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1.
China Occupational Medicine ; (6): 615-620, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-976085

RESUMO

@#Objective - To analyze the relationship between cobalt level of post shift urine and individual exposure level of , cobalt and its compounds in cobalt exposed workers and to explore the feasibility of using urine cobalt as a biomarker. Methods - A total of 148 occupational cobalt exposed workers from a new material company were selected as the exposed , - - group and 44 non occupational cobalt exposed workers from the company were selected as the control group using the typical sampling method. The exposure concentration of time weighted average of cobalt and its compounds in the workplace air of the - two groups was determined by inductively coupled plasma mass spectrometry as the individual exposure level. The cobalt levels - - of pre shift and post shift urinary samples of the two groups were detected by this method. The linear relationship between the - cobalt level of post shift urine and the individual exposure level of cobalt and its compounds in the air of the workplace was Results - 3 analyzed. The individual exposure level of cobalt and its compounds in the exposed group was 1.10 131.71 μg/m with (M) 3 the median of 12.23 μg/m. No cobalt and its compounds were detected in the workplace air in the control group. The cobalt - - levels of pre shift and post shift urines in exposed group were higher than those in the control group at the same time point (M: vs , vs , P ) - - 1.54 0.56 μg/L 8.77 0.83 μg/L all <0.01 . The cobalt level of post shift urine was higher than that in pre shift (M: vs ,P ), urine in the exposed group 8.77 1.54 μg/L <0.01 and it was positively correlated with the individual exposure level ( ,P ) , of cobalt and its compounds Spearman correlation coefficient=0.86 <0.01 . After common logarithm conversion the linear regression equation of the cobalt level of post shift urine and the common logarithm of individual exposure level of cobalt and (x) :ŷ x( ;F , its compounds in the exposed group was as follows = −0.178 + 0.988 coefficient of determination=0.72 =374.75 P ;t , P ) Conclusion - <0.01 = - 19.36 <0.01 . There was a linear correlation between cobalt level of post shift urine and occupational cobalt exposure level of cobalt exposed workers. Urinary cobalt can be used as a biomarker of occupational cobalt

2.
Mol Med Rep ; 19(1): 187-194, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30431114

RESUMO

Various types of mesenchymal stromal cells (MSCs) have been used in urological tissue engineering but to date the existence of MSCs has not been reported in the human bladder. The present study provided evidence that a small number of MSC­like cells exist in the human bladder and designated this class of cells 'human bladder­derived MSC­like cells' (hBSCs). It was demonstrated that hBSCs can be cultured to yield a large population. These hBSCs expressed the surface markers of MSCs and exhibited the capacity for osteogenic, adipogenic and chondrogenic differentiation. On induction with appropriate media in vitro, hBSCs could differentiate into bladder­associated cell types, including urothelial, endothelial and smooth muscle cell­like lineages. In addition, the average telomerase activity of adult hBSCs was higher compared with adult human bone marrow­derived MSCs, but lower than that of human umbilical cord Wharton's jelly­derived MSCs. These findings may inspire future studies on the role of hBSCs in urological tissue engineering applications and in other fields.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Mesenquimais/citologia , Células-Tronco/citologia , Bexiga Urinária/citologia , Adipogenia/fisiologia , Adulto , Idoso , Linhagem da Célula/fisiologia , Células Cultivadas , Condrogênese/fisiologia , Endotélio/citologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/citologia , Osteogênese/fisiologia , Engenharia Tecidual/métodos , Cordão Umbilical/citologia , Urotélio/citologia
3.
Kaohsiung J Med Sci ; 34(10): 576-582, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30309486

RESUMO

To explore the influence of prostate size on the outcome of Plasmakinetic enucleation of the prostate (PkEP) for the treatment of benign prostate hyperplasia (BPH), The data of 892 patients with symptomatic BPH who underwent PkEP were retrospectively reviewed. Among them, 199 (22.31%) had the prostate size smaller than 40 g (Group 1), 409 (45.85%) between 40 and 79 g (Group 2), 197 (22.09%) between 80 and 120 g (Group 3), and 87 (9.75%) larger than 120 g (Group 4). Perioperative variables, perioperative and postoperative complications were recorded. Patients were followed up for 36 months postoperatively. The efficiency of the surgery increased as the prostate size increased. Greater decreases in hemoglobin were noted in groups with larger prostates, while the duration of catheterization after the operation was similar across all groups. During the 3-year follow-up, the postoperative improvement in International Prostate Symptom Score (IPSS), Quality of Life (QOL), maximal flow rate (Qmax) and post-void residual urine volume (PVR), as well as longterm complications including urethral stricture and bladder-neck contracture were comparable across the 4 groups. These findings revealed that PkEP is more efficient for large prostate and can treat all prostates regardless of the size with equivalent symptom relief and micturition improvement.


Assuntos
Próstata/patologia , Próstata/cirurgia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Hiperplasia Prostática/fisiopatologia , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
4.
EBioMedicine ; 34: 85-93, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30078736

RESUMO

BACKGROUND: Uncoordinated 51-like kinase 1 (ULK1) plays a vital role in autophagy. ULK1 dysregulation has recently been found in several human cancers. METHODS: mRNA expression levels of ULK1 and clinical information were analysed from The Cancer Genome Atlas data. ULK1 expression levels were verified in 36 paired fresh ccRCC tissue specimens by western blot analysis. Expression of ULK1 was knockdown by shRNA lentivirus. ULK1 activity was inhibited by SBI-0206965. The effect of inhibition of ULK1 was measured by detecting the apoptotic rate, autophagy, and the ratio of ROS and NADPH. The efficacy of SBI-0206965 in vivo was assessed by the murine xenograft model. FINDINGS: ULK1 mRNA expression was significantly upregulated in clear cell renal cell carcinoma (ccRCC) and overexpression of ULK1 correlated with poor outcomes. We found that ULK1 was highly expressed in 66.7% of ccRCC tumours (p < 0·05). Knockdown of ULK1 and selective inhibition of ULK1 by SBI-0206965 induced cell apoptosis in ccRCC cells. We demonstrated that SBI-0206965 triggered apoptosis by preventing autophagy and pentose phosphate pathway (PPP) flux. Furthermore, blocking the kinase activity of ULK1 with SBI-0206965 resulted in a level of anticancer effect in vivo. INTERPRETATION: Taken together, our results suggested that ULK1 was upregulated in ccRCC tumours and may be a potential therapeutic target. Therefore, SBI-0206965 should be further considered as an anti-ccRCC agent. FUND: This work was supported in part by The National Natural Science Foundation of China (No. 81570748) and Natural Science Foundation of Fujian Province (No. 2018J01345, 2017XQ1194).


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Renais/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/antagonistas & inibidores , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/tratamento farmacológico , Linhagem Celular , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Estimativa de Kaplan-Meier , Neoplasias Renais/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico
5.
Stem Cells Dev ; 26(17): 1283-1292, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28548571

RESUMO

RHO GTPases regulate cell migration, cell-cycle progression, and cell survival in response to extracellular stimuli. However, the regulatory effects of RHO GTPases in mesenchymal stromal cells (MSCs) are unclear. Herein, we show that CDC42 acts as an essential factor in regulating cell proliferation and also takes part in lipotoxic effects of palmitate in human umbilical cord Wharton's jelly derived MSCs (hWJ-MSCs). Cultured human bone marrow, adipose tissue, and hWJ-MSC derived cells had varying pro-inflammatory cytokine secretion levels and cell death rates when treated by palmitate. Strikingly, the proliferation rate of these types of MSCs correlated with their sensitivity to palmitate. A glutathione-S-transferase pull-down assay demonstrated that hWJ-MSCs had the highest activation of CDC42, which was increased by palmitate treatment in a time-dependent manner. We demonstrated that palmitate-induced synthesis of pro-inflammatory cytokines and cell death was attenuated by shRNA against CDC42. In CDC42 depleted hWJ-MSCs, population-doubling levels were notably decreased, and phosphorylation of ERK1/2 and p38 MAPK was reduced. Our data therefore suggest a mechanistic role for CDC42 activity in hWJ-MSC proliferation and identified CDC42 activity as a promising pharmacological target for ameliorating lipotoxic cell dysfunction and death.


Assuntos
Células-Tronco Mesenquimais/citologia , Palmitatos/toxicidade , Cordão Umbilical/citologia , Geleia de Wharton/citologia , Proteína cdc42 de Ligação ao GTP/metabolismo , Adulto , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Pessoa de Meia-Idade
6.
J BUON ; 20(2): 505-13, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26011343

RESUMO

PURPOSE: To observe the efficacy and side effects of adjuvant dendritic cells' (DCs) vaccine combined with cytokine-induced killer cell (CIK) therapy after renal cell carcinoma (RCC) surgery (RCCS). METHODS: DCs vaccine and CIK that loaded the autologous tumor cell lysate were prepared in vitro. Four hundred and ten RCC patients were recruited, and the study group was given DCs-CIK immunotherapy, while the control group was given IFN-α therapy. RESULTS: Disease progression (recurrence, metastasis or death) showed significant differences between the two groups in clinical stage I and II patients, as well as in highly and moderately differentiated disease (p<0.05), while there was no significant difference between the two groups in patients with poorly differentiated disease (p>0.05). The 3- and 5-year overall survival rates of the DCs-CIK group (96% and 96%, respectively) exhibited significant difference compared to the IFN-α group (83% and 74%, respectively (p<0.01). Progression-free survival (PFS) between the two groups was significantly different (p<0.01). Tumor stage and DCs-CIK treatment were independent factors concerning prognosis of RCC (p<0.05). There was no severe toxicity observed in the DCs-CIK treatment group. CONCLUSIONS: Adjuvant post-RCCS DCs-CIK treatment prolonged PFS and reduced mortality, showing better overall activity compared to interferon treatment.


Assuntos
Vacinas Anticâncer/imunologia , Carcinoma de Células Renais/terapia , Células Matadoras Induzidas por Citocinas/imunologia , Células Dendríticas/imunologia , Neoplasias Renais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vacinas Anticâncer/efeitos adversos , Carcinoma de Células Renais/mortalidade , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade
7.
Carbohydr Polym ; 105: 127-34, 2014 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-24708961

RESUMO

A polysaccharide (BEP, Mw=113,432Da) was purified from Boletus edulis, which had a backbone consisting of (1→6)-linked-α-d-glucopyranosyl, (1→2,6)-linked-α-d-galactopyranosyl, (1→6)-linked-α-d-galactopyranosyl, and (1→3)-linked-α-d-rhamnopyranosyl residues, which were branched at O-2 position of (1→2,6)-linked-α-d-galactopyranosyl residue with a single terminal (1→)-linked-α-l-arabinofuranosyl residue. After 32 days' BEP administration to Renca tumor bearing mice, the tumor mass of Renca transplanted in mice was significantly repressed. Furthermore, BEP could significantly increase the spleen and thymus indices, stimulate splenocytes proliferation, augment NK cell and CTL activities in spleen, and promote the secretion of the cytokines IL-2 and TNF-α in Renca tumor bearing mice. Meanwhile oral administration of BEP (100 and 400mg/kg) restored all the altered hematological and biochemical parameters of tumor-bearing mice to normal levels. Thus, these data demonstrate that BEP possesses potential immunomodulatory activity and might be employed as effective therapeutic agents for the prevention of renal caner.


Assuntos
Agaricales , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Fatores Imunológicos/isolamento & purificação , Neoplasias Renais/imunologia , Polissacarídeos/isolamento & purificação , Água , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Feminino , Carpóforos/isolamento & purificação , Carpóforos/metabolismo , Fatores Imunológicos/metabolismo , Fatores Imunológicos/farmacologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Polissacarídeos/metabolismo , Polissacarídeos/farmacologia , Solubilidade/efeitos dos fármacos , Água/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
8.
Mol Med Rep ; 9(4): 1179-84, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24535460

RESUMO

The renal allograft survival rates of patients with immunoglobulin A nephropathy (IgAN), and patients with or without other glomerular diseases, have yet to be fully elucidated. In this study, the clinicopathological factors associated with long-term allograft survival for the prognosis of renal allograft recipients with IgAN were examined. All patients enrolled in this study were diagnosed with IgAN following clinical and pathological examinations. Patients underwent renal graft biopsy and were hospitalized at the Fuzhou General Hospital between June, 2004 and December, 2010. Common demographic and clinical indicators were recorded in patients who had graft loss and in those who had functional renal grafts. Forty-two of the 202 biopsy specimens (20.8%) met the diagnostic criteria for IgAN and were divided into two groups, the graft loss group (n=17) and the functional graft group (n=25). Patients were followed up for 1-257 months after kidney transplantation. The mean patient age was 40.6 ± 9.3 years at the time of renal graft biopsy. Examination results indicated concomitant proteinuria and hematuria in 25 patients (59.5%) and proteinuria alone in six patients (14.3%). Graft loss occurred in 17 patients during the follow-up period. Comparison of the graft loss and the functional graft groups indicated that patients in the graft loss group were more likely to have proteinuria (P=0.047), high creatinine levels at the time of biopsy (P=0.009), low glomerular filtration rates (P=0.013), low serum total protein (P=0.01), a high Banff score (P=0.001), extensive glomerulosclerosis (P=0.002), a greater likelihood of crescent formation (P=0.01), severe tubular atrophy (P=0.013) and more extensive interstitial fibrosis (P=0.033). However, the two groups showed no significant differences in blood pressure, hematuria, BUN, UA, Hb, TG and CHO levels. The allograft survival rate of patients with IgAN was identified to be similar to that of patients with and without other glomerular diseases.


Assuntos
Aloenxertos/patologia , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/terapia , Sobrevivência de Enxerto , Transplante de Rim , Adulto , Estudos de Casos e Controles , Demografia , Feminino , Glomerulonefrite por IGA/mortalidade , Humanos , Masculino , Prognóstico , Taxa de Sobrevida
9.
Biomed Mater Eng ; 24(1): 145-53, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24211893

RESUMO

Calculating an accurate cumulative dose through individual phases for four-dimensional computed tomography (4DCT) images from the lung is time-consuming. Although the dose distribution of different phases is similar, copying the dose distribution of one phase directly to another phase would yield a dosimetric error of approximately 4% without further optimization. To reduce the dosimetric error, three-dimensional B-spline elastic deformable image registration (DIR) was used to quickly obtain a relatively accurate cumulative dose of 4DCT images acquired from ten lung cancer patients. The dose distribution of the end-expiration phase was mapped to the end-inspiration phase using DIR. The mapped dose in the end-inspiration phase was then compared with the directly copied dose by analysis (3cm/3%) and the t-test. The results showed that optimization using DIR was significantly better in the average pass rate (by 0.6-4.7%). Our results indicate it is feasible to map the dose distribution of 4DCT images in lung with DIR, and that the motion amplitude of individual respiratory and different DIR algorithms affect the differences between the mapped and actual dose.


Assuntos
Tomografia Computadorizada Quadridimensional/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Algoritmos , Humanos , Modelos Teóricos , Movimento , Imagens de Fantasmas , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador , Respiração , Software , Raios X
10.
Int J Oncol ; 44(1): 161-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24212916

RESUMO

SCIN is a calcium regulated actin severing and capping protein. Its homologue in zebrafish is found to be related with cell death. In the present study, we found that SCIN is highly expressed in human prostate cancer specimens. However, the functions of SCIN in human prostate carcinoma cells are largely unknown. To address the function of SCIN in prostate carcinoma cells, we used lentivirus-mediated RNAi to knock down SCIN expression in PC3 cells, a prostate carcinoma cell line. We found that in vitro silencing of SCIN could inhibit the proliferation and colony formation ability of PC3 cells. Furthermore, cell cycle analysis showed that reduced SCIN expression lead to G0/G1 cell cycle arrest through the regulation of cell cycle-related genes, such as p21Waf1/Cip1, cyclin-dependent kinase inhibitor 2A (CDKN2A, p16Ink4A) and cyclin A2. These results suggest that SCIN plays an important role in the proliferation of prostate cancer cells and lentivirus-mediated inhibition of SCIN expression may be a potential therapeutic method for the treatment of prostate cancer.


Assuntos
Proliferação de Células , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Gelsolina/biossíntese , Neoplasias da Próstata/genética , Apoptose/genética , Gelsolina/antagonistas & inibidores , Gelsolina/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Lentivirus , Masculino , Neoplasias da Próstata/patologia
11.
Sheng Li Xue Bao ; 65(6): 600-6, 2013 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-24343717

RESUMO

The saturated free fatty acid (FFA), palmitate, could induce apoptosis in various cell types, but little is known about its effects on human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). Here, we investigated whether palmitate induced apoptosis and endoplasmic reticulum (ER) stress in hUC-MSCs. hUC-MSCs were stained by labeled antibodies and identified by flow cytometry. After administration with palmitate, apoptotic cell was assessed by flow cytometry using the Annexin V-FITC/7-AAD apoptosis detection kit. Relative spliced XBP1 levels were analyzed using semi-quantitative RT-PCR. The mRNA of BiP, GRP94, ATF4 and CHOP were analyzed by real-time PCR. Relative BiP and CHOP protein were analyzed using Western blot analysis. The results showed that hUC-MSCs were homogeneously positive for MSC markers; palmitate increased apoptosis of hUC-MSCs and activated XBP1 splicing, BiP, GRP94, ATF4 and CHOP transcription. These findings suggest that palmitate induces apoptosis and ER stress in hUC-MSCs.


Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Células-Tronco Mesenquimais/efeitos dos fármacos , Palmitatos/farmacologia , Fator 4 Ativador da Transcrição/metabolismo , Proteínas de Ligação a DNA/metabolismo , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico/metabolismo , Humanos , Glicoproteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/citologia , Fatores de Transcrição de Fator Regulador X , Fator de Transcrição CHOP/metabolismo , Fatores de Transcrição/metabolismo , Cordão Umbilical/citologia , Proteína 1 de Ligação a X-Box
12.
BMC Cell Biol ; 14: 18, 2013 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-23510080

RESUMO

BACKGROUND: The objective of this study was to evaluate the effect of bone marrow mesenchymal stem cells (BMSCs) on the apoptosis of granulosa cells (GCs) in rats. RESULTS: Cisplatin increased GC apoptosis from 0.59% to 13.04% in the control and cisplatin treatment groups, respectively, which was significantly reduced upon co-culture with BMSCs to 4.84%. Cisplatin treatment increased p21 and bax and decreased c-myc mRNA expression, which was reversed upon co-culture with BMSCs. As compared to young rats, increased apoptosis was observed in the perimenopausal rats (P < 0.001). After 3 months, the apoptosis rate in the BMSC group was significantly lower than that of the control group (P = 0.007). CONCLUSIONS: BMSC therapy may protect against GC apoptosis induced by cisplatin and perimenopause. Further studies are necessary to evaluate therapeutic efficacy of BMSCs.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Cisplatino/administração & dosagem , Técnicas de Cocultura/métodos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Células da Granulosa/efeitos dos fármacos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Perimenopausa/fisiologia , Animais , Apoptose/efeitos dos fármacos , Células da Medula Óssea/fisiologia , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/genética , Estrogênios/administração & dosagem , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células da Granulosa/fisiologia , Células-Tronco Mesenquimais/fisiologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
14.
Zhonghua Yi Xue Za Zhi ; 93(48): 3841-6, 2013 Dec 24.
Artigo em Chinês | MEDLINE | ID: mdl-24548445

RESUMO

OBJECTIVE: To establish a formula for estimating area under the concentration-versus-time curve (AUC) of mycophenolate sodium in Chinese renal allograft recipients with a limited sampling model. METHODS: A total of 35 renal allograft recipients were recruited from 2010 to 2013 to receive enteric-coated mycophenolate sodium (EC-MPS), calcineurin (CNI) and prednisone as immunosuppressive triple therapy. The serum concentration of mycophenolic acid (MPA) was assayed by enzyme multiplied immunoassay technique (EMIT) at pre-dose (C0), 0.5 (C0.5), 1.0 (C1), 1.5 (C1.5), 2.0 (C2), 3.0 (C3), 4.0 (C4), 6.0 (C6), 8.0 (C8) and 12.0 (C12) h post-dose respectively. Pharmacokinetic parameters of MPA (C0, C12, Cmax, Tmax, AUC0-12 h) were calculated by software WINNOLIN. Simplified formulae for estimation of MPA-AUC in tacrolimus (Tac) group or cyclosporin A (CsA) group were established by multiple stepwise regression analysis. RESULTS: There were variable MPA AUC0-12 h levels between 14 and 67 mg×h/L (mean: 37 ± 14). The MPA trough level (C0) had no correlations with MPA AUC0-12 h (r(2) = 0.090) . The simplified MPA AUC formula for Tac group was AUC = 5.678+1.718×C4+2.853×C6+1.812×C8+3.413×C12 with four sampling points (C4, C6, C8, C12). Estimated AUC with the formula had correlations with AUC0-12 h (r(2) = 0.890). The mean absolute predict error (APE) was 3.45% (0.41%-24.71%) and the proportion of APE above 15% stood at 11.1% (2/18) . In CsA group, the simplified MPA AUC formula was AUC = 7.072+1.525×C3+1.558×C4+ 1.573×C6+2.285×C8. The correlation was r(2) = 0.952, mean APE was 6.50% (0.02%-12.91%) and proportion of APE above 15% stood at 0. The above formulae were observed to have agreement with AUC0-12 h by Bland-Altman analysis. CONCLUSION: The simplified MPA AUC formulae with 4-point sampling provide an effective approach for estimating full MPA AUC0-12 h in Chinese renal recipients on EC-MPS plus tacrolimus or cyclosporin A.


Assuntos
Transplante de Rim , Ácido Micofenólico/análogos & derivados , Adulto , Área Sob a Curva , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/farmacocinética , Transplante Homólogo , Adulto Jovem
16.
Yao Xue Xue Bao ; 47(7): 878-83, 2012 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-22993851

RESUMO

The effect of CYP3A4*18B and CYP3A5*3 on concentration/dosage x body surface area ratios (C/D'), adverse effects and acute rejection of tacrolimus in renal transplant patients were investigated. The CYP3A4*18B genotypes of 227 renal transplant patients were determined by PCR-RFLP method. The differences of C/D' ratios, adverse reactions and acute rejection were compared among all of the genotype groups treated with tacrolimus. The frequencies of CYP3A4*18 and CYP3A5*3 alleles in renal transplant patients were 30.8% and 74.2%, respectively. No significant association was found between the C/D's of tacrolimus and CYP3A4*18B genotypes when they were classified by two CYP3A5 genotypes (P > 0.05). While after the effects of CYP3A4*18B genotype were eliminated, the C/D' ratio of tacrolimus in patients with CYP3A5*1/*1 and *1/*3 genotype group was significantly lower than those with CYP3A5*3/*3 genotype groups (P < 0.01). There is no significant difference in adverse effects and acute rejection among different genotypes (P > 0.05).


Assuntos
Citocromo P-450 CYP3A/genética , Imunossupressores/sangue , Transplante de Rim , Tacrolimo/sangue , Adulto , Alelos , Doenças do Sistema Digestório/induzido quimicamente , Relação Dose-Resposta a Droga , Feminino , Genótipo , Rejeição de Enxerto/genética , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico
17.
Chin Med J (Engl) ; 124(5): 664-8, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21518554

RESUMO

BACKGROUND: Immunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody, was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients. METHODS: In this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients (panel reactive antibody > 20%). They were divided into two groups: alemtuzumab group (trial group) and anti-thymocyte globulin (ATG) group (control group). Patients in the alemtuzumab group received intravenous alemtuzumab (15 mg) as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab (15 mg) was given. The control group received a bolus of rabbit ATG (9 mg/kg), which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil (MMF). Acute rejection (AR) and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up. χ(2) test, t test and Kaplan-Meier analysis were performed with SPSS17.0 software. RESULTS: Median follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar (P > 0.05). White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months (P < 0.05). One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary infection or cardiac and pulmonary failure. Cumulative 2-year graft survival rate was 90.9% in the alemtuzumab group and 81.8% in ATG group (P > 0.05) respectively. There was one graft failure in the alemtuzumab group and two graft failures in ATG group, with all graft failures at tributed to rejection episodes. The alemtuzumab group had a 2-year cumulative freedom from rejection rate of 81.8%, compared with 72.7% for the ATG group (P > 0.05). CONCLUSION: Alemtuzumab induction therapy for highly sensitized kidney transplant recipients is an effective and safe protocol yielding an acceptable acute rejection rate.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Adulto , Idoso , Alemtuzumab , Anticorpos Monoclonais Humanizados , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
18.
Chin Med J (Engl) ; 124(6): 935-8, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21518606

RESUMO

Up till 2000 when Edmonton group introduced islet transplant procedure in conjunction with a novel glucocorticoid-free immunosuppressive regimen rendering 100% (n=7) of patients with type 1 diabetes insulin-independent for at least 1 year, islet transplant was taken into the clinic. Although significant progress in clinical islet transplant has occurred during recent years, challenges remain, including shortage of available donor organs, technical aspects of islet preparation and transplantation, immunological rejection post-transplant, unclear long-term outcomes of islet transplantation. Special attention is given to current limitation in islet transplantation together with new possible strategies that raise expectations for the widespread use of islet transplantation in the future.


Assuntos
Diabetes Mellitus/cirurgia , Transplante das Ilhotas Pancreáticas/imunologia , Transplante das Ilhotas Pancreáticas/métodos , Humanos , Imunossupressores/uso terapêutico , Transplante das Ilhotas Pancreáticas/tendências
19.
Diabetes Technol Ther ; 13(5): 537-41, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21406019

RESUMO

BACKGROUND: Recently a considerable number of promising clinical trials have been designed to perform infusion of stem cells by pancreatic arterial intervention to improve the endocrine function of the pancreas for better diabetes control. It is necessary to investigate the pancreatic body and tail (PBT) arterial system for human islets located mostly in the PBT and identify the predominant artery or arteries. However, the arterial system in the PBT is complicated and variable. In this study we comprehensively investigated the anatomical characteristics of arteries feeding the PBT. RESEARCH DESIGN AND METHODS: One hundred two patients with diabetes underwent 64-slice computed tomography angiography (CTA) and digital subtraction angiography (DSA). The target artery was catheterized, and DSA was performed to show the PBT. All images were documented for later analysis. RESULTS: DSA demonstrated that the feeding arteries for the PBT included the dorsal pancreatic artery (DPA) alone (n = 51 [50%]), combined DPA and great pancreatic artery (GPA) (n = 22 [21.6%]), GPA alone (n = 16 [15.7%]), and transverse pancreatic artery (TPA) (n = 11 [10.8%]). DPA was observed to originate from the initial segment of the splenic artery (n = 34 [46.6%]), common hepatic artery (n = 17 [23.3%]), or superior mesenteric artery (n = 14 [19.2%]). The GPA was mostly from the middle (n = 36 [94.7%]), and only two were found to originate from the initial segment of the splenic artery. The TPA (n = 11) was from either the pancreatoduodenal artery (n = 5 [54.5%]) or the gastroduodenal artery (n = 4 [36.4%]). In most case, the predominant artery of the PBT (95.1%, 97 of 102) could be revealed by 64-slice CTA. CONCLUSIONS: The origins and identities of the predominant artery in the PBT are variable. DSA is superior to CTA for preoperative imaging in arterial intervention therapy.


Assuntos
Angiografia Digital , Diabetes Mellitus/patologia , Diabetes Mellitus/fisiopatologia , Pâncreas/irrigação sanguínea , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Ilhotas Pancreáticas/irrigação sanguínea , Ilhotas Pancreáticas/patologia , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Pâncreas/patologia , Fluxo Sanguíneo Regional , Estudos Retrospectivos , Adulto Jovem
20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 26(9): 846-8, 2010 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-20815978

RESUMO

AIM: To explore the effects of Delta1 gene on rat bone marrow-derived dendritic cells (DCs). METHODS: pcDNA3.1/delta1 plasmid was transfected into Rat DCs with lipofectamine gene transfection method. The expression of activation markers(Iad, CD80 and CD86) were examined by flow cytometry, the release of cytokines IL-12 were examined by ELISA and the stimulatory capacity of the resulting DCs in vitro were examined by mixed lymphocyte reaction(MLR). RESULTS: The biological character of DCs in experimental group, empty vector group and control group were examined by electron microscope, flow cytometry and cell growth rate counting. There were no differences of cell cycles, ultrastructure and cell growth rate among these three group cells (P>0.05). It stated that delta1 gene had no effect on the growth of DCs. Even at the stimulation of LPS, In the delta1 transfected DCs, we observed no significant effects on the expression of activation markers(Iad, CD80 or CD86). The release of IL-12 in DCs/delta1 was reduced compared with control DCs(P<0.05). The levels of IFN-gamma and IL-2 of the DCs/delta1 were significantly lower than those of the DCs(P<0.05), and the levels of IL-4 and IL-10 were significantly higher than that in control DCs(P<0.05). CONCLUSION: Our data demonstrates that the delta1 gene transfection does not interfere with the differentiation or maturation of DCs, but reduce the ability to stimulating T cells, and the mechanism may be related to the decrease of Th1 /Th2 ratio by impairing the production of DCs-derived IL-12.


Assuntos
Comportamento Animal/fisiologia , Diferenciação Celular/efeitos dos fármacos , Células Dendríticas/metabolismo , Tolerância Imunológica/imunologia , Animais , Comportamento Animal/efeitos dos fármacos , Diferenciação Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/citologia , Células Dendríticas/fisiologia , Citometria de Fluxo , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Lipopolissacarídeos/farmacologia , Transplante de Órgãos/métodos , Ratos , Ratos Wistar , Equilíbrio Th1-Th2/efeitos dos fármacos , Transfecção/métodos
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