In vitro and in vivo antioxidant activity of ambroxol.

In addition to a mucolytic action, ambroxol has antioxidant and anti-inflammatory properties. The antioxidant effects of ambroxol were studied both in vitro and in vivo. In vitro methods, such as (1) inhibition of hyaluronic acid degradation induced by hydroxy radicals and (2) standard lipid peroxidation assay in rat liver mitochondria and gastric mucosa, induced by tert-butyl hydroperoxide, were used. The in vivo approach was based on the study of the protective effect of pretreatment with ambroxol in a rat model of gastric corpus and antral lesions, induced by indomethacin. The inhibition of the degradation of hyaluronic acid was measured as a change of its viscosity; ambroxol (1,000 microl/l) reduced the degradation by 93%. Lipid peroxidation with tert-butyl hydroperoxide as a source of radicals was followed by the formation of thiobarbituric acid reactive substances. Ambroxol (10 mmol/l) inhibited lipid peroxidation by 96% in the rat liver mitochondria, and by 74% in the gastric mucosa. In vivo, ambroxol was administered p.o. at a dose of 10, 30, and 50 mg/kg, at 5, 30, and 60 min prior to indomethacin administration. The highest inhibition of the number of corpus gastric lesions and lowering of the lesion index (38% and 62%, respectively) was shown after the administration of 50 mg/kg, 30 min before indomethacin administration. Antral lesions were inhibited to a lesser extent by the same dose of ambroxol, administered 30 min before indomethacin treatment. Inhibition of the number of antral lesions reached 27% and the total area of the gastric damage was even larger (the ulcer index reached -5%).

[A heparin-like anticoagulant in a patient with Wegener's granulomatosis]. / Antikoagulans heparinového typu u nemocného s Wegenerovou granulomatózou.

We identified a circulating, heparin-like anticoagulant in a patient with Wegener's granulomatosis. Routine coagulation studies revealed a significant prolongation of the coagulation time, thrombin time, prothrombin time and activated partial thromboplastin time. Thrombin time and activated partial thromboplastin time failed to improve in a 1:1 mixture with pooled normal plasma. Both test were corrected in vitro by addition of protamine sulfate or toluidine blue and in vivo by intravenous administration of protamine sulfate. Recognition of the existence of this or other similar inhibitors in bleeding patients is of value because of the possibility of treatment with protamine sulfate, which neutralizes the anticoagulant.

[Changes in amino acids in a regular dialysis program]. / Aktuální zmeny aminokyselin v pravidelném dialyzacním programu.

BACKGROUND: Dialyzed patients are chronically in a state of negative nitrogen balance, and amino acids, their building stones, are also significantly affected by dialysis. The purpose of the present investigation was to assess whether they should be supplied, how frequently and for how long and how they are influenced by the usual diet of patients. METHODS AND RESULTS: The examination was made in a group of 13 patients included in a regular haemodialysis programme. Their mean age was 53.2 +/- 12.4 years, they were dialyzed for an average period of 55 months, maximum 163 months. The patients were dialyzed three times per week for four hours, bicarbonate dialysate was used. The patients' diet was not modified in any way. A total of 52 haemodialysis were examined: losses of alpha-amino nitrogen were monitored as well as changes of serum concentrations of different amino acids. Their mean losses were 119 +/- 54.69 mmol/4 h: this corresponds to 10.5 +/- 4.8 mg amino acids. The dialysis clearance was on average 122.7 +/- 63.2 ml/min. This value did not differ significantly from the dialysis clearance of urea, but it was significantly higher than creatinine clearance (p < 0.05). During dialysis a significant drop (p < 0.001) of the plasma concentration of amino nitrogen occurred, however, the changes of serum concentrations of amino acids differed. A significant drop was recorded in serum concentrations of histamine, lysine, cysteine, methionine, tyrosine, glycine, asparagine, citrullin, glutamine, taurine. Before the beginning of dialysis the values of valine, lysine, threonine, serine, alanine and asparagine were lower than corresponds to the reference interval in healthy subjects. CONCLUSIONS: Changes of serum concentrations of individual amino acids are significantly influenced not only by their losses into the dialysate but also by their shift from cells into the extracellular fluid and by resorption from the digestive tract during protein intake in the course of dialysis. An adequate supply of high quality protein can compensate for these losses. Investigation of serum concentration of individual amino acids does not record their kinetic changes but can give an idea on the effectiveness of the dietary regime.

[Complications of subclavian and femoral cannulas]. / Komplikace podklíckových a femorálních kanyl.

In the course of 15 years in the author's department some 15,000 cannulas were inserted into the subclavian or femoral vein. This number included cca 2300 cannulas inserted to dialyzed patients. 213 patients (inl. 28 dialyzed) died with the inserted cannula. In these patients the incidence of complications was evaluated. A parietal thrombosis was the most frequent complication and was recorded in 119 cases, i.e. in 56% (in non-dialyzed in 57% and in dialyzed in 50%). In two non-dialyzed patients it was the cause of embolization into the lungs. In the incidence of complications there is no significant difference in dialyzed and non-dialyzed patients. For completeness the authors present a preliminary calculation per approximate number of inserted cannulas during this period. From the total number of 15,000 inserted cannulas fatal complications occurred in 0.06% (in dialyzed in 0.13% and non-dialyzed in 0.047%).

[Controlled clinical study of Consupren versus cyclophosphamide in chronic glomerulonephritis. II. Adverse effects]. / Kontrolovaná klinická studie Consupren versus cyklofosfamid u chronických glomerulonefritid. II. Nezádoucí úcinky.

BACKGROUND: The second part of the study was designed to assess Consupren side effects. METHODS AND RESULTS: The groups of patients studied were described in Part I. Side affects typical of Cy-A were evaluated only in the CS group. Gastrointestinal intolerance, only mild and temporary, was observed in 31%, neurotoxicity in 44%, hypertrichosis in 37%, nephrotoxicity in 25%, and gingival hypertrophy in 19%. Mean values of systolic and diastolic blood pressure did not change significantly in the course of treatment. When changes in blood pressure were individually investigated in particular patients, they were found in 31% in the CS group and in none in the K group. Mean values of uric acid non-significantly increased in the CS group and, on individual investigation, hyperuricaemia was observed in 31%. Mean values of serum potassium did not alter significantly. Signs of possible hepatotoxicity were found in 37% patients of the CS group. In this group, there was a significant decrease in haemoglobin mean values and a decrease in haemoglobin of more than 25 g/l was observed in 44% of CS group patients. In the K group significant decrease in mean leukocyte count was noted, but no patient developed real leukopenia. CONCLUSIONS: The occurrence of side effects was comparable to data known from the literature.

[A controlled clinical trial of Consupren versus cyclophosphamide in chronic glomerulonephritis]. / Kontrolovaná klinická studie Consupren versus Cyklofosfamid u chronických glomerulonefritid.

BACKGROUND: Experience gained from recent studies shows, that Cyclosporine-A (Cy-A) may decrease proteinuria (PU) in some forms of chronic glomerulonephritis (GN) with the nephrotic syndrome. The aim of this study was to test the efficacy of Czech-made Cy-A, Consupren. METHODS AND RESULTS: 30 patients with chronic GN, confirmed by biopsy and PU higher than 3 g/d, corticodependent or corticoresistant, were randomized according to the month of birth to either therapy with Consupren at an initial dose of 5 mg/kg/d (CS group, after dropout of 3 patients who did not finish the treatment, n = 16) or Cyclophosphamide at a dose of 1.5 mg/kg/d (K group, n = 11), and prednisone maintained at the original dose in both groups. The treatment was stopped after six months or after achieving remission. The main criterion of efficacy was PU. The decrease in mean values, statistically evaluated by Holm's procedure was highly significant in the CS group and non-significant in the K group. A similar evaluation of PU corrected by glomerular filtration rate was significant in both groups. Partial or complete remission was reached in 50% of CS group patients and in 34% of K group patients (NS). In the CS group a significant increase in the mean values of albumin and gama-globulin, and a decrease in cholesterol levels were observed. In the K group, these changes were non-significant. CONCLUSIONS: In patients with chronic GN and the nephrotic syndrome, the efficacy of Consupren treatment gives comparable, or even better results versus treatment with Cyclophosphamide.

[Atypical forms of IgA nephropathy]. / Atypické formy IgA nefropatie.

Six cases of a IgA nephropathy were presented that were atypical from the morphological point of view and had less favourable prognosis than a classic form. Immune deposits in glomerular basement membranes were found in all of them. Dominant clinical features were common microscopical hematuria and early proteinuria very conspicuous in several cases.

[Goodpasture's syndrome]. / Goodpastureuv syndrom.

1. The paper summarizes the clinical course, histopathological examinations and immunohistological examinations of 4 personal cases [2 males aged 20 and 26 years, 2 females aged 65 and 18 years] of Goodpasture's pulmorenal syndrome. 2. The characteristic histopathological findings included pulmonary haemorrhage with a focal acute alveolitis and renal lesions that were classed as acute or subacute glomerulonephritis with the finding of scarce multinucleated cells. Such cells are regarded as being of diagnostic value and they are thought to indicate interaction of antibodies with the basement membranes. 3. Immunohistologically, all the cases showed a linear fluorescence following the basement membrane of the interalveolar septa. In 3 of the cases there was linear fluorescence in the glomerular capillary walls. In one case [observation No. 2] who had been hypertensive before death and had had necrotizing arteriitis at postmortem, there was fluorescence of granular type in the kidney believed to indicate the participation of immune complexes in the development of the pathological condition.

[IgA nephropathy]. / Iga nefropatie.

A series of 150 samples of renal tissue obtained by needle biopsy from patients with haematuria were examined immunohistologically. In 15 cases mesangial deposits of IgA were demonstrated. In most cases they were young patients in whom no hypertension, oedema or laboratory findings indicating renal damage could be detected one year later during a follow-up examination. Electron microscopical examination was carried out in the renal tissue of 7 such cases, and showed dense mesangial deposits and a marked subendothelial rarefaction within the basement membrane. The light microscopical findings were variable. Three cases showed minimal lesions, 5 mesangial proliferative glomerulonephritis and 7 mesangial proliferative glomerulonephritis with focal segmental sclerotic alterations within the glomeruli.

[Tuberculosis in patients deceased of renal insufficiency in a long-term hemodialysis program]. / Tuberkulóza u zemrelých s renální insuficiencí v dlouhodobém hemodialyzacním programu.

Eight cases of tuberculosis were seen in a series of patients dying of renal insufficiency after having been subjected to a long-term haemodialysis. In 5 cases Mycobacterium tuberculosis was successfully cultivated (4 were typed as human, 1 as bovine). In 5 cases the disease affected mainly the lymph nodes, not the lungs. In 3 of these a prevalence of abscessing specific granulomas with the presence of leucocytes was noted on microscopical examination. The findings have been regarded as possibly related to an impairment of cellular (lymphocytic) immunity, presumably caused by chronic uraemia or long-term haemodialysis.

[A localized form of metastatic pulmonary calcification in a patient after renal transplantation]. / Lokalizovaná forma metastatického plicního zvápenení u pacienta po renální transplantaci.

A 51-year-old woman with a 20-year history of renal transplantation during the end-stage of chronic renal failure caused by tubulointerstitial nephritis. She died of chronic graft rejection. An interstitial calcification limited to 1. and 2. left segments was encountered as an incidental autoptic finding. There were two unusual microscopic findings, i.e., no involvement of arterioles and larger vessel inclusive veins, and a foreign-body response to some of the calcified tissue.

[Early acute tubulointerstitial nephropathy in transplanted kidneys]. / Casná akutní tubulointersticiální nefropatie transplantované ledviny.

The authors investigated in a group of 124 patients the effect of acute tubular nephropathy and rejection on the period of functional persistence of transplanted kidneys. Transplants which developed tubulointerstitial nephropathy during the first two weeks after transplantation of the kidney had significantly lower cumulative indexes of survival for as long as the second year after transplantation. Grafts which were rejected during the first two weeks after transplantation had a significantly lower cumulative survival index only during the first and second year. The statistical significance was always tested in comparison with grafts where the postoperative course was uneventful. It is better to evaluate the functional prognosis of transplanted kidneys from the maximal achieved glomerular filtration after a load; it did not matter whether tubulointerstitial nephropathy or rejection was involved.

[Calciphylaxis in a patient on long-term dialysis]. / Kalcifylaxe u dlouhodobe dialyzované nemocné.

Calciphylaxis is a special form of soft tissue calcification (in particular blood vessels), affecting specially patients with chronic renal insufficiency and associated secondary hyperparathyroidism. Most severely affected are small arteries with a diameter of 0.2-0.5 mm at the interface of the corium and subcutaneous layer. Calcification of the vascular media with subsequent narrowing of the lumen causes ischaemic changes manifested by the development of painful reddish-violet spots on the skin with necrosis and ulcerations. The authors describe the case of a 73-year-old diabetic female patient with regular dialyzation treatment. The patient developed reddish-violet spots on the lower extremities shortly before admission to hospital. At the site of the spots rapidly progressing necroses developed. The cause of these ischaemic changes were calciphylactic changes confirmed on post-mortem examination and by histological examination.

[Hemorrhage into the digestive tract as a cause of death in patients after kidney transplantation]. / Krvácení do zazívacího traktu jako prícina úmrtí u nemocných po transplantaci ledvin.

The authors investigated the prevalence, cause and possible prevention of haemorrhage into the gastrointestinal tract in 218 patients after transplantation of the kidney (TK). 1. Haemorrhage into the gastrointestinal tract after TK occurred in 32 patients incl. 53.1% who died. In the total mortality after TK haemorrhage into the gastrointestinal tract account for 15.7%. 2. The danger of haemorrhage into the gastrointestinal tract is increased in particular: in the early postoperative period (within one month after transplantation of the kidney), during acute rejection with declining function of the graft, in infectious complications, after graftectomy, in preexisting peptic ulcers. 3. The most frequent cause of haemorrhage were duodenal ulcers. The authors elaborated a system of preventive provisions which involve: a) medicamentous prophylaxis by administration of H2 blockers and antacids not only at the time of transplantation of the kidney and during the early postoperative period but also when there is an increased risk, b) detailed gastroenterological examination before transplantation of the kidney, c) in case of relapsing peptic ulceration in the case-history or haemorrhage into the gastrointestinal tract, subject patients on the waiting list for transplantation of the kidneys during the dialyzation period to proximal gastric vagotomy, or so-called highly selective vagotomy.

[Bone metabolism in patients after kidney transplantation]. / Kostní metabolismus u nemocných po transplantaci ledviny.

The bone metabolism was evaluated in 20 patients after successful transplantation of the kidneys. In case of a functional graft within 22 months after transplantation of the kidneys complete regression of histological signs of secondary hyperparathyroidism was found, i.e. of fibrous osteodystrophy with a decline of the osteoclastic absorption and in 50% of the patients bone histology revealed osteomalacia. On the X-ray of the skeleton in 65% signs of osteoporosis were found, incl. 10% where the results were in discrepancy with the histological finding. The normal plasma calcium level before and after transplantation of the kidney was not affected. Other basic indicators of bone metabolism--phosphates, alkaline phosphatase, the bone isoenzyme of alkaline phosphatase and parathormone attained normal levels within 22 months after transplantation. Bone fluorides remain elevated also after 22 months following successful transplantation of the kidneys, although significantly less than before.

[Determination of urea distribution space on the basis of hemodialysis quantification]. / Stanovení distribucního prostoru mocoviny na podklade kvantifikace hemodialýzy.

By using direct dialysis quantification--DDQ--in 124 haemodialyses made in 14 patients the authors assessed the urea output in mmol in the dialyzation fluid collected after every dialysis. The evaluation of total body fluids, which accounts roughly for 60% of the total body weight, was replaced by a calculated distribution space of urea (Vu) according to the Du/Ppre--Ppost formula. This equation was modified with regard to the degree of ultrafiltration and urea formation. The authors found a 5% difference between the values of the modified Vu equation and total body fluids corresponding to 60% of the body weight.