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1.
Transplant Proc ; 54(2): 537-539, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35067373

RESUMO

Donor evaluation is important to ensure that life threatening diseases like cancer can be prevented from getting passed on to the recipient. The donor patient described in our report showed normal parameters in blood and urine biochemistry analysis. Additionally, kidney ultrasonography and renal artery CT showed no indications of any abnormalities. However, endoscopic analysis performed later turned out to be valuable in detection of a protruding mass of 22 to 25 cm in size at the anal verge, and positron emission tomography revealed liver metastasis. Thus, our study highlights that endoscopic techniques can be really valuable in cancer detection and medical centers must consider including these tests in their donor evaluation diagnostic procedures.


Assuntos
Transplante de Rim , Neoplasias , Humanos , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Transplante de Rim/efeitos adversos , Tomografia por Emissão de Pósitrons , Doadores de Tecidos , Ultrassonografia
2.
Transplant Proc ; 54(2): 540-543, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35067375

RESUMO

BACKGROUND: ABO-incompatible kidney transplantation (KTP) is effective for avoiding transplantation-related issues. It is a viable alternative to ABO-compatible KTP, as both techniques have similar patient and graft survival rates. However, anti-A/B antibody-mediated rejection (AMR) can occur, resulting in poor long-term graft survival. CASE: A 45-year-old man with end-stage renal disease presented with a serum creatinine level of 10.2 mg/dL. We decided to perform KTP with spousal donation. He had panel-reactive antibody class I and II and cross matching test negativity, a 3/6 mismatch on human leukocyte antigen typing, an ABO antibody titer of 1:256, and no donor-specific antibodies. The patient and donor blood types were O+ and A+, respectively. The anti-A/B antibody titer was reduced preoperatively with rituximab (200 mg/body), plasmapheresis, and intravenous immunoglobulin (0.2 mg/kg). Basiliximab and methylprednisolone were used for induction immunosuppression, and tacrolimus, mycophenolate mofetil, and prednisolone were used for maintenance immunosuppression. KTP was successful, and graft function was initially normal. On postoperative day (POD) 5, the serum creatinine level and anti-A/B antibody titer increased from 0.9 mg/dL to 1.9 mg/dL and 1:16 to 1:64, respectively. Graft biopsy revealed acute AMR and tubular injury. We started steroid pulse therapy, plasmapheresis, and subcutaneous bortezomib (2.6 mg, twice a day, every 3 days) with no side effects. The serum creatinine level decreased from 5.7 mg/dL to 1.5 mg/dL on POD 28. Graft biopsy showed no rejection, and normal function was maintained for 40 months. CONCLUSIONS: Acute, early anti-A/B AMR was successfully treated with plasmapheresis and bortezomib.


Assuntos
Transplante de Rim , Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Bortezomib/uso terapêutico , Rejeição de Enxerto , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico , Plasmaferese/métodos
3.
Transplant Proc ; 54(2): 528-532, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35074165

RESUMO

BACKGROUND: Hyperuricemia is a common condition in patients with chronic kidney disease and end-stage kidney disease. It occurs even after kidney transplant because of the use of calcineurin inhibitors and transplanted kidney failure. We describe the case of a patient with end-stage kidney disease who had multiple gouty arthritis with tophi formation despite receiving appropriate treatment but was successfully cured after kidney transplant. CASE REPORT: A 36-year-old male patient undergoing hemodialysis treatment was treated with febuxostat for multiple gouty arthritis and underwent tophi removal twice. He received a deceased donor kidney transplant 10 years after dialysis treatment. He received immunosuppressants (basiliximab, tacrolimus, mycophenolate mofetil) and steroids. Results of renal biopsy performed on days 7 and 21 postoperation showed no specific findings and normal renal function. The uric acid level before transplant was 3.1 mg/dL, and when renal function was normal, it reached 6-7 mg/dL and remained stable. Although hyperuricemia was still present, the tophi disappeared 3 months after transplant. It is presumed that the high-dose steroids interfered with the activation of inflammatory responses during tophi formation, which may have caused the tophi to disappear. It is also presumed that the patient adhered to the diet well after transplant, which suppressed tophi formation. CONCLUSIONS: Our findings suggest that disappearance of multiple tophi and arthritis in patients undergoing hemodialysis can be achieved with kidney transplant, especially when uric acid-lowering drugs are not effective.


Assuntos
Artrite Gotosa , Hiperuricemia , Falência Renal Crônica , Transplante de Rim , Adulto , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Masculino , Diálise Renal/efeitos adversos
4.
Life Sci ; 297: 120228, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34921864

RESUMO

AIMS: Alcoholic liver disease (ALD) comprises an important component in chronic liver diseases, and its clinical significance has increased due to the high consumption of alcohol worldwide. Vitamin C is a potent antioxidant, and several previous studies have suggested that its therapeutic role in ALD is derived from its antioxidant role. However, its anti-inflammatory role in ALD remains to be elucidated. Especially, the relationship between vitamin C and infiltration of neutrophils in ALD has not been discussed to date. For the reason, the present study investigated the precise role of vitamin C in neutrophil infiltration in ALD. MAIN METHODS: In the present study, wild-type C57BL/6 and vitamin C-deficient senescence marker protein 30-knockout mice were pair-fed with a Lieber-DeCarli control or ethanol diet. Ethanol-fed groups were fed with increasing concentrations of EtOH (Lieber-DeCarli control diet for 5 days, 3% EtOH diet for a week, and 5% diet for 2 weeks) with or without vitamin C supplementation. KEY FINDINGS: Vitamin C dramatically attenuated the ethanol-mediated liver disease in the vitamin C-deficient ethanol-fed mice group by suppressing the infiltration of neutrophils accompanied by less CD68-positive cell infiltration. This attenuating role of vitamin C in neutrophil infiltration in the liver is associated with its protective effect for the ethanol-mediated intestinal damage in vitamin C-deficient ethanol-fed mice. SIGNIFICANCE: This study provides a novel possibility of vitamin C to be used as an anti-inflammatory therapeutic agent associated with neutrophil infiltration in ALD, thereby helping to establish strategies for attenuating ALD.


Assuntos
Antioxidantes , Hepatopatias Alcoólicas , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Fígado/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos
5.
Transplant Proc ; 53(6): 1945-1950, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34253379

RESUMO

BACKGROUND: Valganciclovir is used to prevent posttransplant cytomegalovirus (CMV) infection among patients undergoing kidney transplant. However, the optimal dose remains controversial because continuous use decreases kidney function and can induce leukopenia. The purpose of this study was to identify the appropriate dose of valganciclovir for preventing CMV using network meta-analysis. METHODS: We searched the Cochrane Central Register, Ovid MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health, and Web of Science databases for studies published through April 15, 2017, evaluating 900-mg and 450-mg valganciclovir. We performed direct and indirect network meta-analysis using Bayesian models and generated rankings of different doses of valganciclovir by generating a mixed-treatment comparison. RESULTS: Twenty-three studies involving 3478 participants were included. Compared with the control group, there was no difference in the incidence of CMV infection between the low-dose (450 mg) (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.50-1.40) and high-dose (900 mg) (OR, 1.0; 95% CI, 0.61-1.60) groups. Low-dose valganciclovir had the best probability (71.1%) for decreasing CMV infection. Leukopenia was significantly more common in the high-dose group than in the control group (OR, 4.3; 95% CI, 2.69-7.10) and in the low-dose group (OR, 2.9; 95% CI, 1.88-4.67), but there was no significant difference in the incidence of leukopenia between the low-dose and control groups (OR, 1.5; 95% CI, 0.99-2.20). CONCLUSIONS: The incidence of CMV was not different based on the dose of valganciclovir, although the tendency for CMV infection was decreased at 450 mg. However, the low dose of valganciclovir significantly reduced the incidence of leukopenia.


Assuntos
Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus , Valganciclovir/uso terapêutico , Antivirais/efeitos adversos , Teorema de Bayes , Humanos , Metanálise em Rede , Transplante de Órgãos , Estudos Retrospectivos , Valganciclovir/efeitos adversos
6.
Am J Pathol ; 191(9): 1550-1563, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34126083

RESUMO

Despite the increasing clinical importance of nonalcoholic fatty liver disease (NAFLD), little is known about its underlying pathogenesis or specific treatment. The senescence marker protein 30 (SMP30), which regulates the biosynthesis of vitamin C (VC) in many mammals, except primates and humans, was recently recognized as a gluconolactonase. However, the precise relation between VC and lipid metabolism in NAFLD is not completely understood. Therefore, this study aimed to clearly reveal the role of VC in NAFLD progression. SMP30 knockout (KO) mice were used as a VC-deficient mouse model. To investigate the precise role of VC on lipid metabolism, 13- to 15-week-old SMP30 KO mice and wild-type mice fed a 60% high-fat diet were exposed to tap water or VC-containing water (1.5 g/L) ad libitum for 11 weeks. Primary mouse hepatocytes isolated from the SMP30 KO and wild-type mice were used to demonstrate the relation between VC and lipid metabolism in hepatocytes. Long-term VC deficiency significantly suppressed the progression of simple steatosis. The high-fat diet-fed VC-deficient SMP30 KO mice exhibited impaired sterol regulatory element-binding protein-1c activation because of excessive cholesterol accumulation in hepatocytes. Long-term VC deficiency inhibits de novo lipogenesis through impaired sterol regulatory element-binding protein-1c activation.


Assuntos
Deficiência de Ácido Ascórbico/metabolismo , Hepatócitos/metabolismo , Lipogênese/fisiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Progressão da Doença , Metabolismo dos Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Knockout
7.
Life Sci ; 278: 119578, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33965379

RESUMO

Hepatic fibrosis is a common liver disease caused by excessive collagen deposition in the liver. Since liver transplantation is the only current treatment for cirrhosis with worsened fibrosis, a new strategy to develop anti-fibrosis drugs with no adverse effects is necessary. In recent studies, amino acids have been applied as a type of therapy in various fields. l-serine plays a major role in antioxidant production via the maintenance of nicotinamide adenine dinucleotide phosphate hydride production in the mitochondria. l-serine may reduce fibrotic lesions in a mouse model of chronic liver injury. This study used 27 six-week-old C57BL/6 mice and injected them three times a week for eight weeks with carbon tetrachloride (CCl4) (1.5 mg/kg, 10% v/v CCl4 in olive oil) to create a hepatic fibrosis mouse model. The mice, which weighed approximately 20-30 g, were randomly classified into four groups: 1) the olive oil group, which received intraperitoneal injection of olive oil (1.5 mg/kg, 3 times per week for 8 weeks); 2) the CCl4-only group; 3) the CCl4 + losartan (10 mg/kg, PO, 5 days on, weekend off for 8 weeks) group; and 4) the CCl4 + l-serine (100 g/L, free access for 8 weeks) group. Hematoxylin and eosin staining and Masson's trichrome staining showed reduced inflammatory cell deposition and collagen deposition in the liver tissue in the l-serine supplemented group. l-serine was found to reduce the spread of hepatic fibrosis and has potential use in clinical settings. Based on these histopathological observations, l-serine is a potential anti-fibrosis drug.


Assuntos
Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Losartan/farmacologia , Serina/farmacologia , Animais , Peso Corporal , Tetracloreto de Carbono/química , Colágeno/química , Modelos Animais de Doenças , Inflamação , Cirrose Hepática/patologia , Cirrose Hepática Experimental/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio
8.
In Vivo ; 35(3): 1473-1483, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33910825

RESUMO

BACKGROUND/AIM: The pathological role of vascular endothelial growth factor receptor 2 (VEGFR-2) in chronic liver injury and liver regeneration is not fully understood. This study analysed the role of VEGFR-2 in liver fibrosis and its regeneration process. MATERIALS AND METHODS: We administered intraperitoneally 50 mg/kg to 300 mg/kg thioacetamide (TAA) to 9-week-old male mice for 17 weeks. We measured levels of VEGFR-2 protein and identified the location of cells that specifically express VEGFR-2. RESULTS: VEGFR-2 is rarely expressed in normal hepatocytes. However, high VEGFR-2 expression in liver sinusoidal endothelial cells was noted in the TAA group. Conversely, the group that experienced regeneration from liver fibrosis showed significantly higher VEGFR-2 expression in the nucleus of hepatocytes compared to the other groups. CONCLUSION: VEGFR-2 plays a pivotal role in the nucleus of hepatocytes during liver regeneration and VEGFR-2 may be closely related to cell division. Therefore, VEGFR-2 may be a new therapeutic target for liver regeneration.


Assuntos
Regeneração Hepática , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Animais , Proliferação de Células , Hepatócitos , Fígado , Masculino , Camundongos , Fator A de Crescimento do Endotélio Vascular , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética
9.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652881

RESUMO

Senescence marker protein 30 (SMP30) is a cell survival factor playing an important role in vitamin C synthesis and antiapoptosis. Moreover, its cytoprotective role suggests a possibility to be related to cancer cell survival. Mammary carcinoma is a common cancer in both humans and animals. Because of its histopathological diversity, especially in the early stage, histopathological diagnosis may be complicated; therefore, a diagnostic marker is helpful for confirmation. The present study analyzed the expression pattern of SMP30 in mammary carcinoma in humans, dogs, and cats. Immunohistochemistry, immunofluorescence, and western blot analysis were used to investigate SMP30 expression patterns. The expression was specifically observed in neoplastic glandular epithelial cells. The expression increased with the malignancy of glandular epithelial cells with a highly proliferative status. However, SMP30 expression was low in normal mammary gland tissues or well-differentiated adenoma tissues. The patterns were consistently reproduced in canine primary mammary carcinoma cells and MCF-7 and MDA-MB-231 human carcinoma cell lines. This study provides useful information to understand SMP30 expression in various stages of mammary carcinoma and to suggest its utility as a pan-species diagnostic marker, thereby helping to establish strategies for diagnosing mammary carcinoma in several species.


Assuntos
Neoplasias da Mama/patologia , Proteínas de Ligação ao Cálcio/análise , Doenças do Gato/patologia , Doenças do Cão/patologia , Peptídeos e Proteínas de Sinalização Intracelular/análise , Neoplasias Mamárias Animais/patologia , Animais , Biomarcadores Tumorais/análise , Mama/patologia , Neoplasias da Mama/diagnóstico , Doenças do Gato/diagnóstico , Gatos , Linhagem Celular Tumoral , Doenças do Cão/diagnóstico , Cães , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Animais/diagnóstico , Prognóstico
10.
Medicine (Baltimore) ; 100(10): e24853, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725841

RESUMO

BACKGROUND: Rituximab is an induction immunosuppressant essential for ABO-incompatible kidney transplantation (ABOi KT). However, studies on its dosing, which differs among countries and transplant centers, are lacking. Therefore, we retrospectively investigated the effectiveness of the induction dose of rituximab against patient mortality, graft failure, and adverse events. METHODS: We included the studies referring to at least 2 of eligible induction doses (200 mg, 200-500 mg, or 500 mg) of rituximab during ABOi KT and relevant outcomes such as patient survival, graft failure, and bacterial and viral infections. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using generation mixed treatment comparison. Publications were retrieved using CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2020 and analyzed. The GRADE of network meta-analysis approach specified 4 levels of certainty for a given result: high, moderate, low, and very low. RESULTS: Among the 4256 patients from 21 trials, glomerular filtration rate, graft loss, antibody-mediated rejection, T-cell mediated rejection, fungal infection, bacterial infection, and CMV infection did not differ among ABOi groups treated with different rituximab doses. The effect on mortality was significantly higher in rituximab 200 to 500 mg, and rituximab 500 mg groups (odds ratios [OR] 3.5, 95% CrI: 1.3-9.8, and OR 3.0, 95% CrI 1.1-9.8), but not in rituximab 20 mg group (OR 0.45, 95% CrI 0.036-2.5). The incidence of BK virus was significantly lower in the rituximab 200-mg group than in the other groups. DISCUSSION: In ABO-incompatible kidney transplantation, low-dose rituximab is more efficacious than higher doses and reduces serious infection risks. Additional randomized controlled trials might be needed to confirm these findings due to small sample size.


Assuntos
Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Imunossupressores/administração & dosagem , Transplante de Rim , Complicações Pós-Operatórias/prevenção & controle , Rituximab/administração & dosagem , Infecções Bacterianas/prevenção & controle , Teorema de Bayes , Esquema de Medicação , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Humanos , Quimioterapia de Indução , Transplante de Rim/efeitos adversos , Doadores Vivos , Micoses/prevenção & controle , Metanálise em Rede , Viroses/prevenção & controle
11.
J Comp Pathol ; 180: 1-4, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33222865

RESUMO

Myofibromas are mesenchymal tumours of myofibroblastic origin that occur in solitary or multicentric forms. Solitary benign myofibromas mainly occur on the head and neck, especially in the subcutaneous region. They rarely occur in visceral organs in humans, but visceral myofibroma has not been reported in animals. We now report a case of testicular myofibroma in a 6-year-old rabbit in which orchiectomy revealed an enlarged testis with a multinodular surface. The cut surface of the testis showed a thick, homogeneous white-yellow mass surrounding the testicular parenchyma. Histopathologically, the mass was composed of collagen and eosinophilic fascicles of spindle cells that were immunopositive for α-smooth muscle actin but not desmin, S-100 or von Willebrand factor. These features distinguished the myofibroma from other spindle cell tumours. To the best of our knowledge, this is the first report of solitary testicular myofibroma in any animal species.


Assuntos
Miofibroma , Testículo/patologia , Animais , Masculino , Miofibroma/diagnóstico , Miofibroma/veterinária , Coelhos
12.
Transplant Proc ; 52(10): 3125-3128, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32553506

RESUMO

INTRODUCTION: ABO-incompatible living kidney transplantation (ABOILKT) has steadily become more widespread. However, the optimal immunosuppressive regimen for ABOILKT remains uncertain. We aimed to determine the outcomes according to dose of rituximab induction. METHODS: We conducted a systematic review and meta-analysis using random-effects modeling. We searched the following databases for all studies published through May 15, 2019: Cochrane Central Register, OVID MEDLINE, EMBASE, and PubMed. We reviewed all relevant reviews, registered trials, and relevant conference proceedings to compare clinical outcomes and survival according to dose of rituximab as induction in kidney transplantation. RESULTS: Five trials with a total of 390 patients were included. Glomerular filtration rates, graft loss, antibody mediated rejection, T cell mediated rejection, fungal infection (Candida), and patient survival rates did not differ between the 200 mg single dose and 375 mg/m2 in rituximab groups. However, incidence rate of infection 0.470 (95% confidence interval [CI], 0.264 to 0.838) had a lower result than the 200 mg rituximab group. CONCLUSIONS: The using of a 200 mg single dose of rituximab induction in ABOILKT has not only the same results for rejection, graft survival, and patient survival but also low incidence of infection after transplantation.


Assuntos
Incompatibilidade de Grupos Sanguíneos/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim , Rituximab/administração & dosagem , Sistema ABO de Grupos Sanguíneos/imunologia , Anticorpos/farmacologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Relação Dose-Resposta a Droga , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Humanos
13.
Medicine (Baltimore) ; 99(22): e20061, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481375

RESUMO

BACKGROUND: The rates of cardiovascular mortality and morbidity are increased in advanced chronic kidney disease (CKD). Mild to moderate CKD is associated with an increase in cardiovascular events. This study aims to investigate the effects of statins on patient mortality and cardiac events. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies on statins (atorvastatin, rosuvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, and simvastatin + ezetimibe) in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2019 were analyzed. Inclusion criteria were randomized control trials and adult patients (>18 years old). Reviews, observational studies, and clinical trials that did not clearly define outcomes or that did not have thrombosis as an outcome were excluded. We performed direct and indirect network meta-analysis using Bayesian models and ranked different statins using generation mixed treatment comparison (GeMTC) and Stata version 13. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) of network meta-analysis approach specified 4 levels of certainty for a given result: high, moderate, low, and very low. The outcomes were cardiac events, cardiac mortality, and all-cause mortality. RESULTS: Nineteen studies (45,863 patients) were included. Compared with placebos, pravastatin 40 mg group showed a significantly lower patient mortality (odds ratio 0.66 [95% credible interval, 0.46-0.91]).Atorvastatin 80 mg, fluvastatin 40 mg, lovastatin 20 mg, pravastatin 40 mg, and simvastatin 40 mg showed significant results in reducing cardiac events.In rank probability, pravastatin showed the best effect at all-cause mortality rate. Lovastatin, fluvastatin, and pravastatin showed good effects in the 1st, 2nd, and 3rd ranks in cardiac events. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Pravastatin 40 mg demonstrated the best effect on all-cause mortality, and was observed to be effective with high ranking in cardiac events. We anticipate that the data of this study will assist physicians in making informed decisions when selecting statins, such as pravastatin, as a treatment option for CKD patients.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Insuficiência Renal Crônica/complicações , Humanos , Metanálise em Rede
14.
Arch Biochem Biophys ; 688: 108407, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32407712

RESUMO

Prostate cancer has the highest incidence among men in advanced countries, as well as a high mortality rate. Despite the efforts of numerous researchers to identify a gene-based therapeutic target as an effective treatment of prostate cancer, there is still a need for further research. The cathepsin gene family is known to have a close correlation with various cancer types and is highly expressed across these cancer types. This study aimed at investigating the correlation between the cathepsin A (CTSA) gene and prostate cancer. Our findings indicated a significantly elevated level of CTSA gene expression in the tissues of patients with prostate cancer when compared with normal prostate tissues. Furthermore, the knockdown of the CTSA gene in the representative prostate cancer cell lines PC3 and DU145 led to reduced proliferation and a marked reduction in anchorage-independent colony formation, which was shown to be caused by cell cycle arrest in the S phase. In addition, CTSA gene-knockdown prostate cancer cell lines showed a substantial decrease in migration and invasion, as well as a decrease in the marker genes that promote epithelial mesenchymal transition (EMT). Such phenotypic changes in prostate cancer cell lines through CTSA gene suppression were found to be mainly caused by reduced p38 MAPK protein phosphorylation; i.e. the inactivation of the p38 MAPK cell signaling pathway. Tumorigenesis was also found to be inhibited in CTSA gene-knockdown prostate cancer cell lines when a xenograft assay was carried out using Balb/c nude mice, and the p38 MAPK phosphorylation was inhibited in tumor tissues. Thus, the CTSA gene is presumed to play a key role in human prostate cancer tissues through high-level expression, and the suppression of the CTSA gene leads to the inhibition of prostate cancer cell proliferation, colony formation, and metastasis. The mechanism, by which these effects occur, was demonstrated to be the inactivation of the p38 MAPK signaling pathway.


Assuntos
Catepsina A/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias da Próstata/metabolismo , Transdução de Sinais/fisiologia , Animais , Sequência de Bases , Catepsina A/genética , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos Endogâmicos BALB C , Metástase Neoplásica/genética , Metástase Neoplásica/fisiopatologia , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Sci Rep ; 9(1): 18156, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796787

RESUMO

The optimal vascular access type for elderly hemodialysis patients is controversial. We evaluated the impact of comorbidity burden on the association between vascular access type and mortality risk among 23,100 hemodialysis patients aged ≥65 years from the Korean Society of Nephrology End-Stage Renal Disease registry data. Subjects were stratified into tertiles according to the simplified Charlson comorbidity index (sCCI), and the survival and hospitalization rates were compared with respect to vascular access type: arteriovenous fistula (AVF), arteriovenous graft (AVG), and central venous catheter (CVC). Among all tertiles of sCCI, CVC use showed highest risk of mortality than AVF use. In the lowest to middle tertile, no difference was observed in survival rates between the use of AVF and AVG. However, in the highest tertile, AVG use showed higher risk of mortality than AVF use. When subjects were classified according to a combination of sCCI tertile and access type (AVF vs. AVG), patients with the highest CCI with AVG showed 1.75-folded increased risk of mortality than those with the lowest sCCI with AVF. Hospitalization rates due to access malfunction were highest in patients with CVC in all sCCI tertiles. In the highest tertile, patients with AVG showed increased rates of hospitalization compared to those with AVF due to access malfunction. However, hospitalization rates due to access infection were highest in patients with AVG in all tertiles. The use of AVF may be of benefit and switching to AVF should be considered in elderly hemodialysis patients with a high burden of comorbidity.


Assuntos
Fístula Arteriovenosa/etiologia , Cateteres Venosos Centrais/efeitos adversos , Diálise Renal/efeitos adversos , Idoso , Fístula Arteriovenosa/mortalidade , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Cateteres de Demora/efeitos adversos , Comorbidade , Feminino , Hospitalização , Humanos , Falência Renal Crônica/mortalidade , Masculino , Fatores de Risco , Taxa de Sobrevida
16.
Vet Sci ; 6(4)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561583

RESUMO

A black bear of 29-year-old (Ursus americanus) died unexpectedly in captivity without any gross lesions or clinical signs. We identified a firm, lobulated, yellowish tan, and well-circumscribed mass embedded inside the testicular tissue at the time of necropsy. The tumor sections exhibited soft necrotic and hemorrhagic areas beneath its capsule. Histologically, the tumor comprised Sertoli cells arranged in tubules and solid sheets supported by prominent fibrous connective tissues. The Sertoli cells were positive for vimentin and ER-ß expression, whereas it showed negative staining for inhibin-α, cytokeratin 19, and S-100. To the best of our knowledge, this is the rare case report of testicular Sertoli cell tumor in black bear.

17.
Int J Mol Sci ; 20(15)2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387201

RESUMO

The cellular distribution of silica nanoparticles (NPs) in the liver is not well understood. Targeting specific cells is one of the most important issues in NP-based drug delivery to improve delivery efficacy. In this context, the present study analyzed the relative cellular distribution pattern of silica NPs in the liver, and the effect of surface energy modification on NPs. Hydrophobic NP surface modification enhanced NP delivery to the liver and liver sinusoid fFendothelial cells (LSECs). Conversely, hydrophilic NP surface modification was commensurate with targeting hepatic stellate cells (HSCs) rather than other cell types. There was no notable difference in NP delivery to Kupffer cells or hepatocytes, regardless of hydrophilic or hydrophobic NP surface modification, suggesting that both the targeting of hepatocytes and evasion of phagocytosis by Kupffer cells are not associated with surface energy modification of silica NPs. This study provides useful information to target specific cell types using silica NPs, as well as to understand the relationship between NP surface energy and the NP distribution pattern in the liver, thereby helping to establish strategies for cell targeting using various NPs.


Assuntos
Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Fígado/metabolismo , Nanopartículas , Dióxido de Silício , Portadores de Fármacos/química , Células Endoteliais/metabolismo , Células Estreladas do Fígado/metabolismo , Hepatócitos/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Macrófagos do Fígado/metabolismo , Nanopartículas/química , Dióxido de Silício/química , Propriedades de Superfície , Distribuição Tecidual
18.
Transplant Proc ; 51(8): 2606-2610, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31439331

RESUMO

BACKGROUND: Antithymocyte globulin (ATG) is an induction therapy in kidney transplantation, but our knowledge about the relation between outcomes and ATG regimens is limited. We compared ATG effectiveness in kidney transplantation according to dosage and administration schedule. METHODS: Reports from 1970 until May 2018 in CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded were searched. We performed direct and indirect network meta-analysis using Bayesian models and generated rankings for ATG dosage and injection number variations by generation mixed treatment comparison.We compared ATG dose and schedule in kidney transplantation in relation to all-cause death, graft failure, antibody-mediated rejection, T-cell mediated rejection, biopsy-proven acute rejection, and bacterial and viral infection. RESULTS: Ten studies (N = 1065) were analyzed by forming 6 groups: ATG alternate doses, 9 mg/kg, 6 mg/kg, and 4.5 mg/kg; single dose, 6 mg/kg, and 4.5 mg/kg; and control. Compared to placebo, ATG regimen variations were not associated with significant differences in survival, viral infection, renal function, or graft survival. ATG regimens 9 and 4.5 mg alternate dosing tended to reduce biopsy-proven acute rejection but without statistical significance. According to the highest rank probability, the 9 mg alternate dosing group had the highest tendency for cytomegalovirus and bacterial infections but without statistical significance. CONCLUSIONS: The rejection frequency tended to be lower for the 9 and 4.5 mg alternate dosing groups. Infections occurred at a higher rate in the 9 mg alternate dosing group, but the differences in the risk of infection among the groups with different ATG regimens were not statistically significant.


Assuntos
Soro Antilinfocitário/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Metanálise em Rede , Adulto , Feminino , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade
19.
Transplant Proc ; 51(8): 2710-2713, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31447193

RESUMO

BACKGROUND: Hyperlipidemia and cardiovascular disease are risk factors for long-term renal transplant dysfunction. However, no meta-analyses of randomized controlled trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effects of statin use on renal transplant patients using a meta-analysis approach. METHODS: We conducted a systematic review and meta-analysis using random effects modeling. We searched the following databases for all studies published through to June 15, 2018: Cochrane Central Register, OVID MEDLINE, Embase, and PubMed. We reviewed all relevant reviews, registered trials, and relevant conference proceedings to compare clinical outcomes and survival between fluvastatin recipients and controls. RESULTS: Five trials with a total of 3725 patients were included. Glomerular filtration rates, graft loss, tacrolimus level, antibody-mediated rejection, T cell-mediated rejection, proteinuria, fungal infection (candida), and patient survival rates did not differ between the fluvastatin and control groups. However, major adverse cardiovascular events were 1.547 times more common in the control group than in the fluvastatin group (P = .001). CONCLUSIONS: Fluvastatin use was associated with a reduction in major adverse cardiac events among kidney transplant patients.


Assuntos
Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Fluvastatina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Transplante de Rim , Rejeição de Enxerto/epidemiologia , Humanos , Transplante de Rim/mortalidade
20.
Kidney Res Clin Pract ; 38(2): 239-249, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31096315

RESUMO

Background: Significant increases in the prevalence of obesity have been observed among patients with peritoneal dialysis (PD). The impact of body mass index (BMI) on survival remains unknown in Korean PD patients. Methods: Among data of 80,674 patients on PD acquired from the Insan Memorial ESRD Registry database for the years 1985 to 2014, 6,071 cases were analyzed. Subjects were classified by baseline BMI; < 21.19 kg/m2 (quartile 1, n = 1,518), 21.19 to 23.18 kg/m2 (quartile 2, reference; n = 1,453), 23.19 to 25.71 kg/m2 (quartile 3, n = 1,583), and > 25.71 kg/m2 (quartile 4, n = 1,517). Results: Mean age was 65.8 years, and baseline BMI was 23.57 kg/m2. Numbers of male and diabetic patients were 3,492 (57.5%) and 2,192 (36.1%), respectively. Among 6,071 cases, 2,229 (36.7%) all-cause deaths occurred. As a whole, Kaplan-Meier survival curves according to BMI quartiles was significantly different (P = 0.001). All-cause mortality was significantly higher in quartile 4 than in the reference (hazard ratio [HR] = 1.154, 95% confidence interval [CI], 1.025-1.300; P = 0.018). There was no statistical difference in all-cause mortality among BMI quartiles in diabetic patients on PD. In non-diabetic patients, all-cause mortality of quartiles 1 and 3 was not different from the reference, but the HR was 1.176 times higher in quartile 4 (95% CI, 1.024-1.350; P = 0.022). Conclusion: Baseline BMI > 25.71 kg/m2 seems to be an important risk factor for all-cause mortality in Korean PD patients.

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