Incremental iron overload during reperfusion progressively augments oxidative injury

OBJECTIVE: To determine if a relationship exists between the extent of iron-catalyzed injury and the degree of tissue iron overload during reperfusion. METHODS: To selectively increase tissue iron only during early reperfusion, isolated, buffer perfused rabbit hearts were exposed to 20 microM Fe(2+)-100 microM ADP during the last 3 minutes of ischemia and the initial 4 minutes of reperfusion. Control groups were exposed to ADP and iron-ADP regimens that did not increase intracellular iron. All the hearts received 30 minutes of normothermic global ischemia and 30 minutes of reperfusion. Heart function was monitored continuously throughout each experiment. Tissue iron and biochemical markers were analyzed at the end of experiments. RESULTS: Hemodynamic recovery was decreased and tissue lipid peroxide levels were increased in the 20 microM Fe(2+)-100 microM ADP group compared to controls. The recoveries of developed pressure and positive/negative dP/dT at 30 minutes of reperfusion were negatively correlated with tissue iron levels, while cytosol and membrane lipid peroxide levels correlated positively with the iron levels during reperfusion. CONCLUSION: The extent of oxidative injury during reperfusion was directly related to the tissue iron burden present during reperfusion. Increased lipid peroxidation was the principal chemical marker of iron-catalyzed injury.     

The end of the continuum. Bereavement care for the adult

A method has been developed for the simultaneous analysis of the isomeric N-acetyl-S-(dichlorophenyl)cysteines (also known as dichlorophenylmercapturic acids, DCPMAs) in urine. This procedure allows the determination of 2,3- and 3,4-DCPMAs at the concentrations expected in the urine samples of employees occupationally exposed to 1,2-dichlorobenzene (1,2-DCB). The results of a 1,2-DCB exposure study under standardized conditions show a first-order kinetic for the excretion of DCPMAs, as well as acceptable linear correlations between the urinary concentrations of DCPMAs and the amount of inhaled 1,2-DCB. It therefore seems it would be possible to derive a biological tolerance value for 1,2-DCB based on isomeric DCPMAs as analytical parameters.     

Abrasive wear of dental composite resins

Abrasive wear is a major problem in the application of dental composite resins. In this study the friction and wear behaviours of two types of dental composites: one containing relatively coarse filler particles and some microfillers (Estilux) and another containing only microfiller particles (Durafill), have been investigated by using a scratch testing machine. Experimental results show that the coefficients of friction in both composites are essentially constant for applied loads up to 20 N. The wear resistance of Durafill is better than Estilux. Under the same testing conditions, the size, shape and distribution of the filler particles are more important variables than applied load and sliding speed in controlling the wear mechanism. It is shown that for Estilux, plastic ploughing by the diamond indenter is the predominant mechanism. For Durafill, however, the formation and propagation of tensile cracks on the worn surface is the main wear mechanism. The effects of two different indenters, diamond and enamel, on the basic wear mechanisms are also discussed.     

Consumption of reduced-fat products: effects on parameters of anti-oxidative capacity

Plasma levels of fibrinogen, factor VIIc and prothrombin fragment F1 + 2, a marker of thrombin generation in vivo, were studied in 68 subjects with serum total cholesterol (TC) levels between 135 and 349 mg/dl but without clinical evidence of cardiovascular disease and other atherosclerotic risk factors. F1 + 2 plasma levels were directly correlated with TC (p < 0.0004), low-density lipoprotein cholesterol (LDL-C; p < 0.0018) and factor VIIc (p < 0.024). Thirty-five subjects with TC greater than 249 mg/dl (median value of the whole group) showed higher levels of F1 + 2 (p < 0.0001) and fibrinogen (p < 0.0015) than those with TC lower than 249 mg/dl. In subjects with TC > 249 mg/dl and F1 + 2 > 1.2 nM (median value of the whole group), a cholesterol-lowering drug (simvastatin) was able to reduce F1 + 2 (p < 0.009) as well as TC and LDL-C. This study shows a relationship between serum cholesterol and the rate of thrombin generation supporting the hypothesis that a hypercoagulable state may occur in hypercholesterolemic subjects before the onset of clinical evidence of atherosclerotic cardiovascular disease.     

Drugs, memory, and metamemory: A dose-effect study with lorazepam and scopolamine.

This experiment was designed to use the graded dose-related amnesia produced by the benzodiazepine lorazepam (1.0, 2.0 mg/70 kg, oral) and the anticholinergic scopolamine (0.3, 0.6 mg/70 kg, subcutaneous) as a tool to explore the cognitive and neurochemical mechanisms underlying metamemory in the judgment of learning paradigm, with a placebo-controlled independent groups design in healthy volunteers (n=12/group). Results provide evidence for a pharmacological dissociation between effects on memory versus metamemory (relative accuracy of item-by-item monitoring) across a range of levels of memory performance and suggest that the drugs selectively impair those aspects of metamnemonic monitoring that require participants' awareness of their overall current state of functioning (absolute accuracy of prospective item-by-item monitoring, prospective global monitoring) but not those that rely solely on assessment of individual item characteristics (relative accuracy of item-by-item monitoring). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A new ‘Tailor-made’ methodology for the mechanical behaviour analysis of rubber-like materials: II. Application to the hyperelastic behaviour characterization of a carbon-black filled natural rubber vulcanizate

The purpose of this paper is the modelling of the mechanical behaviour of an elastomeric material, through detailed experimental and numerical procedures, specific to large strains. The experimental technique is based on in-plane kinematics measurements using a speckle extensometer, from which the whole two-dimensional field of in-plane displacements is obtained by a digital image processing [Polymer (2002)]. This part of the work concerns the identification of the constitutive equation for a carbon black natural rubber (NR) vulcanizate. We start by quoting some theoretical considerations relative to rubber elasticity and stress-softening effect, which is the counterpart of the filler reinforcement. Then, we describe the experimental procedure and present data for both non-preconditioned and preconditioned samples. Next, the identification of the constitutive law parameters using a minimization algorithm is driven. Finally, we present the validation of the constitutive model, by its implementation into the finite element code SYSTUS and the numerical simulation of the response of a double edge notched tensile (DENT) specimen.     

Renal nerve responses to somatic nerve activation in stroke-prone spontaneously hypertensive rats

Antidepressant-induced adverse sexual effects are becoming more frequently reported by patients who require pharmacotherapy. A MED-LINE search was conducted to generate articles reporting such events. We report here on the sexual side effects associated with tricyclics, monoamine oxidase inhibitors including moclobemide, selective serotonin reuptake inhibitors, bupropion, and on the newer antidepressants venlafaxine and nefazadone. We conclude that adverse sexual effects are an increasingly important side effect of antidepressant medications, and patients must be routinely asked about their occurrence.     

Amifostine (WR-2721) shortens the engraftment period of 4-hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty-three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high-dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.