The effects of intravenous antioxidants in patients with septic shock

Oxidative stress is implicated in septic shock. We investigated the effect of intravenous antioxidant therapy on antioxidant status, lipid peroxidation, hemodynamics and nitrite in patients with septic shock. Thirty patients randomly received either antioxidants (n-acetylcysteine 150 mg/kg for 30 min then 20 mg/kg/h plus bolus doses of 1 g ascorbic acid and 400 mg alpha-tocopherol) or 5% dextrose. Basal vitamin C was low and redox-reactive iron was elevated in all patients. In the 16 patients receiving antioxidants, vitamin C increased (p = .0002) but total antioxidant capacity was unaffected. Lipid peroxides were elevated in all patients but did not increase further in the patients receiving antioxidants. Plasma total nitrite also increased (p = .007) in the antioxidant group. Heart rate increased in patients receiving antioxidants at 60 min (p = .018) and 120 min (p = .004). Cardiac index also increased at 60 min (p = .007) and 120 min (p = .05). Systemic vascular resistance index decreased at 120 min in the antioxidant treated patients (p = .003). The effect of antioxidants on hemodynamic variables has not previously been reported. Antioxidant administration may be a useful adjunct to conventional approaches in the management of septic shock.     

Thermodynamics of dT--dT base pair mismatching in linear DNA duplexes and three-arm DNA junctions

We have used a combination of magnetic-suspension densimetry and calorimetry to derive complete thermodynamic profiles, including volume changes, for the formation of linear DNA duplexes and three-arm branched DNA junctions, from their component strands, with and without dT-dT mismatches. The formation of each type of complex at 20 degrees C is accompanied by a favorable free energy, with a favorable enthalpy term partially compensated by an unfavorable entropy. Formation is associated also with net uptake of water molecules. Using the formation of the fully-paired linear duplex or three-arm junction as reference states, we can establish a thermodynamic cycle in which the contribution of the single-strand species cancels. From this cycle, we determine that substitution of dA for dT has a differential free energy of deltadeltaG degrees of +2.4 kcal mol(-1) for mismatched duplex and +2.0 kcal mol(-1) (on the average) for the mismatched junction. These unfavorable differential free energies result from an unfavorable enthalpy, partially compensated by a favorable entropy, and a negative deltadeltaV. The free energies in the two cases have signs opposed to those of deltadeltaV, a situation that implicates hydration changes in creating the mismatch. When the deltadeltaV terms are normalized by the total number of base pairs involved, the immobilization of structural water molecules (and/or substitution of electrostricted for hydrophobic water molecules) is about 7 times greater for junctions than duplexes. This is consistent with more extensive hydrophobic hydration of branched DNA structures than of duplexes.     

In vivo electrochemical studies of dopamine clearance in subregions of rat nucleus accumbens: differential properties of the core and shell

The effects of the rodent hepatocarcinogens clofibric acid and diprofibrate on the activity of the peroxisomal fatty acyl-CoA oxidase, DNA synthesis, and apoptosis were compared in cultured rat and human hepatocytes. Rat hepatocytes expressed a 10-fold greater level of the peroxisomal fatty acyl-CoA oxidase compared to human hepatocytes. At the highest concentration (1.0 mM), both drugs induced a two- to threefold increase in this enzyme activity in both rat and human hepatocytes. Ciprofibrate (0.1 and 0.2 mM) caused a twofold increase in DNA synthesis in rat hepatocytes, whereas clofibric acid had no effect on DNA synthesis in these cells. In contrast, increasing concentrations of both clofibric acid and ciprofibrate produced inhibition of DNA synthesis in human hepatocytes. By using the terminal transferase dUTP-biotin nick end labeling technique, it was observed that 0.1 and 0.2 mM clofibric acid and ciprofibrate suppressed transforming growth factor-beta (TGF beta)-induced apoptosis by 50% in rat hepatocytes, but they had no effect on TGF beta-induced apoptosis in human hepatocytes. Although clofibric acid and ciprofibrate diminished TGF beta-induced apoptosis, they had no effect on the basal apoptotic levels in the rat hepatocyte cultures. However, both drugs significantly increased the percent of apoptotic cells in the human hepatocyte cultures. It is concluded that primary rat and human hepatocyte cultures respond differently to peroxisome proliferators. The differences in effects on DNA synthesis and apoptosis support the hypothesis that human liver cells are refractory to peroxisome proliferator-induced hepatocarcinogenesis.     

Indoor radon prediction from soil gas measurements

We have studied the intubating conditions in 60 ASA I or II patients, after induction of anaesthesia with propofol 2 mg kg-1, allocated to one of the following three groups: group 1, remifentanil 1 microgram kg-1; group 2, remifentanil 1 microgram kg-1 and lignocaine 1 mg kg-1; group 3, remifentanil 2 micrograms kg-1. No neuromuscular blocking agents were administered. Intubating conditions were assessed using a four-point scoring system based on ease of laryngoscopy, jaw relaxation, position of vocal cords, degree of coughing and limb movement. Overall intubating conditions were acceptable in 35% of patients in group 1, 100% of patients in group 2 and 85% of patients in group 3. There was a statistically significant drop in blood pressure after induction in groups 2 and 3, and two patients in each group required ephedrine 6 mg i.v. boluses, as dictated by the intervention criteria (mean arterial pressure fall > 25% from baseline). Similarly, there was a drop in heart rate in groups 2 and 3, but this did not reach statistical or clinical significance, and no patient required atropine.     

Influence of prior ACE inhibitor therapy on morbidity and mortality following acute myocardial infarction

A 37-year-old woman was taken to a hospital because of sudden chest pain. She lapsed into shock, and the ECG indicated acute myocardial infarction. The ECG later showed ventricular fibrillation, and the patient was given cardiac massage while being transported to our hospital, where she was resuscitated with a percutaneous cardiopulmonary support system. Emergency coronary angiography revealed 99% stenosis of the left main coronary artery. PTCA was performed, and the stenotic lesion was released, but dissection and rapid formation of a thrombus were detected in the LAD. Re-PTCA was performed, but the hemodynamics did not improve, and emergency CABG of the LAD, D1, and LCx was performed. Postoperative max CPK was 18,957 IU/L. Although postoperative MRSA pneumonia developed as a complication, weaning from the respirator was performed 17 days after the operation. The patient was discharged, ambulatory, 74 days after the operation.