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Molecular mechanisms and pathological features of p-Cresyl sulfate (PCS)-induced uremic lung injury (ULI) in chronic kidney disease (CKD) remain unclear. We analyzed pleural effusions (PE) from CKD and non-CKD patients for uremic toxins, reactive oxygen species (ROS), and chemotactic cytokines. Correlations between PE biomarkers and serum creatinine were also studied. Cell viability and inflammatory signaling pathways were investigated in PCS-treated human alveolar cell model. To mimic human diseases, CKD-ULI mouse model was developed with quantitative comparison of immunostaining and morphometric approach. PE from CKD patients enhance expressions of uremic toxins, hydroxyl radicals, and IL-5/IL-6/IL-8/IL-10/IL-13/ENA-78/GRO α/MDC/thrombopoietin/VEGF. PE concentrations of ENA-78/VEGF/IL-8/MDC/PCS/indoxyl sulphate correlate with serum creatinine concentrations. In vitro, PCS promotes alveolar cell death, cPLA2/COX-2/aquaporin-4 expression, and NADPH oxidase/mitochondria activation-related ROS. Intracellular ROS is abrogated by non-specific ROS scavenger N-acetyl cysteine (NAC), inhibitors of NADPH oxidase and mitochondria-targeted superoxide scavenger. However, only NAC protects against PCS-induced cell death. In vivo, expressions of cPLA2/COX2/8-OHdG, resident alveolar macrophages, recruited leukocytes, alveolar space, interstitial edema and capillary leakage increase in lung tissues of CKD-ULI mice, and NAC pretreatment ameliorates alveolarâ»capillary injury. PCS causes alveolarâ»capillary injury through triggering intracellular ROS, downstream prostaglandin pathways, cell death, and activating leukocytes to release multiplex chemoattractants and extracellular ROS. Thus PCS and nonspecific ROS serve as potential therapeutic targets.
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BACKGROUND/PURPOSE: Globally, multidrug-resistant Acinetobacter baumannii (MDRAB) has emerged as an important pathogen in nosocomial outbreaks. This study aimed to investigate the correlation between the biofilm formation and survival of MDRABs, and to investigate the antiseptic efficacy of hand sanitizers for the MDRABs, embedded with biofilm (MDRAB-Bs). METHODS: The MDRABs were selected randomly after pulsed-field gel electrophoresis (PFGE), and their biofilm formation was analyzed. Desiccation and ethanol tolerances were assayed to test the bacterial survival. The antiseptic efficacy of combined chlorhexidine gluconate (CHG) and 70% ethanol agents against MDRAB-Bs were compared with the 70% ethanol cleanser. RESULTS: Eleven MDRABs, which varied in biofilm formation (MRDAB-B) and planktonic type (MDRAB-P), were tested. In desiccation survival, the mean survival time for the MDRAB-Bs was 49.0 days which was significantly higher than that of their planktonic type (17.3 days) (P < 0.005). The MDRAB-Ps could be eliminated after a 10 min contact with a 30% ethanol agent, however, it took 10 min of 70% ethanol to eliminate the MDRAB-Bs. On the other hand, a 2% CHG in 70% ethanol solution completely eliminated all MDRAB-Bs after 1 min contacted time. The 2% CHG in 70% ethanol agent provided a significantly superior efficacy than the 70% ethanol solution at eliminating the MDRAB-Bs (P < 0.005). CONCLUSION: MDRAB with biofilm-formation presented significantly higher desiccation and ethanol resistances than their planktonic type. Moreover, the 2% CHG in 70% ethanol agent provided a superior antiseptic efficacy for MDRAB-Bs than that of the 70% ethanol agent.
Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/fisiologia , Biofilmes/crescimento & desenvolvimento , Clorexidina/análogos & derivados , Dessecação , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Etanol , Infecções por Acinetobacter/microbiologia , Adaptação Fisiológica , Antibacterianos/farmacologia , Clorexidina/farmacologia , Sinergismo Farmacológico , Etanol/metabolismo , Etanol/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
We present the case of a 49-year-old man, who developed Mycobacterium abscessus complex (M. abscessus complex) bacteremia and prostatitis after prostate biopsy. The patient was successfully treated with amikacin with imipenem-cilastatin with clarithromycin. Infections caused by M. abscessus complex have been increasingly described as a complication associated with many invasive procedures. Invasive procedures might have contributed to the occurrence of the M. abscessus complex. Although M. abscessus complex infection is difficult to diagnose and treat, we should pay more attention to this kind of infection, and the correct treatment strategy will be achieved by physicians.
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Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium abscessus , Prostatite/diagnóstico , Antibacterianos/uso terapêutico , Bacteriemia , Biópsia , Claritromicina , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas , Prostatite/tratamento farmacológicoRESUMO
BACKGROUND: The clinical impact of prior exposure to antibiotics on patients with tuberculosis (TB) is largely unknown. This study investigated the survival of patients with severe TB after exposure to a variety of antibiotics. METHODS: A retrospective cohort study was conducted in TB patients with prior exposure to fluoroquinolones (FQs) (FQ group), to third-generation cephalosporins (CEPH group), and to third-generation penicillins (PCN group). To understand the impact of monotherapy with antibiotics on survival, patients with prior exposure to only moxifloxacin, ceftriaxone, or piperacillin were investigated. RESULTS: Patients in the FQ group (N= 401) had a significantly higher survival rate (82.5%) than patients in the CEPH (N = 210) and PCN (N = 172) groups (67.6% and 62.8%, respectively; both p < 0.0001) at 180 d after TB diagnosis. Adjusted odds ratio (AOR) logistic regression analysis demonstrated that patients in the FQ group had significantly more favourable outcomes than those in the CEPH and PCN groups in terms of intensive care unit (ICU) admission rate (versus CEPH cohort: AOR, 1.70; 95% CI: 1.16-2.50; p = 0.0067, versus PCN cohort: AOR, 3.58; 95% CI: 2.42-5.29; both p < 0.0001), mechanical ventilation rate (versus CEPH cohort: AOR, 1.70; 95% CI: 1.09-2.66; p = 0.0205, versus PCN cohort: AOR, 3.92; 95% CI: 2.54-6.05; both p < 0.0001), and acute respiratory failure rate (versus CEPH cohort: AOR, 1.62; 95% CI: 1.07-2.45; p = 0.0223, versus PCN cohort: AOR, 4.29; 95% CI: 2.86-6.43; both p < 0.0001). TB patients with prior exposure to moxifloxacin (N = 198) had a significantly higher survival rate (85.9%) than that of patients with exposure to ceftriaxone (N = 119) and piperacillin (N = 172) monotherapy (survival rates: 69.8% and 62.8%, respectively; both p < 0.001). CONCLUSIONS: TB patients with prior exposure to FQs had more favourable outcomes compared with patients who had prior exposure to third-generation cephalosporins or third-generation penicillins. This study provides new insights into the impact of previous exposure to FQs on the survival of TB patients.
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Antibacterianos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Tuberculose/mortalidade , Idoso , Idoso de 80 Anos ou mais , Ceftriaxona/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Piperacilina/uso terapêutico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Left ventricular (LV) filling impairment is present in patients with chronic obstructive pulmonary disease (COPD). Airflow obstruction is related to reduced LV end-diastolic volume, stroke volume, and cardiac output. The ratio of peak early diastolic filling velocity of the mitral inflow to peak early diastolic velocity of the mitral annulus (E/e'), an echocardiographic parameter, can be applied as a surrogate marker of LV filling pressures. Forty-seven individuals with suspected COPD underwent pulmonary function tests and echocardiography. The ratio of forced expiratory volume in 1s to forced vital capacity (FEV1/FVC) and the E/e' ratio were determined. Multivariate linear regression analysis showed that the FEV1/FVC ratio (ß=0.01; 95% confidence interval, 0.001-0.019; p=0.036) independently predicted the log transformed E/e' ratio. An increase of FEV1/FVC ratio (in percentage) by 1 unit was associated with an increase of the E/e' ratio multiplied by 1.01. Airflow obstruction inversely predicts LV filling pressure in suspected COPD cases.
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Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia , Idoso , Velocidade do Fluxo Sanguíneo/fisiologia , Ecocardiografia Doppler , Teste de Esforço/métodos , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Testes de Função Respiratória , Capacidade VitalRESUMO
OBJECTIVE: To determine whether acid aspiration provokes the development of multidrug-resistant Acinetobacter baumannii (MDRAB) pneumonia in its host. METHODS: Groups of mice were inoculated intratracheally (IT) with 50 µl of 0.1N HCl and 1 × 10(8) colony-forming units (CFU) Ab396 (A+Ab group), or 50 µl of 0.1N HCl and 20 µl of 0.9% saline (A+S group), or 20 µl of 0.9% saline and 1 × 10(8) CFU of Ab396 (S+Ab group), or 50 µl of 0.9% saline and 20 µl of 0.9% saline (S+S group). Cytokines, bacterial loads in the bronchoalveolar lavage fluid (BALF), lung permeability, histopathology of the lungs, and survival rates were evaluated. RESULTS: Only the A+Ab mice developed extensive Ab396 pneumonia and had significantly elevated bacterial loads, increased lung leakage, and lower levels of tumor necrosis factor alpha (TNF-α) compared with the other three groups (p<0.05, Mann-Whitney U-test). Moreover, a strong synergistic effect (p<0.05, two-way analysis of variance) was observed between the acid induction and Ab396 infection, resulting in lung injury and an unfavorable survival outcome. CONCLUSIONS: Lung injury caused by acid aspiration provoked secondary MDRAB pneumonia; also synergistic effects between acid aspiration and Ab396 infection resulted in a detrimental outcome in the infected mice.
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Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Pneumonia Aspirativa/microbiologia , Ácidos/administração & dosagem , Ácidos/efeitos adversos , Infecções por Acinetobacter/mortalidade , Animais , Antibacterianos/farmacologia , Carga Bacteriana , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/microbiologia , Citocinas/biossíntese , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Permeabilidade , Pneumonia Aspirativa/mortalidadeRESUMO
OBJECTIVE: The identification of the optimal agent for administration via the respiratory tract when treating pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB). METHODS: A murine model of acute CRAB pneumonia was established by intratracheal (i.t.) inoculation with 2.5 × 107 colony-forming units (CFU) of A. baumannii strain Ab396 plus 10% porcine mucin. After 4h the infected BALB/c mice were treated intratracheally with 25µl of either 0.85% saline (control group), colistimethate sodium (CMS) (166 666 U/kg, CMS group), imipenem/cilastatin (30/30 mg/kg, imipenem group), or meropenem (20mg/kg, meropenem group), every 8h. The therapeutic efficacy of these agents was examined. RESULTS: A. baumannii strain Ab396 was susceptible to CMS only. However, meropenem treatment did give a significantly superior survival rate (100%) compared to treatment with imipenem (50%), CMS (33%), or saline (0%) (p<0.001 vs. the control and CMS groups, p=0.006 vs. the imipenem group, by log-rank test). Furthermore, compared to the other groups, the meropenem group demonstrated significantly more favorable results in terms of tissue penetration of the antibiotic, bacterial clearance, normalization of the wet lung-to-body weight ratio, and down-regulation of pro-inflammatory cytokine levels in the lungs. CONCLUSIONS: Administration of meropenem via the respiratory tract proved to have the best therapeutic efficacy among the antibiotics tested when treating advanced murine CRAB pneumonia.
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Acinetobacter baumannii/efeitos dos fármacos , Colistina/análogos & derivados , Imipenem/administração & dosagem , Pneumonia Bacteriana/tratamento farmacológico , Tienamicinas/administração & dosagem , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/isolamento & purificação , Doença Aguda , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Carbapenêmicos/uso terapêutico , Cilastatina/administração & dosagem , Cilastatina/farmacocinética , Combinação Imipenem e Cilastatina , Colistina/administração & dosagem , Colistina/farmacocinética , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Combinação de Medicamentos , Farmacorresistência Bacteriana , Feminino , Imipenem/farmacocinética , Meropeném , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Pneumonia Bacteriana/microbiologia , Células-Tronco/efeitos dos fármacos , Tienamicinas/farmacocinéticaRESUMO
CO(2) sequestration by the aqueous carbonation of steel-making slag under various operational conditions was investigated in this study. The effects of the operational conditions, including type of steel-making slag, reaction time, reaction temperature, and CO(2) flow rate, on the performance of the carbonation process were evaluated. The results indicated that the BOF slag had the highest carbonation conversion, approximately 72%, at a reaction time of 1h, an operating pressure of 101 kPa and a temperature of 60°C due to its higher BET surface area of BOF slag compared to UF, FA, and BHC slags. The major factors affecting the carbonation conversion are reaction time and temperature. The reaction kinetics of the carbonation conversion can be expressed by the shrinking-core model. The measurements of the carbonated material by the SEM and XRD instruments provide evidence indicating the suitability of using the shrinking-core model in this investigation. Comparison of the results with other studies suggests that aqueous carbonation by slurry reactor is viable due to its higher mass transfer rate.
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Dióxido de Carbono/química , Aço , Cinética , Microscopia Eletrônica de Varredura , Termogravimetria , Difração de Raios XRESUMO
OBJECTIVES: To examine the effects of reminiscence therapy on psychological well-being, depression, and loneliness among institutionalized elderly people. METHODS: In an experimental study design, 92 institutionalized elderly people aged 65 years and over were recruited and randomly assigned to two groups. Those participants in the experimental group received reminiscence therapy eight times during 2 months to examine the effects of this therapy on their psychological well-being. RESULTS: After providing the reminiscence therapy to the elderly in the experimental group, a significant positive short-term effect (3 months follow-up) on depression, psychological well-being, and loneliness, as compared to those in the comparison group was found. CONCLUSIONS: Reminiscence therapy in this study sample improved socialization, induced feelings of accomplishment in participants, and assisted to ameliorate depression.
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Idoso/psicologia , Depressão/terapia , Institucionalização , Solidão/psicologia , Memória , Casas de Saúde , Psicoterapia/métodos , Idoso de 80 Anos ou mais , Depressão/diagnóstico , Depressão/psicologia , Avaliação Geriátrica , Psiquiatria Geriátrica , Humanos , Masculino , Satisfação Pessoal , Escalas de Graduação Psiquiátrica , Psicoterapia/normas , Autoimagem , Inquéritos e Questionários , TaiwanRESUMO
OBJECTIVES: : To study the efficacy of intratracheal colistin sulfate therapy in a murine model of acute pneumonia caused by a clinical CRAB strain, Ab396. Colistin therapy has currently achieved a favorable outcome in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but parenteral colistin may have limited therapeutic efficacy for CRAB pneumonia. DESIGN: : A controlled, in vivo experimental study. SETTING: : Research laboratory of a medical center. SUBJECTS: : Female BALB/c mice. INTERVENTIONS: : The minimal inhibitory concentrations of antibiotics were measured. Acute pneumonia was established by intratracheal inoculation with an inoculum size of 2.5 x 10 colony-forming units Ab396 plus 10% porcine mucin into the lungs of mice, verified by histopathological examinations, and then treated with or without antibiotics. Mice received intratracheal saline treatment as a control group, intraperitoneal administration (IP) imipenem/cilastatin plus sulbactam (IP IS group, 80/80 mg/kg and 40 mg/kg every 8 hrs, n = 30), IP colistin sulfate (IP CS group, 150,000 U/kg every 8 hrs, n = 30), and intratracheal colistin sulfate (intratracheal CS group, 75,000 U/kg every 8 hrs, n = 30) at 2 hrs after intratracheal inoculation of Ab396. MEASUREMENTS AND MAIN RESULTS: : The minimal inhibitory concentrations of colistin sulfate, imipenem/cilastatin, or sulbactam for Ab396 were 2 microg/mL, 128 microg/mL, or 32 microg/mL, respectively. Compared with the mice in the control, IP IS, and IP CS groups, those in intratracheal CS group had a significantly favorable outcome at 72 hrs after infection (survival rate = 0%, 10%, 0% and 100%, respectively; all p < .001, log-rank test). Furthermore, intratracheal therapy decreased significantly the bacterial loads in the lungs and normalized the wet lung/body weight ratios in mice with acute pneumonia. CONCLUSIONS: : The intratracheal colistin sulfate therapy led to more favorable outcomes than therapies by IP colistin sulfate or imipenem/cilastatin plus sulbactam in mice with early CRAB pneumonia.
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Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/administração & dosagem , Carbapenêmicos/farmacologia , Colistina/administração & dosagem , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Animais , Modelos Animais de Doenças , Farmacorresistência Bacteriana , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Tempo , TraqueiaRESUMO
AIM AND OBJECTIVES: The objective of this study was to examine the efficacy of progressive muscle relaxation training on anxiety in patients with acute schizophrenia. BACKGROUND: Many empirical studies have found progressive muscle relaxation training beneficial in reducing the psychological effects of anxiety. Progressive muscle relaxation training is also effective in reducing the distress symptoms associated with the symptomatology of schizophrenia. DESIGN: An experimental randomised controlled trial using repeated measures. METHOD: The study was designed to examine the effects of progressive muscle relaxation training on patients diagnosed with schizophrenia. Study participants were acute psychiatric inpatients in Taiwan. Eighteen patients were block randomised and then assigned to an experimental or control group. The experimental group received progressive muscle relaxation training and the control group received a placebo intervention. Results from the Beck anxiety inventory were compared between groups as a pretest before intervention, on day 11 of intervention and one week post-test after the intervention was completed. Changes in finger temperature were measured throughout the experiment. RESULTS: The degree of anxiety improvement was significantly higher in the progressive muscle relaxation training group than in the control group after progressive muscle relaxation training intervention (p < 0.0001) and at follow-up (p = 0.0446; the mean BAI score fell from 16.4 pretest to -5.8 post-test. After adjusting for the change in patient finger temperature, the mean change in temperature was significantly different between the two patient groups. The average body temperature increased significantly after applying the progressive muscle relaxation training to patients with schizophrenia. CONCLUSION: This study demonstrated that progressive muscle relaxation training can effectively alleviate anxiety in patients with schizophrenia. RELEVANCE TO CLINICAL PRACTICE: Progressive muscle relaxation training is potentially an effective nursing intervention in the reduction of anxiety in patients diagnosed with schizophrenia, depending on the quality of their mental status at the time of intervention. Progressive muscle relaxation training is a useful intervention as it is proven to reduce anxiety levels across a spectrum of psychiatric disorders.
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Ansiedade/prevenção & controle , Terapia de Relaxamento/métodos , Esquizofrenia/complicações , Doença Aguda , Adulto , Ansiedade/diagnóstico , Ansiedade/etiologia , Ansiedade/fisiopatologia , Temperatura Corporal , Pesquisa em Enfermagem Clínica , Feminino , Dedos/irrigação sanguínea , Humanos , Entrevista Psicológica , Masculino , Análise Multivariada , Escalas de Graduação Psiquiátrica , Análise de Regressão , Terapia de Relaxamento/enfermagem , Esquizofrenia/diagnóstico , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Inquéritos e Questionários , Taiwan , Resultado do TratamentoRESUMO
A 50-year-old Taiwanese woman had a history of massive hemoptysis occurring every 6 months for the past 4 years. After each bout of hemoptysis, chest roentgenography would show diffuse alveolar infiltration of bilateral lungs, which would usually resolve within 7 days. Transbronchial biopsy revealed diffuse alveolar hemorrhage and hemosiderin-laden macrophage infiltration. Idiopathic pulmonary hemosiderosis was diagnosed by excluding other glomerular, cardiac and immunological disorders. An initial dose of 20 mg prednisolone daily was tapered to 10 mg daily 1 month later. The patient is currently undergoing steroid therapy, and there have been no further episodes of hemoptysis.
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Hemossiderose/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Prednisolona/uso terapêutico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Feminino , Hemoptise/etiologia , Hemossiderose/complicações , Humanos , Pessoa de Meia-IdadeRESUMO
Nasogastric (NG) tube misplacement into the airways is a rare complication. The presence of a cuffed endotracheal or tracheostomic tube often gives primary care providers a false sense of security. This report presents a case of inadvertent NG tube insertion into the right lower lobe bronchus of a 79-year-old patient with advanced chronic obstructive pulmonary disease, resulting in pneumonia and septic shock. In this report, the literature is reviewed, the influence of tube size on complications is compared, and the reliability of different methods to verify correct tube position is discussed. We conclude that a cuffed tracheostomic tube does not prevent advancement of a large-bore feeding tube into the tracheobronchial system. If any doubt exists regarding proper tube position, a chest radiograph should be obtained prior to initiation of feeding.
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Brônquios , Doença Iatrogênica , Intubação Gastrointestinal/efeitos adversos , Respiração Artificial , Idoso , Humanos , Masculino , TraqueostomiaRESUMO
BACKGROUND AND PURPOSE: Vibrio vulnificus causes primary bacteremia and necrotizing wound infection, leading to high morbidity and mortality in humans. This study aimed to evaluate the antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of V. vulnificus infection. METHODS: We investigated the dynamics of proinflammatory cytokines and their modulation by antimicrobial agents using a murine model of V. vulnificus infection. The change in cytokine levels was followed over a time course to identify the antimicrobial activity of the drugs against V. vulnificus. BALB/c female mice were challenged with an intraperitoneal infection using a clinical invasive isolate of Vv05191, and their cytokine levels were assayed over various time points. RESULTS: Serum levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 post-infection were found to be inoculum dose-dependent and positively correlated to the subsequent fatality rate in the infected mice. With an inoculum of 6.6 x 10(6) colony-forming units and intraperitoneal administration of cefotaxime, minocycline, or both, the serum and peritoneal fluid cytokine levels increased and then declined gradually. Comparison of the 3 antimicrobial regimens revealed that the magnitude of reduction in cytokine levels was greatest in mice treated with cefotaxime-minocycline combination. Moreover, the peritoneal fluid cytokine level in the combination group was significantly lower than that in the groups treated with minocycline or cefotaxime alone. CONCLUSIONS: The current results support the superiority of the combination therapy in treating invasive V. vulnificus infections.
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Antibacterianos/farmacologia , Cefotaxima/farmacologia , Citocinas/sangue , Minociclina/farmacologia , Vibrioses/tratamento farmacológico , Vibrioses/imunologia , Vibrio vulnificus/efeitos dos fármacos , Animais , Antibacterianos/uso terapêutico , Líquido Ascítico/imunologia , Cefotaxima/uso terapêutico , Citocinas/análise , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Minociclina/uso terapêutico , Análise de Sobrevida , Vibrioses/microbiologia , Vibrio vulnificus/imunologiaRESUMO
OBJECTIVES: Sepsis is a severe inflammatory disorder that may lead to multiple organ failure. Lipopolysaccharide (LPS) is associated with Gram-negative sepsis and can activate monocytes and macrophages to release pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO) and anti-inflammatory mediator such as interleukin-10 (IL-10). In this present study, we used fluvastatin, a HMG-CoA reductase inhibitor, to study its effects upon LPS-induced endotoxic shock in conscious rats. METHODS: The experiments were designed that rats received an intravenous injection of 1mg/kg fluvastatin followed 10min later, by an intravenous injection of 10mg/kg Klebsiella pneumoniae LPS, the latter inducing endotoxic shock amongst conscious rats. Subsequently, the levels of certain biochemical variables and cytokines in serum were then measured during the ensuing 48-h period following sepsis. These included total cholesterol (TCH), triglyceride (TG), blood urea nitrogen (BUN), creatinine (Cre), creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate transferase (GOT), alanine transferase (GPT), tumor necrosis factor-alpha, interleukin-10 and nitric oxide. RESULTS: LPS significantly increased blood TG, BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-10 and NO levels but decreased the blood TCH level. Pretreatment of test rats with fluvastatin decreased blood levels of certain markers of organ injury, suppressed the release of TNF-alpha and increased IL-10, and NO levels following LPS treatment. Fluvastatin did not affect the blood TCH and TG level subsequent to the development of sepsis. CONCLUSIONS: Pre-treatment with fluvastatin suppresses the release of plasma TNF-alpha, increases plasma IL-10, and NO production, and decreases the levels of markers of organ injury associated with endotoxic shock, so ameliorating LPS-induced organ damage amongst conscious rats.