Serum markers of collagen metabolism: construction workers compared to sedentary workers.

BACKGROUND: Evaluation of causal relations between physical load and musculoskeletal disorders is hampered by the lack of knowledge as to the biological relevance of different loading parameters and the large variability between individuals. As indicators of molecular changes in the extracellular matrices of structures of the musculoskeletal system, biomarkers of collagen metabolism may provide important information on biological effects of physical load. The carboxyterminal propeptide of type I collagen (PICP) is a serum marker of synthesis and the carboxyterminal telopeptide region of type I collagen (CTx) reflects degradation of type I collagen. AIMS: To explore the feasibility of biomarkers of type I collagen metabolism as measures of the effects of physical load at tissue level. METHODS: Serum concentrations of PICP and CTx were assessed in a group of male construction workers involved in heavy manual materials handling (n = 47) and in a group of male sedentary workers (n = 49). RESULTS: Serum concentrations of both PICP and CTx seemed to be related to heavy physical work. The ratio PICP/CTx, illustrative of the effective metabolic changes, did not differ between the two groups. CONCLUSIONS: The higher turnover rate but similar effective synthesis may be indicative of an increased type I collagen content in the connective tissues as a result of adaptive remodelling in response to years of exposure to physical load. Further validation of these biomarkers is required with respect to dose-response relations and temporal associations between exposure to back load and biomarker concentrations.

The determination of alpha 1-microglobulin by means of an automated latex immunoassay.

Polystyrene (latex) particles coated with human anti-alpha 1 microglobulin antibodies are used in an automated "kinetic" assay for alpha 1-microglobulin in urine. For values below 12 mg/l, there was no significant difference between two kinds of standard, but above 12 mg/l the results depend on the origin of the alpha 1-microglobulin standard. Correlation between values obtained with both standards was good (r2 = 0.968). The method has a between-run imprecision (CV) of 11-16%. Comparison with two commercial enzyme immunoassays gave a bias of -10% to +40%, while two nephelometric methods differed by 0% to 23%, possibly because the standards used in these methods were of different origin. These results indicate the necessity of standardization of the determination of alpha 1-microglobulin. The detection limit of our method was 0.8 mg/l, enabling the application of the method for epidemiological investigations.

Biochemical parameters in BAL of sarcoisosis.

UNLABELLED: Sarcoidosis can be presented to the physician as an active or silent disorder, which may resolve or lead to pulmonary fibrosis. Various serum or bronchoalveolar lavage fluid (BAL) markers have been suggested when trying to find one marker or a combination of markers which could be representative of the disease. The aim of the study was to evaluate a number of biochemical markers in comparison to cellular parameters in BAL of 45 patients with active or inactive sarcoidosis, as well as in 44 patients with other disorders and of 10 healthy volunteers. Moreover, in order to get insight into ACE activity in different compartments, ACE values in BAL and serum were compared. In active sarcoidosis BAL-procollagen-III-peptide was significantly increased in contrast to the very low values in inactive disease. In healthy volunteers procollagen-III-peptide levels were below the detection limit. In BAL no significant differences were found for beta-2-microglobulin, hyaluronan or ACE. Laminin in BAL was not detectable. Serum ACE, significantly enhanced in sarcoidosis, was not discriminative between active and inactive disease. IN CONCLUSION: only procollagen-III-peptide in BAL was found to discriminate between active and inactive disease. Besides cell differentiation and T-helper/suppressor cell (CD4/CD8) ratio in BAL, no further biochemical parameters pointing to disease or activity of disease were found.

Plasma lipid peroxides and antioxidants in human septic shock.

In order to assess if an oxidant/antioxidant imbalance is involved in human septic shock and its outcome, we measured plasma levels of the lipid peroxides malondialdehyde--as thiobarbituric acid reactive substance--conjugated dienes and fluorescent products, together with the antioxidants alpha-tocopherol, glutathione peroxidase activity and selenium in 12 patients with septic shock and compared them with values of normal controls. At first measurements, malondialdehyde (median 3.9 mumol/l; range 2-38.8) and fluorescent products (median 21.2%; range 9.4-134) were elevated (p less than 0.05), alpha-tocopherol (median 15 mumol/l; range 7-25) and selenium (median 0.76 micrograms/ml; range 0.49-1.09) were depressed (p less than 0.05). Conjugated dienes and glutathione peroxidase activity were in the normal range. In non-survivors (n = 5) initial levels of malondialdehyde and fluorescent products (median 11 versus 3.1 mumol/l; 74 versus 13% respectively) were higher than in survivors (p less than 0.05) and initial selenium levels were lower (median 0.58 versus 0.92 micrograms/l; p less than 0.05). These results are consistent with the concept that an oxidant/antioxidant imbalance--as indicated by elevated plasma lipid peroxides and depressed antioxidants--is involved in human septic shock and a fatal outcome.

Adenosine deaminase activity in tuberculous pleural effusions: a diagnostic test.

The activity of adenosine deaminase (ADA) was investigated in pleural effusions from 10 patients with tuberculous pleurisy and 76 patients with pleural effusions of other aetiology. The ADA activity in the tuberculous patients was significantly higher than in the other groups, with the exception of those with empyema. Specificity (87%) and sensitivity (100%) of this test for tuberculosis is high when a reference limit of more than 53 U/l is taken.

Effect of single and repeated doses of oral omeprazole on gastric acid and pepsin secretion and fasting serum gastrin and serum pepsinogen I levels.

The effect of omeprazole on gastric acid and pepsin secretion and fasting serum gastrin and serum pepsinogen I levels was studied in 12 healthy volunteers. Omeprazole, 40 mg enteric-coated granules, or placebo was given once daily for nine days in a double-blind crossover study design. Twenty-four hours after a single dose of omeprazole, mean basal and mean pentagastrin-stimulated acid output decreased significantly. This effect was more pronounced after nine days of treatment. Basal pepsin output was significantly reduced only in those subjects with basal anacidity during omeprazole treatment. Stimulated pepsin output was slightly reduced after a single dose but unaltered after nine days of omeprazole. Fasting serum gastrin and serum pepsinogen I levels increased significantly during omeprazole treatment. It is concluded that omeprazole is a potent and selective inhibitor of gastric acid secretion, probably without a direct effect on pepsin secretion. However, in cases of basal anacidity during omeprazole administration, basal pepsin secretion is reduced. During omeprazole treatment, fasting serum levels of gastrin and pepsinogen I rise.

Determining reference ('normal') limits in medicine: an application.

We provide an account of a study to assess reference limits for eight routine laboratory determinations at the Academic Hospital of the Free University, Amsterdam and emphasize methodological issues rather than results. We argue that reference limits have use mainly in the first phase of the diagnostic process. Reference and target populations should be grossly comparable, and therefore patients (after slight selection) could well serve as references. However, we found major differences between in- and out-patients, so we suggest that this factor, together with age and sex, be taken into account. To arrive at reliable limits, the size of the reference sample should be at least 100. Laboratory reports should provide percentiles, which enable a more flexible decision than do fixed limits.

Effects of glucose-insulin-potassium (GIK) on the position of the oxyhemoglobin dissociation curve, 2.3-diphosphoglycerate, and oxygen consumption in canine endotoxin shock.

The effects of glucose-insulin-potassium (GIK) on hemodynamics, oxygen transport, P50, 2,3-diphosphoglycerate (2.3-DPG), and adenosine triphosphate (ATP) were evaluated in canine endotoxin shock. Ten dogs were studied under general anesthesia and controlled ventilation. Shock was induced with Escherichia coli endotoxin (1.5 mg/kg body wt). Thereafter two groups of five dogs each were formed by randomization. The one group received GIK (glucose 50%, 2 g/kg, insulin 3 U/kg, and 10 mmole K) in the period between 90 and 120 min after endotoxin. The other group received an equal amount of NaCl infusion and served as a control group. Observations were completed at 180 min after endotoxin. GIK resulted in a significant increase of cardiac output, stroke volume, mean arterial pressure, and oxygen consumption. Serum phosphate levels decreased. No changes were observed of P50 in vitro (at 37 degrees C and pH 7.40) and of P50 in vivo, nor of 2.3-DPG and ATP in the red cells. The data suggest that the increased oxygen consumption after GIK in canine endotoxin shock is caused only by improvement of cardiac output and oxygen availability and not by an effect on oxygen unloading capacity of hemoglobin.