Mitochondrial Homeostasis and Cellular Senescence

Cellular senescence refers to a stress response aiming to preserve cellular and, therefore, organismal homeostasis. Importantly, deregulation of mitochondrial homeostatic mechanisms, manifested as impaired mitochondrial biogenesis, metabolism and dynamics, has emerged as a hallmark of cellular senescence. On the other hand, impaired mitostasis has been suggested to induce cellular senescence. This review aims to provide an overview of homeostatic mechanisms operating within mitochondria and a comprehensive insight into the interplay between cellular senescence and mitochondrial dysfunction

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives:We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT(> MIC) (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving beta-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of >= 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025].Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections

Reference values and prediction equations for FVC and FEV1 in the Greek elderly

Spirometry prediction equations obtained from middle-age adults, when extrapolated for the elderly, may lead to inaccurate interpretations. The purpose of this study was to determine prediction equations for forced vital capacity (FVC) and forced expiratory volume (FEV1) in the Greek elderly population. Spirometry prediction equations for normal FVC and FEV1 have been derived from tests on 71 healthy persons (38 men, 33 women) aged older than 60 years (range, 65-85 years), nonsmokers, white race, urban population using techniques and equipment that meet American Thoracic Society recommendations. Regression analysis using age, height, and weight as independent variables was used to provide prediction equations and values for both sexes. The FVC age coefficient in this healthy group was about 47.19 mL/y for elderly men and 34.27 mL/y for elderly women, and the FEV1 age coefficient was about 52.8 mL/y for elderly men and 46.4 mL/y for elderly women. Values from this study predicted equations were compared with those from some of the most commonly used sources of spirometry predicted equations. The FVC and FEV1 predicted values were found to be of less mean square error than that of other compared studies. Higher correlation is between FVC and FEV1 predicted values by the present model and FVC and FEV1 observed Values in both sexes. The higher correlation between FVC and FEV1 predicted and observed from this study allows the use of our model for predicting in a rather reliable way the FVC and FEV1 for elderly Creek individuals

Validity of St. George's respiratory questionnaire for greek patients with chronic obstructive pulmonary disease

The purpose of the present study was to examine the validity of St. George's Respiratory Questionnaire (SGRQ), a disease-specific survey of health-related quality of life, in adult Greek patients with chronic obstructive pulmonary disease (COPD). Questionnaire scores, dyspnea scores, spirometry values, and demographic data were collected from 72 patients with a diagnosis of COPD exacerbation. Follow-up visits were performed at 1-mo. intervals for the first 3 mo. after discharge and a final visit was performed 6 mo. after discharge. 27 (37.5%) patients were readmitted during the follow-up period. Recovery after exacerbation was prolonged and questionnaire scores were sensitive to the patients' health-status changes across time. The SGRQ discriminated COPD patients according to disease stage, and the SGRQ scores during the recovery course were related to readmission. Correlations between the SGRQ and %FEV1 were not significant during exacerbation but a significant negative correlation was observed during the stable phase of the disease. The SGRQ appeared to have acceptable discriminant and concurrent validities in Greek COPD patients who differed according to their exacerbation stage. © Perceptual and Motor Skills 2010