , Prebióticos , Probióticos/uso terapêutico , Zinco/uso terapêutico , Doença Aguda , Animais , Quimiocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Quimioterapia Combinada , Fibrose , Fatores de Transcrição Forkhead/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL
14.
J Med Food ; 21(3): 215-224, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29336663

RESUMO

Disruption of the balance among the microbiota, epithelial cells, and resident immune cells in the intestine is involved in the pathogenesis of inflammatory bowel disease (IBD). Probiotics exert protective effects against IBD, and probiotic commensal Lactobacillus species are common inhabitants of the natural microbiota, especially in the gut. To investigate the effects of Lactobacillus acidophilus on the development of IBD, L. acidophilus was administered orally in mice with dextran sodium sulfate (DSS)-induced colitis. DSS-induced damage and the therapeutic effect of L. acidophilus were investigated. Treatment with L. acidophilus attenuated the severity of DSS-induced colitis. Specifically, it suppressed proinflammatory cytokines such as interleukin (IL)-6, tumor necrosis factor-α, IL-1ß, and IL-17 in the colon tissues, which are produced by T helper (Th) 17 cells. Moreover, in vitro L. acidophilus treatment directly induced T regulatory (Treg) cells and the production of IL-10, whereas the production of IL-17 was suppressed in splenocytes. In addition, we found that L. acidophilus treatment decreased the levels of α-smooth muscle actin, a marker of activated myofibroblasts, and type I collagen compared with control mice. These results suggest that L. acidophilus may be a novel treatment for IBD by modulating the balance between Th17 and Treg cells, as well as fibrosis development.


Assuntos
Colite/dietoterapia , Colo/imunologia , Mucosa Intestinal/imunologia , Lactobacillus acidophilus/imunologia , Probióticos/uso terapêutico , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Actinas/metabolismo , Animais , Biomarcadores/metabolismo , Células Cultivadas , Colite/imunologia , Colite/patologia , Colágeno Tipo I/metabolismo , Colo/metabolismo , Colo/patologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/metabolismo , Fibrose , Regulação da Expressão Gênica , Interleucina-10/agonistas , Interleucina-10/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos Endogâmicos C57BL , Miofibroblastos/imunologia , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Distribuição Aleatória , Organismos Livres de Patógenos Específicos , Baço/imunologia , Baço/metabolismo , Baço/patologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Células Th17/metabolismo , Células Th17/patologia
15.
J Med Food ; 21(4): 364-371, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29346012

RESUMO

Osteoarthritis (OA), a degenerative disorder, induces pain, joint inflammation, and destruction of the articular cartilage matrix. Probiotic complex, rosavin, and zinc have been used as dietary supplements that exhibit anti-inflammatory and antioxidant properties. However, there is no evidence demonstrating a synergic effect in OA. This study aims to determine whether combination with probiotic complex, rosavin, and zinc decreases progression of monosodium iodoacetate (MIA)-induced OA rat model. The combination improved pain levels by preventing cartilage damage. The expression of proinflammatory cytokines and catabolic factors was reduced by the combination within the joint tissue. However, the combination increased anti-inflammatory cytokines as well as the anabolic factor production. The gene level of catabolic factors was decreased with treatment of the combination in chondrocytes isolated from OA patients. These results suggest that the combination can improve MIA development through the inhibition of proinflammatory cytokines and cartilage destruction, thus playing a key role as a therapeutic candidate for OA treatment.


Assuntos
Artrite Experimental/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Citocinas/metabolismo , Dissacarídeos/uso terapêutico , Osteoartrite/tratamento farmacológico , Probióticos/uso terapêutico , Zinco/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/complicações , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Cartilagem Articular/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Suplementos Nutricionais , Dissacarídeos/farmacologia , Combinação de Medicamentos , Sinergismo Farmacológico , Ácido Iodoacético , Articulações/efeitos dos fármacos , Articulações/metabolismo , Masculino , Osteoartrite/complicações , Osteoartrite/metabolismo , Osteoartrite/patologia , Dor/tratamento farmacológico , Dor/etiologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos Wistar , Rhodiola/química , Oligoelementos/farmacologia , Oligoelementos/uso terapêutico , Zinco/farmacologia
16.
J Med Food ; 21(1): 39-46, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29346060

RESUMO

Probiotic complex, zinc, and coenzyme Q10 (CoQ10) are recognized dietary supplements with an anti-inflammatory role. Although these supplementations are individually known to benefit rheumatoid arthritis (RA), there is no evidence suggesting any synergic effect. The primary goal of this study is to determine whether probiotic complex, zinc, and CoQ10 attenuate the development of collagen-induced arthritis (CIA). The combination of probiotic complex, zinc, and CoQ10 reduced CIA severity by downregulating the levels of IgG, IgG1, and IgG2a in serum. Joint inflammation, bone destruction, and cartilage damage were also improved by the complex. There was a decrease in the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-17, and vascular endothelial growth factor (VEGF) in the joint synovium. The balance between helper T 17 (Th17) cells and regulatory T (Treg) cells was shown to be controlled reciprocally by the complex. These findings suggest that the combination of probiotic complex, zinc, and CoQ10 can ameliorate the development of CIA by inhibiting the expression of proinflammatory cytokines, and is thus an important therapeutic candidate for RA treatment.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Probióticos/administração & dosagem , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Ubiquinona/análogos & derivados , Zinco/administração & dosagem , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Modelos Animais de Doenças , Quimioterapia Combinada , Humanos , Interleucina-17/genética , Interleucina-17/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos DBA , Células Th17/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Ubiquinona/administração & dosagem
17.
Clin Ther ; 40(1): 123-134, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28291581

RESUMO

PURPOSE: Sevelamer, a noncalcium phosphate binder, has been shown to attenuate the progression of vascular calcification and improve survival in patients with chronic kidney disease undergoing dialysis compared with calcium-based binders. Using real-world data from a cohort study and the Health Insurance Review and Assessment Service database, we conducted a cost-effectiveness analysis comparing sevelamer with calcium acetate in dialysis patients from the perspective of the National Health Insurance Service in South Korea. METHODS: Data (demographic, diagnostic, laboratory, and survival) from 4674 patients undergoing dialysis enrolled in a multicenter prospective cohort study conducted in South Korea between September 2008 and December 2012 were linked to phosphate binder use, hospitalization, and cost data available from the Health Insurance Review and Assessment Service database. After propensity score matching, a dataset comprising comparable patients treated with either sevelamer (n = 501) or calcium acetate (n = 501) was used in the cost-effectiveness analysis. A Markov model was used to estimate costs, life years, quality-adjusted life years (QALYs), and cost-effectiveness over each patient's lifetime. Forty-month treatment-specific overall survival (OS) data available from the dataset were extrapolated to lifetime survival with the use of regression analysis. FINDINGS: Patients had a mean age of 56.3 years and were treated with dialysis for a mean duration of 67.6 months. Compared with calcium acetate, sevelamer was associated with an incremental cost of South Korean Won (₩) 12,246,911 ($10,819) and a gain of 1.758 life years and 1.108 QALYs per patient. This outcome yielded incremental cost-effectiveness ratios of ₩6,966,350 ($6154) and ₩11,057,699 ($9768) per life year and QALY gained, respectively. Conclusions regarding sevelamer's cost-effectiveness were insensitive to alternative assumptions in time horizon, discount rate, hospitalization rate, costs, and health utility estimates, and they remained consistent in 100% of the model iterations, considering a willingness-to-pay threshold of ₩31,894,720 ($28,176) per QALY gained. IMPLICATIONS: This analysis of real-world data found that sevelamer's higher cost relative to calcium acetate was adequately offset by improved survival among patients undergoing dialysis in South Korea. As such, sevelamer offers good value for money, representing a cost-effective alternative to calcium-based binders.


Assuntos
Acetatos/economia , Quelantes/economia , Diálise Renal/economia , Insuficiência Renal Crônica/economia , Sevelamer/economia , Acetatos/uso terapêutico , Adulto , Idoso , Povo Asiático , Compostos de Cálcio/economia , Compostos de Cálcio/uso terapêutico , Quelantes/uso terapêutico , Análise Custo-Benefício , Feminino , Hospitalização/economia , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Análise de Regressão , Insuficiência Renal Crônica/terapia , República da Coreia , Sevelamer/uso terapêutico
18.
Lab Invest ; 97(11): 1271-1281, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28759009

RESUMO

We previously reported that long-term treatment with a calcineurin inhibitor impairs autophagy process in pancreatic beta cells. This study investigated the effect of Korean red ginseng extract (KRGE) on autophagy modulated by oxidative stress. In mice with tacrolimus (Tac)-induced diabetes mellitus, KRGE alleviated islet dysfunction and decreased oxidative stress and autophagic vacuoles. In vitro, KRGE decreased autophagosome formation and attenuated lysosomal degradation, accompanied by improved beta cell viability and insulin secretion. Addition of 3-methyladenine (3-MA), an inhibitor of autophagosomes, to KRGE further improved cell viability and insulin secretion, and bafilomycin A (BA), an inhibitor of lysosomal function, reduced the effects of KRGE. At the subcellular level, Tac caused mitochondrial dysfunction (impaired mitochondrial oxygen consumption, ATP production, and increased reactive oxygen species production). But KRGE improved these parameters. The effect of KRGE on mitochondrial function enhanced by 3-MA but decreased by BA, suggesting a causal relationship between KRGE effect and autophagy modulation in Tac-induced mitochondrial dysfunction. These findings indicate that KRGE modulates autophagy favorably by reducing Tac-induced oxidative stress, and this effect is closely associated with improvement of mitochondrial function.


Assuntos
Antioxidantes/uso terapêutico , Autofagia , Diabetes Mellitus/prevenção & controle , Suplementos Nutricionais , Células Secretoras de Insulina/metabolismo , Panax/química , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/metabolismo , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Autofagossomos/patologia , Autofagossomos/ultraestrutura , Autofagia/efeitos dos fármacos , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Imunossupressores/efeitos adversos , Imunossupressores/antagonistas & inibidores , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/ultraestrutura , Masculino , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/metabolismo , Raízes de Plantas/química , Distribuição Aleatória , Ratos , Tacrolimo/efeitos adversos , Tacrolimo/antagonistas & inibidores
19.
PLoS One ; 12(4): e0175830, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28414758

RESUMO

BACKGROUND: The optimal timing for initiating dialysis in end-stage renal disease (ESRD) is controversial, especially in the elderly. METHODS: 665 patients ≥65 years old who began dialysis from August 2008 to February 2015 were prospectively enrolled in the Clinical Research Center for End-Stage Renal Disease cohort study. Participants were divided into 2 groups based on the median estimated glomerular filtration rate at the initiation of dialysis. Propensity score matching (PSM) was used to compare the overall survival rate, cardiovascular events, Kidney Disease Quality of Life Short Form 36 (KDQOL-36) results, Karnofsky performance scale values, Beck's depression inventory values, and subjective global assessments. RESULTS: The mean patient age was 72.0 years, and 61.7% of the patients were male. Overall, the cumulative survival rates were lower in the early initiation group, although the difference was not significant after PSM. Additionally, the survival rates of the 2 groups did not differ after adjusting for age, sex, Charlson comorbidity index and hemoglobin, serum albumin, serum calcium and phosphorus levels. Although the early initiation group showed a lower physical component summary score on the KDQOL-36 3 months after dialysis, the difference in scores was not significant 12 months after dialysis. Furthermore, the difference was not significant after PSM. The Karnofsky performance scale, Beck's depression inventory, and subjective global assessments were not significantly different 3 and 12 months after dialysis initiation. CONCLUSIONS: The timing of dialysis initiation is not associated with clinical outcomes in elderly patients with ESRD.


Assuntos
Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Idoso , Cálcio/sangue , Feminino , Taxa de Filtração Glomerular/fisiologia , Hemoglobinas/metabolismo , Humanos , Avaliação de Estado de Karnofsky , Falência Renal Crônica/sangue , Falência Renal Crônica/metabolismo , Masculino , Fósforo/sangue , Pontuação de Propensão , Estudos Prospectivos , Qualidade de Vida , Diálise Renal/métodos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/terapia , Albumina Sérica/metabolismo , Taxa de Sobrevida
20.
Nephrology (Carlton) ; 19(8): 490-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24796922

RESUMO

AIMS: Chronic cyclosporine (CsA) treatment induces autophagic cell death characterized by excessive autophagosome formation and decreased autophagic clearance. In this study, we evaluated the influence of ginseng treatment on autophagy in chronic CsA nephropathy. METHODS: Mice were treated with CsA (30 mg/kg) with or without Korean red ginseng (KRG) extract (0.2, 0.4 g/kg) for 4 weeks. The effect of KRG on CsA-induced autophagosome formation was measured using phospholipid-conjugated form of LC3-II, beclin-1, and autophagic vacuoles were visualized with electron microscopy. Autophagic clearance was evaluated by accumulation of p62/sequestosome 1 (p62) and ubiquitin, then double immunolabeling for p62 and either LC3-II or ubiquitin. To demonstrate the association between the effects of KRG treatment on autophagy and apoptosis, double immunolabelling for LC3-II and active caspase-3 was performed. Multiple autophagy pathways were also examined. RESULTS: KRG co-treatment significantly decreased the expression of LC3-II, beclin-1, and the number of autophagic vacuoles compared with the CsA group, and these changes were accompanied by improvements in renal dysfunction and fibrosis. CsA-induced accumulation of p62 and ubiquitin was also decreased by KRG treatment, and these proteins were colocalized with LC3-II and with each other. KRG treatment simultaneously reduced the expression of both active caspase-3 and LC3-II in the injured area. KRG treatment during chronic CsA nephropathy induced the expression of AKT/mTOR, which is a pathway that inhibits autophagy, and reduced AMPK expression. CONCLUSION: Ginseng treatment attenuated CsA-induced excessive autophagosome formation and autophagic aggregates. These findings suggest that ginseng has a renoprotective effect against CsA-induced autophagic cell death.


Assuntos
Autofagia/efeitos dos fármacos , Nefropatias/tratamento farmacológico , Nefropatias/prevenção & controle , Panax , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Animais , Doença Crônica , Ciclosporina/efeitos adversos , Nefropatias/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos ICR
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