Thomas Brzozowski

Bio: Thomas Brzozowski is an academic researcher from Jagiellonian University Medical College. The author has contributed to research in topics: Gastric mucosa & Gastric acid. The author has an hindex of 31, co-authored 78 publications receiving 2575 citations. Previous affiliations of Thomas Brzozowski include Jagiellonian University.

Role of prostaglandins in gastroprotection and gastric adaptation.

Abstract: Since Robert discovery that pretreatment with prostaglandin (PG) applied in non-antisecretory dose can prevent the injury of gastric mucosa induced by necrotizing agents, much attention was paid to the role of these cyclooxygenase (COX) products in the mechanism of gastric mucosal integrity and ulcer healing. The ability of exogenous PG to attenuate or even completely prevent mucosal damage caused by corrosive substances such as absolute ethanol, hyperosmolar solutions or concentrated bile has been termed "cytoprotection". Increased generation of endogenous PG in the gastric mucosa exposed to the topical contact with "mild irritant" such as 20% ethanol, 1 mM NaCl or 5 mM taurocholate also prevented gastric injury caused by strong irritants via phenomenon of adaptive cytoprotection. Other mediators such as growth factors, nitric oxide (NO) or calcitonin gene related peptide (CGRP) as well as some gut hormones including gastrin and cholecystokinin (CCK), leptin, ghrelin and gastrin-releasing peptide (GRP) have been also found to protect gastric mucosa against the damage induced by corrosive substances. This protective action of gut hormones has been attributed to the release of PG or activation of sensory nerves because it could be abolished by the pretreatment with indomethacin or large neurotoxic dose of capsaicin and restored by the addition of exogenous PGE(2) or CGRP, respectively. Short (5 min) ischemia of the stomach applied before prolonged ischemia-reperfusion (I/R) attenuated markedly the gastric lesions produced by this I/R and also prevented the mucosal damage provoked by necrotizing substances. This protection could be abolished by the pretreatment with non-steroidal anti-inflammatory drugs (NSAID) and was accompanied by an enhancement of gastric mucosal COX-2 expression and activity. Exposure of gastric mucosa to single insult of acidified aspirin (ASA) causes severe mucosal damage with occurrence of multiple haemorrhagic lesions but with repeated application of ASA, the attenuation of mucosal lesions is observed, despite the profound inhibition of PGE(2) generation. This phenomenon called "gastric adaptation" does not appear to depend upon endogenous biosynthesis of PG but possibly involves enhanced production of growth factors increasing cell proliferation and mucosal regeneration. Unlike short lived gastroprotection by PG, NO, CGRP, mild irritants or short ischemia, gastric adaptation appears to be long-lasting phenomenon accompanied by increased resistance of the adapted mucosa to subsequent damage induced by corrosive agents.

Lipid peroxidation, reactive oxygen species and antioxidative factors in the pathogenesis of gastric mucosal lesions and mechanism of protection against oxidative stress - induced gastric injury

Abstract: The gastric mucosa plays an important role in the physiological function of the stomach. This mucosa acts as gastric barrier, which protects deeper located cells against the detrimental action of the gastric secretory components, such as acid and pepsin. Integrity of the gastric mucosa depends upon a variety of factors, such as maintenance of microcirculation, mucus-alkaline secretion and activity of the antioxidizing factors. The pathogenesis of gastric mucosal damage includes reactive oxygen species (ROS), because of their high chemical reactivity, due to the presence of uncoupled electron within their molecules. Therefore they cause tissue damage, mainly due to enhanced lipid peroxidation. Lipid peroxides are metabolized to malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). The local increase of MDA and 4-HNE concentration indicates ROS-dependent tissue damage. Superoxide dismutase (SOD) is the main enzyme, which neutralizes ROS into less noxious hydrogen peroxide. A decrease of SOD activity is an indicator of impairment of the protective mechanisms and significantly contributes to cell damage. Hydrogen peroxide is further metabolized to water in the presence of reduced glutathione (GSH). GSH can also work synergetically with SOD to neutralize ROS. The reactions between GSH and ROS yields glutathione free radical (GS(•)), which further reacts with GSH leading to free radical of glutathione disulphide (GSSG(•)). This free radical of GSSG can then donate an electron to the oxygen molecule, producing O2 (•-) Subsequently, O2 (•-) is eliminated by SOD. Adecrease of the GSH level has detrimental consequences for antioxidative defense cellular properties. Gastric mucosa, exposed to stress conditions, exhibits an enhancement of lipid peroxidation (increase of MDA and 4-HNE), as well as a decrease of SOD activity and GSH concentration. This chain reaction of ROS formation triggered by stress, appears to be an essential mechanism for understanding the pathogenesis of stress - induced functional disturbances in the gastric mucosa leading to ulcerogenesis.

Role of reactive oxygen metabolites in aspirin-induced gastric damage in humans: gastroprotection by vitamin C.

Abstract: Background: The roles of active oxygen metabolites and anti-oxidative defenses in aspirin (ASA)-induced gastric damage have been little studied. Aim: We determined the effects of aspirin (400 mg b.d.) with or without vitamin C (480 mg b.d.) for 3 days on gastric mucosa in human volunteers. Methods: Gastric injury was assessed endoscopically; gastric blood flow, reactive oxygen release (quantified by chemiluminescence), lipid peroxidation, myeloperoxidase, superoxide dismutase and glutathione peroxidase activity and intragastric vitamin C content were measured. Expression of superoxide dismutase and glutathione peroxidase mRNAs was assayed semi-quantitatively. Results: ASA produced erosions, a marked increase in chemiluminescence, lipid peroxidation, and myeloperoxidase activity. It also resulted in a suppression of gastric blood flow, intragastric vitamin C levels, superoxide dismutase and glutathione peroxidase activities. The addition of vitamin C significantly attenuated gastric damage and reversed the effects of ASA on these parameters. Superoxide dismutase and glutathione peroxidase mRNAs were decreased in ASA-treated subjects; the addition of vitamin C restored their regular levels. Conclusions: (i) free radical-induced lipid peroxidation and suppression of antioxidizing enzymes play an important role in gastric damage induced by aspirin; (ii) increased myeloperoxidase activity suggests activated neutrophils to be the major source of these radicals; (iii) vitamin C protects against ASA-induced damage due to its anti-oxidizing activity.

Effects of treatment with melatonin and tryptophan on liver enzymes, parameters of fat metabolism and plasma levels of cytokines in patients with non-alcoholic fatty liver disease – 14 months follow up

Abstract: Non-alcoholic fatty liver disease (NAFLD), most common chronic hepatic pathology, that occurs in the developed countries is estimated at 1/3 of the population. Amongst the numerous pathogenetic factors, oxidative stress and apoptosis of hepatocytes initiate many inflammatory processes and are involved in the progression of disease, particularly in transformation of non-alcoholic steatohepatitis (NASH) to cirrhosis. The aim of our study was to determine the effects of tryptophan and melatonin on the selected biochemical parameters in patients with NAFLD, and additionally, to evaluate the effects of tryptophan and melatonin in improvement of liver tissue in selected NAFLD patients. Seventy four patients with NAFLD confirmed by histopathological examination of liver biopsy samples, were admitted to the study. They were randomly assigned to three groups. Group I received the preparation Essentiale forte in the dose of 3 x 1 tablet per day and tryptophan 2 x 500 mg/day over the period of 14 months, group II received Essentiale forte and melatonin 2 x 5 mg/day over 14 months and group III received only Essentiale over the period of 14 months. In nine patients of groups I, II, and III, the liver biopsy was performed after 14-months of treatment period. Out of nine patients whom biopsy was performed, three of them were from group I, four from group II and two of them were from group III, respectively. After the 14-month treatment period, gamma-glutamyl transferase (GGPT) activity and levels of triglycerides and LDL-cholesterol were found to be significantly reduced in group I and II. The level of melatonin after the therapy was significantly elevated in group I and II and did not change in group III. Statistically significantly lower levels of IL-1, IL-6 and TNF-α were observed in patients receiving melatonin and tryptophan, comparing with group III treated with Essentiale forte only. These study findings demonstrate that melatonin and tryptophan substantially reduce the levels of pro-inflammatory cytokines and improve some parameters of fat metabolism in patients with NAFLD. In few patients with NASH melatonin and tryptophan reduced the inflammation in liver. We conclude that melatonin is worth considering for the therapy of NAFLD, particularly in patients with impaired fat metabolism accompanied by hypertriglyceridemia and hyper-LDL cholesterolemia.

Gastrocytoprotection by colloidal bismuth subcitrate (De-Nol) and sucralfate. Role of endogenous prostaglandins.

Abstract: This study compares the gastroprotective effects of colloidal bismuth subcitrate (De-Nol) with those of sucralfate and a methylated analogue of prostaglandin E2 (PGE2) against acute gastric lesions induced by acidified aspirin and absolute ethanol in rats. Both De-Nol and sucralfate given orally prevented dose dependently the formation of gastric lesions by these ulcerogens, De-Nol being, respectively, twice and seven times more potent, on a weight basis, than sucralfate. As the gastroprotective activities of both De-Nol and sucralfate on ethanol lesions can be reversed by pretreatment with indomethacin and as De-Nol and sucralfate increase the mucosal generation and luminal release of PGE2, we postulate that mucosal prostaglandins may be involved in the mechanism of action of these drugs on the gastric mucosa.

A Comparison of Continuous Intravenous Epoprostenol (Prostacyclin) with Conventional Therapy for Primary Pulmonary Hypertension

Abstract: Background Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospective, randomized trial to improve survival. Methods We conducted a 12-week prospective, randomized, multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol (formerly called prostacyclin) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension (New York Heart Association functional class III or IV). Results Exercise capacity was improved in the 41 patients treated with epoprostenol (median distance walked in six minutes, 362 m at 12 weeks vs. 315 m at base line), but it decreased in the 40 patients treated with conventional therapy alone (204 m at 12 weeks vs. 270 m at base line; P<0.002 for the comparison of the treatment groups). Indexes of the quality of life were improved only in the epoprostenol group (P<0.01). Hemodynamics improved at 12 weeks in the epoprostenol-treated pat...

Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial.

Abstract: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease