RESUMEN

INTRODUCTION: Multiorgan failure (MOF) is a primary cause of morbidity and mortality in sepsis patients in intensive care units (ICU). Finding risk factors and solving preventable problems of MOF in patients who have sepsis can be a favourable step for decreasing mortality. We aimed to examine multiorgan failure and mortality related risk factors in intensive care unit patients who have sepsis. MATERIALS AND METHODS: A retrospective data collection and prognostic cohort study was performed. Between January 2009-March 2010, patients accepted to the 22-bed pulmonary intensive care unit with the diagnosis of sepsis were enrolled. Patients' demographic data, ICU severity scores, application of mechanical ventilation, causative agent of sepsis, number of ICU days and presence of mortality were recorded. Logistic regression analysis was carried out for risk factors. RESULT: 347 patients with sepsis were involved in the study. 43 of the patients (12.4%) developed MOF and overall mortality rate was 14.9% (n= 52). Presence of resistant pathogen, presence of shock, application of TPN and high APACHE II score were found to be risk factors for MOF [p= 0.015 Odds ratio (OR) 3.47 confidence interval (CI): 1.27 - 9.47, p= 0.001, OR: 30.8 CI: 11.41 - 83-49, p= 0.028, OR: 3.08, CI: 1.13 - 8.39, p= 0.003, OR: 1.10, CI: 1.04-1.18, respectively]. Risk factors for overall mortality were presence of nosocomial infection, high 3rd day SOFA score, presence of shock, application of TPN and sedation (p= 0.005, OR: 3.39, CI: 1.45 - 7.93; p= 0.001, OR: 1.51, CI: 1.27 - 1.81; p= 0.014, OR: 3.24, CI: 1.27 - 8.25; p= 0.003, OR: 3.64. CI: 1.54 - 8.58; p= 0.001, OR: 3.38, CI: 1.51 - 7.57, respectively). CONCLUSIONS: In sepsis patients who need ICU follow up, presence of resistant pathogen, presence of shock, application of TPN and high APACHE II scores are risk factors for developing MOF. Thus, rational use of antibiotics, reducing the use of TPN, application of infection control programmes and prevention of shock will further reduce multiorgan failure and mortality.

Asunto(s)

Insuficiencia Multiorgánica/etiología , Sepsis/complicaciones , APACHE , Anciano , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Estudios de Cohortes , Infección Hospitalaria/mortalidad , Infección Hospitalaria/terapia , Farmacorresistencia Microbiana , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/epidemiología , Nutrición Parenteral Total/estadística & datos numéricos , Pronóstico , Respiración Artificial/métodos , Estudios Retrospectivos , Factores de Riesgo , Sepsis/mortalidad , Sepsis/terapia , Choque Séptico/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones

RESUMEN

The purpose of this study was to evaluate the cytotoxic effect of thalidomide on 4T1 and 4THMpc mouse breast cancer cell lines. Mouse breast cancer cells (4T1) and cells derived from metastatic lesions (4THMpc) were treated with various doses of thalidomide [10(-2)-100 µM dissolved in dimethyl sulfoxide (DMSO) as recommended] and 1.4 µM DMSO (maximum DMSO concentration in the highest thalidomide dose) as a DMSO control against the untreated control groups. MTT was used to evaluate the cytotoxic effects of the treatments. Therefore, we investigated the role of thalidomide on apoptosis. A fluorometric EnzChek caspase-3 enzyme activity assay kit was used to evaluate the apoptotic effects of thalidomide. Thalidomide dissolved in DMSO exhibited cytotoxic effects on 4T1 and 4THMpc cells compared to the control groups incubated without any supplement. Treatment with thalidomide resulted in apoptosis of mouse breast cancer cells in a time- and dose-dependent manner as demonstrated by caspase-3 enzyme activity. However, DMSO alone suppressed cell proliferation more effectively than thalidomide. In cultured mouse breast cancer cells the inhibitory effect of thalidomide may be partially attributed to the solvent DMSO alone.

RESUMEN

Glycyrrhiza species possess preventive and therapeutic potentials against various cancers. In the present study, we have evaluated regulation of apoptotic cell death by aqueous extracts of leaf and flower of an endemic Glycyrrhiza species; Glycyrrhiza flavescens subsp. antalyensis, in mouse melanoma cell lines. Both leaf and flower extracts induced apoptosis in terms of induction of caspase-3 activity, TNF-α and IFN-γ release. Concentrations of both TNF-α and IFN-γ in extract-treated groups were significantly and dose dependently exalted as compared to their relative controls. The effects of extracts on caspase-3, TNF-α and IFN-γ processes mediate the plausible mechanism of apoptosis induction of G. flavescens subsp. antalyensis.

Asunto(s)

Proliferación Celular/efectos de los fármacos , Glycyrrhiza/química , Interferón-alfa/metabolismo , Melanoma Experimental/patología , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Línea Celular Tumoral , Melanoma Experimental/metabolismo , Ratones

RESUMEN

Radiotherapy is widely used in the treatment of cancer. On the other hand, endostatin is considered to be a potent inhibitor of angiogenesis. Therefore, to test whether ES combined with RT overcomes the limitations of each monotherapy the present study investigated the effects of endostatin (ES), radiotherapy (RT) or combination therapy on the growth of mouse breast cancer cells as well as on the expression of substance P in vitro. The breast cancer cell lines 4T1 and 4THMpc were treated with recombinant murine ES (0.5, 1, 2, 4 and 8 µg/ml) alone, RT (45 Gy) alone or as a combination therapy. Cell proliferation was evaluated using an MTS assay and the results were verified by the Live/Dead assay. Immunoprecipitation and Western blotting analysis were performed to determine whether the substance P levels of the two cell lines occurred due to substance P content. Results showed that ES alone resulted in a low but significant inhibition in the growth of 4T1 and 4THMpc cell lines (27.63 and 21.75%, respectively). RT alone inhibited the growth of 4T1 (30.81%) and 4THMpc (39.64%) cells. A combination of ES with RT enhanced growth inhibition in the cells (83% in 4T1 and 80% in 4THMpc). The amount of substance P, both in the conditioned media and the cell lysates, increased within 72 h after RT. This increase was inhibited when ES and RT were applied in combination. These data indicate that ES inhibits the in vitro growth of breast cancer cells and potentiates the anti-tumor effects of RT at appropriate doses via alteration of the amount of substance P and thus an increase of radioresponse.

RESUMEN

Thalidomide is an anti-angiogenic agent that is used in the treatment of cancer. However, in many cases, particularly in patients with breast cancer, thalidomide treatment alone is insufficient and must be combined with other drugs or therapies. In the clinical setting, thalidomide is most commonly used in combination with radiation therapy. However, the exact mechanisms of its effect are unkown. Radiotherapy alters the expression of substance P, which is considered a crucial pro-angiogenic peptide. To determine whether thalidomide and radiotherapy in combination overcome the limitations of each as monotherapy, we examined the effects of the combination on the growth of breast cancer cells as well as on the expression of substance P in vitro. Mouse breast cancer cells (4T1) and cells produced from metastatic lesions (4THMpc) were treated with radiotherapy (RT) (45 Gy) alone, thalidomide (Thal) (40 µg/ml) alone or combination therapy (40 µg/ml Thal + 45 Gy RT), and compared with control cells. MTS, Live/Dead and trypan blue exclusion assays were used to evaluate the cytotoxic effects of the treatments. The levels of substance P in the conditioned media and in the cell lysates were determined by a substance P ELISA kit, and changes in the protein content were analyzed by Western blotting. Thalidomide alone resulted in a significant inhibition in the growth of the 4T1 (34.1%) and 4THMpc (52.6%) cell lines. RT alone inhibited the growth of the 4T1 (19.2%) and 4THMpc (23.31%) cell lines. The combination therapy enhanced the growth inhibition noted in the 4T1 (47.9%) and 4THMpc (62.03%) cell lines. The expression of substance P in the conditioned media and in the cell lysates increased within 72 h of RT. This increase was significantly enhanced with the combination therapy. These data indicate that thalidomide inhibits breast cancer cell growth and potentiates the anti-tumor effects of radiation at appropriate doses.