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Biomedical subjects

P Pils

Publications and source records attributed to P Pils.

At least 19 recordsLinked to original sources

8-Hydroxydeoxyguanosine in leukocyte DNA and urine of quartz-exposed workers and patients with silicosis.

OBJECTIVE: To examine radical-induced DNA damage and its elimination in workers exposed to quartz and in patients with silicosis, and to assess the relationship of these effects to lung function. METHODS: Blood and spontaneous urine samples were obtained from active, quartz-exposed workers without silicosis (n = 63), and from retired workers with silicosis (n = 42). Levels of 8-hydroxydeoxyguanosine (8-OHdG) were determined in peripheral blood leukocyte DNA and urine, by the use of high-performance liquid chromatography coupled with ultra violet- (UV) and electrochemical detection. RESULTS: No significant differences in the mean levels of 8-OHdG in leukocyte DNA and of urinary excretion of 8-OHdG were found between silicosis patients and quartz-exposed healthy workers. However, in the group of silicosis patients with increased oxidative DNA damage the urinary excretion of 8-OHdG was lower than in the corresponding group of active workers without silicosis. In the case of silicosis, urinary 8-OHdG correlated positively, and 8-OHdG in DNA correlated negatively, with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Healthy workers with a personally estimated high dust exposure in the workplace showed higher levels of 8-OHdG in DNA than did workers with moderate dust exposure. No association of 8-OHdG formation and/or elimination with duration of employment, field of activity, smoking or age was found. CONCLUSION: Our findings suggest that a less effective repair of 8-OHdG is associated with a higher degree of pulmonary airway obstruction in patients with silicosis.

8-Hydroxy-2'-Deoxyguanosine↗

Increased serum osteocalcin levels in patients with paraplegia.

Osteocalcin(OC) is a specific serum parameter of bone formation. Since bone metabolism disturbances, including osteoporosis, are seen in paraplegia, the serum levels of OC, midregional parathyroid hormone(mPTH), intact para-thyroid hormone (iPTH) and calcitonin (CT) serum levels were determined in 13 patients with paraplegia or tetraplegia and 15 control subjects by radioimmunoassay in a cross sectional study. In addition, the urinary hydroxyproline/creatine and the urinary calcium/creatinine ratio was determined. Serum OC levels were significantly increased in the patients with spinal cord injury (p less than 0.02), whereas serum levels of mPTH, iPTH and CT were not statistically different. The urinary hydroxyproline/creatinine ratio was significantly higher in the patients than in the controls (p less than 0.02), and the urinary calcium/creatinine ratio also tended to be higher in the patients. In a follow up study over 6 months after spinal cord injury, serum OC, serum iPTH, urinary hydroxyproline/creatinine ratio and the calcium/creatinine ratio were determined in 6 patients at monthly intervals. Hyperhydroxyprolinuria preceded the gradual increase of serum OC from normal to clearly elevated levels. Our data suggest that increased bone resorption in paraplegia is linked to an enhanced osteoblastic activity.

Adolescent↗

Influence of verapamil on gastric acid secretion and gastrin release in dogs.

Gastric secretion is supposed to be calcium-dependent. The effect of verapamil (0.3 mg/kg/h i.v.), a calcium channel-blocking agent, on stimulated gastric acid secretion and gastrin release was investigated in 8 mongrel dogs. Stimulation was either performed by bombesin (1.0 microgram/kg/h i.v.) or by insulin (0.3 U/kg i.v.). Verapamil significantly inhibited both the bombesin- and the insulin-stimulated gastric acid secretion. Mean total gastric acid output over a 120-min period was 9.5 +/- (SEM) 2.2 mmol after bombesin stimulation and 6.3 +/- 2.0 mmol after bombesin and verapamil (p less than 0.01). The respective values were 15.3 +/- 2.0 mmol for insulin stimulation and 7.0 +/- 1.6 mmol for insulin and verapamil (p less than 0.01). There was no significant influence of verapamil on plasma gastrin concentrations. Thus, the impairment of acid secretion by verapamil is not due to an inhibition of gastrin release in intact dogs.

Animals↗

Insulin and the in vitro protein synthesis of liver and skeletal muscle ribosomes in experimental acute uraemia.

Tissue dependent alteration of liver and muscle protein synthesis was previously observed in acute uraemia, when intracellular amino acids were used as substrate. Since protein synthesis depends also on substrate availability, it was of interest to investigate the role of isolated liver and skeletal muscle ribosomes of nephrectomized rats and their susceptibility to in vivo insulin stimulation. Under marked uraemic conditions, no difference was demonstrated between controls and uraemic animals; after insulin administration and in the presence of endogenous messenger both liver and muscle ribosomes showed an enhancement of [3H]-phenylalanine incorporation of 20% and 54% respectively in controls, and of 32% and 45% respectively in uraemic rats. This study may rule out the influence of acute uraemia on protein synthesis capacity of isolated ribosomes and emphasize the importance of intracellular amino acid availability in altered protein synthesis.

Acute Disease↗

Increased danger of bone marrow damage in simultaneous azathioprine-allopurinol therapy.

Two renal transplant recipients with reversible bone marrow damage in the course of a simultaneous azathioprine-allopurinol therapy are discussed. Anemia, leukocytopenia and thrombocytopenia were found in both patients. Discontinuation of the azathioprine-allopurinol treatment was followed by increase of hematocrit, hemoglobin, erythrocytes, white blood cells and platelets. Interaction of azathioprine and allopurinol seems to be responsible for bone marrow damage in these patients. It can be concluded that the dose of azathioprine should be reduced when allopurinol is given concomitantly.

Adult↗

[Pharmacokinetics of trimethoprim and sulfametrol in patients with end stage renal failure and hemodialysis treatment (author's transl)].

In 6 patients with regular dialysis treatment the pharmacokinetics of intravenously administered trimethoprim and sulfametrol were investigated not only during dialysis procedure but also during the dialysis-free interval. Half-life of the free plasma sulfametrol component is normal even in cases with absent renal function and can be markedly reduced by hemodialysis treatment. The N4-acetylated main metabolite of the sulfonamide is - similar to trimethoprim - hardly dialyzable. Half-life of the latter drug component is prolonged in patients with far advanced renal failure. Due to the excellent dialysanceof the free plasma sulfonamide component the elimination of total sulfametrol is normal during hemodialysis despite cumulation of the N4-acetylated metabolite. Because of the tendency of this metabolite to cumulation, in dialysis patients the compound preparation of trimethoprim and sulfametrol should be used only for trasient treatment of acute infections.

Adult↗

Parenteral nutrition and repeated hemodialysis of bilaterally nephrectomized conscious dogs. I. Experimental model.

The experimental model of the anephric, daily hemodialyzed conscious dog with exclusive nutrition was realized by means of a closed batch hemodialysis system (Rhodial 75) and a highly permeable polyacrylonitrile membrane (RP 6 dialyzer). Technical details, parenteral feeding, hemodialysis, and amino acid solutions preparations were described to realize a stable condition of the animals for further metabolic analyses during the early anephric period.

Amino Acids↗

Parenteral nutrition and repeated hemodialysis of bilaterally nephrectomized conscious dogs. II. Metabolic studies.

To realize equilibrated metabolic conditions after bilateral Nx, three male mongrel dogs were exclusively fed by parenteral infusions with a dog-specific compound of EAA, glutamate, and/or glucose (0.19 g nitrogen and/or 52-70 kcal per kg and day). Daily dialyses required by infusion volumes up to 65 ml/kg/day were performed by means of a closed batch hemodialysis system (Rhodial 75) and highly permeable membranes (RP 6), which allowed a precise ultrafiltration control and direct dialysate analysis. Comparing the urea nitrogen production in a pre- and post-nephrectomy period with a 4 successive days' schedule of only glucose, followed by amino acid administration, a marked decrease of net urea nitrogen excretion was noted after nephrectomy, when EAA were supplied.

Amino Acids, Essential↗

[Alpha 1-antitrypsin level in serum of dialyzed and renal transplant patients (author's transl)].

alpha 1-Antitrypsin in serum was determined by radial immunodiffusion in 30 healthy persons, 18 dialyzed patients and 11 renal transplant recipients with an observation time up to 24 months after surgery. There was no significant difference in serum alpha 1-antitrypsin concentrations in dialyzed patients when compared to the controls (2570 +/- 570 and 2280 +/- 450 mg/l respectively). alpha 1-Antitrypsin concentration increased significantly from the first day after successful renal transplantation, then decreased again 10 days thereafter. Long term follow up controls 3, 6, 12, 18 and 24 months respectively after surgery--with a good renal transplant function--revealed values within the normal range. An acute rejection episode of the transplant was connected with a significant increase of alpha 1-antitrypsin concentration in the serum. Determination of alpha 1-antitrypsin level in serum can be useful in the diagnosis and prognosis of acute renal transplant rejection.

Female↗

Persistent pituitary-thyroid dysfunction patients following renal transplantation.

Pituitary-thyroid function, which is known to be altered in patients with chronic renal insufficiency, has been evaluated after successful kidney transplantation in 36 patients and compared with that in 15 healthy subjects. Thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was in the low range of normal in 24, and markedly decreased in 12 patients (< 0.0005). In the former group serum thyroxine was normal, whereas triiodothyronine was lowered; in the latter group thyroxine, although within the normal range, and triiodothyronine levels were reduced when compared with that of healthy controls. This differential TSH response to TRH was unrelated to kidney transplant function, duration of renal insufficiency or duration of the preceding hemodialysis, or to the dose and dosing schedule of prednisolone therapy. However, a slight negative correlation between the dose of prednisolone administered and TSh responsiveness to TRH as well as serum triiodothyronine was established (P < 0.05). Thus, corticoid treatment may in part be responsible for the alteration in TSH secretion and in the peripheral conversion of thyroxine to triiodothyronine. Other, as yet undefined factors, such as patients' variability in pituitary susceptibility to the polypragmatic therapy administered, have to be suspected as the major causes of the persistent pathological pituitary-thyroid function tests observed after renal transplantation.

Adolescent↗

[Parenteral feeding and urea nitrogen balance after binephrectomy. The hemodialysed dog as an experimental model].

In order to realize equalibrated metabolic conditions after bilateral nephrectomy, 6 male mongrel dogs were exclusively fed by parenteral infusions with a dog specific compound of essential amino acids, glutamate and/or hypertonic glucose (0.19 g nitrogen and/or 52-76 kcal per kg and day). Daily dialyses required by infusion volumes up to 1500 ml/day were performed in the anephric, conscious dogs by means of a closed batch haemodialysis system (Rhodial 75 R-Rh¿one-Poulenc-France) and highly permeable membranes (RP 6 R-polyacrylonitrile-Rh¿one-Poulence-France), which allowed a precise ultrafiltration control, improved tolerance to important ultrafiltration volumes and direct dialysate analysis. Comparing the urea nitrogen production in a pre- and post-nephrectomy period with a 4 successive days schedule of only glucose, followed by amino acid administration, a marked net reduction of nitrogen supply: urea nitrogen excretion ratio to one third was demonstrated after nephrectomy, when amino acid infusions were administrated instead of glucose. After a short review of protein synthesis in acute uraemia, the possible relation of the data provided by this study and the evident clinical benefit of parenteral nutrition in acute uraemia was pointed out.

Amino Acids↗

[Insulin and in vitro protein synthesis of isolated liver ribosomes in experimental acute uraemia (author's transl)].

Liver protein synthesis was shown to be enhanced in acute experimental uraemia, when intracellular amino acids were used as substrate. Since protein synthesis also depends on substrate availability and amino acid concentration is higher in uraemic liver cells, it was of interest to investigate the in vitro protein synthesis capacity of isolated liver ribosomes in the presence of standardized amino acids with and without in vivo insulin stimulation. It was demonstrated that protein synthesis capacity of isolated liver ribosomes remains unaltered in acute uraemia and can be stimulated by in vivo insulin application. Our data suggest that in acute uraemia, intracellular substrate availability plays the essential role in impaired liver protein synthesis.

Acute Disease↗

[Dietary Management of chronic renal failure (author's transl)].

Poor dietary protein intake in chronic uremia decreases plasma urea levels, stabilizes the patients condition, but may induce overall nitrogen balance negativity. Since nutrients protein was classified by its essential amino acid content and therefore its biological value, many attempts were performed in order to lower the protein intake, without marked catabolism. After a short review of the most important diets of low protein and high calories content, the definition of the "protein unit" was pointed out for its practical importance and its variability. The subsequently enhanced patient acceptance of more palatable food, led to striking clinical improvement and stabilization of the uremic condition.

Blood Urea Nitrogen↗