Emigration of Scientists From Czechoslovakia During the Soviet Domination.

Czechoslovakia was created after the First World War in 1918 as a common state of Czechs, Moravians, and Slovaks. After several transformations, 2 separate republics were established from Czechoslovakia in 1993: the Czech Republic and the Slovak Republic. The objective of this article was to analyze the Prague Spring (1968), the period after the invasion into Czechoslovakia by Warsaw Pact Troops (1968), the period of cruel normalization (1968-1989), and the influence of Soviet domination in the Czechoslovak Republic on people with higher education. The invasion of the Warsaw Pact Troops into Czechoslovakia and the period of normalization had a highly negative impact on the life and work of the Czechoslovak people. Many eminent scientists left the Republic. The reason for this was persecution for their attitude to the situation behind the Iron Curtain. Professor Jan Brod, a world-renowned nephrologist and cardiologist, one of the signatories of the Two Thousand Words Manifesto, emigrated to the Federal Republic of Germany in 1968. Professor William Ganz, a world-renowned cardiologist of Slovak origin, emigrated to the United States in 1966. With Jeremy Swan, he was a coinventor of the Swan-Ganz balloon flotation catheter. Primary reasons for the emigration of scientists from Czechoslovakia was the suppression of the nascent democracy (the Prague Spring in 1968 by the invasion of Warsaw Pact Troops and the continuation of Soviet rule).

Professor Rastislav Dzúrik: the Man and the Scientist.

Rastislav Dzrik, finished his medical study at the Medical School of Comenius University in Bratislava in 1953. After graduation he began to work at the Institute of chemistry and biochemistry of the Medical School and in 1957 he continued working at the IIIrd Internal Clinic of this faculty, which became later the base of "Internal School of Professor T. R. Niederland" with biochemical focusing. In the year 1967 ProfessorDzrik in cooperation with ProfessorJan Brod founded the Nephrological Section of the Slovak Internal Society and then the postgraduate scientific-research activity in nephrology began. The main topics of his scientific activity, in which he received many priority results, were: Isolation and characteristic of inhibitor of glucose utilisation and of inhibitor of renal gluconeogenesis; Effect of "middle molecular substances, especially in the development of renal insufficiency; Isolation and identification of hippurate and pseudouridine. His publishing activity was manifested in more than 500 scientific papers, several monographs and many chapters in various textbooks and manuals of internal medicine and clinical biochemistry, and more than 1,000 citations. The most important success of Professor Dzrik was the textbook "Nephrology which was published in 2004 and he was its main editor. Rastislav Dzriks impact on the field of Nephrology in Slovakia was manifold. It included his complex work of clinical nephrology, his pedagogical activities, and last but not least his excellent organizing abilities.

Associate Professor Eduard Neubauer: the first nephrologist in Slovak Republic.

AssociateProfessor Eduard Neubauer, MD, PhD. worked from 1945 to the end of 1964 at the Department of Internal Medicine of Faculty Hospital and Medical School of P. J. afrik University in Kosice, which was led by Professor Frantiek Pr. During this period he was dealing with clinical and experimental nephrology, as the first in Kosice and in Slovak Republic also. In 1954 he founded the Clinical Nephrological Laboratory according to the model of Prague laboratories led by ProfessorJan Brod. He devoted himself to functional examination of kidneys. He was especially interested in clearance methods in the diagnosis and treatment of renal diseases and hypertension. He published altogether 55 scientific works in domestic and international journals. In December 1964 he left Czechoslovakia and went with his wife to Canada. After retirement he lived in Ottawa, where he died in 1983.

[Plasma and salivary markers of oxidative and carbonyl stress in patients with acute intermittent porphyria]. / Markery oxidacného a karbonylového stresu v plazme a slinách u chorých s akútnou intermitentnou porfýriou.

BACKGROUND: Acute intermittent porphyria (AIP) is an autosomal inherited disease caused by deficiency of the third enzyme in the heme biosynthetic pathway, porphobilinogen deaminase. The clinical course of the disease is characterized by acute attacks, most often with abdominal pain.The aim of our study was to investigate selected markers of oxidative and carbonyl stress in plasma and saliva in patients with AIP and to find out whether saliva could be used for monitoring the disease progression. Saliva is an attractive biological fluid for determination of biochemical markers in various pathological conditions. The advantage is that saliva can be collected non-invasively, and the examination needs only a small volume of saliva. METHODS: Blood and total non-stimulated saliva were collected from 16 patients with AIP in remission, and from 20 healthy individuals. Markers of oxidative and carbonyl stress - advanced glycation end products (AGEs), and thiobarbituric acid reacting substances (TBARS) were determined by spectrofluorometric methods, advanced oxidation protein products (AOPPs), total antioxidant capacity (TAC) and ferric reducing ability of plasma/saliva (FRAP/FRAS) were investigated by spectrophotometric methods in the above mentioned groups. RESULTS: Advanced glycation end products and thiobarbituric acid reacting substances in plasma and saliva were significantly higher in patients with AIP in comparison to the control group (p < 0.001) and (p < 0.05). Advanced oxidation protein products in AIP if compared to the control group did not show statistical significance (p > 0.05), but the levels in the saliva were significantly lower (p < 0.001). The concentrations of markers of antioxidant status of plasma and saliva were significantly lower in AIP if compared to the control group (p < 0.001). CONCLUSIONS: According to the best of our knowledge this is the first study to demonstrate increased concentrations of markers of oxidative and carbonyl stress and decreased antioxidant status of plasma and saliva in patients with AIP. Moreover, the study suggests that the saliva might be a promising fluid to study relevant biomarkers in a wide array of human biomedical conditions.Key words: acute intermittent porphyria - biomarkers - oxidative and carbonyl stress - plasma and saliva.

Renal replacement therapy in acute poisonings--one center experience.

The authors described three groups of patients after acute poisonings. In the first group were 60 patients after carbon tetrachioride poisoning, the second group consisted of 81 patients after mushroom poisoning and 20 patients after ethylene glycol poisoning were in the third group. Besides two patients with rare poisonings after potassium dichromate and after paraquat poisoning were analysed. All groups of patients with the kidney damage were presented from the diagnostic, differential diagnostic, conservative, ntra- and extracorporeal elimination treatment point of view. In the group of patients suffering from acute carbon tetrachloride poisoning and with acute renal failure following therapy was used: conservative treatment, exchange blood transfusion--in 4 patients in hepatic coma, renal replacement therapy (peritoneal dialysis, haemodialysis, plasmapheresis). From the total number of 60 patients 58 survived and 2 patients died in liver coma. Survival of patients after mushroom poisoning depended on amount of oral use of mushroom (Amanita phalloides), on early admission in dialysis centre and on early beginning of renal replacement therapy within 24 hr after acute poisoning. Twenty four patients from 81 patients of this group died. Main clinical signs of ethylene glycol poisoning were various neurological symptoms (cramps, hemiparesis, coma), severe metabolic acidosis (pH = 7.06 +/- 0.14), leucocytosis (26.4 +/- 5.5x 10(9)/L) and the signs of acute toxic hepatitis and of acute renal failure. Calcium oxalic crystals in urine were present in 17 patients and leucocytosis was observed in every patient. In the first 4 patients we administered intravenously ethylalcohol as an antidotum and later in other patients we used ethylalcohol in dialysis solution. The concentration of ethylalcohol in dialysis solution was 100 mg%. Severe metabolic acidosis improved in 17 patients using bicarbonate haemodialysis and 3 patients died before the possibility to use bicarbonate haemodialysis. Eighty-four hours after acute potassium dichromate poisoning and 24 hours after exchange blood transfusion during haemodialysis a 41-year old man died in haemorhagic shock, which developed after the extensive chemical burns of mucous membrane of gastrointestinal tract caused by this poison. Our patient after paraquat poisoning was treated by repeated charcoal haemoperfusion and haemodialysis. Despite of that therapy the patient died in severe respiratory insufficiency.

Professor Frantisek Pór, MD--an outstanding internist in the former Czechoslovakia.

Professor Frantisek Pór, MD, (1899-1980) graduated at the German Medical Faculty of Charles University (GMF-CHU) in Prague in 1926. In January 26, 1945 he was captured, together with his wife, by the Gestapo and they were deported to the concentration camp to Sered' and later to Terezín (Czechoslovakia) from where they were liberated by the Soviet Army on May 8, 1945. He was a founder and the head of the Internal Clinic of the new Medical Faculty in Kosice, from October 1, 1948 until 1971. Professor Pór, MD created a school of internal medicine specialists in Eastern Slovakia and many of his co-workers achieved considerable success in internal medicine in Slovakia. He was the founder of Eastern Slovakian Medical Meetings in Nový Smokovec, in the High Tatras, in 1961, the 50th Meeting was held in 2011. Since 1994 the Medical Society in Kosice has organized an annual Meeting in his memory.

Renal function abnormalities after marathon run and 16-kilometre long-distance run.

Renal functions were investigated in 29 marathon runners and in 20 runners in connection with 16-kilometre long-distance run. Body weight in runners decreased after marathon run in average of 1.3 +/- 0.5 kg and after 16-kilometre long-distance run in average of 1.4 +/- 0.4 kg. Blood pressure decreased after both runs. Total proteinuria and albuminuria significantly increased after both runs. The significant non-glomerular erythrocyturia was found in 9 runners after marathon run and in 3 runners after 16-km long-distance run. Total catalytic activity of serum creatine kinase, and its isoenzyme MB significantly increased after both runs. Increase of isoenzyme MB creatine kinase after runs was lower than 6% of total catalytic activity of creatine kinase. These increases were caused by rhabdomyolysis and were connected with myoglobinuria. Serum myoglobin significantly increased after marathon run and after 16-km run. Serum urea, creatinine, phosphorus and osmolality significantly increased after both runs. Calculated GFR significantly decreased after both runs. FE(Na), FE(Ca), FE(P), FE(OSM) and FE(H2O) significantly decreased after both runs. FE significantly increased after marathon run, but after 16-km run non-significantly decreased. Renal function abnormalities were caused by dehydration, microtraumas in extrarenal urinary tract, protein catabolism, decreased urinary excretion of osmotically active substances, rhabdomyolysis, activation of renin-angiotensin-aldosterone system and other factors. Renal function abnormalities in runners were already not present 2-6 days after marathon run and after 16-kilometre long-distance run and investigated parameters were in normal range or they did not significantly differ from the initial values.

Kidney damage in acute intermittent porphyria.

BACKGROUND: Acute intermittent and variegate porphyria are an autosomal dominant hereditary diseases caused by the deficient activity of porphobilinogen deaminase in the haem biosynthesis. Acute intermittent porphyria (AIP) in 11 patients (8 women and 3 men) and variegate porphyria (VP) in one patient were diagnosed and long-term treated during 15-22 years. Eleven patients had in acute attack abdominal pain, they were agitated and restless and suffered from insomnia. Besides they had various neurological signs. Examination of kidney function during remission showed hypertension and tubulointerstitial impairment of the kidneys in 10 patients (hyposthenuria and impairment of tubular excretory phase in isotopic renography). Deficiency of serum erythropoietin in 4 patients, significant deficiency of plasma and erythrocyte vitamin B6, significant hyperoxalaemia and hyperoxaluria in all patients were found. Direct relationship between plasma oxalic acid and effect of pyridoxal-5-phosphate (PLP), (effect of PLP was in indirect relationship with the concentration of erythrocyte vitamin B6), in AIP patients was found. Deficiency of vitamin B6 was probably a cause of hyperoxalaemia and hyperoxaluria in those patients. The effective therapy was repeated i.v. administration of haem-arginate during acute attacks (4-5 days). Besides during remission the patients were treated by pyridoxine (40-60 mg/day), by glucose, sodium chloride and phenothiazines. All patients showed significant improvement and had regular ambulatory check-up every three months. Currently, they are in clinical and laboratory remission.

Vitamin B6 and oxalic acid in clinical nephrology.

OBJECTIVE: Vitamin B(6) (VB(6)) is a water-soluble vitamin, which is important for the normal functioning of multiple organ systems. It is metabolized to the active molecule pyridoxal-5-phosphate (PLP). Oxalic acid (OA) is thought to be a uremic toxin that participates in the pathogenesis of the uremic syndrome. The objectives of this study were as follows: (1) to evaluate the plasma and erythrocyte VB(6) (effect of PLP; effect of PLP was in indirect relationship with the concentration of erythrocyte VB(6)), and plasma and urinary OA in marathon runners, in patients with acute intermittent porphyria (AIP) and variegate porphyria, and in patients with stage 1 chronic kidney disease (CKD), chronic glomerulonephritis and nephrotic syndrome (CGNS); (2) to examine the influence of water diuresis in healthy subjects, and the influence of sodium diuresis (high sodium intake) and an intravenous administration of furosemide on the urinary excretion of VB(6) and OA in CKD stage 3-4 patients; and (3) to evaluate the influence of erythropoietin treatment on erythrocyte VB(6) (effect of PLP) in hemodialysis (HD) patients, and the influence of continuous ambulatory peritoneal dialysis (CAPD) therapy on plasma VB(6) and OA and their peritoneal clearance and transfer. DESIGN AND SETTING: This study was conducted at the Nephrological Clinic of L. Pasteur Faculty Hospital and of Medical School of P. J. Safarik University. A combination of 29 marathon runners, 15 patients with CG and NS, 11 patients with AIP, 1 patient with variegate porphyria, 15 healthy subjects, 27 CKD stage 3-4 patients, 30 HD, and 27 CAPD patients were used in the study. RESULTS: After a marathon run, plasma and erythrocyte VB(6) significantly decreased and plasma OA increased. Plasma (15.5 +/- 3.8 nmol/L) and erythrocyte VB(6) (effect of PLP: 42.1% +/- 7.5%) were decreased and plasma OA (9.8 +/- 2.3 micromol/L) was significantly elevated in patients with CGNS and stage 1 CKD. In patients with AIP, deficiency of plasma (24.3 +/- 5.2 nmol/L) and erythrocyte VB(6) (effect of PLP: 46.2% +/- 7.0%) and hyperoxalemia (9.39 +/- 2.5 micromol/L) were present. The urinary excretion of VB(6) and of OA during maximal water diuresis and after intravenous administration of furosemide increased significantly (P < .01), but was not affected by the high intake of NaCl (P > .05). Erythropoietin treatment in HD patients led to the erythrocyte VB(6) deficiency. This finding is an indirect evidence that erythrocyte VB(6) is consumed by the hemoglobin synthesis much more during EPO treatment. In CAPD patients, plasma value of VB(6) (127.3 +/- 66.9 micromol/L) was in the normal range and plasma OA (23.6 +/- 7.4 micromol/L) was significantly elevated. Mean value of peritoneal clearance of VB(6) was 8.8% and of OA was 76.9% of urea clearance. CONCLUSION: Our study indicates that deficiency of VB(6) led to hyperoxalemia and hyperoxaluria in patients with CKD. Deficiency of VB(6) in CKD stage 4-5 patients potentiates the uremic hyperoxalemia and hyperoxaluria.

Nephrology and Doctors Honoris Causa at P. J. Safárik University in Kosice in the years 1993-2006 (Slovak Republic).

The authors present a brief history of the activities of 7 important and well-known foreign nephrologists in Kosice and in the region of Eastern Slovakia who were awarded the honorary title Doctor Honoris Causa by P. J. Safárik University in Kosice. The above-mentioned professors presented their papers as guest professors to the students of the Medical Faculty of P. J. Safárik University and in meetings of medical societies and at many symposia and congresses with international participation in the region of Eastern Slovakia. All of the awarded nephrologists have visited the Faculty Hospital of L. Pasteur, the Fourth Internal Clinic and the Nephrological Clinic. During their stays, they stimulated the thinking of researchers in other metabolic studies within clinical nephrology and toxicology. In addition they contributed to the establishment in 1997 of the Nephrological Clinic of the Medical Faculty of P. J. Safárik University and the Faculty Hospital of L. Pasteur, the first one of its kind in the Slovak Republic.

Vitamins and quality of life in hemodialysis patients.

BACKGROUND: Dialysis patients have decreased quality of life compared to healthy controls. In recent years the quality of life in hemodialysis patients has been considered from many points of view. The aim of this retrospective study was to improve quality of life in dialysis patients by supplementing some important vitamins. PATIENTS AND METHODS: Eighty-three patients underwent hemodialysis treatment 3 x 4 hr/weekly using a standard dialyzer with a cellulose membrane. During the investigation of plasma and erythrocyte vitamin E, vitamin E-coated dialyzer was used. Patients who were treated with erythropoietin (EPO) were supplemented over 3 months with Pyridoxine: 20 mg/day, folic acid: 10 mg/week, vitamin C: 60 mg/day. Some erythrocyte and plasma vitamins and plasma malondialdehyde were investigated in all patients. Erythrocyte vitamin B6 was determined by indirect enzymatic method as an effect of pyridoxal-5-phosphate (PLP). Erythrocyte folic acid was determined by radioimmunoassay method, erythrocyte vitamin E and plasma malondialdehyde were determined by fluorometric methods, plasma vitamin C was determined by spectrophotometric method. RESULTS: During above mentioned EPO treatment and supplementation, vitamins significantly increased blood hemoglobin (from 100+/-5 to 110+/-4 g/L, p<0.05), erythrocyte vitamin B6 that means decreased effect of PLP (from 30.4+/-2.4 to 16.4+/-1.9%, p<0.01), increased erythrocyte folic acid (from 343.3+/-72 to 734.5+/-98 ng/mL) and plasma vitamin C (from 63.5+/-15 to 88.3+/-10 micromol/L). Three-month use of vitamin E-coated dialyzer led to the increase of erythrocyte vitamin E (from 6.7+/-0.5 to 7.4+/-0.4 micromol/L, p<0.05) and to the significant decrease of plasma malondialdehyde (from 2.8+/-0.5 to 2.2+/-0.4 micromol/L, p<0.01). CONCLUSIONS: 1. Investigated vitamins were decreased in hemodialysis patients and after supplementation increased to normal range. 2. Increased plasma malondialdehyde, as a product of lipid peroxidation, significantly decreased during the use of vitamin E-coated dialyzer. 3. Adequate supplementation of above mentioned vitamins led to increased quality of life in hemodialysis patients from some clinical points of view.

Oxalic Acid as a uremic toxin.

OBJECTIVE: Oxalic acid (OA) is thought to be a uremic toxin that participates in the pathogenesis of uremic syndrome. The objectives of this study were to: (1) evaluate the plasma levels of OA in patients with chronic renal disease with various levels of glomerular filtration rate and after renal transplantation; (2) investigate the salivary secretion of OA and ascorbic acid in healthy subjects and in patients with chronic renal failure (CRF); (3) examine the influence of water and sodium diuresis and furosemide administration on the urinary excretion of OA and ascorbic acid in healthy subjects and in CRF patients without dialysis treatment; and (4) evaluate the influence of renal replacement therapy (RRT) on secondary hyperoxalemia in hemodialysis patients. DESIGN AND SETTING: This study was conducted at the Nephrological Department of P.J. Safárik University. Sixty-one patients with chronic renal disease, 64 CRF patients, 32 continuous ambulatory peritoneal dialysis (CAPD) patients, 15 hemodialysis patients, 21 patients after renal transplantation, and 15 healthy subjects were examined. Maximal water diuresis, diets with low (2 g/day) and high (15 g/day) sodium intake, administration of intravenous furosemide (20 mg), and renal replacement therapy (CAPD, hemodialysis, hemofiltration, and postdilution hemodiafiltration) were utilized in the study. RESULTS: In patients with chronic renal disease and those after renal transplantation, direct relationships between plasma OA and serum creatinine were found (r = 0.904 and 0.9431, respectively, P < .01). Despite a high level of plasma OA in uremic patients (23.1 +/- 10 micromol/L), there was no significant difference in salivary OA between control subjects (128 +/- 19 micromol/L) and CRF patients (135 +/- 24 micromol/L). The urinary excretion of OA during maximal water diuresis (from 37.5 to 110.3 micromol/4 hours) and after intravenous furosemide (from 34.5 to 66.7 micromol/3 hours) increased significantly, but was not affected by high intake of NaCl. The most significant decrease of plasma OA was observed during postdilution hemodiafiltration (63.3%). CONCLUSION: Our study indicates that renal replacement therapy is not effective for a permanent reduction of elevated plasma levels of OA.

The 50-year history of the Nephrology Department in Kosice (Slovak Republic).

The authors present the development of clinical nephrology from 1954 to 2004 at the Louis Pasteur Faculty Hospital and the Medical Faculty of P.J. Safárik University in Kosice (Slovak Republic), recounting its role in the delivery of preventive and therapeutic care, teaching and research. On October 24, 1997 a Nephrology Clinic was established, the first in the Slovak Republic. This led to the further qualitative development of nephrology not only in Kosice but in the whole Slovak Republic.

Vitamin E-coated dialyzer and antioxidant defense parameters: three-month study.

Atherosclerotic cardiovascular disease is the most frequent cause of death in patients with end-stage renal disease who have undergone dialysis treatment. Oxidative stress, increased lipid peroxidation, and impaired function of antioxidant systems may contribute to the accelerated development of atherosclerosis in chronic renal failure patients during renal replacement therapy. The aim of this study was to investigate the influence of a vitamin E-coated dialyzer on antioxidant defense parameters in hemodialysis (HD) patients. In 14 HD patients, hemodialysis was performed using a vitamin E-coated dialyzer (Terumo CL-E15NL; Terumo Corporation, Tokyo, Japan) during a 3-month study. In these patients, erythrocyte (ER) antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR) and catalase (CAT), plasma total antioxidant capacity (TAC), RBC glutathione (GSH), plasma malondialdehyde (MDA), plasma, and RBC vitamin E were investigated. Each parameter was measured at the beginning of the study, after the 1st, 2nd, and 3rd month of the study, and 10 weeks after the interruption of the use of vitamin E-coated dialyzer. All HD patients were treated by erythropoietin (EPO) and received vitamin C 50 mg/d, pyridoxine 20 mg/d, and folic acid 5 mg/wk during the entire study. The 3-month treatment with the vitamin E-coated dialyzer led to a significant decrease of plasma MDA level (from 2.85 +/- 0.44 to 2.25 +/- 0.37 micromol/L) and to an increase of plasma TAC, RBC, GSH, and the vitamin E levels both in plasma (from 25.9 +/- 2.8 to 33.6 +/- 3.8 micromol/L) and in the RBCs (from 6.7 +/- 0.8 to 7.4 +/- 0.7 micromol/L) by 30% and 10.5%, respectively. Ten-week interruption of the use of the vitamin E-coated dialyzer led to near initial values of MDA (2.90 +/- 0.28 micromol/L), plasma (28.6 +/- 3.5 micromol/L), and RBC (6.9 +/- 0.7 micromol/L) vitamin E and of other investigated parameters. Statistical analysis of results was performed by conventional methods and analysis of variance. The findings of the current study confirm the beneficial effect of the vitamin E-coated dialyzer against oxidative stress in HD patients.