Renal function and tubular phosphate handling in long-term cyclosporine- and tacrolimus-based immunosuppression in kidney transplantation.

The aim of the study was to assess impaired tubular phosphate reabsorption and renal function among patients on cyclosporine- or tacrolimus-based immunosuppression for 2 years after kidney transplantation. Among 60 cadaveric kidney allograft recipients observed for 48 months, 40 received cyclosporine, azathioprine, and prednisone (group A and B). Group C consisted of 20 patients receiving tacrolimus with steroid withdrawal at 3 months after transplantation. Renal function and calcium-phosphate metabolism-iPTH, 25-OHD, 1,25(OH)(2)D concentration, phosphate reabsorption (TRP; mmol/L), and tubular maximum phosphate reabsorption per glomerular filtration rate (TmPO(4)/GFR; mmol/L)-were assessed at 1, 6, 12, 18, and 24 months (groups A and C) or 24, 30, 36, 42, and 48 months (group B). Renal function after 24 months of observation was significantly better among tacrolimus-treated patients (serum creatinine concentration mumol/L; C: 94.6 +/- 16.8 vs A: 110.5 +/- 22.1 vs B: 121.1 +/- 30.9; P < .05). Among tacrolimus-treated recipients, TRP and TmPO(4)/GFR remained within normal values during the whole observation period. In groups A and B, TRP improved during the first year of observation; after 2 years it reached values observed in group C (TRP: A: 0.67 +/- 0.1; B: 0.72 +/- 0.13; C: 0.76 +/- 0.07; P = NS), whereas TmPO(4)/GFR remained low in group A after 2 years (A: 0.78 +/- 0.19; B: 0.91 +/- 0.25; C: 0.94 +/- 0.15; P < .05). Tacrolimus-treated patients exhibit significantly faster recovery from tubular phosphate reabsorption impairment compared with cyclosporine-treated recipients. Tacrolimus-based immunosuppression led to better kidney allograft function during 2-year observation.

Tacrolimus decreases tubular phosphate wasting in renal allograft recipients.

The aim of the study was to elucidate whether cyclosporine- and tacrolimus-based immunosuppression impairs tubular reabsorption of phosphate after kidney transplantation. Sixty cadaveric allograft recipients were included in the study. Forty patients receiving triple immunosupression with cyclosporine, azathioprine, and prednisone were studied for 1, 6, 12 months (groups A1 and A2, 20 patients) and for 24, 30, and 36 months (groups B1 and B2, 20 patients) after transplantation. Twenty patients who received tacrolimus with steroid withdrawal after 3 months were included in the study (group C). Recipients from groups A2 and B2 were treated additionally with vitamin D and calcium carbonate. Serum iPTH, 25-OHD, 1.25(OH)(2)D concentrations were determined, and TRP (mmol/L) and TmP/GFR (mmol/L) were calculated using Walton-Bijvoet nomogram. Higher values of total calcium serum concentration in group A were detected. Lower inorganic phosphate serum concentrations were detected in groups A and C, in contrast to group B where they remained within normal values. TmP/GFR values were significantly higher in group C in the first and third examination in comparison with patients of group A. Moreover, TRP index values were significantly higher than analogous values of groups A and B. Tacrolimus-treated patients exhibit significantly faster recovery from tubular phosphate reabsorption impairment compared to cyclosporine-treated recipients. No correlation between iPTH, 25-OHD, 1,25(OH)(2)D concentration, and tubular dysfunction parameters was observed. Amelioration of phosphate handling, in spite of hyperparathyroidism intensity, can follow early steroid avoidance.

[Relationship between the physiochemical properties of asbestos and pulmonary fibrosis]. / Zaleznosc miedzy wlasciwosciami fizykochemicznymi azbestu a zwlóknieniem tkanki plucnej.

The work presents a review of the literature on the effect of physiochemical properties on the intensity of pulmonary fibrosis. Exposure to asbestos fibres induces inflammatory processes which contribute to collagen deposition in the lung tissue. The toxicity of asbestos fibres depends on physiochemical properties of asbestos. Owing to their advantageous aerodynamics, straight needle-like amphiboles can penetrate much easier into the pulmonary tissue than curly serpentine fibres. With magnesium as its main cation, chrysotile has an unstable structure and tends towards the fragmentation into smaller particles. Therefore, its phagocytosis by macrophages and its clearance from the lung tissue are more effective than those of amphiboles. On the other hand, chrysotile undergoes longitudinal fragmentation into thin elementary particles, thus, it proliferates easier respirable fibres in the pulmonary tissue. Fibrosis induced by long fibres (L < 5 microns) is more extensive than that produced by short fibres (L < 5 microns) because of incomplete phagocytosis by macrophages which releases a stimulus to the synthesis of fibronectin and collagen.

[The role of pulmonary macrophages in the development of pulmonary fibrosis caused by asbestos]. / Udzial makrofagów plucnych w procesie zwlóknienia pluc wywolanego pylem azbestowym.

The role of alveolar and interstitial macrophages in asbestos-induced pulmonary fibrosis is discussed. Asbestosis is thought to result from a series of cellular interaction involving the pulmonary macrophages and lung fibroblasts. Inhaled asbestos fibres activate serum complement-dependent chemoattractant for macrophages which accumulate at alveolar duct bifurcations playing a central role in phagocytosis fibers and forming early pulmonary lesions. After phagocytic stimulation macrophages release various chemotactic factors for neutrophils and other inflammatory cells including TNF, neutrophil chemotactic factor and many proinflammatory mediators such as prostaglandins, leukotrienes, thromboxane. Apart from that, macrophages produce free radical oxygen and release lysosome enzymes which may cause lung tissue injury. There is also concomitant accumulation of fibroblasts proliferating in response to macrophages-derived growth factors, interleukin-1 and fibronectin. As a result of those processes collagen production increase and pulmonary fibrosis develops.

[Contribution and role of polymorphonuclear leucocytes in inflammatory reactions of asbestosis]. / Udzial i rola granulocytów obojetnochlonnych w reakcji zapalnej w azbestozie.

The mechanism of lung fibrosis after asbestos exposure is unknown. Observations suggest that neutrophils may play a role in the development of the lung injury in asbestosis. They are attracted to the lungs by macrophages mediators and there they phagocyte asbestos fibres. A cytotoxic effect of asbestos exerted on polymorphonuclear leucocytes releases proteolytic enzymes such as collagenase and elastase. Besides, asbestos produces highly reactive oxidants in neutrophils responsible for an additional damage of tissues. However, the role of polymorphonuclear leucocytes in pathogenesis of asbestosis still remains controversial.

[The role of pulmonary epithelial cells in lung cellular reaction to asbestos exposure]. / Rola komórek nablonkowych w odpowiedzi biologicznej tkanki plucnej na pyl azbestu.

The damage of pulmonary alveolar epithelial cells occurs in many inflammatory conditions caused by various agents, e.g. asbestos, that involve interstitial lung disease in experimental animals and in humans. After exposure to asbestos alveolar epithelial cells contain significant amount of asbestos fibers and show histologic changes which indicate a marked epithelial injury. The alveolar epithelial injury is manifested by swelling, debris and patchy necrosis of type I cells partly detached from its basement membrane. Besides, regenerative hyperplasia of type II pneumocytes with ultrastructurally cisternal dilation of the rough endoplastic reticulum and significantly greater number of lamellar bodies are found. Following the cessation of exposure, epithelial cells are cleared out of asbestos fibers and return to the normal condition. These data provide insight into pathogenesis of diffuse lung disease and the role of alveolar cells in early and late phases of asbestosis.

[Concentration of acute phase proteins in serum of children with rheumatoid arthritis]. / Stezenie bialek ostrej fazy surowicy u dzieci z reumatoidalnym zapaleniem stawów.

An attempts was made at evaluation of the changes of acute phase proteins-seromucoid (BRS), alpha 1-acid glycoprotein (alpha 1-AGP), alpha 1-antitrypsin (alpha 1-AT), haptoglobin (Hp), C3 protein of complement system (C3), C1 esterase inhibitor (C1-INH), and transferrin (Tf) in the serum of children with rheumatoid arthritis. The patients were divided into clinical and age groups. The studies carried out have shown in ill children increase of BRS, alpha 1-AGP, alpha 1-AT, Hp, and C1-INH levels, During remission increased levels of alpha 1-AGP and Hp persisted. In the studied clinical groups a positive correlation was found between the intensity of changes of the studied indices and the degree of disease activity. In the age groups greater increase of the levels of the studied acute phase proteins was found in the group of preschool children and the group of puberty spurt. The obtained results suggest that the determination of acute phase proteins may be useful in laboratory investigation of children with rheumatoid arthritis.

[The role of oxygen free radicals in asbestos cytotoxicity]. / Rola rodników tlenowych w cytotoksycznosci azbestu.

Despite numerous experiments, the cytotoxicity of asbestos is still far from being well understood. There is an increasing evidence which supports the contribution of free oxy-radicals resulting from the phagocytosis of asbestos fibres concerning macrophages neutrophils, pulmonary epithelial and endothelial cells. Both in vitro and in vivo studies revealed an asbestos-induced generation of hydrogen peroxide, hydroxyl radical and superoxide anion. The intensity of the process varies with the physico-chemical properties of the asbestos fibres. Oxygen free radical activity accounts for the lipid peroxidation of cell membranes as well as for the damage of structural proteins and DNA. However, the cells contain antioxidant enzymes such as catalase, superoxide dismutase, etc., which prevent the toxic effect of oxidants. Their activity increases when the cells are exposed to asbestos.

Serum peptide III-procollagen and ACE in asbestos workers.

Type-III-procollagen peptide (P-III-P) concentration and angiotensin-converting-enzyme (ACE) activity were measured in the serum of asbestos workers. The subjects were classified into four groups (A, B, C, D) according to the duration of exposure (in years). A gradual increase of ACE activity in group B and P-III-P concentration in group C was found. The increase in ACE activity can be regarded as the response to the progressing inflammatory state, and the increase in P-III-P concentration may be related to the fibrosis of the lung tissue.

Serum levels of certain trace elements (Ag, Co, Cr) in healthy subjects (part II).

In 95 healthy subjects including 55 women and 40 men the serum levels of Ag, Co and Cr were determined by means of neutron activation analysis using the method of gamma spectrometry without separation of different elements from the sample. It was found that people aged over 60 years had higher serum silver levels than younger subjects. In women a statistically significantly higher serum cobalt level was demonstrated in relation to men. Men and women aged over 60 years had serum chromium levels very similar while women aged below 60 years had lower serum chromium levels.

Serum levels of certain trace elements (Cu, Au, Mn) in healthy subjects (Part I).

In 95 healthy subjects of either sex the serum concentrations of Cu, Au, and Mn were determined by means of neutron activation analysis (NAA). It was found that copper concentration in the serum of healthy subjects increased with age up to 70 years of life. In subjects aged below 60 years a higher gold level was demonstrated in the serum than in the subjects aged above 60 years. Serum manganese level was higher in men than in women.

Effects of lead, copper, and zinc on the rat's lactate dehydrogenase in vivo and in vitro.

Following subacute intoxication of rats with Pb-, Cu-, and Zn-salts (separately or in mixture) for 5 weeks, the chelating agent D-penicillamine was administered for 3 weeks. In the course of the 3-month experiment, lactate dehydrogenase (LDH) was estimated in serum and in cytoplasmic fraction of the kidney. Pb2+ treatment resulted in an increase of LDH activity, Cu2+ in a slight decrease, whereas Zn2+ had no effect, respectively. Mixture of these metals caused a significant rise in the enzymatic activity. Seven weeks after the stoppage of the administration of toxic substances, altered LDH activity, both in serum and in kidney returned to normal. D-penicillamine treatment was found to accelerate a restoration of the enzyme activity. In the experiments in vitro, Cu2+ inhibited significantly the kidney LDH activity, Pb2+ and Zn2+ being 100- and 400-times less efficient, respectively. Cu2+ inhibition was reversed by D-penicillamine, whereas inhibition of LDH by Zn2+ or Pb2+ was irreversible.

Biochemical studies on populations with long- or short-term exposure to environmental pollution.

Three groups of populations were studied: I. living for about 10 years, II. living for about 3 years near copper smelteries, and III. living in rural area, far from any source of air pollution. Lead content in blood was found to be 182.0 and copper 274.6 microgram/100 ml for group I, Pb - 69.2 and Cu - 253.3 microgram/100 ml for group II, and Pb - 43.8 and Cu - 143.3 microgram/100 ml for group III. Inhibition of glycolytic cycle enzymes and delta-aminolevulinic acid dehydratase was proportional to the duration of exposure to environmental pollution. Ceruloplasmin concentration in serum, as well as serum and red cells aminotransferases activities, were increased in group II and decreased in group I, suggesting certain mechanism of adaptation.