Comparative Analysis of Stress-Protective Activity and Prevention of Fatigue during Physical Load of Standardized Humic Acids from Peat and Officinal Preparations of Succinic Acid in Experiment.

The effect of humic acids and substances with similar action - derivatives of succinic acid (ethylmethylhydroxypyridine succinate) and combined agent consisting of succinic acid, nicotinamide, riboflavin, and riboxin on the performance and stress resistance of experimental rats was studied. Performance was assessed in the test of exhaustive forced swimming with a load, stress resistance was evaluated by the serum level of corticosterone and open field behavior, and the state of anaerobic metabolism was estimated by the serum level of lactate after swimming test. Humic acids from peat showed anti-stress activity comparable to that of the officinal preparation and preventive effect on fatigue during physical exercise. They can be recommended as a component for the development of drugs that increase human performance and stress resistance.

[Speciality of restoring the psychophysiological parameters of laboratory rats with the help of balneological procedures during the periods of equinox]. / Osobennosti vosstanovleniya psikhofiziologicheskikh pokazatelei laboratornykh krys s pomoshch'yu bal'neologicheskikh protsedur v periody ravnodenstviya.

Currently methods development for restoring physiological functions and increasing the adaptive capabilities of the body after prolonged stress exposure of various genesis is an urgent problem in the field of balneology and physiotherapy. It is known that the adaptive potential of the organism is not the same in different seasons of the year. In this regard, it becomes necessary to take into account the seasonality factor when carrying out recreational activities. PURPOSE OF THE STUDY: To perform a comparative study of balneotherapeutic procedures effectiveness in the form of water and antler baths in relation to the restoration of the psychophysiological parameters of laboratory rats after a consistent stressful effect of light desynchronosis and physical activity to a state of complete fatigue during autumn and spring equinoxes. MATERIAL AND METHODS: The experiment was carried out during the periods of the spring and autumn equinoxes on 160 male Wistar rats weighing 220-250 g. In each season, the animals were divided into 8 groups of 10 individuals. Two groups were in natural lighting conditions. Animals of the 1st group (intact) were not exposed to experimental influences; rats of the 2nd group were exposed to physical activity in the form of a swimming test until complete fatigue for 5 days in a row in the morning; animals of groups 3-8 were exposed to stress loads in the form of 10-day light desynchronosis (light or dark deprivation) followed by physical activity. In the 4-th, 5-th, 7-th and 8-th groups, post-experimental post-stress recovery programs were carried out using water baths (groups 4 and 7) and baths with drug «Pantovanna¼ (groups 5 and 8). After the completion of exposures, the animals were tested in the «open field¼ according to the standard method. The level of corticosterone in the blood serum was determined by ELISA. RESULTS: It was found that in laboratory rats sensitivity to stressful influences - light desynchronosis followed by physical activity to the point of fatigue, as well as active post-stress recovery were determined by the nature of desynchronosis and the season of the year. The stress load was accompanied by a phase of exhaustion during the spring equinox and by a phase of anxiety during the autumn equinox. In the spring, antler baths as a procedure for active post-stress recovery were ineffective; in autumn, they had a normalizing effect on the level of corticosterone and behavior only after dark deprivation. CONCLUSION: The conducted experiment indicates the need to take into account the season of the year and the direction of the transmeridian flight to sanatorium-and-spa treatment with balneotherapy procedures. Using the example of equinoxes under experimental conditions on laboratory rats, it has been shown that balneological procedures will more effectively perform rehabilitative functions when the light phase of the day expands as a result of such a shift, but not the dark one.

[Experimental study of the features of post-stress recovery of psychophysiological functions using balneological treatments during the solstice]. / Eksperimental'noe issledovanie osobennostei poststressornogo vosstanovleniya psikhofiziologicheskikh funktsii s pomoshch'yu bal'neoprotsedur v period solntsestoyanii.

The development of new programs and methods of rehabilitation after the action of various stress factors on the body continues to be an actual problem. There are post-stress recovery programs include both standard pharmacotherapy and physical therapies. However, when prescribing certain types of physiotherapy procedures, the season of the year is not taken into account. OBJECTIVE: During the summer and winter solstices to study the features of post-stress recovery of psychophysiological functions of laboratory rats after light or dark deprivation, followed by physical exertion and rehabilitation procedures in the form of water and antler baths. MATERIAL AND METHODS: The experiment was carried out on 160 male Wistar rats. The animals were divided into 8 groups of 10 individuals at each solstice period (winter, summer). Group 1 was not exposed to any impact. Group 2 was presented with physical activity (swimming test). These two groups were in natural light conditions. Groups 3-8 underwent light desynchronosis (light or dark deprivation) followed by physical activity. After the above-mentioned influences, procedures were carried out in the form of water baths (groups 4 and 7) and baths with a preparation based on pantogematogen «Pantovanna¼ (groups 5 and 8). Behavioral responses were assessed using the open field test. The content of corticosterone was determined by enzyme immunoassay. RESULTS: During the periods of the winter solstice, dark or light deprivation increased the resistance of animals to the stress of subsequent physical activity, i.e. showed a training effect, while during the summer solstice the studied stress factors led to depletion of serum corticosterone levels, although the structure of behavior did not undergo significant changes. Post-stress recovery in the form of water and antler baths for 10 days was determined by the nature of desynchronosis and the solstice period. Pantobaths were effective in summer and winter only under TT conditions. However, in winter, after the CC-regime, the antlers intensified the stressful effect of physical activity on the animals' organism. CONCLUSION: The experiment carried out indicates the need to take into account the season of the year and the direction of the transmeridian flight to balneological resorts. Using the example of solstices in experimental conditions on rats, we have shown that balneological procedures will perform best the restorative functions when expanding as a result of such a movement of the light phase of the day, but not the dark one. It is possible that this feature can also persist for a person, since a more rapid adaptation to new light-dark conditions has been established also with the expansion of the light phase, but not the dark one.

[An effect of mexidol on the level of corsticosteron in the blood serum and beam zone cells in rats with light desynhronizes and physical loads]. / Vliyanie meksidola na uroven' kortikosterona v syvorotke krovi i kletki puchkovoi zony kory nadpochechnikov u krys pri svetovykh desinkhronozakh i fizicheskikh nagruzkakh.

OBJECTIVE: In order to develop methods and means of maintaining normal human functioning under conditions of desynchronizes, the effect of mexidol on the level of corticosterone in the blood serum and the state of the cells of the beam zone of the adrenal cortex of rats after light or dark deprivation and physical activity to a state of fatigue. MATERIALS AND METHODS: The experiments were performed on 7 groups of rats (10 animals each) in the spring. The model of physical activity is the method of forced swimming of rats until exhaustion in its own modification. For the induction of experimental desynchronizes, the animals of the experimental groups were kept around the clock for 10 days with artificial bright light of 150 LX or a complete darkening of 2-3 LX. Mexidol was administered intramuscularly at a dose of 10 mg/kg animal 30 minutes before the swimming test. Control animals under similar conditions were administered 0.9% sodium chloride solution. The level of corticosterone in the serum was determined using enzyme immunoassay. The measurements were carried out on a programmable photometer for STAR FAX 303 PLUS microsamples (USA). Histological analysis of the adrenal glands was carried out according to standard methods. Microscopy of preparations, imaging and measurements were carried out using an Axio Lab A1 microscope, an AxioCamERc 5s camera and ZEN 2012 software («Carl Zeiss Microscopy¼, Germany). Statistical processing of the results was carried out using standard parametric and non-parametric methods, depending on the nature of the distributions. RESULTS AND CONCLUSION: Mexidol under combined successive stress loads - desynchronizes and physical activity - demonstrated anti-stress properties not only at the level of corticosterone in the blood serum of rats, but also at the level of adrenal glands. The severity of this effect of the drug depended on the number of stress loads (isolated physical or shown in conditions of desynchronizes), the phase of stress and the nature of deprivation. Under natural lighting conditions and after light deprivation, when animals were in the anxiety phase of varying severity, the drug worked more reliably than after dark deprivation in conditions of developing depletion. Nevertheless, even in the latter case, he showed himself as a means of preventing exhaustion in animals and the breakdown of adaptation.

[The effect of circulating tumor cells on the survival of patients with pancreatic cancer 5-year results]. / Vliv prukazu cirkulujících nádorových bunek na prezívání pacientu s karcinomem pankreatu - petileté výsledky.

INTRODUCTION: Pancreatic cancer (PDAC) is one of the most aggressive malignancies. Its incidence increases worldwide and, despite the developments in cancer research, mortality rates have not decreased. Poor prognosis of the disease is due to many factors, mainly late diagnosis. Distant metastases and peritoneal carcinomatosis are caused by hematogenous and lymphogenous spreading of the tumorous cells. One of the factors that may influence patient survival are so-called circulating tumor cells (CTCs). The aim of our work was to evaluate the possible influence of CTCs on the survival of patients with PDAC. METHOD: We included patients who underwent a radical or palliative surgical intervention at the First Department of Surgery of Medical Faculty and University Hospital in Olomouc between 1 January 2008 and 31 December 2012. The required samples for CTCs detection were taken from each patient. The detection of the CTCs was performed using real-time RT-PCR. The results were statistically processed and evaluated. RESULTS: We included 126 patients in total, of which 88 were treated radically and 38 received palliative treatment. Mean age was 63 years in patients with radical and 64 years in patients with palliative surgery. Mean survival time in radically treated patients was 29.6 months, in patients with palliative treatment the mean survival time was 8.5 months. The survival time of radically treated patients with CTCs was 27.2 months, without CTCs it was 33.8 months. CONCLUSION: We did not prove a statistically significant difference in survival between radically treated PDAC patients with and without detected CTCs in our work.Key words: pancreatic cancer - circulating tumor cells survival.

[Determination of CEA, EGFR and hTERT expression in peritoneal lavage in patients with pancreatic adenocarcinoma using RT - PCR method]. / Stanovení exprese CEA, EGFR a hTERT v peritoneální lavázi u pacientu s adenokarcinomem pankreatu metodou RT-PCR.

INTRODUCTION: The aim of this study is to assess the significance of CEA, EGFR and hTERT as markers of occult tumor cells for predicting treatment outcomes in pancreatic cancers, as well as determining the cut-off values of these markers individually in peritoneal lavage. METHOD: The study compared 87 patients undergoing palliative operations (bypass surgery, biological sampling for subsequent oncological treatment) for either stage III or IV (UICC) pancreatic ductal adenocarcinomas with a control group of 24 healthy patients. Abdominal cavity lavage was performed at the beginning of the surgery in both groups, using 100 ml of physiological solution (phosphate buffered saline, pH 7.2). The samples were transported in bottles containing 1.5 ml 0.5 M EDTA and 10 ml of fetal bovine serum. Total RNA samples were all processed and purified by reverse transcription. Occult tumor cells in the peritoneal lavage were detected by the real-time RT-PCR method using CEA, EGFR and hTERT as markers of tumor cells. Another aim was to calculate the cut-off values of these markers. Statistical analysis was done using software R (www.r-project.org) and Statistica (StatSoft, Inc. USA). RESULTS: Mean expression of CEA, EGFR and hTERT in peritoneal lavage in the control group was 2501, 716749 and 104 copies of mRNA / mg RNA. Threshold, cut-off values were determined as the "mean + 2 times standard deviation". Absolute expression values were further normalized to expression of the house-keeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH). After normalization, cut-off values of the tested markers were 4.89, 115.88 and 0.02 copies of mRNA/GAPDH mRNA. As regards absolute expression of the markers tested, only hTERT was able to statistically significantly (p<0.001) distinguish the analysed groups, where patients with advanced pancreatic adenocarcinoma had a higher expression of hTERT. Absolute expression of CEA or EGFR was not able to discriminate between the two groups. The more accurate normalized expression values of the test markers demonstrated a statistically significantly higher expression of hTERT (p<0.005) and CEA (p<0.001) in patients with advanced adenocarcinoma compared to the control group. CONCLUSION: Absolute hTERT expression in peritoneal lavage of patients with advanced pancreatic cancer was significantly higher compared to the control group.

[Effect of thermal curing of the ethyl cellulose film on the rapidity of release of diclofenac sodium from pellets]. / Vliv tepelného osetrení ethylcelulosového filmu na rychlost uvolnování sodné soli diklofenaku z pelet.

Coated pellets controlling drug release are a very popular dosage form which is widely used in medical practice. At present the coatings of water-insoluble polymers formed from aqueous dispersions are preferred. However, film formation from an aqueous polymeric dispersion is different from that from their organic solutions. A stable film on the pellets surface is produced by coalesces of discrete latex particles at an optimum temperature. The present experimental paper studied the changes of diclofenac sodium dissolution profiles from coated pellets, when their coatings from an aqueous polymeric dispersion of ethyl cellulose were cured for different time periods (1-72 hours) and a temperature of 60 degrees C. Drug release rate was decreasing with the increasing time of the layer curing up to 24 hours. At this time the dissolution curve was similar to a strait line. When the curing time further increased, the drug release was again faster. All prepared samples (with or without seal coat, cured for a period of 24 hour or uncured) were filled into hard gelatine capsules and stored in blisters in three different stability boxes (25 degrees C/60% RH, 30 degrees C/65% RH, 40 degrees C/75% RH) for 6 or 12 months. The best drug dissolution profile and stability were observed for the pellets with the seal coat and ethyl cellulose coating cured for 24 hours.

[The effect of polymeric dispersion type on the release of diclofenac sodium from coated pellets]. / Vliv typu polymerové disperze na uvolnování diklofenaku sodné soli z obalených pelet.

Recently, coated pellets have gained attention of the pharmaceutical industry as they represent a relatively easy way leading to controlled drug release. Pellets of appropriate properties containing approx. 40% of diclofenac sodium were prepared by roto-agglomeration. For the coating, two different aqueous dispersions (Surelease and Eudragit RS 30 D) were selected. Generally, the drug release rate slowed down as the coating load increased from 10 to 22%. However, big differences between diclofenac sodium release from pellets coated with Surelease and Eudragit RS 30 D at equivalent coating loads were observed. Although Eudragit RS 30 D provided membranes successfully controlling drug release over an extended period of 24 hours, the coating process with Surelease led to a film of a very poor quality. Faster release from ethyl cellulose coated pellets could be explained in terms of a higher solubility of diclofenac sodium in alkaline aqueous dispersion of ethyl cellulose and its migration into the coat during the coating process and/or the unsatisfactory curing of the ethyl cellulose film. Therefore possible interactions between the coating and the drug should be always considered as suggested in this study.

Methyl-alpha-D-mannopyranoside, mannooligosaccharides and yeast mannans inhibit development of rat adjuvant arthritis.

Methyl-alpha-D-mannopyranoside, mannooligosaccharides obtained by acetolysis of yeast mannan, and pure mannans isolated from the cell walls of pathogenic (Candida albicans) and nonpathogenic (Saccharomyces cerevisiae) yeasts were used for treatment of rat adjuvant arthritis. The arthritis was induced by the application of Freund's complete adjuvant into the tail region of rats. The mannose substances were injected into the arthritic rats intraperitonealy at different time intervals. Levels of serum albumin, changes in hindpaws swelling and radiographs were measured in infected rats as variables of the inflammation and destructive arthritic changes. While mannan from C. albicans inhibited both the inflammation and destructive arthritic changes, mannan from S. cerevisiae showed less effect. However, acetolysate of S. cerevisiae mannan as well as simple methyl-alpha-D-mannopyranoside inhibited both inflammation and destructive arthritic changes to a similar degree as mannan isolated from C. albicans. The effect, which is not dose dependent indicates its possible immunoregulatory mechanism. This is the first time a therapeutic effect of simple carbohydrates on rat adjuvant arthritis has been described.