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P Benes

Publications and source records attributed to P Benes.

At least 19 recordsLinked to original sources

Detection of procathepsin D in rat milk.

The presence of procathepsin D, a zymogen of the soluble lysosomal aspartic proteinase cathepsin D, was detected in rat milk using Western blot analysis and assay of proteolytic activity in acidic buffers. No other forms of cathepsin D were found. Two different polyclonal anti-procathepsin D antibodies were used for immunochemical detection of procathepsin D. Both antibodies we found to recognize rat procathepsin D. Proteolytic activity in acidic buffers was detected using a fluorogenic substrate specific for cathepsin D and was abolished by pepstatin A, a specific inhibitor of aspartic proteinases. This study represents third demonstration of presence of procathepsin D in mammal breast milk. Potential sources and physiological functions are discussed.

Amino Acid Sequence↗

Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: a randomized, double-blind, placebo controlled study.

We conducted a controlled, double-blind study of parenteral glutamine supplementation in an unselected group of consecutive autologous transplant patients. Patients received 30 g of alanyl-glutamine dipeptide (Dipeptiven; Fresenius-Kabi, Bad Homburg, Germany) or glutamine-free amino acid solution i.v. from day +1 to day +14 or to discharge. All patients were assessed for clinical status, mucositis, blood counts, oral intake and immune reconstitution. Parenteral nutrition was administered according to predefined guidelines. Forty patients were randomized; 21 into the glutamine and 19 into the placebo arm. Glutamine patients had less days with diarrhoea (3.3 +/- 4.0 vs 4.3 +/- 3.0, P = 0.03), but they had more severe oral mucositis (mean 4 +/- 4.7 vs 1.4 +/- 2.3 days of mucositis score >13, P = 0.04), spent more days on opioids (mean 3.5 +/- 4.2 vs 1.2 +/- 2.2 days, P = 0.03) and left hospital later than placebo patients (mean 13.5 +/- 3.1 vs 11.7 +/- 2.4 days after transplant, P = 0.06). There were more relapses (P = 0.02) and deaths (P = 0.05) in the glutamine group. The cost of supportive care (mean 2960 +/- 1694 vs 1534 +/- 513 Euro, P = 0.002) was also greater for glutamine patients, mainly due to the cost of glutamine dipeptide itself. The described mode and dosage of glutamine administration did not produce meaningful benefit in our autologous transplant patients and it was certainly not cost-effective.

Adult↗

Plasminogen-activator-inhibitor-1 promoter polymorphism as a risk factor for adult periodontitis in non-smokers.

Periodontal diseases belong to the most common chronic disorders affecting mankind. Smoking and impaired plasminogen activation with hypercoagulation and fibrinolysis inhibition have been proposed as having a role in predisposition to these diseases. We investigated relationships among adult periodontitis, smoking, and a variation in the deletion/insertion (4G/5G) promoter polymorphism of the plasminogen-activator-inhibitor-1 (PAI-1) gene in 304 Caucasian subjects. An association was detected between the deletion (4G) allele (and 4G/4G genotype) and periodontitis (P = 0.0022, P(corr) < 0.01; P = 0.014, P(corr) < 0.05). A stronger association occurred in non-smokers (P = 0.00021, P(corr) < 0.01; P = 0.0024, P(corr) < 0.05) where the presence of the PAI-1 gene 4G allele appears to be one of the risk factors for periodontitis.

Adult↗

[Effect of parenteral glutamine on restoration of lymphocyte subpopulations after high-dose chemotherapy and autologous hematopoietic cell transplantation: data from a double-blind randomized study].

Within the framework of a randomized double blind study focused on the effect of glutamine on the clinical course of autologous transplantation of peripheral cells the authors assessed lymphocyte sub-populations (CD3, CD4, CD8, CD19 and CD57+ cells) before transplantation and 14, 28 and 42 days after transplantation. A total of 36 patients were investigated (18 glutamine, 18 placebo). In the whole group of patients the authors found restoration of CD4 and CD19 cells to pretransplantation values one day +42 after transplantation, in CD8 and CD57 cells a statistically significant increase as compared with the pre-transplantation state occurred. In the glutamine group they observed on day +28 a more rapid restoration of CD8 and a marginally better restoration of CD19 positive cells, while patients who were given placebo restored CD57+ cells more rapidly. All these differences were balanced on day +42, only CD19+ cells were at that time marginally higher in the placebo group. With the exception of CD19+ lymphocytes the authors observed weak correlations between the number of lymphocytes on day +42 after transplantation and the number of transplanted CD34+ cells. It may thus be stated that the drop of lymphocyte sub-populations has a short-term character, the restoration correlates among others with the administered amount of haematopoietic cells. Significant importance of glutamine for the restoration of the lymphocyte sub-population was however not proved.

Adult↗

[Parenteral glutamine does not improve the nutritional status in patients during high-dose chemotherapy and autologous peripheral stem cell transplantation].

BACKGROUND AND AIM: High-dose chemotherapy is aggressive treatment modality adversely affecting both energy/protein demands and oral intake/resorption of nutrients. Aminoacid glutamine is known for its' proteoanabolic effect and as an energy source for enterocytes and immune system. Nutritional parameters have been studied in a controlled, randomised, double-blinded trial of parenteral glutamine supplementation of autologous stem cell transplant patients. METHODS: Forty consecutive patients with haematological and solid cancer and multiple sclerosis were treated from 1999 to 2001 by high-dose chemotherapy with autologous stem cell transplantation. Patients were randomly assigned either for parenteral administration of 30 g of alanyl-glutamine dipeptide (Dipeptiven, Fresenius-Kabi) or isonitrogenous glutamine-free amino acid solution from day +1 to day +14 or to discharge from hospital. Patients were closely monitored from admission to day +100. Nutritional parameters included: oral dietary intake, body weight, body composition, energy expenditure, concentration of serum proteins and nitrogen balance. Parenteral nutrition in dose of 26.5 kcal/kg and 1 g of aminoacid/kg was given to patients who did not reach adequate oral intake for 5 days and withheld after three consecutive days of adequate intake. RESULTS: Nutritional assessment on admission differed according to the method used but no parameter of nutrition predicted the clinical course of treatment. Inadequate oral intake period lasted (mean +/- SD) 6.8 +/- 5.9 days, average length of stay being 17.5 +/- 3.9 days. Patients were unable to use sipping of enteral feed. Resting energy expenditure neither on admission nor in critical period differed from predicted value. Serum protein concentrations significantly decreased on discharge with normalisation as soon as to day +28, correlating inversely with changes in extracellular water content. Nitrogen urine loss was 10-16 g/day. Only 42.5% of patients were treated with parenteral nutrition. Cumulative nitrogen balance at day +9 was -30.7 +/- 24.1 g N. Body weight at day +28 significantly decreased (-2.94 +/- 4.4 kg), mostly consisting of loss of pure body cell mass. Glutamine supplementation did not improve any of the listed nutritional parameters. CONCLUSIONS: High-dose chemotherapy with autologous stem cell transplantation causes proteocatabolism of medium severity. Nutritional status of patients cannot be improved by the mode and dosage of parenteral glutamine used in our study. Optimal nutritional monitoring and treatment for this group of patients is suggested.

Adult↗

Methylenetetrahydrofolate reductase polymorphism, type II diabetes mellitus, coronary artery disease, and essential hypertension in the Czech population.

Increased plasma concentrations of homocysteine have been found in patients with coronary artery disease (CAD) and essential hypertension (EH) and in patients with diabetic complications. The 677C/T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism is related to the MTHFR enzyme activity and to the plasma homocysteine concentration. This study was designed to investigate an association of this polymorphism with CAD, EH, and type II diabetes mellitus in the Czech population. The MTHFR genotypes were assessed by the polymerase chain reaction-based methodology in a sample of 1199 unrelated Caucasian subjects with CAD, EH, type II diabetes, or a combination of these diseases, and in healthy subjects. Allele frequencies of the MTHFR polymorphism differed considerably between women with and without type II diabetes mellitus (P = 0.00069), with a higher frequency of the C allele in the diabetic women. In addition, the MTHFR T allele frequency was significantly higher in normotensive subjects with CAD compared with normotensive subjects without this disease (P = 0.020). Both associations were confirmed by multiple logistic regressions. In conclusion, while the C allele of the 677C/T MTHFR polymorphism is associated with type II diabetes mellitus in women, the T allele is associated with CAD only in normotensive subjects of Czech origin.

Aged↗

The C766T low-density lipoprotein receptor related protein polymorphism and coronary artery disease, plasma lipoproteins, and longevity in the Czech population.

Low-density lipoprotein receptor related protein (LRP) is a multifunctional endocytic receptor involved in various biological processes including the regulation of the coagulation-fibrinolysis balance, the lipoprotein metabolism, and cellular migration, all of which relate to the development of atherosclerosis. Polymorphisms affecting the function or expression of LRP may thus influence the individual risk of atherosclerosis development. This study investigated the association between the C766T LRP polymorphism, coronary artery disease (CAD), and plasma lipoprotein levels in a large sample of Caucasian subjects of Czech nationality. In addition, the 4G/5G promoter polymorphism of the gene coding for plasminogen activator inhibitor 1 (PAI-1), the known ligand of LRP with strong antifibrinolytic potential, was ascertained to investigate its possible association with CAD. Both polymorphisms were studied using polymerase chain reaction analysis in 654 patients with angiographically confirmed CAD and in 525 controls. No statistically significant differences in allele frequencies of the polymorphisms studied were detected between patients and controls, even when men, women, hypertonic, and type II diabetic subjects were compared separately. However, the frequency of the T allele of the LRP polymorphism was significantly higher in patients than controls when only subjects with the 5G/5G PAI-1 genotype were analyzed. In addition, the T LRP allele frequency was significantly lower in subjects aged 60 years or over than in those who were younger in both groups. No significant association was observed between the LRP or PAI-1 polymorphisms and plasma lipoprotein levels in the CAD patients. Our results demonstrate that the T allele of the C766T LRP polymorphism is negatively related to longevity, and that it increases the risk of CAD development in subjects with the 5G/5G PAI-1 genotype.

Aged↗

Single effects of apolipoprotein B, (a), and E polymorphisms and interaction between plasminogen activator inhibitor-1 and apolipoprotein(a) genotypes and the risk of coronary artery disease in Czech male caucasians.

To evaluate whether polymorphisms in genes whose products are involved in lipid metabolism and fibrinolysis alter the risk of coronary artery disease (CAD), allele frequencies of four genetic polymorphisms were ascertained by PCR-based methods in 175 Czech male patients with coronary artery disease and in 222 Czech men with no symptoms of CAD. The following polymorphisms were studied: apolipoprotein B (apo B) signal peptide insertion/deletion polymorphism, 5' apolipoprotein(a) [apo(a)] TTTTA repeat polymorphism, apolipoprotein E (apo E) varepsilon2, varepsilon3, varepsilon4 polymorphism, and plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter polymorphism. Apo B and apo(a) allele frequencies differed significantly between the CAD and the control groups (P<0.01 each), with higher frequencies of apo B deletion and apo(a) shorter repeat alleles in the CAD group. We did not observe any differences in allele frequencies of either PAI-1 or apo E polymorphisms but the genotype frequencies of apo E were slightly different between the two groups (P<0.05). In addition, we observed a gene-gene interaction between the PAI-1 and apo(a) polymorphisms with respect to the risk of CAD. None of the polymorphisms studied were associated with the severity of CAD or a history of myocardial infarction. Our findings support the idea that several polymorphisms in apolipoprotein genes may by themselves and/or in interaction with other polymorphisms contribute to risk factors for CAD in men.

Adult↗

Transfer of aciclovir from plasma to human breast milk.

Aciclovir (CAS 59277-89-3) is frequently used in herpes simplex virus diseases, but administration to lactating women occurs only rarely. Therefore, information about the pharmacokinetics of aciclovir in human breast milk is limited. The concentration in breast milk is 2 to 3 fold increased compared to plasma. The reason for this increase is unknown until now. An active transport mechanism has been assumed. The aim of this study was to prove whether the higher concentration of aciclovir in human breast milk is due to only a passive transfer. Two chambers separated by a semipermeable membrane were used. The first chamber contained plasma with aciclovir, the second chamber breast milk without aciclovir. The increase in aciclovir concentration in the second chamber was determined. The concentration of aciclovir in breast milk exceeded that of plasma after 2 h and reached a higher concentration. Thus, the higher aciclovir concentration in human breast milk is due to passive diffusion. No active transport mechanism is needed.

Acyclovir↗

Radiotracer analysis of cadmium speciation in soil solutions using electrophoresis, dialysis, centrifugation, and ultrafiltration.

Speciation of carrier-free 109Cd, added in cationic form to pre-filtered extracts obtained by leaching forest soil samples with distilled water, was analyzed using electrophoresis, dialysis, centrifugation, and ultrafiltration. Rapid establishment of isotopic equilibrium between the added 109Cd and stable cadmium present in the extracts was observed. All the data obtained indicated that 109Cd and also stable cadmium were present in the analyzed extracts in the form of neutral or negatively charged organic complexes or small colloids. The results of electrophoresis enabled the characterization, at least semiquantitative, of the abundance and electrophoretic mobility of the forms present. The incomplete dialysis of 109Cd from the soil extracts through cellophane membrane against water proved the presence of organic associates with molecular weights higher than 10(4). Dialysis against the same, but unlabeled extract was always complete, indicating the reversible (labile) nature of the organic forms of cadmium. Assessment of the stability constants of the organic forms using a simple discrete two-site model suggested that humate and/or fulvate complexes of cadmium were formed.

Cadmium↗

Radiotracer method in the study of environmental speciation and migration of contaminants.

Principles, advantages, and limitations of the use of radiotracer method for the analysis of speciation and migration of contaminants in the environment are briefly discussed. Several recent examples of use in the author's laboratory are given: development of the separation method for methylmercury and inorganic mercury in hair, analysis of the speciation of cadmium in soil solutions, study of the interaction of 137Cs and 58Co with suspended sediments in river water, and determination of input data for mathematical modeling of radiocesium migration in a small river.

Radioactive Pollutants↗

TNF alpha primes polymorphonuclear leukocytes for an enhanced respiratory burst to a similar extent as bacterial lipopolysaccharide.

We examined whether preincubating polymorphonuclear leukocytes (PMN) with TNF alpha would result in an enhanced respiratory burst upon subsequent stimulation by various agents. Bacterial lipopolysaccharide (LPS), a known primer of PMN, was used as control. We found that both LPS (0.01 to 10.0 microgram/ml) and recombinant TNF alpha (0.001 to 1.0 microgram/ml) act as direct stimulants of PMN as measured by chemiluminescence. Sixty minutes of preincubation of PMN with 1 microgram/ml TNF alpha or 10 micrograms/ml LPS resulted in similar priming for the respiratory burst elicited by opsonized zymosan, phorbol myristate acetate, zymosan, zymosan-activated serum, aggregated immunoglobulin, and f-met-leu-phe (FMLP) depending on the method of measurement used, i.e., chemiluminescence, production of O2-, and H2O2. Priming with TNF alpha for an enhanced response to stimulation by FMLP could be abrogated by anti-TNF alpha antibody. Cell-surface receptor numbers and binding-affinity constants for FMLP remained stable under conditions leading to priming. We conclude that TNF alpha is able to prime PMN for an enhanced respiratory burst to a similar extent as with LPS. Because PMN cell-surface receptors for FMLP are unaltered by priming, the enhanced respiratory burst seems to be due to changes in intracellular metabolism.

Antibodies↗

[Radius-femoral dysplasia. A new form of hereditary metaphyseal dysplasia].

Höhle and Braun described a new form of hereditary metaphyseal dysplasia. It is characterized by changes in distal metaphyses of femoral bones which are formed as Erlenmeyer flasks, further by club-shaped dysplasias of the metaphyses of the other long bones, absence of skeletal hyperostosis and by characteristic varus-deformations of radial bones. An extensive family history research showed that the oldest carriers of these anomalies came from a small town in northern Bohemia. Completely identical case reports were published describing the carriers of metaphyseal dysplasia characters whose origin was also traced to the same region. The authors aim at drawing attention to this new disease, finding more carriers of metaphyseal dysplasia characters and at giving an impulse to an extensive research into this extremely systemic rare bone disease.

Adult↗