Biomedical subjects

Mihály Boros

Publications and source records attributed to Mihály Boros.

17 recordsLinked to original sources

PubMed2006

Gender differences in ischemia-reperfusion-induced microcirculatory and epithelial dysfunctions in the small intestine.

Female sex hormones have been reported to preserve endothelial integrity and to reduce inflammation. However, gender-related differences in the intestinal mucosal barrier function during compromised perfusion after ischemia and transplantation have not been defined. Herein, we applied intravital microscopy to determine the mucosal epithelial and intestinal microcirculatory responses in ileal villus and longitudinal muscle layers in a murine model of 30-min intestinal ischemia and 90-min reperfusion. In male animals, the entire reperfusion period was characterized by a significantly increased epithelial permeability. This was associated with an early leukocytic inflammatory response and late alterations in functional capillary density, capillary red blood cell velocity and mitochondrial redox state. In contrast, the female intestine exhibited a delayed increase in epithelial permeability during postischemic reperfusion. This was associated with a late leukocytic inflammatory response which did not affect the microcirculatory function. Nonetheless, at the end of the 90-min reperfusion period, the neutrophilic infiltration and structural mucosal disintegration in the female intestine were found to be pronounced to a similar extent as in the male intestine. These results suggest that in small intestinal ischemia-reperfusion the leukocytic inflammatory response and microcirculatory dysfunction develop more rapidly and are initially more pronounced in males, but the hormonal status in females is not capable of preventing the final manifestations of reperfusion injury.

Animals↗

PubMed2006

Intestinal nitric oxide synthase activity changes during experimental colon obstruction.

OBJECTIVE: The experiments in this study were designed to follow the time course of nitric oxide (NO) synthesis in the large bowel during acute mechanical ileus. MATERIAL AND METHODS: Occlusion of the mid-transverse colon was maintained for 420 min in anesthetized dogs. Strain-gauge transducers were used to analyze motility changes on the hepatic and lienal flexures, respectively. Constitutive NO synthase (cNOS) and inducible NOS (iNOS) activities were determined in tissue biopsies, and plasma nitrite/nitrate (NOx) level was measured in the portal blood. Following completion of the baseline studies, the animals were treated with either 7-nitroindazole (7-NI, selective neuronal NOS inhibitor), or N-nitro-L-arginine (NNA, non-selective NOS inhibitor). RESULTS: In the sham-operated group the cNOS activities differed significantly in the oral and aboral tissue samples (oral: 102.9; versus aboral: 62.1 fmol/mg protein/min). The obstruction elicited a significant increase in portal NOx and elevated tissue inducible NO synthase (iNOS) activity. NNA treatment decreased the motility index in both intestinal segments for 60 min, but 120 min later the motility index was significantly elevated (2.5-fold increase in the oral part, and 1.8-fold enhancement in the aboral segment, respectively). Treatment with 7-NI decreased the cNOS activity in the oral and aboral parts by approximately 40% and 70%, respectively, and suppressed the motility increase in the aboral colon segment. CONCLUSIONS: The motility of the colon was either significantly increased or decreased, depending on the type and selectivity of the NOS inhibitor compounds applied. NO of neuronal origin is a transmitter that stimulates peristaltic activity; but an increased iNOS/nNOS ratio significantly moderates the obstruction-induced motility increase.

Animals↗

PubMed2005

[Dual effects of nitric oxide in acute colon obstruction].

UNLABELLED: Nitric oxide (NO) plays central role in the pathophysiology of large bowel diseases. In the gastrointestinal tract the predominant form of nitric oxide synthase (NOS) isoenzymes is neuronal NOS (nNOS). The aims were to investigate the role of NO and the activation of NOS isoforms during acute colonic obstruction. Haemodynamic changes, large bowel motility and plasma levels of nitrate-nitrite (NOx) were observed for 7 hrs in anaesthetized dogs. Group 1 (n=6) served as sham-operated control. In groups 2 (n=8), 3 (n=6), and 4 (n=6) colon obstruction was initiated. Groups 3 and 4 were treated with non-selective NOS inhibitor N-nitro-L-arginine (NNA, 4 mg/kg) or with the selective nNOS inhibitor 7-nitroindazol (7-NI, 5 mg/kg) 3 hr after the obstruction. At the end of the experiments, tissue biopsies were taken from the oral and aboral parts of the colon to determine the constitutive and inducible NOS (cNOS and iNOS, respectively) activities. RESULTS: The cNOS activity of the colon was significantly higher orally then aborally in each group. After obstruction the characteristic features of hyperdynamic sepsis were observed. The obstruction caused significant increase in iNOS activity, which was significantly reduced by the NOS inhibitors. The obstruction increased the motility on both parts of the colon. The administration of NNA transiently inhibited, but later significantly increased the motility of the colon segments. Inhibition of nNOS by 7-NI treatment did not influence the hemodynamic parameters but decreased the motility. CONCLUSION: Neuronal NO increases colon motility at the early stage of large bowel obstruction, however, during a concomitant sepsis the excess of inducible NO will moderate this effect.

Acute Disease↗

PubMed2005

[Effects of phosphatidylcholine pretreatment during acute experimental biliary reflux].

UNLABELLED: Biliary regurgitation plays important role in gastro-esophageal reflux disease and postoperative complications. Our major aims were to find out the consequences of short-term exposure with luminal bile on mucosal microcirculation and nitric oxide synthesis, and to determine the effects of systemic phosphatidylcholine pretreatment in this condition. The experiments were performed on inbred mongrel dogs. Group 1 (n=5) served as a saline-treated control, while in group 2 (n=5) the esophagus was exposed to bile for 3 h. In group 3 (n=5) the animals were pre-treated with 7-nitroindazole (7-NI), to inhibit the neuronal isoform of nitric oxide synthase. In group 4 (n=5) phosphatidylcholine (PC) solution (50 mg/kg) was administered iv before the biliary challenge. The microcirculation of the mucosa was observed by intravital videomicroscopy; myeloperoxidase and nitric oxide synthase activities, the degree of mast cell degranulation and tissue damage were evaluated via tissue biopsies. Exposure to bile evoked significant mast cell degranulation and leukocyte accumulation, and the red blood cell velocity (VRBC) and the diameter of the postcapillary venules (VD) increased significantly. The tissue ATP content and constitutive nitric oxide synthase activity decreased, while the inducible nitric oxide synthase activity increased significantly as compared with the control values. 7-NI treatment significantly exacerbated the mucosal mast cell degranulation and tissue damage. In contrast, PC pretreatment reversed the bile-induced ATP depletion, the inducible nitric oxide synthase and myeloperoxidase activity increases, and the mast cell degranulation. CONCLUSIONS: The neuronal nitric oxide synthase--mast cell axis plays an important role in the esophageal mucosal defense system. Systemic PC pretreatment affords effective protection through ameliorating the bile-induced ATP depletion and secondary inflammatory reaction.

Adenosine Triphosphate↗

PubMed2004

[Heterogeneity of small intestinal microcirculation].

INTRODUCTION: Microcirculatory disorders play important roles in the impairment of the mucosal barrier of the small intestine. Circulatory failures may increase the heterogeneity of microvascular perfusion, however, conventional methods are inadequate to describe an evolving heterogeneity in time or space. The authors aims were to examine and characterize the microcirculatory reactions in the mucosa and longitudinal muscle of the small intestine in clinically relevant experimental models of circulatory disorders. METHODS: Intravital videomicroscopy with orthogonal polarization spectral imaging technique was used to visualize the microcirculation. A mathematical approach was applied to describe the temporal variability in perfusion based on the calculation of average red blood cell velocity from the relative time periods of observed velocity, while spatial heterogeneity was calculated as a function of the perfused area. The authors' experiments were performed after 1. sham operation, 2. during hemorrhagic shock and crystalloid resuscitation, 3. during 2-hr endotoxin infusion, 4. in response to nitric oxide synthesis inhibition, and 5. after superior mesenteric artery occlusion and reperfusion. RESULTS: During hemorrhagic shock a fluctuating flow pattern appeared in the mucosa, the average red blood cell velocity decreased by 40% in the villi and by 60% in the muscle. Ischemia caused 20% flow reduction in both layers, while endotoxin caused a temporary 20% decrease in the mucosa, and a persistent, over 25% decrease in the muscle layer. Nitric oxide synthesis inhibition resulted in a 40% decrease in both structures. CONCLUSIONS: Heterogeneity of microcirculatory perfusion may appeared both spatially (between or within anatomical layers) and in time (periodically) after the insults. A redistribution of blood flow favouring the mucosa evolves in the small intestine after systemic circulatory disorders. Heterogenous perfusion-related microcirculatory changes can be characterized with mathematical approaches, and these calculations should be taken into account during the comparison of the consequences of distinct circulatory failures involving the small intestine.

Animals↗

PubMed2004

[Surgery of benign liver tumors: indications for treatment. Personal experience and review of the literature].

BACKGROUND AND AIMS: Our aim is to give an audit of our experience over the past two decades in the form of a retrospective study. PATIENTS/METHODS: Between 1 January, 1982 and 15 December, 2001, 133 patients with benign liver tumor (adenoma: 22, focal nodular hyperplasia: 27, hemangioma: 83, lipoma: 1) were treated. A total of 113 patients underwent surgery, while 20 asymptomatic cases were merely observed. The mean age, the female/male ratio and the size of the tumor in the adenoma cases were 38.3+/-10.2 years, 20/2 and 7.7+/-2.4 cm, while for focal nodular hyperplasia they were 39.5+/-12.4, 24/3 and 6.3+/-2.7 cm, and for hemangioma 49.01+/-10.7, 62/21 and 6.5+/-3.6 cm. The results were compared and analyzed statistically. RESULTS: Enucleation was performed in 53.1% of the patients, non-anatomical resection in 24.8%, segmentectomy in 6.2%, lobectomy in 4.4%, extended lobectomy in 1.8%, stitching in 5.3%, exploration in 3.5% and liver transplantation in 0.9%. The overall 30-day postoperative mortality was 0.9% (1/113). Minor or major complications occurred in a total of 27.4%. CONCLUSIONS: Patients with asymptomatic focal nodular hyperplasia or hemangiomas must be excluded from surgery. Surgery is indicated only when growth or severe complaints are observed. Adenomas must be resected because of the precancerous behavior and the danger of bleeding from a rupture.

Adult↗

PubMed2004

Microcirculatory heterogeneity in the rat small intestine during compromised flow conditions.

OBJECTIVE: To characterize and compare microcirculatory changes in the rat small intestinal tissue layers when temporal or spatial microvascular perfusion heterogeneity is present. METHODS: Intravital videomicroscopy with an orthogonal polarization spectral imaging technique was used to visualize the microcirculation of the intestinal mucosa and the longitudinal muscle during systemic (hemorrhagic shock, endotoxemia, and nitric oxide synthesis inhibition) and local (ischemia-reperfusion) circulatory disorders. The average capillary red blood cell velocity (A-RBCV) was calculated from the relative durations of the observed velocity or as a function of the perfused area, respectively. RESULTS: During hemorrhagic hypotension/resuscitation, timewise (flowmotion) and spatial heterogeneity were found to evolve in the mucosal villi and muscle layer. During resuscitation, the A-RBCV decreased by 40% in the villi and by 60% in the muscle. Reperfusion after a 30-min period of mesenteric ischemia caused a 20% reduction in A-RBCV in both layers, while endotoxin infusion caused a temporary 20% decrease in the mucosa, and a persistent, >25% decrease in the muscle. Nitric oxide synthesis inhibition resulted in spatial heterogeneity within the villi and in a 40% decrease in A-RBCV in both structures. CONCLUSIONS: Calculations of timewise variability and of heterogeneity within and between layers can be used for the comparison of distinct intramural microcirculatory changes.

Abdominal Muscles↗

PubMed2004

Flow motion in the intestinal villi during hemorrhagic shock: a new method to characterize the microcirculatory changes.

Conventional parameters are often inadequate to describe the dynamic flow changes in microcirculation. We used a novel approach to characterize oscillatory flow conditions in a canine model of hemorrhagic shock. Microcirculation in the ileal mucosal villi was visualized using intravital microscopy with the orthogonal polarization spectral imaging technique. The distribution of red blood cell velocity (RBCV) was estimated from the relative time periods of observed RBCV, and the average RBCV (A-RBCV) and its SD were then computed from the first and second moments of the RBCV distribution, respectively. Hemorrhagic shock (for 60 min) was followed by resuscitation with saline, hypertonic saline-Dextran solution (HSD, 7.2% NaCl-10% Dextran, 4 mL/kg), or HSD supplemented with the selective endothelin-A receptor antagonist ETR-p1/fl peptide (100 nmol/kg), respectively. The macrohemodynamic derangement (70% decrease in cardiac index and ileal blood flow) during shock was associated with the appearance of flow motion in the villi and an enhanced endothelin-1 release. The calculated A-RBCV was decreased by 40%. At resuscitation onset, continuous flow periods were transiently seen in 33%, 40%, and 50% of the experiments after saline, HSD, and HSD + ETR p1/fl treatment, respectively. HSD with or without endothelin-A antagonist treatment resulted in an increased relative duration of high-flow periods (by 20%) and a significant, 20% to 40% rise in A-RBCV. These results demonstrate that time-wise variability of RBCV should be used for the analysis of oscillatory flow conditions. The probabilistic estimation of A-RBCV provides a quantitative basis for comparison of the effectiveness of different resuscitation or vasoactive strategies.

Animals↗

PubMed2003

Simultaneous generation of methane, carbon dioxide, and carbon monoxide from choline and ascorbic acid: a defensive mechanism against reductive stress?

Indirect evidence suggests that an abnormal increase in reducing power (reductive stress) may be associated with abnormal clinical states. We have recently proposed that under such conditions biomolecules with electrophilic methyl groups (EMGs) bound to positively charged nitrogen or sulfur moieties may act as electron acceptors and that this poising mechanism may entail the generation of methane gas. Here we report for the first time the generation of methane by rat liver mitochondria. We also report the formation of methane from choline in the presence of hydrogen peroxide, catalytic iron, and ascorbic acid. In this system, carbon monoxide and carbon dioxide are formed from the ascorbate molecule in parallel with methane generation. In view of these findings, we try to explain the essential role of biomolecules with EMG moiety. We hypothesize that this concerted reaction may be a defensive response to reductive stress and may provide the protection needed against redox imbalance in living systems.

Animals↗

PubMed2003

Thoracic epidural anesthesia improves the gastric microcirculation during experimental gastric tube formation.

BACKGROUND: Gastric tube formation is a surgical technique to reestablish the continuity of the gastrointestinal tract after esophagectomy. Our aims were to study the microcirculatory consequences of experimental gastric tube formation and characterize the effects of thoracic epidural anesthesia (TEA) during this condition. METHODS: The experiments were performed on mongrel dogs anesthetized with pentobarbital. The stomach was prepared for replacement according to the method of Akiyama, and TEA was induced with bupivacaine (1 mg/kg). Macrohemodynamics, intramucosal pH, and gastric motility changes were monitored, and intravital video-microscopy with orthogonal polarization spectral imaging technique was used to observe the gastric microcirculation. RESULTS: The gastric pull-up induced a significant decrease in intramucosal pH. The functional capillary density of the mucosa or subserosa did not change; the red blood cell velocity in the capillaries of the upper part of the gastric tube was decreased in the mucosa, as well as on the serosal side. After epidural anesthesia the red blood cell velocity returned to the baseline, and the gastric and intestinal motility index was significantly increased. CONCLUSIONS: TEA significantly improves the microcirculation of the distal portion of the gastric tube and increases the intestinal and gastric motility after gastric pull-up. The procedure is favorable and should be recommended during reconstructive esophageal surgery.

Anesthesia, Epidural↗

PubMed2003

[Changes in microcirculation of esophageal mucosa during acute experimental reflux. Pathogenic role of the biliary component].

UNLABELLED: Our aims were to examine microcirculation during experimental reflux esophagitis in dogs. We compared the effects of microcirculation of the mucosa to 3-hr exposure with acid, mixed acid and bile, we measured the changes in constitutive and inducible nitric oxide synthase activity (cNOS and iNOS). METHODS: The microcirculation of the upper esophagus was investigated by intravital videomicroscopy. The functional capillary density (FCD), relative vessel area (RVA) and red blood cell velocity (RBCV) were measured. Mucosal barrier integrity was examined by vascular and epithelial permeability indices. Myeloperoxidase (MPO) enzyme activity, cNOS, iNOS activities and microscopic damage were examined in biopsies. RESULTS: The vascular permeability index, the RBCV and the RVA increased significantly in the treated groups, the FCD significantly decreased after acid exposure. The MPO and iNOS activities were significantly elevated in all treated groups. The cNOS activity did not change after exposure to acid + bile or acid, but significantly decreased after sole bile treatment. Severe mucosal damage was observed after bile exposure. CONCLUSION: Bile induced characteristic microcirculatory changes during experimental reflux esophagitis. Tissue damage and leukocyte infiltration could be exacerbated by bile-induced cNOS inhibition.

Animals↗

PubMed2003

[Microcirculation of the small intestines in local and generalized circulatory disorders].

INTRODUCTION: Microcirculatory disturbances are known to affect the integrity of the gastrointestinal barrier. In our experiments, we aimed at characterizing the intramural microcirculatory reactions in response to various circulatory disorders using intravital microscopy with orthogonal spectral imaging technique. For the analysis and comparison of the microcirculatory reactions in the intestinal ileal mucosa, longitudinal muscle and Peyer's patches, a novel mathematical formula was established. METHODS: The microcirculatory consequences of mesenteric artery occlusion, endotoxemia, hemorrhagic shock and nitric oxide synthesis inhibition were characterized. RESULTS: During reperfusion, red blood cell velocity (RBCV) decreased by approx. 20% in all layers which persisted by end of the observation. In response to endotoxin, microcirculation of the muscle was more affected than that of the mucosa. In the hypovolemic phase of hemorrhagic shock and the late phase of resuscitation, a characteristic oscillatory flow pattern appeared in the villi and the weighed arithmetic average of RBCV decreased by 50%. NO synthesis inhibition caused an approx. 40% fall in RBCV in all layers and a spatial heterogeneity in the villi. CONCLUSION: Systemic circulatory disorders are characterized by a non-uniform microcirculatory failure and a redistribution of blood flow between the different layers favouring the mucosa. Using the suggested mathematical formula, the microcirculatory alterations can be characterized and compared.

Animals↗

PubMed2002

Experience with different methods of treatment of nonparasitic liver cysts.

BACKGROUND AND AIMS: In a search for the optimal management of nonparasitic liver cysts, a study was made of the effectiveness of different methods. PATIENTS AND METHODS: Between 1 January 1982 and 15 December 2001 we treated 132 patients with nonparasitic liver cysts. In 72 patients 31 cysts were treated with enucleation, 60 with deroofing, and 24 with stitching by laparotomy; two liver resections were also performed. In a further 34 patients 36 cysts were treated with deroofing by minimally invasive surgery. In an additional 26 patients 32 cysts were treated with various interventional radiological methods. RESULTS: There was no mortality. The morbidity rate after laparotomy was significant (22.2%). The rate of recurrence after enucleation and deroofing was 6.5% and 13.8%, respectively, but there were no recurrences after stitching and liver resection. The recurrence rate following laparoscopic deroofing was 19.4%, and that following interventional radiological procedures was 50%. CONCLUSIONS: Treatment is required only if cysts are highly symptomatic or if growth is detected. Interventional radiological methods do not prove more favorable than surgery. Laparoscopic fenestration is preferred because of its low morbidity and the short period of hospitalization. Traditional surgical methods should be reserved merely for cases in which laparoscopic deroofing is not feasible.

Adult↗

PubMed2002

Dynamic in vivo observation of villus microcirculation during small bowel autotransplantation: effects of endothelin-A receptor inhibition.

BACKGROUND: The aims of this study were to characterize the structural and microcirculatory changes in single intestinal villi during ischemia and reperfusion and determine the site of action of endothelin (ET)-A receptor inhibition during compromised mucosal perfusion. METHODS: Small bowel autotransplantation was performed in anesthetized dogs. One group was treated with the ET-A receptor antagonist ETR-p1/fl peptide. The epithelial thickness and villus microcirculatory parameters were observed by orthogonal polarization spectral imaging; the leukocyte-endothelial cell interactions were quantified with fluorescence videomicroscopy. RESULTS: Sixty-minute cold ischemia and 240-min reperfusion induced a decrease in villus functional capillary density and leukocyte-endothelial cell interactions. The epithelial layer was gradually removed, but denuded villi were not observed. ET-A receptor inhibition reduced the leukocyte adherence and attenuated epithelial exfoliation and the decrease in villus functional capillary density. CONCLUSIONS: ET-A receptor activation mediates microvascular dysfunction through precapillary blockades and leukocyte-endothelial cell interactions after cold ischemia and reperfusion in the canine small bowel.

Animals↗

PubMed2002

Endothelin-a receptor antagonist treatment improves the periosteal microcirculation after hindlimb ischemia and reperfusion in the rat.

OBJECTIVES: To examine the microcirculatory changes in the rat tibial periosteum after hindlimb ischemia and reperfusion and to evaluate the effects of endothelin-A (ET-A) receptor antagonist therapy in this condition. The healing and functioning of vascularized bone autografts depend mainly on the patency of the microcirculation, and the activation of ET-A receptors may be an important component of the tissue response that occurs during ischemia-reoxygenation injuries. METHODS: Wistar rats were subjected to 1 hour of hindlimb ischemia and 3 hours of reperfusion. The periosteal microcirculation was visualized by intravital fluorescence microscopy. The leukocyte rolling and adherence in the postcapillary venules and the functional capillary density of the periosteum were determined. Two separate groups were treated with the selective ET-A receptor antagonist BQ 610 or the novel ET-A receptor antagonist ETR-p1/fl peptide at the onset of reperfusion. RESULTS: Reperfusion was accompanied by a significant decrease in functional capillary density and by an increase in the primary and secondary leukocyte-endothelial cell interactions. ET-A receptor inhibition reduced the leukocyte rolling and firm adherence and attenuated the decrease in functional capillary density in both treated groups. CONCLUSIONS: ET-1 plays a major role in microvascular dysfunction in the periosteum during reperfusion. The ET-1-ET-A receptor system might be an important target for tissue salvage therapy in transplantation surgery.

Animals↗

PubMed2002

Endothelin-1 induces mucosal mast cell degranulation and tissue injury via ETA receptors.

The effects of endothelin-1 (ET-1) on mucosal mast cells are of special interest, since they may be an important component of the tissue response that occurs during ischaemic preconditioning or ischaemia/re-oxygenation injuries. Increasing doses of ET-1 were administered intravenously to anaesthetized rats. In a second series of experiments, animals were pretreated with the ET(A) receptor antagonists BQ-610 or ETR-P1/fl peptide, or with the ET(B) receptor antagonist IRL-1038. Intestinal perfusion changes were recorded, and the proportion of degranulated mast cells and the degree of mucosal damage were determined in ileal biopsies. ET-1 induced dose-dependent alterations in the haemodynamic and morphological parameters, and caused significant mast cell degranulation. These changes were inhibited significantly by pretreatment with the ET(A) receptor antagonists, but not with the ET(B) receptor antagonist. We conclude that a cross-talk exists between endothelial cell-derived humoral mediators and the intestinal mast cell system.

Analysis of Variance↗

PubMed2002

Dalteparin sodium treatment during resuscitation inhibits hemorrhagic shock-induced leukocyte rolling and adhesion in the mesenteric microcirculation.

BACKGROUND: Ischemia/reperfusion-induced polymorphonuclear neutrophil leukocyte (PMN) adhesion and extravasation are pivotal for the development of postinjury multiple organ failure. We hypothesized that the deleterious microcirculatory consequences of hemorrhagic shock (HS) could be altered by low-molecular-weight heparin (LMWH) therapy. Our aim was to investigate the effects of dalteparin sodium on leukocyte-endothelial cell interactions when LMWH treatment was initiated before HS or during resuscitation. METHODS: Anesthetized dogs underwent HS (40 mm Hg mean arterial pressure for 60 minutes) and resuscitation either with shed blood or with lactated Ringer's (LR) solution. LMWH or conventional heparin sodium pretreatment was administered subcutaneously before hemorrhage; or LMWH was given intravenously during resuscitation. Mesenteric postcapillary venules were observed by intravital video microscopy before and after HS, and 60 minutes, 120 minutes, and 180 minutes after resuscitation, and leukocyte rolling and firm adherence were determined. RESULTS: HS significantly increased PMN rolling and adhesion in the mesenteric microcirculation. LMWH, but not heparin sodium pretreatment, significantly inhibited both primary and secondary interactions. LMWH treatment was also effective when initiated during resuscitation. LMWH exerted the same inhibitory effect regardless of the type of resuscitation. CONCLUSION: LMWH treatment during resuscitation effectively inhibits PMN rolling and adhesion.

Animals↗