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1.
Gastrointest Endosc ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38851454

RESUMO

BACKGROUND AND AIMS: This study aims to identify the cause of disinfection failure of multiple flexible gastrointestinal endoscopes and to enhance the cleaning and disinfection procedures. METHODS: Samples from endoscopy devices, surrounding objects, cleaning water, automatic sterilizer, and integrated endoscopic washing workstation in a Digestive Endoscopy Center were collected and analyzed for microbial contamination and DNA/gene contents, between May and July 2021. RESULTS: The sample analysis revealed that the sink irrigation tubing of the washing workstation was contaminated with Burkholderia cepacia. After effective disinfection measures, the B. cepacia detection in the disinfected endoscope dropped from 13.23% to 0% (p=0.041). The presence of B. cepacia was confirmed through homology search and gene sequencing. CONCLUSIONS: The primary reason for endoscope disinfection failure is the contamination of the sink irrigation tubing by the B. cepacia bacteria. These findings emphasize the need for thorough cleaning of irrigation tubings in integrated endoscopic washing workstations, which is generally neglected in routine maintanance.

2.
Front Public Health ; 11: 1209646, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37575121

RESUMO

Background: This study aimed to understand the hospital-acquired COVID-19 infection rate and infection prevention and control status of emergency support frontline healthcare workers (ESFHCWs) under closed-loop management, and to explore the related factors affecting hospital-acquired COVID-19 prevention and control status. Methods: The study site was a provincial-level tertiary hospital in the Xinjiang Uygur Autonomous Region specializing in treating COVID-19 patients. ESFHCWs were assigned from different hospitals in Zhejiang Province to provide emergency medical support in this specialized hospital. All ESFHCWs were managed using a closed loop. A self-designed questionnaire was used to estimate basic information, work experience, and the status of infection prevention and control (SIPC). A total of 269 ESFHCWs responded to the questionnaire. A generalized linear regression model was used to estimate the factors influencing SIPC. Results: There were six hospital-acquired COVID-19 cases, with an infection rate of 2.23%. The independent risk factors influencing COVID-19 prevention and control status were work seniority, anxiety disorder, and consumption of gastrointestinal, anti-inflammatory and anti-asthmatic, and hypnotic sedative drugs. Compared with ESFHCWs with more than 10 years of work seniority, ESFHCWs with less than 5 years of work seniority and 5-10 years of work seniority had lower COVID-19 SIPC scores. Among ESFHCWs with anxiety disorder, the SIPC score was significantly lower than that of ESFHCWs without anxiety disorder. The SIPC scores of ESFHCWs taking other medications (gastrointestinal, anti-inflammatory and anti-asthmatic, and hypnotic sedative drugs) were lower than those of ESFHCWs who did not. Conclusion: The closed-loop management method may be effective in reducing the infection rate of hospital-acquired COVID-19 among ESFHCWs. HCWs with less than 10 years of work seniority, anxiety disorder, and other medications (gastrointestinal, anti-inflammatory and anti-asthmatic, and hypnotic sedative drugs) were probably not suitable for participating in emergency assistant actions because of their poor SIPC scores. Further studies are needed to develop the selection criteria for ESFHCWs.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Hospitais , Pessoal de Saúde
3.
Jpn J Infect Dis ; 76(5): 289-294, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37258178

RESUMO

This study examined the management of occupational bloodborne pathogen exposure at a tertiary hospital in China. This prospective study was conducted at the Zhejiang Hospital of Traditional Chinese Medicine between January 2016 and December 2019. Data on bloodborne occupational exposure management were collected. In total, 460 exposures were reported. The majority of exposures (40.2 %) were from hepatitis B virus (HBV)-positive index patients. Of the 460 cases, 453 (98.5%) exposures were reported timeously, and 371 (80.7%) cases received emergency treatment response and management. Sixty-eight personnel (93.2%) received timely prophylaxis treatment. Only 82/113 (72.6%) personnel completed the recommended follow-up period. Outsourced personnel(P = 0.002) and interns (P = 0.011) were independent follow-up factors. Although adequate compliance was achieved with timely reporting and prophylactic medication, there is room for improvement in terms of emergency treatment response and follow-up compliance. Furthermore, HBV vaccination and improved follow-up with outsourced personnel are recommended.


Assuntos
Infecções por HIV , Hepatite B , Exposição Ocupacional , Humanos , Patógenos Transmitidos pelo Sangue , Estudos Prospectivos , Pessoal de Saúde , Exposição Ocupacional/prevenção & controle , Centros de Atenção Terciária , Hepatite B/tratamento farmacológico , Hepatite B/prevenção & controle
4.
Front Public Health ; 9: 700041, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34676191

RESUMO

Background: To evaluate the effectiveness between daily and after-each-case room disinfection in the endoscopy unit. Methods: This study was conducted in an endoscopy unit of the First Affiliation of Zhejiang Chinese Medical University. We cultured samples from the surface of endoscopy unit items, including operation unit air, isolation gown of an endoscopist, control panel buttons, workstation mouse, and the bed head of the patient. All the samples were divided into daily and after-each-case room disinfection groups. In addition, each group was subdivided into sedation and nonsedation gastroscopy with and without ventilation room groups. Results: The qualified rate of bed head samples of the patient were lower in the daily room disinfection group (76.67%) compared with the after-each-case group (100%). The isolation gown, mouse at the workstation, and the bed head of the patient demonstrated the lowest bacterial and fungal load in the after-each-case room disinfection group compared with the daily room disinfection group (p < 0.05). In the subgroup analysis, a higher microbial load was observed for the isolation gown of the endoscopist used during nonsedation gastroscopy in an unventilated room under the after-each-case room disinfection pattern (p < 0.05); a higher microbial load was observed for the control panel buttons used during nonsedation gastroscopy under the after-each-case room disinfection pattern (p < 0.05). Conclusions: For risk-free or low-risk patients, daily room disinfection provides the basic health requirements of the endoscopy procedure. However, it is better to adopt the after-each-case room disinfection for the isolation gown of the endoscopist and bed head of the patient. For the patients with high risk, the after-each-case room disinfection is more suitable for every endoscopy unit (www.ClinicalTrials.gov, NCT04399005).


Assuntos
Desinfecção , Fungos , Animais , Bactérias , Gastroscopia , Humanos , Camundongos , Ventilação
5.
Blood Purif ; 50(1): 57-64, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32506055

RESUMO

BACKGROUND: With an estimated basic reproductive number of 3.77, the Coronavirus Disease 2019 (COVID-19) continues to spread. It is urgent to exert adequate efforts for the management of dialysis patients, caregivers, and healthcare personnel (HCP). This study aimed at reporting practical workflow, identification of high-risk or suspected cases of CO-VID-19, and subsequent response measures. METHODS: At the time of the COVID-19 outbreak, precautions and practice protocols were applied in our dialysis units (DUs). This single-center study retrospectively reviewed all high-risk/suspected cases from January 23, 2020, to February 10, 2020. Epidemiological, clinical feature, and detailed data on all cases were recorded. RESULTS: Practical workflow for the clinical management of dialysis patients, caregivers, and HCP was initiated. A total of 6 high-risk/suspected cases were identified. Female gender, older age, presence of cardiovascular disease, diabetes, anuresis, immunocompromised status, hypoalbuminemia, and underweight were noticeable features in these cases. Direct evidence of infection or epidemiological risk was detected in five cases. Close monitoring for temperature and oxygen saturation during hemodialysis sessions may be reasonable. No confirmed COVID-19 cases were reported in our DU, but certain cases showed rapid deterioration due to other critically severe condition needing hospitalization. Portable dialysis machines are of great need to ensure dialysis care provision. CONCLUSIONS: Our study described a practical workflow for patient-centered management during COVID-19 outbreak. Potential risk factors and underlying clinical patterns were reported. Further studies regarding the efficacy of infection control precautions and practice protocols tailored for dialysis settings are warranted.


Assuntos
COVID-19/prevenção & controle , Controle de Infecções/métodos , Falência Renal Crônica/terapia , Diálise Renal , Idoso , COVID-19/complicações , COVID-19/diagnóstico , Surtos de Doenças , Feminino , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos , Estudos Retrospectivos
6.
Gut Pathog ; 12: 41, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32944084

RESUMO

BACKGROUND: The aim of this study is to evaluate the prophylactic effects of probiotic mixture BIFICO on antibiotic-induced gut dysbiosis (AIGD) and the influence on the change of the gut microbiota. METHODS: We conducted a prospective, randomized, controlled study and divided 196 patients who required intravenous beta-lactam antibiotics into three groups: a control group (no probiotics), a regular group (840 mg of BIFICO), and a double-dosage group (1680 mg of BIFICO). The symptoms of antibiotic-related diarrhea, bloating and abdominal pain and the incidence of AIGD were evaluated 7 days and 8-14 days after antibiotic use, with 10 patients in each group. 16S rDNA sequencing was performed to detect changes of the gut microbiota. RESULTS: Within 7 days of the initiation of antibiotic treatment, the incidences of AIGD in the control group, regular group (840 mg of BIFICO), and double-dosage group (1680 mg of BIFICO) were 21.88%, 14.93%, and 6.15% respectively. On days of 8-14th, the incidences of AIGD in the control group, regular group, and double-dosage group were 25%, 14.93%, and 4.62%, respectively. The incidence of AIGD in the double-dosage group within 7 days and 14 days were both significantly lower than that in relevant control group (P < 0.05). On day 14, the incidence of AIGD in the double-dosage group was lower than that in the regular group (P < 0.05). The number of operational taxonomic units (OTUs) in the control group after antibiotic treatment was significantly reduced compared to that prior to treatment, while those of the regular and double-dosage groups were stable. The species abundance, especially Parabacteroides, Phascolarctobacterium and Roseburia, of the double-dosage group was greater than that of the regular group and the control group. CONCLUSIONS: BIFICO may reduce the occurrence of AIGD in a dose-dependent manner and can stabilize the gut microbiota balance.

7.
Braz J Med Biol Res ; 53(5): e9331, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348426

RESUMO

The melamine and cyanuric acid (CA) complex has been suggested to cause the toxic effects observed in melamine-contaminated food or milk. However, the cytotoxic and genotoxic effects of co-exposure to melamine and CA are not fully clear. Therefore, the cytotoxic effects of melamine and CA were first examined by co-exposure in human kidney 293 cells using the MTT assay. During a 24-h period for the three concentrations tested (0.5, 1, and 5 mg/mL), neither melamine nor CA alone showed significant toxic effects on 293 cells at 0.5 mg/mL, while higher concentrations led to decreased in cell viability. However, co-exposure to several combinations of melamine and CA [100:1, 10:1, 1:10, and 1:100 (v:v), at a final concentration of 0.5 mg/mL] did cause cytotoxicity with higher levels of CA leading to higher cytotoxicity. By contrast, while neither melamine nor CA alone induced phosphorylated-H2AX (γH2AX) foci formation, melamine and CA at a 100:1 ratio induced γH2AX foci 24 h post-treatment. The alkaline comet assay also revealed the presence of DNA damage following melamine and CA co-exposure. In vivo assay also revealed the presence of melamine-CA complex in the kidney. These data indicated that the cytotoxic and genotoxic effects of melamine and CA co-exposure differ from those of melamine or CA alone.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Rim/efeitos dos fármacos , Triazinas/toxicidade , Animais , Humanos , Rim/embriologia , Testes de Mutagenicidade , Ratos , Fatores de Tempo
8.
J Infect Public Health ; 13(5): 718-723, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32253173

RESUMO

BACKGROUND: This study aimed to assess potential failure mode, implement countermeasures against risks and improve disinfection quality monitoring using healthcare failure mode and effect analysis (HFMEA). METHODS: Between July 2017 and March 2018, a multidisciplinary team was formed to conduct HFMEA and implement improvement interventions. Fourteen monitoring departments and seven monitoring items were involved. The qualification rate of monitoring process was used to evaluate the influence of HFMEA on the standardization monitoring management of disinfection quality. RESULTS: After HFMEA, the qualification rate of overall monitoring process of disinfection quality improved from 16.5% to 78.7% (P < 0.001), and the qualification rates of each monitoring step were all significantly improved. The qualification rate implemented by the clinical laboratory improved from 20.1% to 100.0% (P < 0.001). The qualification rate implemented by thirteen monitoring departments improved from 20.1% to 78.7% (P < 0.001), where seven reached 100%. Out of seven monitored items, three had the qualification rate of 100.0%, while the remaining four items showed significant rising in qualification rates (P < 0.001). CONCLUSION: HFMEA were helpful in improving the qualification rate of disinfection effect monitoring process.


Assuntos
Desinfecção/normas , Análise do Modo e do Efeito de Falhas na Assistência à Saúde/métodos , Atenção à Saúde , Desinfecção/métodos , Administração Hospitalar/normas , Humanos , Gestão da Segurança/normas , Inquéritos e Questionários
9.
Braz. j. med. biol. res ; 53(5): e9331, 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1098113

RESUMO

The melamine and cyanuric acid (CA) complex has been suggested to cause the toxic effects observed in melamine-contaminated food or milk. However, the cytotoxic and genotoxic effects of co-exposure to melamine and CA are not fully clear. Therefore, the cytotoxic effects of melamine and CA were first examined by co‐exposure in human kidney 293 cells using the MTT assay. During a 24-h period for the three concentrations tested (0.5, 1, and 5 mg/mL), neither melamine nor CA alone showed significant toxic effects on 293 cells at 0.5 mg/mL, while higher concentrations led to decreased in cell viability. However, co-exposure to several combinations of melamine and CA [100:1, 10:1, 1:10, and 1:100 (v:v), at a final concentration of 0.5 mg/mL] did cause cytotoxicity with higher levels of CA leading to higher cytotoxicity. By contrast, while neither melamine nor CA alone induced phosphorylated-H2AX (γH2AX) foci formation, melamine and CA at a 100:1 ratio induced γH2AX foci 24 h post-treatment. The alkaline comet assay also revealed the presence of DNA damage following melamine and CA co-exposure. In vivo assay also revealed the presence of melamine-CA complex in the kidney. These data indicated that the cytotoxic and genotoxic effects of melamine and CA co-exposure differ from those of melamine or CA alone.


Assuntos
Humanos , Animais , Ratos , Triazinas/toxicidade , Dano ao DNA/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Rim/efeitos dos fármacos , Fatores de Tempo , Rim/embriologia , Testes de Mutagenicidade
10.
Exp Ther Med ; 14(5): 4655-4662, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29201164

RESUMO

Electroacupuncture (EA) accelerates intestinal functional recovery in sepsis. The present study investigated ghrelin and ghrelin receptor (GSH-R) levels during EA in rats with acute bowel injury (ABI). Rats were grouped into four groups: Sham, ABI, ABI+EA and ABI+GHRA+EA (n=12 per group). ABI was induced by cecal ligation and puncture (CLP). EA on bilateral Zusanli acupoints was performed following CLP. GSH-R blocker (GHRA) was used following CLP but prior to EA for ABI+GHRA+EA rats. Rats were sacrificed 12 h following CLP. Serum ghrelin, tumor necrosis factor-α (TNF-α) and high mobility group box 1 (HMGB1) levels, as well as ghrelin and GSH-R protein expression, water content, pathological changes and myeloperoxidase (MPO) and diamine oxidase (DAO) activities in the bowel tissues, were measured. ABI rats, compared with the sham rats, had significantly lower levels of ghrelin and GSH-R in the serum and bowel tissue, and higher Chiu's score (all P<0.05). The ABI+EA rats, compared with the ABI rats, had significantly reduced serum TNF-α and HMGB1 levels, bowel water content, MPO activity and Chiu's score (all P<0.05), and significantly higher serum ghrelin (121.2±10.7 vs. 86.7±6.4 pg/ml), bowel ghrelin (0.12±0.02 vs. 0.08±0.01), GSH-R (0.05±0.04 vs. 0.03±0.01) and DAO activity (18.74±4.18 vs. 13.52±2.33 U/ml; all P<0.05), indicating an improvement of the intestinal mucosal barrier. GHRA reversed the protective effects of EA. Therefore, EA improved ABI recovery by promoting ghrelin secretion and upregulating GSH-R expression.

11.
J Crit Care ; 41: 216-221, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28582721

RESUMO

PURPOSE: Effective cleaning of surfaces within hospital wards is necessary to reduce pathogen transmission. We investigated the roles of sequential enhanced cleaning by culturing pathogens from high-touch surfaces in a general intensive care unit. METHODS: A before-after controlled study was conducted during a 17-month period in the 25-bed general intensive care unit. The study comprised a baseline period (period 1) and 4 sequential tiered interventions: each patient zone was wiped with a single clean microfiber cloth daily (period 2), fluorescent markers and adenosine triphosphate assay were used to monitor and provide feedback on the effectiveness of cleaning (period 3), wiping a single patient zone with 3 clean microfiber cloths daily (period 4), and withdrawal of the feedback (period 5). RESULTS: Compared with period 1, the cultures of multidrug-resistant organisms from high-touch surfaces were reduced by 41.0% (prevalence ratio [OR] = 0.59, P < .001), 70.8% (OR = 0.29, P < .001), 82.6% (OR = 0.17, P < .001), and 70.8% (OR = 0.29, P < .0001) in the subsequent sequential interventions, respectively. CONCLUSION: Adoption of fluorescent markers and adenosine triphosphate bioluminescence reduced environmental contamination. Use of 3 cleaning cloths for 1 patient zone was more effective compared with a single cloth.


Assuntos
Infecção Hospitalar/prevenção & controle , Desinfecção , Controle de Infecções , Unidades de Terapia Intensiva , Medicina Tradicional Chinesa , China , Contagem de Colônia Microbiana , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Monitoramento Ambiental , Zeladoria Hospitalar , Humanos , Medições Luminescentes , Estudos Prospectivos
12.
J Zhejiang Univ Sci B ; 16(1): 70-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25559958

RESUMO

In many traditional Chinese medicine (TCM) hospitals, most patients are elderly with chronic diseases. Nosocomial bloodstream infections (nBSIs) are an important cause of morbidity and mortality. A retrospective surveillance study was performed to examine the epidemiology and microbiology of nBSIs in a TCM hospital from 2009 to 2011. A total of 482 patients with nBSIs were included in the study period. The incidence rate was 5.7/1000 admissions. Escherichia coli (25.5%) was the most common Gram-negative and coagulase-negative staphylococcus (CoNS) (14.1%) was the most common Gram-positive organism isolated. One-third of the E. coli and Klebsiella pneumoniae isolated from the nBSIs were the third-generation cephalosporin-resistant. Half of the Acinetobacter species isolates were resistant to imipenem. Of all the CoNS isolates, 90.7% were resistant to methicillin. Carbapenems and glycopeptide were the most frequently used for nBSI therapy. Only about one-third of patients (157/482) received appropriate empirical therapy. Septic shock, hemodialysis, Pitt bacteremia score >4, urinary tract infection, and appropriate empirical therapy were most strongly associated with 28-d mortality. The incidence of nBSIs was low in the TCM hospital but the proportion of nBSIs due to antibiotic-resistant organisms was high. A high Pitt bacteremia score was one of the most important risk factors for mortality in nBSIs. Therefore, the implementation of appropriate empirical therapy is crucial to improve the clinical outcome of nBSIs.


Assuntos
Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Acinetobacter , Adulto , Idoso , Idoso de 80 Anos ou mais , Cefalosporinas/química , China , Coagulase/química , Escherichia coli , Feminino , Humanos , Klebsiella pneumoniae , Masculino , Medicina Tradicional Chinesa , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Choque Séptico/metabolismo , Staphylococcus , Resultado do Tratamento
13.
Biomed Rep ; 2(6): 893-897, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25279165

RESUMO

DNA-damaging agents have been reported to be associated with cardiovascular complications, however, the underlying mechanisms remain to be clarified. In the present study, the possible vascular effects of cisplatin was assessed by measuring its effects on the contractile function of thoracic aortic rings dissected from Sprague-Dawley (SD) rats. Contraction of the aortic ring was induced by 60 mM KCl or 10-6 M phenylephrine (PE) in an ex vivo perfusion system. Cisplatin (200 µM) counteracted KCl- and PE-induced contraction by 57.6 and 91.8%, respectively, in endothelium-intact aortic rings. Similar results were obtained in endothelium-denuded aortas. Electromicroscopy analysis revealed severe damage to blood vessel walls in vivo by cisplatin. In addition, cisplatin significantly inhibited adenosine triphosphate (ATP)-induced intracellular Ca2+ concentration ([Ca2+]i) increases in human umbilical vein endothelial cells (HUVECs). These results suggested that the DNA-damaging agent cisplatin can affect the contractile function of thoracic aortas. In addition, in accordance with its DNA-damaging properties, the cardiovascular toxicity of cisplatin may be the result of its direct cytotoxicity.

14.
Toxicol In Vitro ; 25(1): 91-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20888899

RESUMO

H2AX is phosphorylated (γH2AX) by members of the phosphatidylinositol 3-kinase (PI3K) family, including ataxia telangiectasia-mutated (ATM), ATM- and Rad3-related (ATR) and DNA-PK in response to DNA damage. While it has been reported that benzo[a]pyrene (BaP) cannot induce γH2AX alone in several cell lines, we have shown that BaP alone could induce γH2AX in human amnion FL cells. Thus, we further examined the ability of BaP to induce γH2AX in different cell systems. It was shown that BaP-induced γH2AX in HeLa cells in a time- and dose-dependent manner. BaP also induced γH2AX in ATM(-/-) mouse fibroblasts, DNA-PKcs(-/-) mouse fibroblasts, and a genetically modified human osteosarcoma U2OS cell line. PI3K inhibitors caffeine and wortmannin were then used in an effort to identify the kinase(s) responsible for BaP-induced γH2AX. Unexpectedly, in BaP-treated HeLa cells, caffeine pretreatment did not inhibit but rather increased γH2AX level. On the other hand, caffeine or wortmannin can inhibit BaP-induced γH2AX in either U2OS, DNA-PKcs(-/-) or ATM(-/-) cells. Taken together, these data suggest that BaP alone can induce H2AX phosphorylation in certain cell systems, and that members of the PI3K family, including ATM, ATR, and DNA-PK can participate in the phosphorylation of H2AX in the various cell types.


Assuntos
Benzo(a)pireno/farmacologia , Proteínas de Ciclo Celular/metabolismo , Proteína Quinase Ativada por DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Histonas/metabolismo , Mutagênicos/farmacologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Androstadienos/farmacologia , Animais , Proteínas Mutadas de Ataxia Telangiectasia , Cafeína/farmacologia , Ciclo Celular , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Linhagem Celular , Proteína Quinase Ativada por DNA/antagonistas & inibidores , Proteína Quinase Ativada por DNA/genética , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Humanos , Camundongos , Concentração Osmolar , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Fatores de Tempo , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , Wortmanina
15.
Mutat Res ; 691(1-2): 1-8, 2010 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-20540955

RESUMO

Cisplatin has been widely accepted as one of the most efficient anticancer drugs for decades. However, the mechanisms for the cytotoxic effects of cisplatin are still not fully understood. Cisplatin primarily targets DNA, resulting in the formation of DNA double strand breaks and eventually causing cell death. In this study, we applied two-dimensional electrophoresis coupled with LC-MS/MS to analyze the nuclear proteome of HeLa cells treated with cisplatin, in an effort to uncover new mechanistic clues regarding the cellular response to cisplatin. A total of 19 proteins were successfully identified, and these proteins are involved in a variety of basal metabolic and biological processes in cells, including biosynthesis, cell cycle, glycolysis and apoptosis. Six were related to the regulation of mRNA splicing, and we therefore asked whether the Fas gene might undergo alternative splicing following cisplatin treatment. This proved to be the case, as the splicing forms of Fas were modified in cisplatin-treated HeLa cells. This work provides novel information, from the perspective of the nuclear response, for understanding the cytotoxicity caused by cisplatin-induced DNA damage.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Dano ao DNA , Proteínas Nucleares/efeitos dos fármacos , Proteoma/efeitos dos fármacos , Processamento Alternativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Proteoma/metabolismo , Receptor fas/genética
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