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Biomedical subjects

R Rokyta

Publications and source records attributed to R Rokyta.

At least 19 recordsLinked to original sources
PubMed2005

Perfusion pressure manipulation in porcine sepsis: effects on intestinal hemodynamics.

Limited information is available about selection of the threshold for arterial blood pressure in critically ill patients, particularly in sepsis when normal organ blood flow autoregulation may be altered. The present experimental study investigated whether increasing perfusion pressure using norepinephrine in normotensive hyperdynamic porcine bacteremia affects intestinal macro- and microcirculation. Nine pigs received continuous i.v. administration of Pseudomonas aeruginosa (PSAE) to develop hyperdynamic, normotensive (mean arterial pressure [MAP] 65 mm Hg) sepsis. Norepinephrine was used to achieve 10-15 % increase in MAP. Mesenteric arterial blood flow (Q(gut)), ileal mucosal microvascular perfusion (LDF(gut)) and ileal-end-tidal PCO(2) gap (PCO(2) gap) were measured before norepinephrine, after 60 min of norepinephrine infusion and 60 min after norepinephrine infusion had been discontinued. During a 12 h period of PSAE infusion all pigs developed hyperdynamic circulation with significantly decreased MAP. Although the mesenteric blood flow remained unchanged, infusion of PSAE resulted in a gradual fall of ileal microvascular perfusion, which was associated with progressively rising PCO(2) gap. Norepinephrine which induced a 10-15 % increase in perfusion pressure (i.e. titrated to attain near baseline values of MAP) affected neither Q(gut) nor the intestinal blood flow distribution (Q(gut)/CO). Similarly, norepinephrine did not change either LDF(gut) or PCO(2) gap. In this hyperdynamic, normotensive porcine bacteremia, norepinephrine-induced increase in perfusion pressure exhibited neither beneficial nor deleterious effects on intestinal macrocirculatory blood flow and ileal mucosal microcirculation. The lack of changes suggests that the gut perfusion was within its autoregulatory range.

Animals↗
PubMed2005

Occurrence of bicuculline-, NMDA- and kainic acid-induced seizures in prenatally methamphetamine-exposed adult male rats.

Stimulant drugs are often associated with increased seizure susceptibility. Inhibitory gamma-aminobutyric acid (GABA) and excitatory N-methyl-D-aspartate (NMDA) systems play an important role in the effect of stimulants on epileptic seizures. No studies investigating the effect of prenatal methamphetamine (MA) exposure on seizures are available. In this study, bicuculline (GABAA receptor antagonist), NMDA (NMDA receptor agonist) and kainic acid (non-NMDA receptor agonist) were used to induce seizures in adult male rats. Three groups of animals were tested in each seizure test: prenatally MA- (5 mg/kg) exposed, prenatally saline-exposed, and absolute controls without any prenatal exposure. In bicuculline-induced seizures, the latency to onset of tonic-clonic seizures was shorter in MA-exposed rats than in controls, but it did not differ from saline-exposed rats. There were no differences in clonic seizure onset between groups. In NMDA-induced seizures, the latency to onset of clonic-tonic seizures was shorter in prenatally MA-exposed rats than in controls; however, the latency to onset of saline-exposed animals did not differ from either MA-exposed or from control rats. There were no differences in seizure susceptibility in kainic acid-induced clonic seizures. There were no differences in seizure incidences or stereotypical behavior in any seizure model. The question remains as to how much the present data demonstrate the effect of prenatal drug exposure on seizure susceptibility per se, and how much they may be explained by the effect of prenatal stress or by other mechanism(s).

Animals↗
PubMed2005

Seizure susceptibility in prenatally methamphetamine-exposed adult female rats.

The purpose of the present study was to examine the effect of prenatal methamphetamine (MA) exposure on seizures induced by bicuculline and N-methyl-d-aspartate in adult female rats. The present results show that prenatal MA exposure alters seizures in a model-specific manner and that the seizure susceptibility of adult female rats may be affected by the stage of their estrous cycle.

Animals↗
PubMed2005

Tail-flick latency and self-mutilation following unilateral deafferentation in rats.

Unilateral deafferentation induced by transection of the C(4)-C(8) dorsal roots of spinal cord, followed by a complex of abnormal self-mutilating behavior, is interpreted as an animal model of chronic nociception. The objective of our study was to test the differences in tail-flick latency between intact control and unilaterally deafferented animals and to assess the changes in their acute nociceptive sensation. The initial hypothesis was that deafferentation-induced painful sensation might cause stress-induced analgesia that should be manifested as prolonged tail-flick latency. The experiment was carried out on 11 male and 10 female adult Wistar rats. The tail-flick latency was repeatedly measured over a period of 10 consecutive weeks both in the preoperative baseline period and following multiple cervical dorsal rhizotomy. Contrary to our hypothesis, unilateral deafferentation was followed by a significant shortening of the tail-flick latency both in males and females. In deafferented animals, compared to the controls, variations of tail-flick latency were reduced. In individual animals after deafferentation, concurrent dynamic changes were observed in self-mutilating behavior, in a loss and regaining of body weight, and in tail-flick latency. Our data suggest that changes in tail-flick latency may be interpreted in terms of central sensitization and that tail-flick latency might be considered as a useful marker of chronic nociception.

Animals↗
PubMed2004

Fluid challenge in patients at risk for fluid loading-induced pulmonary edema.

BACKGROUND: This study evaluated the effects of protocol-guided fluid loading on extravascular lung water (EVLW) and hemodynamics in a group of patients at high risk for volume expansion-induced pulmonary and systemic edema. METHODS: Nine acutely admitted septic patients with acute lung injury (ALI) were prospectively studied. In addition to sepsis and ALI, the following criteria indicating increased risk for edema formation had to be fulfilled: increased vascular permeability defined as microalbuminuria greater than fivefold normal and hypoalbuminemia < 30 g l(-1). Two hundred-ml boluses of a 10% hydroxyethyl starch (HES) was titrated to obtain best filling pressure/stroke volume relation. Extravascular lung water and intrathoracic blood volume (ITBV) were measured using a transpulmonary double-indicator dilution technique. Baseline data were compared with data at the end of fluid loading and 3 h postchallenge. RESULTS: At study entry the mean EVLW was 13 ml kg(-1), and the mean EVLW/ITBV ratio (indicator of pulmonary permeability) was 0.72 (normal range 0.20-0.30). To attain optimal preload/stroke volume relation 633 +/- 240 ml of HES was needed. Fluid loading significantly increased preload (CVP, PAOP and ITBV), and stroke volume. Effective pulmonary capillary pressure (Pcap) rose only slightly. As a result, the Pcap-PAOP gradient decreased. Despite increased cardiac output, EVLW did not change by plasma expansion. CONCLUSION: In this selected group of at-risk patients, the optimization of cardiac output guided by the concept of best individual filling pressure/stroke volume relationship did not worsen permeability pulmonary edema.

APACHE↗
PubMed2004

Effects of anesthesia and nociceptive stimulation in an experimental model of brachial plexus avulsion.

Unilateral dorsal rhizotomy of brachial plexus nerves (C5-Th1) performed under general anesthesia is known to induce self-mutilation in rats. The aim of this study was to determine the effect of different anesthetic agents, and of pre-rhizotomy nociceptive stimulation on the appearance of self-mutilation. Self-mutilation appeared in 78% of animals after rhizotomy had been performed under pentobarbital anesthesia. When ketamine was used as the general anesthetic, self-mutilation was almost suppressed (13%) and consisted of superficial erosions. Mechanical nociceptive stimulation, when applied just before the induction of ketamine anesthesia and subsequent rhizotomy, provoked self-mutilation in 91% of rats. Furthermore, a serious type of self-mutilation consisting of total amputation of the distal part of the forepaw was present in 28% of all self-mutilating animals after previous nociceptive stimulation. In terms of self-mutilation, these results suggest 1) the crucial role of anesthesia, especially that which involved NMDA receptors (ketamine), and 2) the need of an additional factor to chronic deafferentation, formed either by activity of nociceptive pathways just before rhizotomy (nociceptive stimulation preceding ketamine anesthesia) or by injury discharges (pentobarbital anesthesia).

Anesthesia↗
PubMed2004

GABA(B) receptor agonist baclofen has non-specific antinociceptive effect in the model of peripheral neuropathy in the rat.

Baclofen, which is a specific agonist of the metabotropic GABA(B) receptor, is used in clinical practice for the treatment of spasticity of skeletal muscles. It also exerts an analgesic effect, but this effect is still not clear and especially controversial in neuropathic pain. In this work, we studied the antinociceptive effects of baclofen in a model of chronic peripheral neuropathic pain - loose ligation of the sciatic nerve (chronic constriction injury, CCI). As controls we used sham-operated animals. The changes of thermal pain threshold were measured using the plantar test 15-25 days after the operation. The obtained results suggest that baclofen increases pain threshold in both groups. The antinociceptive effect of baclofen was dose-dependent and the maximum response without motor deficits was observed at a dose of 15 mg/kg s.c. In the rats with CCI, significant differences between affected (ipsilateral) and contralateral hind paw were present. This difference was dose-dependent, the highest value (6.2+/-1.37 s) was found at the dose of 20 mg/kg. Based on our results and previous findings it could be summarized that baclofen has antinociceptive action, which is attenuated in the model of chronic neuropathic pain probably due to the degeneration of GABA interneurons after chronic constriction injury.

Analgesics↗
PubMed2004

[The significance of free radicals and antioxidants due to the load induced by sport activity].

Sport performance is followed by a high production of free radicals. The main reasons are reperfusion after the previous imbalance between the increased need of the organism and the ability of blood supply by oxygen, increased production of ATP, decomposition of the cells particularly white blood cells, oxidation of the purin basis from DNA, stress, output of epinephrine release of free iron, increased temperature in the muscle and its inflammation, and the reception of free radicals from external environment. Peroxidation of lipids, proteins, DNA and other compounds follows the previous biochemical steps. Antioxidants are consumed by free radicals, antioxidative enzymes are released into blood plasma, intracellular calcium is increased, the production of nitric oxide rises, the levels of hydrogen peroxide and hypochlorous acid increase. These penetrate through the membranes and oxidatively damage the tissues. Training improves the ability of the organism to balance the increased load of free radicals. The damage can be lowered by the application of a mixture of antioxidants, the most important are vitamin C, A, E, glutathione, selenium, carnosine, eventually bioflavonoids and ginkgo biloba. The lack of antioxidants can significantly diminish the sport performance and therefore the supplementation with antioxidants is for top sportsmen but also for aged people advisable.

Antioxidants↗
PubMed2003

[Acute kidney failure in critically ill patients and its prevention].

Acute renal failure often complicates the course of critically illness and can contribute to high morbidity and mortality. In most cases acute renal failure represents a part of the multiple organ dysfunction syndrome and it is usually related to the ischemic and/or toxic injury of tubular cells (acute tubular necrosis, ATN). The presented paper reviews the mechanisms involved in this two types of tubular cells injury. It analyzes the measures of kidney protection during critical illness, which include optimization of systemic and intrarenal hemodynamics as well as avoidance of nephrotoxic drugs. It describes the most common nephrotoxic drugs and proposes principles of their safer use. Potential strategies to stimulate kidney function recovery are also discussed.

Acute Kidney Injury↗
PubMed2003

Lymphocyte subset numbers depend on the bacterial origin of sepsis.

OBJECTIVE: To determine the quantitative variances in peripheral blood lymphocyte subsets during sepsis, and their clinical significance. METHODS: Peripheral blood lymphocyte subsets were enumerated in 32 non-surgical septic patients during the first 14 days of hospitalization; results from septic patients were compared with those from 34 healthy controls. Influences of the severity and the bacterial etiology of sepsis on changes in lymphocyte subsets were also assessed. RESULTS: Significant decreases (P < 0.05) from normal values of CD4+, CD8+ and total T-lymphocytes were observed in septic patients, but the decline persisted only for CD4+ T-lymphocytes and natural killer (NK) cells for 3 and 7 days, respectively. In addition, the numbers of CD3+/DR+ lymphocytes were significantly elevated on day 14. There were no correlations between these alterations and the severity of sepsis. Gram-positive sepsis (n = 10), which was mainly due to Streptococcus pneumoniae and Staphylococcus aureus, caused prolonged decreases in CD4+, CD8+ and total T-lymphocytes, and a reduction in NK cells, that lasted for >or=14 days. Conversely, patients with sepsis due to Gram-negative pathogens (Neisseria meningitidis, n = 8; enterobacteria, n = 2) achieved full recovery of the subsets within 3 days. Moreover, the patients with Gram-negative sepsis demonstrated a significant increase in B-lymphocytes, and a rise in the numbers of CD3+/DR+ and CD4+ T-lymphocytes, which were more rapid than in patients with Gram-positive sepsis. CONCLUSION: Our results indicate that Gram-positive sepsis causes stronger suppression of peripheral blood lymphocyte subsets in comparison to sepsis due to Gram-negative pathogens.

Adolescent↗
PubMed2003

The teaching of physiological disciplines in the 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.

The physiological disciplines are being taught from the 1st year of medical study up to the end of the 4th year, it means 8 semesters altogether. It is necessary to explain the curriculum of the 3rd Faculty of Medicine, Charles University in Prague. This Faculty has had a new curriculum since 1997, so the first students, who had been taught as to this system, already finished their study. The duration of medical study is 6 years, i.e. 12 semesters. This composed of three cycles: I Basic biomedical sciences. The first two years represent the first cycle, which is based on the integrative principle. II. Principles of clinical medicine. The second cycle is concerned on the problem-based learning. III. Clinical preparation. The third cycle represents clinical application. In the first two years the integrative study is composed of different modules. The first module I A--Structure and functions of human body is the greatest module in the first two years, which is composed of anatomy, histology and embryology, biochemistry and physiology. The module I B--Cell biology and genetics is composed of genetics and cell biology and this module is finished by the examination after two semesters at the end of the first year.

Curriculum↗
PubMed2003

Enteral nutrition and hepatosplanchnic region in critically ill patients - friends or foes?

Enteral nutrition (EN) is a preferred way of feeding in critically ill patients unless obvious contraindications such as ileus or active gastrointestinal bleeding are present. Early enteral nutrition as compared to delayed EN or total parenteral nutrition decreases morbidity in postsurgical and trauma patients. The hepatosplanchnic region plays a pivotal role in the pathophysiology of sepsis and multiple organ dysfunction syndrome. The beneficial effects of EN on splanchnic perfusion and energy metabolism have been documented both in healthy volunteers and animal models of sepsis, hemorrhagic shock and burns. By contrast, EN may increase splanchnic metabolic demands, which in turn may lead to oxygen and/or energy demand/supply mismatch, especially when hyperemic response to EN is not preserved. Therefore, the timing of initiation and the dose of EN in patients with circulatory failure requiring vasoactive drugs are a matter of controversy. Interestingly, the results of recent clinical studies suggest that early enteral nutrition may not be harmful even in patients with circulatory compromise. Nevertheless, possible onset of serious complications, the non-occlusive bowel necrosis in particular, have to be kept in mind. Unfortunately, there is only a limited number of clinically applicable monitoring tools for the effects of enteral nutrition in critically ill patients.

Animals↗
PubMed2003

Oxidative stress in the brain tissue of laboratory mice with acute post insulin hypoglycemia.

Malondialdehyde (MDA), Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and selenium-dependent glutathione peroxidase (GSPHx) are currently considered to be basic markers of oxidative stress. MDA is one of the end-products of the peroxidation of membrane lipids, whereas enzymes Cu,Zn-SOD and GSHPx belong to the natural antioxidants. The role of oxygen free radicals in the pathogenesis of many diseases is well documented. The aim of this study was to ascertain the influence of insulin-induced acute hypoglycemia on oxidative stress in the brain tissue. Hypoglycemia was induced in ICR mice by intraperitoneal administration of insulin at a dose 24 IU/kg. There was a correlation between the severity of hypoglycemia and the levels of MDA, Cu,Zn-SOD and GSHPx. The results showed that in severe hypoglycemia (serum glucose concentration below 1.0 mmol/l) the lipoperoxidation in brain tissue expressed as the level of MDA was higher in comparison with normoglycemic controls (glycemia around 3.7 mmol/l) as well as in comparison with the levels of MDA during moderate hypoglycemia (glycemia ranging between 1-2 mmol/l). This indicates the enhancement of lipoperoxidation in the brain tissue during severe hypoglycemia. However, both enzymes - Cu,Zn-SOD or GSHPx - did not show a similar tendency.

Acute Disease↗
PubMed2003

[Rhabdomyolysis--development, causes, sequelae and therapy].

Rhabdomyolysis is a syndrome characterized by striated muscle necrosis and the release of intracellular muscle constituents into the circulation. The severity of illness ranges from asymptomatic elevations of muscle enzymes in the serum to life-threatening cases associated with extreme enzyme elevations, electrolyte imbalances, and acute renal failure. This chapter reviews recent knowledge of pathophysiologic mechanisms leading to myocytes injury, diseases its causes, consequences and treatment options. Particular attention is focused on rhabdomyolysis in critically ill patients.

Humans↗
PubMed2003

[Gene therapy of pain].

Possible practical applications of gene therapy for pain are at the beginning. Very intensive research on animal models has been effectuated and some partial results of clinical applications in men already exist. The article describes different possibilities of these applications, namely the application of viral vectors and antisense nucleotides as well as the first experimental results of possible gene therapy. BDNF (brain derived nervous factor), herpes simplex virus, cytokine-interleukin 10, viral mediated transfer of the decarboxylase of the glumatic acid and down--regulated genes are recently used. Experimation of beta endorphin is also possible. In the article describes also possible molecular and gene therapy of pain and the molecular neurosurgical approach to the treatment of pain, which is called the molecular neurosurgery. From all these results it is possible to conclude, that gene therapy will be definitely used for the treatment of pain and that only the intensive research in this field may bring some important results.

Animals↗
PubMed2003

Differences in hormonal and inflammatory parameters in male Lewis and Long Evans rats with adjuvant arthritis.

The purpose of the present study was (i) to compare secretory responses of prolactin and corticosterone to the acute stress of immobilization in male rats of the Lewis and Long Evans strains and (ii) to compare secretion of the two hormones in rats with fully developed adjuvant arthritis (AA) and their relationship with the intensity of the inflammatory reaction. A short immobilization of 5 min induced equal elevations of both hormones in both strains, but 20-min immobilization produced significantly stronger responses in Long Evans rats than in Lewis rats. AA inhibited prolactin secretion equally in both strains (from 11.6 +/- 1.3 ng/ml to 4.2 +/- 0.6 ng/ml in Lewis rats, p < 0.01, and from 3.7 +/- 0.6 to 2.12 +/- 0.1 ng/ml in Long Evans rats, p < 0.05), but caused a conspiciously larger elevation of corticosterone in the Long Evans than in the Lewis animals (11.5 +/- 1.2 microg/dl in Long Evans rats versus 5.1 +/- 0.5 microg/dl in Lewis rats, p < 0.01) while basal levels were similar. The larger corticosterone response in the Long Evans rats was associated with a stronger inflammatory reaction assessed by hind paw swelling (2.3 +/- 0.1 ml for Long Evans rats versus 1.8 +/- 0.08 ml for Lewis rats, p < 0.01) and plasma levels of nitric oxide (47.5 +/- 5.7 microM for Long Evans rats versus 28.7 +/- 2.5 microM for Lewis rats, p < 0.01) than in the Lewis males with lower corticosterone levels. In conclusion, there are significant, obviously genetically based, differences in the corticosterone responses to both immobilization and AA between the two strains, with the Long Evans rats reacting more strongly than the Lewis rats. The lack of the expected inverse relationship between corticosterone levels and the intensity of the inflammation indicates that the activity of corticosterone is not its primary determinant and that other important factors are involved.

Animals↗
PubMed2002

[Fluid resuscitation in conditions with disorders of capillary permeability].

Fluid resuscitation remains a cornerstone in the treatment of various types of circulatory failure. Alterations in microvascular permeability are a hallmark of a number of inflammatory conditions including sepsis, septic shock, burns and the acute respiratory distress syndrome. As a result, the loss of plasma fluid into the interstitial space leads to hypovolaemia and tissue hypoperfusion. Administration of large volumes of fluids in often necessary to restore the nutritional blood flow to tissues. This strategy, however, involves the risk of interstitial edema formation, which in turn may further impair tissue oxygen distribution. The presented paper briefly reviews the principles of transvascular fluid exchange and the pathophysiology of capillary permeability. It discusses the ongoing controversy on the optimal way and the end points of volume replacement as well as the choice of fluid in conditions associated with capillary leakage.

Capillary Leak Syndrome↗