Dioxin Induces Genomic Instability in Mouse Embryonic Fibroblasts

Ionizing radiation and certain other exposures have been shown to induce genomic instability (GI), i.e., delayed genetic damage observed many cell generations later in the progeny of the exposed cells. The aim of this study was to investigate induction of GI by a nongenotoxic carcinogen, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mouse embryonic fibroblasts (C3H10T1/2) were exposed to 1, 10 or 100 nM TCDD for 2 days. Micronuclei (MN) and expression of selected cancer-related genes were assayed both immediately and at a delayed point in time (8 days). For comparison, similar experiments were done with cadmium, a known genotoxic agent. TCDD treatment induced an elevated frequency of MN at 8 days, but not directly after the exposure. TCDD-induced alterations in gene expression were also mostly delayed, with more changes observed at 8 days than at 2 days. Exposure to cadmium produced an opposite pattern of responses, with pronounced effects immediately after exposure but no increase in MN and few gene expression changes at 8 days. Although all responses to TCDD alone were delayed, menadione-induced DNA damage (measured by the Comet assay), was found to be increased directly after a 2-day TCDD exposure, indicating that the stability of the genome was compromised already at this time point. The results suggested a flat dose-response relationship consistent with dose-response data reported for radiation-induced GI. These findings indicate that TCDD, although not directly genotoxic, induces GI, which is associated with impaired DNA damage response

Cardiovascular imaging 2010 in the International Journal of Cardiovascular Imaging

Cardiovascular Aspects of Radiolog

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis

This is the final version. Available on open access from BMC via the DOI in this recordBACKGROUND: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. METHODS: This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI)  1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). CONCLUSIONS: In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01179243 . Registered on August 3, 2010

Lack Of Effect Of N-Acetylcysteine Treatment To Ameliorate The Progression Of Multiple Organ Failure

Objective: To investigate whether prolonged infusion of the oxygen free radical scavenger N-acetylcysteine (NAC) that is commenced immediately after admission to intensive care unit (ICU) could ameliorate the development or progression of multiple organ failure (MOF). Methods: After receiving ethical committee approval, a prospective randomized, double-blind, placebo controlled study was performed in the Anesthesiology and Reanimation Intensive Care Unit, Hacettepe University Hospital, Ankara, Turkey between December 2002 and May 2003. Twenty-six patients were randomized to receive either NAC in 5% dextrose 40 mg/kg/day or the same volume of 5% dextrose both in 4 divided doses. Two patients were withdrawn due to ICU stay <24 hours. Treatment effect on organ function was assessed by the sequential organ failure assessment (SOFA) scores according to physiological parameters of respiratory, hematological, hepatic, cardiovascular, central nervous system (CNS) and renal system scores that were obtained on admission, then daily. Chi-square, Mann Whitney U tests were used for statistical analysis. Results: There was no significant difference between the 2 groups in any of the 5 organ dysfunction parameters, total maximum SOFA, delta SOFA length of intensive care stay, days of mechanical ventilation and mortality. In the NAC treatment group, the maximum SOFA coagulation score was higher than the control group (p<0.05). Conclusion: N-acetylcysteine (40 mg/kg/day) that was commenced immediately after admission to ICU did not ameliorate the progression of MOF in this small cohort of patients. We believe routine prophylactic use of low-dose NAC in all critically ill patients does not provide positive protection.Wo

Effect of Preoperative I. M. Administration of Diclofenac on Suxamethonium-Induced Myalgia

We have studied the effects of preoperative administration of diclofenac on suxamethonium-induced myalgia, plasma met-enkephalin-like activity (E-LA), prostaglandin E2-like activity (PGE2-LA), leukotriene C4-like activity (LTC4-LA) and histamine-like activity (H-LA). Thirty-four ASA I patients undergoing elective ophthalmic surgery were allocated randomly to two groups to receive either saline placebo or diclofenac 75 mg i.m. 20 min before operation, in a double-blind design. Anaesthesia was induced with thiopentone 5-7 mg kg-1 followed by suxamethonium 1. 5 mg kg-1 and maintained with 67% nitrous oxide and halothane in oxygen. Plasma PGE2-LA, LTC4-LA, H-LA and E-LA were measured before premedication, 1 min after the administration of suxamethonium and 24 h after operation. Muscle fasciculations, intubation conditions and postoperative myalgia were graded numerically. Postoperative myalgia in the diclofenac group was significantly (P < 0.05) less (47.1%) than in the control gro up (76.5%). Post-suxamethonium and 24-h concentrations of plasma PGE2-LA and LTC4-LA were also significantly (P < 0.05) greater than baseline in the control group. Plasma H-LA was increased in both groups after suxamethonium and this increase was significant (P < 0.05) in the control group. We conclude that diclofenac reduces significantly the incidence and intensity of suxamethonium-induced myalgia.WoSScopu

Hypovolemic Cardiac Arrest After Dental Extraction. An Unexpected High-Flow Maxillar Arteriovenous Malformation

Wo

The Effect Of Acute Normovolemic Hemodilution And Acute Hypervolemic Hemodilution On Coagulation And Allogeneic Transfusion

Objective: In this study, acute normovolemic hemodilution (ANH) and hypervolemic hemodilution (HHD) were compared with no hemodilution with regards to the effectiveness in blood usage and coagulation parameters. Methods: The study was performed from February to August 2001 at Hacettepe University Hospital, Ankara, Turkey. Thirty patients undergoing hip arthroplasty surgery were prospectively randomized into: ANH group [autologous blood 15 mL kg(-1) was withdrawn and replaced by 6% hydroxyethyl starch (HES)] or HHD group (HES was administered without removal of any autologous blood) or the control group (no hemodilution). In all groups, blood was given when hemoglobin concentration was <9 g dl(-1). Results: Three groups were clinically similar regarding blood loss, mean arterial pressures and coagulation parameters. But allogeneic transfusion requirements were significantly less in hemodilution groups (20% in ANH, 40% in HHD) compared to the control group (100% of patients). Conclusion: We conclude that hemodilution (both ANH and HHD) decreases the demand for homologous blood without adversely affecting hemodynamics or coagulation parameters and HHD seems to be a simple and valuable alternative to ANH in orthopedic patient undergoing hip replacement.Wo

A Comparison of Low and High Flow Desflurane Anaesthesia in Children

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Urinary lipid and protein oxidation products upon halothane, isoflurane, or sevoflurane anesthesia in humans: potential biomarkers for a subclinical nephrotoxicity

Objective: To investigate whether lipid and protein oxidation products are elevated and correlated with routine clinical markers of hepatic and renal function in patients anesthetized with halothane, isoflurane, or sevoflurane. Methods: Urine and blood samples were collected from patient groups. Excretion of aldehydes, acetone, and o,o'-dityrosine was measured before and after anesthesia. Blood samples were analysed for clinical markers. Results: Urinary concentrations of aldehydes, acetone, o,o'-dityrosine and glucose were significantly increased after anesthesia in halothane and sevoflurane groups earlier than clinical markers. Significant correlations were found in sevoflurane group. Conclusion: Lipid and protein oxidation contributes to subclinical sevoflurane nephrotoxicity. Oxidation products may serve as early biomarkers. © 2013 Informa UK, Ltd

Comparison Of Halothane, Enflurane And Isoflurane Kidney Effects Through Alanine Aminopeptidase Urine Creatinine Values

The kidney effects of halothane, enflurane and isoflurane were evaluated by using the ratio of urinary excretion of alanine aminopeptidase (AAP) to urine creatinine. Thirty patients in ASA class 1 or 2 were studied, None had renal disease nor received nephrotoxic drugs. Groups 1, 2 and 3 received halothane, enflurane and isoflurane respectively, Creatinine and AAP activities in urine spot tests, serum creatinine and BUN levels were determined preoperatively and on the first and second postoperative days. Urine AAP activity and AAP/urine creatinine values increased significantly on the first and second postoperative days compared with the preoperative values in all groups (P < 0.05). The present study did not reveal any significant difference in the kidney effects of halothane, enflurane and isoflurane through AAP/creatinine in spot urine values.Wo