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Biomedical subjects

J Lutz

Publications and source records attributed to J Lutz.

At least 19 recordsLinked to original sources

Influence of anti-inflammatory drugs and free radical scavengers on intestinal ischemia induced oxidative tissue damage.

The influence of oxygen free radical scavengers and anti-inflammatory drugs on postischemic lipid peroxidation and myeloperoxidase activity was shown. The best results were obtained from vitamin E and the antiinflammatory treatment with CP and SUL, whereas an iron elimination only showed slight effects on myeloperoxidase activity above all. In experiments without therapy a linear increase of lipid peroxides dependent on reperfusion durance was found, whereas myeloperoxidase already showed a remarkable increase during ischemia and early reperfusion. This difference can be interpreted by scavenging mechanisms, which are overcharged after an appointed durance of reperfusion.

Animals

Influence of free radical scavengers on myeloperoxidase activity and lipid peroxidation in acute skin grafts.

Activated neutrophil granulocytes are an important source of oxygen free radicals in acute skin grafts. Lipid peroxidation and immigration of PMNs, indicating inflammatory mechanisms, affect each other to a variable extent. The effect of the scavengers allopurinol and alpha-D-tocopherol on both lipid peroxidation and neutrophilic infiltration was investigated. A possible mechanism for the superior effect of allopurinol compared to vitamin E was discussed.

Allopurinol

Effect of hyperbaric oxygen treatment and perfluorochemical administration on glutathione status of the lung.

Exposure to hyperoxia, especially under hyperbaric conditions, causes an enhanced oxidative stress particularly in lung tissue. To test the potential hazardous effect of either a single or repeated hyperbaric oxygen treatment (HBO) on the cellular defence system the glutathione status of lung tissue from rats exposed to HBO was investigated. When daily exposed to 2.5 ATA of > 95% O2 for 90 min over 8 or 14 days the content of reduced glutathione in lung tissue (GSH) increased by 16-19%. Oxidized glutathione (GSSG) tended to increase after 8 days and was 56% higher after 14 days. While the GSSG/GSH ratio was unchanged after 8 days, it increased by 39% after 14 days. Thus, the GSH increase after 8 days can be understood as a adaptive process to protect the lung from oxidative stress. The distinct increment of the cellular GSSG that lead to an increase of the GSSG/GSH ratio after 14 days reflects a situation, in which the cellular defence system is overwhelmed by oxidative stress. The additional pretreatment with perfluorochemicals in a dose of 2g/kg every second day aggravated the observed changes (GSH +39-19%, GSSG +118%). In a second experiment rats were exposed to a single session with 7 ATA of O2 for 60 min. GSH in the lungs increased for 40%, it was not elevated by PFC. However, GSSG increased to a much higher degree in untreated as well as in PFC-treated animals (+240%, +163%), elevating the ratio GSSG/GSH markedly (+145%, +176%). Allopurinol given as radical scavenger in a dose of 50 mg/kg was able to suppress the increased oxidative stress widely. Thus adaptive and overloading processes are involved under the treatment with increased oxygen pressures. As the administration of PFC aggravates the observed changes, a still increased blood oxygen offer must be considered as the causative agent. A radical scavenger is capable to suppress the increased oxidative stress widely.

Animals

Magnetometric studies on the reticulo-endothelial system of the liver after administration of different lipid emulsions.

A comparison of the burdening effects on the reticulo-endothelial system (RES) by soybean oil emulsions with two different emulsifiers [soybean lecithin (SOB) and egg lecithin (EGG)] or by a perfluorochemical emulsion (Fluosol-DAR, PFC) was performed using a magnetometric method. This method is based on measuring the relaxation of injected iron oxide (gamma-Fe2O3) above the liver after magnetization in a strong external magnetic field. Three different methods of evaluation of the data were chosen. First, according to the conventional monoexponential function, second, according to a monoexponential function with a constant, and third, using the ratio of the initial dynamic to total magnetic field strength. In contrast to SOB and EGG, the PFC emulsion which was used depressed the RES-capacity to less than 31% of the control values (p less than 0.001). Following the administration of SOB the phagosomal motion was significantly lowered after 6 h (p less than 0.01) and 1-2 days (p less than 0.05); thereafter no significant difference of the relaxation constants remained as compared to the control group. The fatty emulsion with egg lecithin showed no significant lowering of the RES-capacity during the entire observation period (p greater than 0.05). Our results indicate that the RES-capacity is diminished not only by a PFC emulsion, but also temporarily by a soybean lecithin emulsion, though not by an egg lecithin emulsion, when given in the same dosages.

Animals

Combination of treatment with perfluorochemicals and free radical scavengers.

P-cyclohexylmorpholine, given as oxygen carrier of second generation, was tested in two experimental models: the ischemic intestine and the lung under hyperbaric oxygen condition. In both instances in separated groups either alpha-tocopherol or allopurinol was additionally given as oxygen free radical scavenger. The thiobarbituric acid reaction (TBAR) was used as screening test for the occurrence of lipid peroxidation in organ probes; further the content of glutathione in reduced (GSH) and oxidized form (GSSG) was determined. Whereas only slight increases of TBAR substances and GSSG could be found compared to controls, the effect of the administrated scavenging drugs was very impressive: they could suppress nearly totally the effect of an enhanced oxidative stress.

Animals

Differences in glutathione status and lipid peroxidation of red and white muscles: alterations following ischemia and reperfusion.

Glutathione status and products from lipid peroxidation [measured as thiobarbituric acid reactive substances (TBARS)] were determined in red and white muscle tissue of the rat. Marked differences between both muscle types were found in reduced glutathione (GSH) and oxidized glutathione (GSSG) content, exhibiting 163% and 183%, respectively, higher levels in red than in white muscle tissue, while the ratio of GSSG/GSH showed no differences. These characteristics may be due to an adaptive mechanism related to the 48% higher baseline level of TBARS in red muscle tissue. Immediately after 4 h of tourniquet-ischemia GSH, GSSG, and TBARS were increased (16%, 32%, 45% in white muscle; 19%, 49%, and 42% in red muscle, respectively), whereas the GSSG/GSH ratio remained unchanged. During the subsequent reperfusion period, GSH decreased within 2 h by 39% in white and 89% in red muscle to a minimal level of 5 mmol/g protein in both types of muscle. No recovery from the depletion was observed up to 12 h of reperfusion. The GSH decrease was parallelled by a marked increase of the GSSG/GSH ratio (150% in white and 450% in red muscle) and followed by about 150% increase in TBARS in both muscle types. This suggests that the increase in damaging TBARS is a secondary event after depletion of cellular antioxidants. Treatment of the animals during the reperfusion period with methyl-prednisolone, deferoxamine, or superoxide dismutase and catalase did not prevent the GSH decrease, but were effective in reducing the GSSG/GSH ratio to near normal and reducing the TBARS increase by about 50%.

Animals

Intestinal, hepatic and renal production of thiobarbituric acid reactive substances and myeloperoxidase activity after temporary aortic occlusion and reperfusion.

Ischemia induced oxygen free radical damage was formerly attributed only to xanthine oxidase in intestine, liver, kidney and heart. A reevaluation indicated neutrophils as one of the major sources of postischemic oxidative tissue damage, chiefly in the intestine. Our data, obtained from the same occlusion time period for intestine, liver and kidney, showed a certain oxidative damage in intestine and kidney already during ischemia, expressed by an increase of thiobarbituric acid reactive substances (TBARS), whereas the liver sustained damage of this kind only during reperfusion. Oxidative stress was expressed by a comparison of the increase of TBARS, though this test is not a measure of a specific product of lipid peroxidation, but rather comprises several breakdown products of free radical damage. Myeloperoxidase as measure of neutrophil stimulation increased in the intestine and liver. The kidney sustained damage without an increase of myeloperoxidase activity, but showed a similar pattern of increase of TBARS as in the intestine. Our data suggest a major role of neutrophils in intestinal ischemia induced damage, where neutrophils can effect initiation and propagation. In the liver neutrophils may play a minor role concerning propagation, but they may act as an important initiating mechanism. Hepatic tissue shows a high ischemic tolerance, which is demonstrated by a missing increase of TBARS in spite of a certain increase of myeloperoxidase activity during ischemia. This can be interpreted by the high capacity of antioxidative mechanisms of liver tissue and the ability of a higher oxygen extraction ratio under nearly ischemic conditions. In the kidney there appears a smaller contribution of neutrophils. The similar pattern of increase of TBARS in kidney and intestine demonstrates a comparable low ischemic tolerance of these two tissues, whereas different initiating and propagating systems may occur.

Animals

[Real time collection of pain profile in treatment with ibuprofen].

In an open three-center pilot study, 17 patients suffering from chronic persistent pain syndrome, due to osteoarthritis of the hip and knee or spondylarthrosis, were treated orally with 1800-2400 mg Ibuprofen per day for 3 weeks. The chronic pain syndrome and joint status were assessed by the physician at the beginning, and after 7, 14 and 21 days. Self-assessments were made by the patients six times daily during the full study period by means of battery-driven electronic diaries (E.D.). The data entered by the patients were stored in the E.D. and after online transfer, processed and evaluated in a PC using appropriate software programs. E.D. were returned by 16 of 17 patients for evaluation. The technical functioning of the instrument was perfect; its use was accepted by patients and physicians. The closely-meshed real-time recording of pain course and other subjective data, such as adverse events or medication, etc., enables the physician to calculate more exactly and reliably improvement rates, as well as to carry out prognostic trend analyses and individual benefit-risk-ratio estimates. By comparing different kinds of data, each entered at the same time, plausibility checks are possible. The procedure presented here is considered to be a new valuable tool for reviewing subjective data from clinical drug trials.

Adult

Severity of oxygen free radical effects after ischemia and reperfusion in intestinal tissue and the influence of different drugs.

The influence of different drugs on ischemia induced oxygen free radical damage was examined in intestinal tissue of rats by determination of thiobarbituric acid reactive substances (TBARS). Some methodical aspects of this method were considered. Experiments were done with and without the use of polymerized stromafree hemoglobin (PHb) as an additional oxygen carrier. Reversible total occlusion of the superior mesenteric artery was performed for 90 min, reperfusion time was 2.5 hours. Despite higher O2 availability PHb did not increase the TBARS level any further. Superoxide dismutase with catalase; allopurinol; ciprofloxacin; and deferoxamine produced a highly significant reduction of TBARS, even if used together with PHb.

Allopurinol

Mother-daughter pairs: spinal and femoral bone densities and dietary intakes.

Bone mineral density (BMD) of the lumbar spine (L1-L4) and femur (femoral neck, Ward's triangle, and trochanter) was measured in 37 healthy, white mother-daughter pairs by dual-photon absorptiometry. Mothers and daughters were aged 52 +/- 7 and 25 +/- 4 y (mean +/- SD), respectively. Three-day dietary intakes were evaluated. Significant correlations between mother-daughter pairs for BMD of all lumbar and femoral areas [except for L2 (r = 0.26, P = 0.054)] indicated familial resemblances in bone mineralization. Total calcium intake was significantly correlated with three BMD values for the daughters (L2, femoral neck, and trochanter) but not for the mothers. When mothers were classified as pre- (n = 20) or postmenopausal (n = 17), correlation coefficients for BMD were higher for premenopausal mothers and their daughters and lower for postmenopausal mothers and their daughters, except for the trochanter. The results suggest that the nature of inheritance of bone mass of women may have at least two components, one influencing the level of peak bone mass and one related to bone loss at menopause.

Absorptiometry, Photon

Acoustic interference in a recognition task.

Phonetic or acoustic characteristics of stimuli in recall studies have consistently been shown to generate more interference over short intervals than semantic characteristics. We performed three experiments to determine whether this characteristic also applied to recognition processes over short intervals. Subjects were shown study lists of eight words and were asked to recognize which of those words recurred on subsequent eight-word lists. Delays varied from 0 to 100 s between study and test, with a rehearsal-preventing task inserted during the delays. Phonetic distractors generated greater interference than semantic distractors at all delay levels, and semantic distractors generated greater interference than random distractors. These distractor-type differences were not present in long-term recognition tasks. The deterioration in performance over time was considerably slower in these recognition experiments than in previous recall studies.

Adult

Esmolol, the first ultra-short-acting intravenous beta blocker for use in critically ill patients.

Esmolol is the first intravenous, short-acting, titratable beta-blocker available for use in critical care and surgical settings. The predominant pharmacodynamic actions of the drug include a reduction in HR, BP, rate-pressure product, LVEF, and cardiac index. A desirable pharmacokinetic feature of esmolol is its esterase-induced rapid metabolic inactivation, which results in a return of all hemodynamic parameters to pretreatment levels within 30 minutes after discontinuation of the infusion. Control over the magnitude and duration of beta-blockade and the relative cardioselectivity of esmolol make it an ideal agent for use in critically ill patients, including those who, because of other conditions, are at risk if treated with beta-blockers. The clinical indications for esmolol therapy include SVT and perioperative tachycardia and hypertension. In patients with myocardial ischemic conditions (acute myocardial infarction and unstable angina), esmolol was safe and produced clinically significant reductions in HR and rate-pressure product. In general, untoward reactions to esmolol have been minimal, mild, and transient. Although attention must be given to the possibility of systolic hypotension during esmolol administration, this complication often occurs at doses beyond those which provide optimal therapeutic response and may be avoided by titrating to the minimal effective dose. If systolic hypotension occurs, it is reversible by either reducing the dose or discontinuing the esmolol infusion. A nursing plan of care should be developed for patients receiving esmolol therapy. Dosage and administration must be individualized. Careful titration of the esmolol infusion and monitoring of therapeutic and safety parameters by nursing professionals will promote the achievement of maximum beta-blocker effect while avoiding persistent and unnecessary adverse reactions.

Coronary Disease

Half life and changes in the composition of a perfluorochemical emulsion within the vascular system of rats.

The decline of the concentration of perfluorochemicals (PFC) after a single injection of three different doses was studied in the circulation of rats. The doses used amounted to 4.4, 10 and 14 g/kg body weight of Fluosol-DA, an emulsion of 7 parts of perfluorodecalin (FDC) and 3 parts of perfluorotripropylamine (FTPA). This also allowed testing of the composition of the emulsion remaining in the circulation and of that found in the liver. After two days a decrease of the half life from 34.0 +/- 0.7 to 17.1 +/- 4.3 h was found within the circulation at the highest dose. At the same time a change in the composition of the emulsion in the blood stream occurred, favouring the fraction of FTPA. FTPA increased from 28.3 +/- 1.4 to 54.4 +/- 8.1% on the fourth day. Whereas in the cells of the liver PFC droplets may be broken up, freed from their surfactant layer and handled according to their individual components, for PFC in the blood stream an unchanged composition should be assumed. Both results, the decreasing half life and the change in composition of the circulating emulsion may best be explained by a shrinking and instability of the emulgator film, showing the necessity for development of a superior surfactant.

Animals

Role of fluid replacement, increased oxygen availability by perfluorochemicals and enhanced RES function in the treatment of mesenteric occlusion shock.

UNLABELLED: Experiments were carried out on 183 rats to study the effect of a complex therapy for treatment of mesenteric shock. The superior mesenteric artery (SMA) was temporarily ligated for 90 min under ether anesthesia; this was followed by an analgesic treatment. After release of the ligated artery, fluid therapy was instituted by administering the equivalent of 7.5% of body weight of one of three different solutions: ringer lactate (RL), hydroxyethyl starch (HES) in RL, and perfluorochemicals (PFC, 4 g/kg b.wt. in RL with HES), the latter with the aim to improve the oxygen transport to the tissue. The same fluid therapy was carried out on rats pretreated with E. coli endotoxin. Endotoxin pretreatment was chosen to compensate the negative effect of PFC on the reticuloendothelial system (RES) as shown in previous studies. Survival time and survival rate were recorded as well as hematocrit values at different times before and after treatment. Experimental groups were: CONTROLS: (1) SMA occlusion without release; (2) 90-min occlusion without therapy. Treated animals: (3) RL therapy; (4) therapy with HES in RL; (5) therapy with PFC in RL and HES; (6), (7), and (8) identical therapies as Groups 3, 4, and 5, respectively, but with endotoxin pretreatment. Survival time increased to the same extent if HES or PFC were added to RL. There was a further increase both in survival times and rates with endotoxin pretreatment (Groups 6, 7, and 8 vs. Groups 3, 4, and 5). The highest survival time and rate were obtained in Group 8, which received PFC therapy with endotoxin pretreatment. There was a slight negative correlation between survival time and hematocrit values if all groups were considered together.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals