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[Lipid peroxidation markers in the exhaled breath and microsomal oxidation in patients with chronic diffuse liver diseases].

Low-molecular hydrocarbons (butan, pentan) from the exhaled air as lipid peroxidation (LPO) markers were quantified in patients with chronic diffuse liver diseases. The study was also made of microsomal oxidation enzymic activity by antipirin metabolism. The above parameters were followed up in the course of antioxidant treatment. As shown by total butan and pentan levels, LPO activity varied with the disease, being high in hepatic cirrhosis and primary biliary cirrhosis, but low in chronic active hepatitis and fat dystrophy. Increased levels of butan and pentan occurred in association with inhibited activity of P450-dependent monooxygenases. This was determined by antipirin biotransformation and confirmed by a strong inverse correlation between the amount of hydrocarbons and antipirin metabolites (4-hydroxy- and norantipirin) clearance. In the course of antioxidant therapy the most pronounced inhibiting action on formation of low-molecular hydrocarbons was distinctive of essenciale, pikamilon and copmplivit. Relevant efficacy of carsil was weaker. Similar regularity for these drugs takes place in relation to activation of microsomal oxidation.

Adult↗

[Expired ethane as a non-invasive marker of the course of experimental multiple organ dysfunction syndrome (MODS)].

UNLABELLED: BACKGROUND AND WORK HYPOTHESIS: The mechanisms of organ damage in MODS are unclear. Given that lipid peroxidation induced by oxygen radicals may play a key role in organ damage, expired ethane, a marker of lipid peroxidation, could be correlated to the entity and evolution of experimental MODS. STUDY DESIGN AND METHODS: Forty wistar male rats (250 +/- 15 g body weight) were intraperitoneally injected with 10 ml of Zymosan mineral oil suspension (2.5%) to provoke MODS. Survival and symptoms were noted daily. On the 2nd, 7th and 14th day the animals underwent thorax CT scanning. CT images were processed to evaluate the relative density of lung parenchima. Expired ethane was measured using mass spectrometer and percentual changes were noted. Relative organ weight (liver and lung) were measured in 2nd, 7th and 14th day. STATISTICAL ANALYSIS: Pearson's linear correlation. RESULTS: The results show that maximal lung damage took place at the same moments as ethane concentrations peaked. A strict correlation (r = 0.93; p < 0.0001) was found between lung density and expired ethane. Strict correlation was found between organ weight, symptoms, survival and ethane production. CONCLUSIONS: Lipid peroxidation, as expressed by ethane production, might be an important cause of organ damage in MODS.

Animals↗

Facilitated method for measurement of biliary secretion rates in healthy humans.

We have developed a facilitated method for determining secretion of constituents into bile. The ratio of constituent/bilirubin was measured in gallbladder bile and multiplied by bilirubin secretion rate, estimated by measuring endogenous production of carbon monoxide (VCO) by breath sampling. Accuracy of this method was assessed by measuring secretion rate of 99mTechnetium-labeled disofenin during steady-state constant intravenous infusion. In nine subjects, mean (+/- SEM) secretion of disofenin by the CO method was 104.2 +/- 7.2% of expected and by standard marker perfusion was 97.8 +/- 13.1% of expected. In ten subjects, secretion rate of cholesterol by the CO method averaged 103 mumol/h by the CO method compared to 113 by marker perfusion (NS). Compared to marker perfusion (which is believed to reflect 24-h secretion rate), the CO method significantly underestimated secretion rate of bile acid (1110 vs. 1332 mumol/h, P = 0.076) and lecithin (295 vs. 413 mumol/h, P = 0.01), probably because gallbladder bile contained a disproportionate amount of fasting versus postprandial bile. Thus, this new method provides an accurate secretion rate for biliary constituents secreted at a relatively constant rate, including cholesterol, with less variability than marker perfusion. However, it can be used to estimate secretion of bile acid and lecithin only when a 20-30% underestimation of 24-h secretion is acceptable.

Adult↗

[Determination of anti-HTLV-I/II antibodies: Experience in 28,897 blood donations in Buenos Aires].

PURPOSE: The first human retrovirus, HTLV-I, was isolated in 1980; HTLV-II was described later. The former is endemic in southwestern Japan, the Caribbean and equatorial Africa; whereas the latter prevails in intravenous drug addicts, being also endemic in American indian populations. Both viruses are either sexually transmitted, from mother to child mainly by breast-feeding, by blood transfusion or by sharing contaminated needles. With regard to transmission, since they are intracellular viruses, it occurs only when whole blood or cellular components are transfused; this is not the case when either plasma or plasma derivatives are used. The likelihood of transmission decreases as the storage time increases. HTLV-I is associated, at least, with two diseases: adult T-cell leukaemia/lymphoma (ATLL), and the tropical spastic paraparesis (TSP) or HTLV-I-associated myelopathy (HAM). ATLL occurs after a latency period of 20 to 30 years; whereas the incubation period ranges from 3 to 5 years in the case of the neurological disease. Most individuals infected with the virus remain healthy; the risk of developing the hematological complication is 2-4% whereas it is below 1% in the case of TSP. No clear association of HTLV-II with any known disease has been reported as yet. In this study, we have assessed the prevalence of HTLV-I and HTLV-II in the sera of the blood donors who have come to our Division, with the aim of avoiding the spreading of this oncogenic virus by transfusion. This study could serve as a measure of the infection in the general population. MATERIAL AND METHODS: A total of 28,897 samples were analyzed from May 1993 to January 1995. Anti-HTLV-I/II antibodies were analyzed by the method of passive agglutination of gelatin participles (PA). Samples which reacted were tested again by the same method, and those reacting for the second time were further confirmed by Western blot (WBT), a method with the ability to differentiate between antibodies anti-HTLV-I and anti-HTLV-II. RESULTS: Of the 28,897 samples, 47 were repeatedly reactive by PA (0.16%). Analysis by WBT resulted in 10 reactive results with HTLV-I (0.035%), 2 reactive results with HTLV-II (0.007%); in one sample it could not be determined whether the anti-HTLV-I or anti-HTLV-II antibody was present. Of the remaining samples, 21 were non-reacting, whereas 13 were indeterminated. CONCLUSION: Prevalence of HTLV-I and HTLV-II seropositive blood donors is low and similar to that found in other non-endemic countries. We believe that routine evaluation of anti-HTLV-I and HTLV-II antibodies in blood donors would be warranted in our country, since transmission of the viruses by transfusion of blood components has been clearly shown. It is possible that the recipients of the reactive units do not develop the disease. Nevertheless, these individuals constitute an important source of virus dissemination, both during the perinatal period and by sexual intercourse. In fact, advise to seropositive donors would prevent transmission by these routes. Lastly, it should be noticed that investigation of anti-HTLV-I/II antibodies could result in a surrogate method for detecting other viral infections transmitted by these routes.

Adolescent↗

Nitric oxide in exhaled air is a new marker of airway inflammation.

The measurement of exhaled NO has excited considerable interest, as it may provide a simple noninvasive means of measuring airways inflammation. There is now persuasive evidence that levels of NO are increased in association with airway inflammation and are decreased with anti-inflammatory treatment. Correlation of exhaled NO with more direct measurements of inflammation in the airways, such as induced sputum, bronchoalveolar lavage and bronchial biopsies, is needed. The great advantage of exhaled NO is that the measurement is completely noninvasive. It can, therefore, be performed repeatedly, and also in children and patients with severe airflow obstruction, where more invasive techniques are not possible. However, the measurement is not specific, and exhaled NO is increased in inflammation due to asthma, bronchiectasis, and respiratory tract infections. This means that absolute values are less important than serial measurements in individual patients. The value of this approach has been demonstrated in asthmatic patients, where the dose of inhaled steroid is changed, resulting in increased levels when the dose is reduced and lower levels when the dose is increased. Because exhaled NO is reduced by anti-inflammatory treatments, it may be of use in monitoring whether therapy is adequate. The technique may also have application in the monitoring of the anti-inflammatory effects of new antiasthma drugs, such as selective phosphodiesterase inhibitors, leukotriene antagonists and synthesis inhibitors, and immunomodulators. Because the measurement is precise and reasonably reproducible, it may facilitate the measurement of dose-response effects with anti-inflammatory treatments, which is difficult at present. The analysers for exhaled NO that are currently available are expensive, but in the future it is likely that technological advances will make it possible to miniaturize these analysers, so that they are portable and may even be used at home in conjunction with peak flow meters. -his may lead to their application in epidemiological research, which may be a useful screening measurement for community studies. Although we have discussed exhaled nitric oxide, other volatile substances may also be detected in exhaled air. Thus, ethane and pentane, which are volatile products of lipid peroxidation, and hydrogen peroxide, may be used to detect oxidant stress in the respiratory tract and may also be useful as markers of inflammation. There is little doubt that this is a rapidly expanding area of research.

Biomarkers↗

Reconstructing week-long exposures to volatile organic compounds using physiologically based pharmacokinetic models.

Reconstruction of human exposure to toxic chemicals using physiologically based pharmacokinetic (PBPK) models and biomarkers is an attractive prospect, because biomarker measurements generally provide the most direct evidence of dose. Previously it has been shown that it is possible to reconstruct short-term (30 minute) exposure to chloroform, and that it is possible in some cases to resolve the total dose between two routes of uptake (Georgopoulos et al., 1994). In this paper it is shown that it is mathematically feasible to reconstruct longer term exposures to volatile organic compounds (VOCs), using benzene as a paradigm for other VOCs, and exhaled breath concentration as a biomarker of exposure. First, it is shown that exhaled breath concentration is an appropriate biomarker for long-term exposure to benzene, since benzene accumulates in fat and is eliminated in exhaled breath. Application of a benzene PBPK model (Travis et al., 1990) showed that benzene continues to accumulate in the fat compartment for over 10 days, and consequently fat acts as an integrator of dose during this period. Second, the benzene PBPK model is used to reconstruct exposure using the maximum likelihood approach. Since no data were available for long-term exposures of this duration, "data" with a normally distributed random error and 30% coefficient of variation were generated by the PBPK model for a variety of daily exposures. It was shown that in most cases it is possible to estimate cumulative exposure within 40% of the actual values, even when the exposure concentration-time profile is unknown. The estimated exposure is found to always be an underestimate of the true exposure when the exposure concentration is assumed to be constant.

Benzene↗

[Nitric oxide in expired air from rats with experimental bronchitis].

Bronchitis was evoked in 20 rats by SO2 inhalation. Ten rats were exposed to SO2 only, 10 others were exposed to SO2 and treated with heparin simultaneously. The control group consisted of other 10 rats. NO concentration in the air exhaled by all animals was determined. The experiment was carried out in a specially constructed chamber. It lasted 15 weeks. In the group of animals exposed to SO2 only, NO concentration was found beginning from the %th week, with the maximum concentration in the 10th week. In the group of animals exposed to SO2 and treated with heparin NO concentration was much lower than in the above group. NO was not found in the control group. The conclusion is that NO concentration in the exhaled air is a result of bronchial inflammation, and can be decreased during treatment with heparin.

Animals↗

Evaluation of pulmonary arterial hypertension.

PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) is defined as a group of diseases characterized by a progressive increase of pulmonary vascular resistance leading to right ventricular failure and premature death. The purpose of this review is to analyze the current knowledge of the evaluation of PAH patients. RECENT FINDINGS: Recently, the diagnostic approach has been more clearly defined according to the new clinical classification and with consensus reached on algorithms of various investigative tests and procedures that exclude other causes and ensure an accurate diagnosis of PAH. The diagnostic procedures include clinical history and physical examination, ECG, chest radiography, transthoracic Doppler echocardiography, pulmonary function tests, arterial blood gases, ventilation and perfusion lung scan, high-resolution CT of the lung, contrast-enhanced spiral CT of the lung and pulmonary angiography, blood tests and immunology, abdominal ultrasound scan, exercise capacity assessment, and hemodynamic evaluation. SUMMARY: Invasive and noninvasive markers of disease severity, either biomarkers or physiologic parameters and tests that can be widely applied, have been proposed to reliably diagnose PAH and monitor the clinical course.

Electrocardiography↗

Manganese accumulation by the antennule of the Norway lobster Nephrops norvegicus (L.) as a biomarker of hypoxic events.

In laboratory tests, manganese accumulation by the appendages of the sediment burrowing Norway lobster. Nephrops norvegicus (L.) (including the lateral antennules) was approximately three times greater [600 microg Mn g(-1) (dry weight) after 5 days in 20 mg Mn l(-1)] than that by the carapace. The accumulation was linearly dose-dependent (10-40 mg Mn l(-1)) and duration-dependent (2-30 days). and showed no decrease after 3 weeks in undosed seawater. A high manganese uptakc to the lateral antennules during hypoxia in the field was verified from the SE Kattegat, Sweden. These results indicate that accumulation of Mn on the mobile appendages of the Norway lobster fulfils most of the criteria for a biomarker of exposure to hypoxia. Using these measurements in conjunction with Mn concentrations in the internal tissues, it may be possible to resolve both the timing and the extent of the Mn exposure and the underlying hypoxic event.

Animals↗

A new in vitro blood load test using a magnesium stable isotope for assessment of magnesium status.

Magnesium (Mg) status is currently assessed by various biochemical biomarkers, most of which, however, have some limitations. We developed an in vitro blood load test as a new Mg biomarker using a Mg stable isotope. This test is based on the hypothesis that cellular Mg uptake is increased in Mg deficiency. For this purpose, Wister male rats were fed either Mg-deficient or Mg-adequate diets for 1 mo and blood was sampled and incubated with the (25)Mg isotope (10 mg/L) for 2 h at 37 degrees C. Erythrocytes, lymphocytes and platelets were isolated and (25)Mg concentrations were determined by inductively coupled plasma/mass spectrometry. The feasibility of this approach was then tested on human blood. (25)Mg enrichments in erythrocytes, lymphocytes and platelets from Mg-deficient rats were greater than those from controls. (25)Mg enrichment was low in human erythrocytes (3%) compared with rat erythrocytes (38%), whereas high (25)Mg enrichments were obtained in human lymphocytes and platelets, suggesting that lymphocytes and platelets may be more appropriate cells than erythrocytes for examining Mg status in humans with this approach. More studies are required to validate the utilization of this test as a Mg status biomarker in humans.

Animals↗