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Biomedical subjects

P Maruna

Publications and source records attributed to P Maruna.

At least 19 recordsLinked to original sources

[Changes in levels of acute phase proteins in patients with central hypercortisolism].

BACKGROUND: Acute phase protein reaction depends on complex interaction of proinflammatory cytokines and hormones, especially glucocorticoids. Glucocorticoids are essential factors for hepatocellular microenvironment and proteosynthesis during both rest and inflammatory period. Cushing's disease represents a model of glucocorticoid hyperstimulation of acute phase protein synthesis without interleukin-6 and other cytokine influence. METHODS AND RESULTS: 20 patients (age of 38 +/- 11, 11 males, 9 females) with a diagnosis of central hypercorticolism were examined. Plasma levels of 11 acute phase proteins were estimated. These results were compared with plasma ACTH, interleukin-6, and U-cortisol concentrations and correlated to the control group (healthy volunteers, age 30 +/- 5, 13 males, 7 females). Plasma levels of albumin and prealbumin in patients with Cusing's disease were significantly lower. We proved significant elevation of alpha 1-acid glycoprotein, haemopexin, and fibrinogen compared with healthy subjects. The positive correlation of alpha 1-acid glycoprotein and U-cortisol (r = 0.51, p < 0.01), haemopexin and U-cortisol (r = 0.47, p < 0.05) respectively was found. CONCLUSIONS: The interaction between glucocorticoids and proinflammatory cytokines in acute phase protein synthesis depends on permissive effects of corticoids on cytokine signal transduction in hepatocytes. However, our results document that corticoida themselves significantly stimulate acute phase protein synthesis, and this stimulation differs from inflammatory pattern of hepatic proteosynthesis.

Acute-Phase Proteins↗

Leptin as an acute phase reactant after non-adjustable laparoscopic gastric banding.

BACKGROUND: Leptin is a hormone that regulates food intake; its concentrations are elevated in the majority of obese individuals. During inflammation, plasma leptin is usually increased and may contribute to the anorexia and cachexia of infection. The purpose of this study was to characterize the dynamics of circulating leptin in the early postoperative period in relation to the acute phase response in extremely obese patients undergoing laparoscopic non-adjustable gastric banding (LNAGB). We compared plasma leptin changes with 4 proinflammatory cytokines and BMI. METHODS: The prospective study was performed on 18 patients with 3rd degree obesity. Plasma concentration of leptin, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, soluble IL-2 receptor (sIL-2R), and IL-6 were estimated before operation and 24, 48, and 72 h after NALGB. RESULTS: We demonstrate statistically significant elevation of plasma leptin concentration (32.2 +/- 10.2 micrograms/l) 24 h after operation compared with preoperative status (18.4 +/- 5.2 micrograms/l, p < 0.05). There was diminished correlation of plasma leptin and BMI in this period. Leptin levels +48 and +72 h after banding quickly returned to preoperative levels. The regression coefficient was the highest for leptin and TNF-alpha 24 h after surgery (r = 0.40, p < 0.05), and for leptin and IL-6 24 h after surgery (r = 0.29, p < 0.05). There was no significant correlation between leptin and IL-1 and between leptin and sIL-2R respectively. CONCLUSIONS: During the non-infectious stress response (as with abdominal surgery), leptin shows itself as an acute phase reactant. Proinflammatory cytokines can be the main regulatory factors of leptin in this period. Significant correlation between leptin and TNF-alpha (similarly demonstrated by other authors in models of bacterial inflammation) indicates that TNF-alpha can be a crucial regulator of leptin generation in the early postoperative period.

Acute-Phase Reaction↗

[Dynamics of leptin plasma levels after abdominal surgical procedures].

UNLABELLED: In addition to its basic role as regulator of the amount of body fat and food intake leptin plays a part also as an acute phase reactant. A rise of the leptin level during this period may be associated with anorexia and cachexia in relation to general inflammatory manifestations. The objective of the present study was to characterize the dynamics of the leptin concentration in patients after intraabdominal surgery. PATIENTS AND METHODS: The prospective study was implemented in a group of 16 men subjected to planned surgery--resection of colorectal carcinoma. The plasma leptin concentration (RIA), TNF alpha, IL-beta. IL-6, sIL-2R (ELISA), CRP, alpha-1-antitrypsin, alpha-1-acid glycoprotein and ceruloplasmin (nephelometry) were assessed before surgery and then +24, +48 and +72 hours after the beginning of the operation and compared with concentrations in healthy subjects. RESULTS: Plasma leptin concentrations culminate +24 hours after surgery and in this stage they do not correlate with the BMI. Within 48 hours the concentration reaches rapidly normal levels. TNF alpha, IL-6 and sIL-2R reach maximal levels 24-48 hours after the onset of surgery with a subsequent slow decline. All acute phase proteins (APP) have prolonged dynamics with an elevation within +72 hours. A significant correlation was proved between the leptin concentration and TNF alpha 24 hours after surgery (r = 0.43, p < 0.05) and between leptin and IL-6 24 hours after surgery (r = 0.32, p < 0.05). CONCLUSION: The dynamics of the plasma leptin concentration during the postoperative period differ from the typical development of early indicators of the systemic inflammatory response--cytokines as well as from the dynamics of APP. Leptin elevation during this period may contribute to anorexia of patients after major surgery. However, rapid normalization of the level within 48 hours after surgery indicates however that leptin is involved also in other, so far unspecified factors with an anorectic action.

Abdomen↗

[Leptin--a new acute phase reactant].

Leptin, 16 kDa protein and the product of the Ob gene was discovered six years ago and characterized as a fat cell hormone which maintains via specific receptors in the hypothalamus by a feedback mechanism the energy balance and body weight. Research conducted during the last three years detected further properties of this protein which include it, in addition to its basic role in mammalian metabolism, also among acute phase reactants. Leptin is as to its structure, pattern of the receptor and the postreceptor transduction mechanism close to the group of cytokines of interleukin 6, in particular the granulocytic colony stimulating factor. During infectious and non-infectious inflammatory reactions leptin synthesis is stimulated by a combination of inflammation promoting cytokines. The mechanism of induction is not known so far but the majority of investigations proves an indirect stimulating effect of the tumour necrosis factor and interleukin 1, depending on non-specified cytokines of the second stage. Investigations of cell lines and animal experiments provided evidence of some local and systemic effects of leptin which may play a physiological part in the acute phase reaction. Leptin mediates at least partly the anorectic effect of the tumour necrosis factor and interleukin 1 during inflammation. Synergically with bacterial antigens it activates macrophages, enhances their phagocytic capacity and stimulates secretion of pro- and anti-inflammatory factors from macrophages. Leptin stimulates neovascularization, it has a stimulating effect on precursors of white blood cells and potentiates the effect of erythropoietin on red blood cells. It is obviously an essential factor for T-lymphocyte proliferation and development. The authors discuss also the role of leptin in the modulation of the hypothalamo-pituito-adrenal stress axis. Leptin is a factor of the inflammatory mediator network, probably essential for an adequate course of the inflammatory defence reaction.

Acute-Phase Proteins↗

[Percutaneous electrogastrography in the perioperative period in laparoscopic gastric banding at the First Surgical Clinic of the General Faculty Hospital in Prague].

Percutaneous electrogastrography (EGG) is a method which makes non-invasive follow-up of the myoelectric gastric activity possible. The authors present the results of assessment of the myoelectric gastric activity during the perioperative period in patients undergoing, at the First Surgical Clinic General Faculty Hospital, laparoscopic non-adjustable gastric banding. The data were recorded using a Microdigittrapper and evaluated using spectral analysis and Fourier's transformation. The authors mention also briefly conditions which must be met to ensure the study, and the physiological and pathophysiological background of the method. In 14 patients the ECG record was made 24 hours prior to surgery and then 5 hours, 24 and 48 hours after surgery on fasting and after a fluid bolus. The assembled results of the dynamics of perioperative changes on the EGG were compared with results obtained in a group of healthy volunteers. The most frequent finding during the early postoperative period was bradygastria, the return to preoperative values occurred on average 48 hours after surgery. Percutaneous electrogastrography is a non-invasive method which can provide the surgeon during the early postoperative period with information on myoelectric gastric activity.

Adult↗

Serum leptin levels in septic men correlate well with C-reactive protein (CRP) and TNF-alpha but not with BMI.

Leptin, an adipocyte-derived signaling factor, is a member of the IL-6 cytokine family. However there is no direct evidence of leptin stimulation of the acute phase protein (APP) synthesis which is typical for all other IL-6-like factors. The purpose of this study was to characterize the dynamics of circulating leptin in relation to ten APPs. We used postoperative septic patients as a model of cytokine network hyperstimulation and intensive APP reaction. The prospective study was performed on 22 patients with proven postoperative intraabdominal sepsis after large abdominal surgery. Plasma levels of leptin, TNF-alpha, IL-1beta, soluble IL-2 receptor (sIL-2R), IL-6 (ELISA analysis) and ten APPs (nephelometric analysis) were estimated. We have demonstrated a statistically significant elevation of plasma leptin concentrations in the septic group compared with healthy subjects (p<0.001). The correlation of plasma leptin and BMI during postoperative sepsis was diminished. The regression coefficient was the highest for leptin and CRP (r=0.48, p<0.05), and for leptin and alpha-1-antitrypsin (r=0.46, p<0.05) in the septic group. There was significant correlation between TNF-alpha and leptin (r=0.47, p<0.05) and between IL-6 and leptin (r=0.45, p<0.05) in septic patients. No significant correlation was found between leptin and "negative" APP and between leptin and IL-1beta. Leptin has thus been shown as an acute phase reactant with a potential hematopoietic, immunomodulatory and hepatocyte stimulating activity during the infectious and non-infectious stress response. The significant correlation between leptin and CRP and leptin and alpha-1-antitrypsin indicates that leptin can participate in APP synthesis regulation during a systemic inflammatory response.

Adult↗

Physiology and genetics of procalcitonin.

Procalcitonin (PCT), a protein of 116 amino-acids with molecular weight of 13 kDa, was discovered 25 years ago as a prohormone of calcitonin produced by C-cells of the thyroid gland and intracellularly cleaved by proteolytic enzymes into the active hormone. Circulating levels of PCT in healthy subjects are below detection limit. Since 1993 when its elevated level was found in patients with bacterial infection, PCT became an important protein in the detection and differential diagnostics of inflammatory states. The production of PCT during inflammation is linked with a bacterial endotoxin and with inflammatory cytokines (TNF, IL-6). PCT detectable in the plasma during inflammation is not produced in C-cells of the thyroid. The probable site of PCT production during inflammation are the neuroendocrine cells in the lungs or intestine. There is no evidence of plasma PCT binding to cellular receptors of calcitonin, and the role of PCT in calcium and phosphate metabolism during sepsis is still not clear. Other hypothetical roles of PCT (cytokine network regulation, PCT as an endogenous non-steroid antiinflammatory drug) are being considered.

Analgesics↗

[Cytokines in the diagnosis of peritoneal inflammation].

Early diagnosis of peritoneal inflammation in the initial stage with equivocal clinical manifestations is not always simple. At present there are in the literature many new laboratory indicators which to a different extent describe the inflammatory process. In the present paper the authors focused attention on the practical importance of the use of cytokines in the diagnosis of peritoneal inflammations. They compare the diagnostic impact of clinical examination as compared with assessed plasma concentrations of inflammation promoting cytokines. The authors maintain that the diagnosis of secondary peritonitis is based on the clinical examination of the patient. Elevated values of PCT or IL-6 can support this clinical conclusion. In postoperative peritonitis dynamic investigation of cytokines is important. The diagnosis of tertiary peritonitis is based on laboratory findings.

Biomarkers↗

[Postoperative immunosuppression--a physiological process and source of complications. Minireview].

Postoperative immunosuppression reflects non-specific neurohumoral stress responses to surgical trauma. Surgical stress in the early stage is characterised by a dysbalance of the adrenocortical response, the index of the formation of glucocorticoids and dehydroepiandrosterone is shifted to the glucocorticoids. This non-specific hormonal response has an impact on the balance between TH1 and TH2 lymphocyte response. Inhibition of the TH1 response occurs, the clinical reflection of which is a decline of cell-mediated immunity. Postoperative immunosuppression and dysbalance of cell-mediated and humoral immunity are physiological processes, part of the neurohumoral stress response to surgical trauma. Its potential pathological consequences, although proved so far only experimentally, make it on the one hand an important factor for evaluation of the risk of postoperative complications and on the other hand a possible of object of therapeutic intervention in oncological or high risk patients.

Adjuvants, Immunologic↗

[Preventing the development of secondary infections in severe acute pancreatitis].

Severe acute pancreatitis is in its first stage characterized by the syndrome of systemic inflammatory response (SIRS). The extent of activation of the mediator defense cascade of the organism depends on a hitherto unknown primary insult which cannot be influenced by therapeutic care. The cause of the development of sepsis or multiorgan failure is the supraliminal action of secondary insults (ischaemic reperfusion syndrome, hypoxia, impaired physiological function of the gut). By early and aggressive therapeutic action the effect of these adverse factors can be markedly reduced. Then also better therapeutic results in severe acute pancreatitis may be expected.

Humans↗

[Use of procalcitonin in surgery].

Procalcitonin (PCT) is a new early indicator of developing systemic bacterial infection. As compared with other anti-inflammatory markers (cytokines, acute stage proteins), the attained plasma levels during extensive but uncomplicated surgery are by orders lower than maximal levels during sepsis. The authors assume that PCT will be used in surgical practice as an early indicator of developing systemic bacterial infection (in multiple injuries, after surgery) and for subsequent evaluation of the effectiveness of treatment of septic conditions.

Bacterial Infections↗

[Pathophysiology of development of acute pancreatitis].

Acute pancreatitis is a severe illness with unclear prognosis and mortality rate ranging from 5 to 70%. Dynamic observation of changes in systemic inflammatory response of the body may be helpful in estimating the development of acute pancreatitis as well as giving an idea of therapeutical possibilities. It is obvious, that the intensive therapeutic intervention may reduce the influence of secondary insults (ischemic-reperfusion syndrome, hypoxia, disrupted physiological function of the bowel) on pancreatic tissue. Surgery is limited only for precisely specified indications in the latter stage of acute pancreatitis (secondary inflammation of the necrosis). In this paper we conclude some pathophysiological mechanisms involved in the development of acute pancreatitis.

Acute Disease↗

[The significance of cytokines in the early diagnosis of postoperative intraabdominal sepsis].

The objective of the investigation was to evaluate the possible use of selected cytokines and cytokine receptors in the early diagnosis of postoperative intraabdominal sepsis. The investigation was focused on the dynamics of plasma levels of tumour necrotizing factor-alfa (TNFalfa), interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, soluble receptors IL-2 and IL-6 (sIL-2R and sIL-6R) and the receptor antagonist IL-1 (IL-1ra). The investigated parameters were tested on model operations (resection of large bowel and resection of pancreas). These two groups were compared with values recorded in patients with sepsis and with healthy subjects. Based on the assembled results the authors recommend to use for postoperative investigations the first 48 hours and to follow up the following parameters: IL-6, IL-ra or sIL-2R. During the first 48 hours these indicators differentiate sufficiently specifically incipient sepsis from an uncomplicated postoperative condition. During the subsequent period, i.e. more than 48 hours after surgery, it is useful to include in the examination pattern also some acute stage proteins (C reactive protein, alfa1-antitrypsin and haptalobin) which differentiate sepsis between the 3rd and 5th day after surgery.

Abdomen↗

[Cytokine therapy].

Cytokines, mediators of intercellular communication, penetrate as a new therapeutic group in to haematology, oncology, immunology and other disciplines. Recently two main spheres of indication of wider clinical use are in the foreground: 1. treatment of leukaemias and advanced solid tumours (interferons, interleukin-2, tumour-necrosis factor and others) and 2. treatment of impaired haematopoiesis (in clinical practice in particular erythropoietin, granulocyte-macrophage and granulocyte colonies stimulating factor). Other possibilities are offered by cytokines in the treatment of viral diseases (in addition to hepatitis B and C, perspectively also AIDS), inborn immunodeficiencies, progressive systemic sclerosis and other indications. In particular in oncological diseases, contrary to original assumptions, monotherapy with cytokines will not be greatly extended and a combination of cytokines with classical treatment will be used. The limiting factor in addition to cost is the considerable toxicity of some cytokines which calls for alternative routes of administration (local, compartmental etc).

Cytokines↗

The effect of protoporphyrinogen oxidase inhibitors on microsomal and mitochondrial cytochromes.

Neurological dysfunction is a characteristic feature of acute porphyrias, unexplained until now. One of the possible explanations is a deficiency of heme in the central nervous system, caused by a block in porphyrin biosynthesis. To test this possibility, the content of brain mitochondrial cytochrome a3 was determined after intracerebroventricular administration of the protoporphyrinogen oxidase-inhibiting herbicide fomesafen. It was established in in vitro experiments that fomesafen is a potent inhibitor of brain mitochondrial protoporphyrinogen oxidase (PROTOOX). Addition of 10(-6) M fomesafen to incubation mixture decreased PROTOOX from 1.02 nmol/mg/h (controls) to 0.42 nmol/mg/h. 10(-5)M of fomesafen decreased this activity to 0.27 nmol/mg/h. In in vivo experiments, 5 microleters of fomesafen solution containing 0.2 M fomesafen/l was administered to male rats by intracerebroventricular injection. The content of brain mitochondrial cytochrome a3 was determined 72 hours later. A slight decrease of the a3 content was observed (control rats 0.25 nmol/mg protein, treated rats 0.22 nmol/mg). Brain cytochrome P450 activities were below detection limits in both control and treated groups. In a separate experiment, male ICR mice were fed 1000 ppm of the protoporphyrinogen oxidaseinhibiting herbicide oxadiazon in the diet for 10 days. Liver microsomal cytochrome P450 content was decreased and liver porphyrins increased. An increase of porphyrin content was also observed in the testes of oxadiazon-fed mice, but testicular cytochrome a3 content was unchanged. The results indicate that, contrary to liver microsomal cytochromes P450, the mitochondrial cytochromes are not susceptible to changes in heme biosynthesis.

Animals↗

[Acute phase proteins].

Various plasma protein patterns following inflammation and metabolic stress were described since diagnostic value of ESR was established. This reactive dysproteinemia is now recognized to reflect the shift in hepatic proteosynthesis after the immunoendocrinological activation. Four main groups of mediators are necessary for expression of hepatic positive and negative acute phase proteins (APPs): first and second "wave' of proinflammatory cytokines, further glucocorticoids and growth factors including insulin. Actual data showing details of the immunological and endocrinological regulation of stress hepatocyte proteosynthesis are summarized and our own results are presented. We evaluated the diagnostic use of APPs in some defined clinical situations (neutropenic period after bone marrow transplantation, postoperative complications) and correlated APPs with the plasma levels of the circulating interleukin-6 and cortisol. In another study, APPs, plasma and urinary TNF, interleukin-6, interleukin-8 and adhesive molecules ICAM-1, VCAM-1 were found to be significantly different in various glomerulopathies. Finally, our experimental data indicate the nitric oxide participation in oestradiol regulation of coeruloplasmin synthesis in rat.

Acute-Phase Proteins↗

[Evaluation of laparoscopic and laparotomy cholecystectomy by comparing the dynamics of acute phase proteins].

The authors investigated in two groups of surgical patients subjected to laparoscopic (n = 10) and laparotomic (n = 10) cholecystectomy changes in the levels of nine acute stage proteins. The objective was to evaluate the extent of surgical stress of the two surgical procedures with regard to changes of serum levels of albumin, transfirrin, prealbumin, alpha 1-antitrypsin, alpha 1-acid glycoprotein, alpha 2-macroglobulin, haptoglobin, ceruloplasmin and C-reactive protein. Before operation no significant differences (p < 0.05) were found between the investigated indicators. Changes of acute stage proteins up to the third day following surgery indicate a lower surgical trauma and more favourable course during the early postoperative period in patients operated by the laparoscopic route.

Acute-Phase Proteins↗

Methylene blue inhibition of oestradiol-induced increase of ceruloplasmin serum levels in rats.

The administration of oestrogens increases the hepatic synthesis and plasma level of ceruloplasmin both in man and laboratory animals. Methylene blue, an oxidizing agent and inhibitor of soluble guanylate cyclase, is widely used to block the effects of endothelium-derived relaxing factor (nitric oxide). We describe the inhibitory effect of methylene blue on the increase of ceruloplasmin plasma level in rats during oestradiol treatment.

Animals↗