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Biomedical subjects

M Pawlik

Publications and source records attributed to M Pawlik.

At least 19 recordsLinked to original sources
PubMed2006

Interaction of nonsteroidal anti-inflammatory drugs (NSAID) with Helicobacter pylori in the stomach of humans and experimental animals.

Helicobacter pylori (H. pylori) and non-steroidal anti-inflammatory drugs (NSAID) are major pathogenic factors in peptic ulcer disease but whether these two factors exert synergistic or antagonistic action on the gastric mucosa has been a subject of controversy. The classic concept states that there is an increased ulcer occurrence and bleeding in patients with both H. pylori infection and NSAID use. However, the question whether the H. pylori eradication therapy in NSAID users reduces the occurrence of peptic ulcer has not been fully addressed. Studies on secondary prevention of NSAID-associated ulcers in H. pylori patients have indicated that H. pylori eradication results in impaired ulcer healing with an effect on the rate of peptic ulcer occurrence. On the other hand, the treatment of H. pylori in patients with no prior history of chronic NSAID therapy has been shown to decrease the risk of peptic ulcer. Studies in experimental animals revealed for instance, that the H. pylori infection augments the gastric mucosal damage induced by NSAID in Mongolian gerbils. In rats with preexisting chromic gastric ulcers, H. pylori infection attenuated significantly the aspirin-induced inhibition of ulcer healing and accompanying fall in the gastric blood flow at the margin of these ulcers, suggesting negative interaction between aspirin and H. pylori on ulcerogenesis. Accumulated evidence in humans and animals shows that both aspirin and H. pylori upregulate the expression of cyclooxygenase (COX)-2 both at mRNA and protein levels at the ulcer margin, but failed to influence significantly that of COX-1. It was, therefore, proposed that H. pylori may in fact, antagonize, aspirin-induced delay of ulcer healing due to suppression of acid secretion by the enhancement in PGE(2) possibly derived from COX-2 expression and activity and to the overexpression of growth factors such as TGF alpha and VEGF. The present review summarizes and further addresses the issue of the interaction between these two major ulcer risk factors determined in the stomach of humans and experimental animals.

Animals↗
PubMed2006

Helicobacter pylori infection in coronary artery disease.

The role of inflammation in the pathogenesis and progression of coronary artery disease (CAD) has been increasingly discussed, but still remains unclear. Inflammatory changes in the vessel wall play an important role in the pathogenesis of atherosclerosis. Systemic inflammatory reaction can be detected by showing increased plasma levels of different proinflammatory cytokines and acute-phase proteins. Infectious agents have been linked to coronary heart disease on epidemiological and pathogenetic grounds. The prevalent condition and the exact mechanism of initiation of atherosclerotic vascular disease remain unclear. Nevertheless, many similarities exist between the processes of inflammation and atherogenesis, and the evidence is growing for the role of an active inflammation in the atherosclerosis in the coronary circulation and elsewhere. Although the seroepidemiological and eradication studies have suggested a causal relationship between Helicobacter pylori (Hp) infection and coronary heart disease; the issue is still controversial. The detection of Hp specific DNA in atheromatous plaque material from coronary arteries, but more important, the reduction in restenosis of coronary vessels after Hp eradication could be interpreted as an evidence for the involvement of a Hp infection in the progression of CAD induced by a local inflammatory process.

Coronary Artery Disease↗
PubMed2006

Neural aspects of ghrelin-induced gastroprotection against mucosal injury induced by noxious agents.

Ghrelin, identified in oxyntic mucosa has been recently implicated in the control of food intake and growth hormone (GH) release but whether this hormone can influence the gastric secretion and gastric mucosal integrity have been little studied. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion in rats equipped with gastric fistula (GF) and gastric lesions induced in rats by 75% ethanol and ischemia-reperfusion (I/R) with or without vagotomy or functional ablation of afferent sensory nerves by capsaicin. The number and the area of gastric lesions was measured by planimetry, the GBF was assessed by H(2)-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. Ghrelin (5-80 microg/kg i.p. or 600-5000 ng/rat i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and I/R. These protective effects of ghrelin were accompanied by the significant rise in the gastric mucosal blood flow (GBF) and plasma ghrelin and gastrin levels. Ghrelin given i.p. or injected i.c.v. in standard doses 20 microg/kg or 5000 ng/kg, respectively, significantly attenuated the gastric mucosal damage and significantly raised the GBF. Ethanol applied i.g. in smaller concentrations (12.5% and 25%) produced a significant increase in plasma immunorective ghrelin levels and this effect was inhibited in rats receiving ethanol in higher concentrations (75% and 100%). Ghrelin-induced protection after its i.p. or i.c.v. administration and accompanying increase in the GBF were completely abolished by vagotomy and capsaicin-deactivation of sensory nerves. Concurrent treatment with CGRP added to ghrelin restored the gastroprotective and hyperemic effects of ghrelin applied i.p. or i.c.v. in rats with capsaicin denervation. We conclude that central and peripheral ghrelin exerts a potent protective and gastric secretory effects in rats exposed to ethanol and I/R, and that these actions involve vagal nerve integrity, partially depending upon afferent nerves and hyperemia mediated by sensory neuropeptides such as CGRP released from these nerves.

Animals↗
PubMed2005

Clearance of moxifloxacin during continuous haemofiltration (CVVHF) in vitro.

BACKGROUND/AIMS: The clearance of moxifloxacin is reported to be unaltered in the presence of renal insufficiency. There is little information about the clearance of intravenous moxifloxacin in renal replacement therapies during intensive care. The aim of this study was to determine the clearance of moxifloxacin during continuous veno-venous haemofiltration (CVVHF) in vitro. METHODS: The elimination of moxifloxacin (reservoir with 600 mL of washed human erythrocytes, 100 mL of NaHCO3 and various amounts of Ringer solution and human albumin to give a total volume of 1000 mL, pH 7.35 +/- 0.5; haematocrit 41 +/- 2) during CVVHF in vitro with two filter conditions (during priming, after priming), three protein concentrations (human albumin: 0 g/L, 20 g/L, 40 g/L) and two filtration velocities [(i) standard condition: blood flow at 100 mL/min and turnover of 2 L/h; (ii) blood flow at 50 mL/min and turnover of 1 L/h] were investigated. RESULTS: A new filter needs 20 min of priming before moxifloxacin reaches a steady relative filtration rate. The sieving coefficient with 0 g/L albumin was 1.07, with 20 g/L 0.90 and with 40 g/L 0.80. Under standard filtration conditions (i) the renal clearance was between 26.7 and 35.7 mL/min, and under the altered conditions (ii) it was 15.2 mL/min. CONCLUSION: During CVVHF in vitro we found filtration clearances of moxifloxacin of the same order as its renal clearance in healthy subjects. The high sieving coefficient, nearly independent of blood protein concentration, would suggest that moxifloxacin is filtered almost as freely as creatinine. These results do not indicate a need for dose adjustment under appropriate haemofiltration conditions and normal hepatic function.

Anti-Bacterial Agents↗
PubMed2004

[Autologous transfusion -- from euphoria to reason: clinical practice based on scientific knowledge (Part II). Intraoperative blood salvage with blood irradiation -- from an anaesthesiological point of view].

The requirement for intraoperative blood salvage (IBS) in cancer surgery stems from the high transfusion rate, the unfavourable effects of an anaemia, and the impact of transfusion risks like immunomodulation in tumor patients. The advantages of IBS are availability, the low waste rate, and the excellent quality of this autologous, unstored blood. The only effective elimination of the risk of tumor cell dissemination after retransfusion of wound blood is achieved by blood irradiation. The combination of the established methods of IBS and blood irradiation is practical, and allows a very efficient saving of blood. For Jehovah's witnesses it may open the possibility for tumor surgery. From an anaesthesiological point of view it is part of the therapy, but any context that puts it compatible to medicolegal regulations is welcome. For him as the one responsible for the therapy of intraoperative blood loss it represents the safest and best blood for an optimal hemotherapy in tumor patients. In addition, first data indicate a better outcome of these patients.

Anesthesiology↗
PubMed2004

Importance of brain-gut axis in the gastroprotection induced by gastric and remote preconditioning.

Limitation of the damage to the organs such as heart, liver, intestine, stomach and brain by an earlier brief complete occlusion of their arteries is defined as ischemic preconditioning (IP). No study so for has been undertaken to check whether brain-gut axis is involved in the gastroprotection exhibited by gastric IP or in that induced by repeated brief episodes of ischemia of remote organs such as heart and liver. This study was designed to determine the possible involvement of vagal and sensory afferent nerves, in the mechanism of gastric and remote organ IP on the gastric mucosa in rats exposed to prolonged ischemia-reperfusion with or without functional ablation of sensory nerves by capsaicin or in those with removed vagal innervation by vagotomy. This gastric IP was induced by short ischemia episodes (occlusion of celiac artery 1-5 times for 5 min) applied 30 min before subsequent ischemia followed by 3 h of reperfusion (I/R) and compared with remote IP induced by occlusion of left descending coronary artery or hepatic artery plus portal vein. The area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured by H(2)-gas clearance method and mucosal biopsy samples were taken for the assessment of calcitonin gene-related peptide (CGRP) by RIA. Exposure of gastric mucosa to standard 3 h of I/R produced numerous gastric lesions and significant fall in the GBF and mucosal CGRP content. Two 5 min short ischemic episodes by occlusion of coronary or hepatic arteries, significantly reduced gastric damage induced by I/R with the extent similar to that exhibited by two short (5 min) episodes of gastric ischemia. These protective effects of gastric and remote IPs were accompanied by a restoration of the fall in the CGRP content caused by I/R alone. Protection and hyperemia induced by gastric IP were significantly attenuated in capsaicin-denervated or vagotomized animals and completely removed in those exposed to the combination of vagotomy and capsaicin-denervation. The IP-induced protection and hyperemia were restored by the administration of exogenous CGRP to gastric IP in capsaicin-treated animals. Gastroprotective and hyperemic actions of remote IP were markedly diminished in capsaicin-denervated rats and in those subjected to vagotomy. We conclude that brief ischemia in remote organs such as heart and liver protects gastric mucosa against gastric injury induced by I/R as effectively as gastric IP via mechanism involving both vagal and sensory nerves releasing vasodilatatory mediators such as CGRP.

Animals↗
PubMed2004

Influence of central and peripheral administration of pancreatic polypeptide on gastric mucosa growth.

UNLABELLED: Previous studies have shown that pancreatic polypeptide (PP) inhibits exocrine pancreatic secretion. The aim of present study was to determine the influence of PP administration on gastric growth and blood flow. METHODS: Study was performed on regularly fed, fasted or fasted and subsequently refed rats. Rats were treated with saline (intraperitoneally - i.p.), caerulein (0.24 nmol/kg/dose, i.p.), pentagastrin (0.38 micromol/kg/dose, i.p.) or PP (5 nmol/kg/dose, i.p. or 10 pmol/dose intracerebroventricularly - i.c.v.). Saline, caerulein, pentagastrin and PP were administered alone or in combination, 3 times daily during last 48 h of experiment. RESULTS: Treatment with pentagastrin increased gastric mucosa weight, mucosal DNA synthesis and gastric blood flow in all group tested. Intraperitoneal and i.c.v administration of PP alone reduced mucosal DNA synthesis in regularly fed and refed animals, and decreased gastric blood flow in refed animals. Combination of PP i.p. or i.c.v plus pentagastrin significantly reduced the pentagastrin-evoked increase in gastric mucosa weight, gastric DNA synthesis and gastric blood flow in fasted animals, as well as regularly fed animals. In refed animals, influence of PP administration on the pentagastrin-evoked increase in gastric mucosa weight was weak and statistically insignificant, but still i.p or i.c.v administration of PP significantly reduced gastric blood flow and mucosal DNA synthesis in this group of animals. Administration of caerulein caused weak, but significant increase in gastric DNA synthesis, gastric mucosa weight and gastric blood flow in fasted rats. In regularly fed animals, caerulein significantly increased only gastric DNA synthesis and gastric blood flow. In fasted animals with subsequent refeeding, caerulein was without effect on parameters tested in the stomach. Neither i.p. nor i.c.v administration of PP affected the caerulein-evoked effects in the stomach. CONCLUSIONS: Peripheral and central administration of PP inhibits food- and pentagastrin-stimulated growth of gastric mucosa. Similar effects of low central doses of PP as the high peripheral doses of PP suggests a crucial role of the central nervous system in the inhibitory effect of PP on gastric mucosa growth.

Animals↗
PubMed2004

The role of female and male sex hormones in the healing process of preexisting lingual and gastric ulcerations.

Studies in different animal species and in humans have suggested that sex hormones influence gastric acid secretion and contribute to the integrity of the oral and gastroduodenal mucosa but the effect of male and female sex hormones on the healing of the preexisting ulcers in the oral cavity and stomach have not been studied. We compared the effects of major male hormone, testosterone, and female hormone, progesterone, on the healing of lingual and gastric ulcers induced by acetic acid technique in male rats with intact or removed testicles (testectomy) and female rats with intact or removed ovaries (ovariectomy). The gastric acid secretion was determined in rats with gastric ulcers equipped with chronic gastric fistula (GF). Rats were sacrificed at day 7 upon ulcer induction; the ulcer area was measured by planimetry and the lingual and gastric blood flow (GBF) was determined by H(2)-gas clearance method and venous blood was collected for determination of plasma gastrin and plasma proinflammatory cytokine interleukin (IL)-1 beta levels. Gastric acid output from GF rats was significantly reduced while plasma gastrin was significantly enhanced in testectomized animals as compared to those in intact control rats and these effects were reversed by supplementation of testectomized animals with testosterone. The area of lingual and gastric ulcers in placebo-control rats decreased significantly at day 7 and this effect was significantly accelerated by testectomy or ovariectomy. In contrast, testosterone significantly delayed ulcer healing while producing a significant fall in the gastric blood flow and lingual blood flow determined at the margin of these ulcers. Treatment with progesterone significantly accelerated ulcer healing and increased the gastric and lingual blood flow at margin of these ulcers. Testosterone applied alone or supplemented in testectomized animals produced the significant increment in plasma IL-1 beta levels as compared to the respective levels of this cytokine in placebo-control animals. We conclude that: 1) major male (testosterone) and female (progesterone) sex hormones exhibit opposite effect on healing of preexisting ulcers in the oral cavity and stomach because testosterone markedly delayed while progesterone significantly accelerated this healing; 2) testosterone-induced delay in ulcer healing involves the fall in the gastric microcirculation at the margin of lingual and gastric ulcers and the excessive production and release of proinflammatory cytokine IL-1 beta; and 3) testectomy improves the gastric ulcer healing due to inhibition of gastric acid secretion and the rise in plasma gastrin, which exerts gastroprotective, trophic and ulcer healing action on the gastric mucosa.

Animals↗
PubMed2004

Healing of chronic gastric ulcers in diabetic rats treated with native aspirin, nitric oxide (NO)-derivative of aspirin and cyclooxygenase (COX)-2 inhibitor.

Previous studies have demonstrated that the gastric mucosa of diabetic rats is highly vulnerable to acute injury but the influence of nonsteroidal anti-inflammatory drugs (NSAID) and their new nitric oxide (NO) releasing derivatives of aspirin (NO-ASA) on the ulcer healing under diabetic conditions has been little studied. In this study streptozocin (STZ, 70 mg/kg injected intraperitoneally) was used to induce diabetes mellitus in rats. Four weeks after STZ injection, gastric ulcers were induced using the acetic acid method and rats with gastric ulcers received the treatment with 1) aspirin (ASA, 30 mg/kg-d i.g.), 2) NO-ASA applied in equimolar dose of 50 mg/kg-d i.g., 3) rofecoxib (5 mg/kg-d i.g.), the selective cyclooxygenase-(COX)-2 inhibitor and 4) SNAP (5 mg/kg-d i.g.), a donor of NO, combined with ASA (30 mg/kg-d i.g.). Ten days after the induction of the ulcers, the healing rate and the gastric blood flow (GBF) were measured by planimetry and hydrogen (H(2))-gas clearance method, respectively and the plasma cytokine such as IL-1beta, TNF-alpha and IL-10 were determined. In addition, the effect of insulin (4 IU/day/rat i.p.) with or without the blockade of NO-synthase by L-NNA (20 mg/kg-d i.p.) on the ulcer healing and the GBF in non-diabetic and diabetic rats was determined. In the diabetic rats, a significant delay in ulcer healing (approximately by 300%) was observed with an accompanied decrease in the GBF at ulcer margin. The prolongation of the healing in diabetic animals was associated with an increase in the plasma cytokine (IL-1beta, TNF-alpha and IL-10) levels. ASA and rofecoxib, that significantly suppressed the mucosal prostaglandin (PG) E(2) generation in ulcer area, delayed significantly the rate of ulcer healing and decreased the GBF at ulcer margin, while elevating plasma IL-1beta, TNF-alpha and IL-10 concentrations in non-diabetic rats and these alterations were significantly augmented in diabetic animals. In contrast to ASA, the treatment with NO-ASA failed to influence both, the ulcer healing and GBF at ulcer margin and significantly attenuated the plasma levels of IL-1beta, TNF-alpha and IL-10 as compared to those recorded in ASA- or rofecoxib-treated animals. Co-treatment of SNAP with native ASA abolished the deleterious effect of ASA on ulcer healing, GBF at ulcer margin and luminal NO release in diabetic rats. Administration of insulin in rats with diabetes, opposed the delay in ulcer healing, and the fall in the GBF at ulcer margin and these effects were counteracted by the concurrent treatment with L-NNA. We conclude that: 1) ulcer healing is dramatically impaired in experimental diabetes and this effect involves the fall in the gastric microcirculation at the ulcer margin and increased release of proinflammatory cytokines; 2) classic NSAID such as ASA and selective COX-2 inhibitors such as rofecoxib, prolong ulcer healing under diabetic conditions probably due to suppression of endogenous PG and the fall in the GBF at the ulcer margin suggesting that both COX isoforms, namely, COX-1 and COX-2, are important sources of PG during ulcer healing in diabetes; and 3) NO-ASA counteracts the impairment of ulcer healing in diabetic rats induced by ASA, mainly due to the release of NO that compensates for PG deficiency resulting in enhancement in the GBF at ulcer margin and suppression of cytokine release in the ulcer area.

Animals↗
PubMed2003

Effect of carboxymethyl cellulose and ionic strength on stability of mineral suspensions in potash ore flotation systems.

The adsorption of sodium carboxymethyl cellulose from aqueous solutions varying in ionic strength from that of distilled water to 50% NaCl/KCl brine (about 3.5 mol/dm(3)) onto illite and dolomite has been studied. The purpose of this work was to investigate the solvency effects in the phenomena underlying the potash flotation process that is carried out in saturated brine. Based on viscosity measurements, the adsorption results were analyzed in terms of a simple model of polymer macromolecules in solution. Suspension stability measurements carried out concomitantly with adsorption tests showed the ranges of carboxymethyl cellulose concentration over which the tested suspensions either were aggregated or were restabilized.

Adsorption↗
PubMed2003

Triple eradication therapy counteracts functional impairment associated with Helicobacter pylori infection in Mongolian gerbils.

Gastric Helicobacter pylori (Hp) infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis resulting from the long-term Hp infection but functional aspects accompanying this Hp-induced progression from gastritis to the cancer, especially changes in gastric acid secretion, gastric blood flow (GBF) and gastrin-somatostatin link have been little studied. It is unclear whether Hp eradication therapy alters the functional and the histopathological changes in this animal model of Hp-infection. We examined the effects of intragastric (i.g.) inoculation of Mongolian gerbils with Hp strain (cagA+ vacA+, 5 x 10(6) CFU/ml) that had been isolated from a patient with gastric ulcer as compared to those induced by vehicle (saline) in gerbils with or without gastric fistula (GF) at 1.2, 4, 6, 9, 12 and 30 wks upon gastric inoculation with this bacteria. An attempt was made to evaluate the influence of anti-Hp triple therapy with omeprazole, amoxicillin and tinidazol on gastric Hp-infection and Hp-induced functional impairment of the gastric mucosa. Gastric mucosal biopsy specimens were taken for the assessment of the morphological changes and the presence of Hp infection using rapid urease test (CLO-test) and the density of Hp-colonization were assessed by counting of the number of bacterial colonies per plate. Gastric blood flow (GBF) was measured by H2-gas clearance technique and the venous blood and the gastric content were collected for the measurement of plasma gastrin levels and the gastric luminal somatostatin level by radioimmunoassay (RIA). The Hp in gastric mucosa was detected in all animals by culture and rapid urease test at various periods upon Hp inoculation. Basal gastric acid in non-infected conscious gerbils with GF reached the level of about 28 +/- 4 micromol/h and this was reduced by over 50% immediately upon the Hp-inoculation and persisted for time intervals tested up to 30 wk. Early lesions were seen 4 wks after the Hp-inoculation and consisted of chronic gastritis with thickened gastric mucosal foldings and elongated interfoveolar ridges. Edema and congestion as well as significant mucosal inflammatory infiltration with lymphoid infiltrate in lamina propria of the mucosa occurred in all infected gerbils. Adenomatous hyperplasia with cellular atypia was observed at 12 wk upon Hp-inoculation together with increased mitotic activity and numerous apoptotic bodies formation, while lamina propria was reduced leaving dilated atypical gastric gland situated "back-to-back". This glandular atypia failed to show lamina propria or submucosa infiltration corresponding to gastric intraepithelial neoplasia. The GBF in Hp-infected gerbils was significantly lower, and a 6-7 fold increase in plasma gastrin levels combined with a significant fall in gastric luminal somatostatin contents observed at all tested periods as compared to vehicle-controls and these effects were counteracted by anti-Hp triple therapy. We conclude that: 1). Hp-infection in Mongolian gerbils in early stages before adenocarcinoma formation results in the development of typical functional and pathological changes such as suppression of gastric secretion and impairment of both, gastric mucosal microcirculation and gastrin-somatostatin link, and 2). this deleterious influence of Hp on gastric morphology and gastric functions is greatly attenuated in gerbils treated with Hp-eradication therapy.

Amoxicillin↗
PubMed2003

Importance of nitric oxide (NO) and adenosine in the mechanism of gastric preconditioning induced by short ischemia.

PURPOSE: Gastric mucosa subjected to repeated brief episodes of ischemia exhibits an increased resistance to damage caused by a subsequent prolonged ischemic insult and this is called gastric preconditioning. In this study, L-NNA, a non-selective NO-synthase inhibitor, and aminoguanidine, a relative inhibitor of inducible NO-synthase (iNOS), were applied prior to short ischemia (occlusion of celiac artery 1-5 times for 5 min) followed by a subsequent exposure to 0.5 h of ischemia and 3 h of reperfusion (I/R). MATERIAL AND METHODS: Male Wistar rats were used in all studies. RESULTS: Short ischemia reduced significantly I/R-induced lesions while raising significantly the GBF and luminal NO content. These effects were attenuated by L-NNA and aminoguanidine and restored by addition of L-arginine and SNAP to L-NNA and aminoguanidine. Pretreatment of with adenosine (10 mg/kg i.p.) significantly reduced I/R lesions and accompanying fall in the GBF induced by I/R. These protective and hyperemic effects of standard preconditioning and adenosine were significantly attenuated by pretreatment with 8-phenyl theophylline (SPT, 10 mg/kg i.g.), an antagonist of adenosine A1 and A2 receptors. CONCLUSIONS: We conclude that gastric ischemic preconditioning is considered as one of the major protective mechanism in the stomach that involves key vasodilatory mediators such as NO and adenosine.

Adenosine↗
PubMed2002

Mineral matter distribution on coal surface and its effect on coal wettability.

Coal is an organic sedimentary rock composed of organic macerals and mineral matter. As it is demonstrated in this paper the discrete mineralogical nature of coal largely influences the wetting of the coal surface by water. Both advancing and receding contact angles were measured using the captive-bubble technique with an automatic bubble shape analysis software. The distribution and amount of mineral inclusions on the coal surface were determined by scanning electron microscopy and examined using the image analysis system. To determine the amount and size distribution of mineral grains, the coal surface layer, on which the contact angles were measured, was separated from the larger piece used in the measurements by microslicing. The separated surface layer was subjected to a low-temperature ashing followed by particle size analysis. As expected, a significant scatter of contact angle values was obtained for the same coal samples. Increasing the amount of mineral matter on the coal surface reduced the value of both advancing and receding contact angles. Also, the scatter of contact angle values increased with the increasing mineral matter content from about 1 to 50 wt%. The results reveal that an important factor in analysis of contact angle variation on coal surfaces is the size of the hydrophilic mineral inclusions. Both the advancing and the receding contact angles decrease with increasing size of the mineral grains. Additionally, the scatter of contact angle values increase with increasing size of the mineral matter grains. Finally, the results of fractal dimension analysis of mineral matter grains distributed over the coal surface indicate that there is no significant effect from the shape of hydrophilic mineral inclusions on both advancing and receding contact angles.

Journal Article↗
PubMed2001

Ischemic preconditioning, the most effective gastroprotective intervention: involvement of prostaglandins, nitric oxide, adenosine and sensory nerves.

Various organs, including heart, kidneys, liver or brain, respond to brief exposures to ischemia with an increased resistance to severe ischemia/reperfusion and this phenomenon is called "preconditioning". No study so far has been undertaken to check whether such short, repeated gastric ischemic episodes protect gastric mucosa against severe damage caused by subsequent prolonged ischemia/reperfusion and, if so, what could be the mechanism of this phenomenon. The ischemic preconditioning was induced by short episodes of gastric ischemia (occlusion of celiac artery from one to five times, for 5 min each) applied 30 min before prolonged (30 min) ischemia followed by 3 h of reperfusion or 30 min before topical application of strong mucosal irritants, such as 100% ethanol, 25% NaCl or 80 mM taurocholate. Exposure to regular 30-min ischemia, followed by 3-h reperfusion, produced numerous severe gastric lesions and significant fall in the gastric blood flow and prostaglandin E(2) generation. Short (5-min) ischemic episodes (1-5 times) by itself failed to cause any gastric lesions, but significantly attenuated those produced by ischemia/reperfusion. This protection was accompanied by a reversal of the fall in the gastric blood flow and prostaglandin E(2) generation and resembled that induced by classic gastric mild irritants. These protective and hyperemic effects of standard preconditioning were significantly attenuated by pretreatment with cyclooxygenase-2 and cyclooxygenase-1 inhibitors, such as indomethacin, Vioxx, resveratrol and nitric oxide (NO)-synthase inhibitor, N(G)-nitro-L-arginine (L-NNA). The protective and hyperemic effects of standard preconditioning were restored by addition of 16,16 dm prostaglandin E(2) or L-arginine, a substrate for NO synthase, respectively. Gastroprotective and hyperemic actions of standard ischemic preconditioning were abolished by pretreatment with capsaicin-inactivating sensory nerves, but restored by the administration of exogenous CGRP to capsaicin-treated animals. Gene and protein expression of cyclooxygenase-1, but not cyclooxygenase-2, were detected in intact gastric mucosa and in that exposed to ischemia/reperfusion with or without ischemic preconditioning, whereas cyclooxygenase-2 was overexpressed only in preconditioned mucosa. We conclude that: (1) gastric ischemic preconditioning represents one of the most powerful protective interventions against the mucosal damage induced by severe ischemia/reperfusion as well as by topical mucosal irritants in the stomach; (2) gastric ischemic preconditioning resembles the protective effect of "mild irritants" against the damage by necrotizing substances in the stomach acting via "adaptive cytoprotection" and involves several mediators, such as prostaglandin derived from cyclooxygenase-1 and cyclooxygenase-2, NO originating from NO synthase and sensory nerves that appear to play a key mechanism of gastric ischemic preconditioning.

Adenosine↗
PubMed2001

Distinct properties of wild-type and the amyloidogenic human cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type.

Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; however, variant cystatin C dimerizes at lower concentrations and has an increased susceptibility to a serine protease. We studied the effect of the L68Q amino acid substitution on cystatin C properties, utilizing full length cystatin C purified in mild conditions from media of cells stably transfected with either the wild-type or variant cystatin C genes. The variant cystatin C forms fibrils in vitro detectable by electron microscopy in conditions in which the wild-type protein forms amorphous aggregates. We also show by circular dichroism, steady-state fluorescence and Fourier-transformed infrared spectroscopy that the amino acid substitution modifies cystatin C structure by destabilizing alpha-helical structures and exposing the tryptophan residue to a more polar environment, yielding a more unfolded molecule. These spectral changes demonstrate that variant cystatin C has a three-dimensional structure different from that of the wild-type protein. The structural differences between variant and wild-type cystatin C account for the susceptibility of the variant protein to unfolding, proteolysis and fibrillogenesis.

Amino Acid Substitution↗
PubMed2001

Sensory nerves and calcitonin gene related peptide in the effect of ischemic preconditioning on acute and chronic gastric lesions induced by ischemia-reperfusion.

Ischemic preconditioning is considered as the most powerful gastroprotective intervention against mucosal lesions and ulcerations but the mechanism of this phenomenon has been little examined. In this study we tested the effects of inactivation of sensory nerves in new rat model combining acute gastric erosions with subsequent ulcers induced by ischemia-reperfusion (I/R). I/R lesions were produced in rats by clamping the celiac artery for 0.5 h followed by 3 h of reperfusion in rats with intact or inactivated sensory nerves by pretreatment with capsaicin for two weeks before the I/R. The animals were killed at 0 and 3 h and 3 days after I/R and the area of gastric lesions was determined planimetrically, the gastric blood flow (GBF) by H2-gas clearance technique and the plasma levels of gastrin by RIA. Gastric mucosal content of calcitonin gene related peptide (CGRP) was assessed by RIA. Following I/R, gastric erosive lesions occurred after 3 h and these erosive lesions then progressed into gastric ulcers within 3 days in all rats. Sensory-inactivation with capsaicin caused several fold increase in the area of early (at 3 h) acute lesions and later (at 3 d) gastric ulcers induced by I/R. This enhancement of acute and then chronic gastric lesions was accompanied by a significant fall in GBF, an elevation of plasma gastrin and a decrease in mucosal expression of CGRP. Ischemic preconditioning markedly reduced acute lesions and chronic ulcerations induced by I/R and attenuated the changes in plasma gastrin and mucosal CGRP contents but these effects were significantly more pronounced in rats with intact sensory nerves but less in capsaicin-inactivated animals. We conclude that: 1) The I/R resulted in the formation of early acute gastric lesions followed 3 days later by chronic gastric ulcers and this gastric injury was accompanied by an impairment of gastric microcirculation, hypergastrinemia and suppression the gastric mucosal CGRP; 2) Gastric ischemic-preconditioning significantly attenuated both acute mucosal damage and chronic ulcers induced by I/R and this was accompanied by a rise in gastric blood flow; 3) The inactivation of sensory nerves with capsaicin enhanced the formation of I/R-induced acute and chronic gastric lesions and strongly attenuated the gastroprotection afforded by I/R possibly due to the decline in mucosal blood flow and the fall in expression of integrity peptides such as CGRP and 4) The excessive release of gastrin may limit the extent of mucosal lesions observed during progression of gastric erosions into ulcers induced by I/R.

Animals↗
PubMed2001

Brain-gut axis in gastroprotection by leptin and cholecystokinin against ischemia-reperfusion induced gastric lesions.

Leptin, a product of ob gene controlling food intake, has recently been detected in the stomach and shown to be released by CCK and implicated in gastroprotection against various noxious agents but it is unknown whether centrally applied leptin influences ischemia-reperfusion (I/R)-induced gastric erosions that progress into deeper gastric ulcerations. In this study we compared the effects of leptin and CCK-8 applied intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) on gastric mucosal lesions induced by I/R and topical application of 75% ethanol. Several major series of Wistar rats were used to examine the effects of leptin and CCK applied centrally on gastroprotection against I/R and ethanol in rats with A) vagotomy by cutting of vagal nerves, B) suppression of NO-synthase with L-NNA (20 mg/kg i.p.), C) inactivation of sensory nerves by capsaicin (125 mg/kg s.c.) and D) inhibition of CGRP receptors with CGR(8-37) (100 microg/kg i.p.) applied with or without the i.c.v. pretreatment with leptin or CCK-8. Rats were anesthetized 1 h after ethanol administration or at 3 h and 3 days upon the end of ischemia to measure the gastric blood flow (GBF) and then to determine the area of gastric lesions by planimetry. Blood was withdrawn for the measurement of plasma leptin and gastrin levels by radioimmunoassay (RIA). Leptin (0.1-20 microg/kg i.p.) dose-dependently attenuated gastric lesions induced by 75% ethanol and I/R; the dose reducing these lesions by 50% (ED50) was 8 microg/kg and 6 microg/kg, respectively and this protective effect was similar to that obtained with CCK-8 applied in a standard dose of 10 microg/kg i.p. This protective effect of leptin was accompanied by a significant increase in GBF and plasma gastrin levels whereas CCK-8 increased plasma leptin levels but failed to affect plasma gastrin levels. Leptin and CCK-8 applied i.c.v. in a dose of 625 ng/rat reduced significantly the area of I/R induced gastric lesions and raised the GBF and plasma leptin levels with the extent similar to those achieved with peripheral administration of leptin or CCK-8 (10 microg/kg i.p.). The protective and hyperemic effects of centrally administered leptin or CCK-8 (625 ng/rat i.c.v.) were completely abolished by vagotomy and significantly attenuated by sensory denervation with capsaicin or by CGRP antagonist, CGRP(8-37). The pretreatment with L-NNA to inhibit NO-synthase activity attenuated significantly the protective and hyperemic effects of CCK but not those of leptin while capsaicin denervation counteracted leptin-induced protection and rise in the GBF but attenuated significantly those of CCK. We conclude that: 1) central leptin exerts a potent gastroprotective activity against I/R-induced gastric erosions that progress into deeper gastric lesions and this protection depends upon vagal activity and sensory nerves and involves hyperemia probably mediated by NO and 2) leptin mimics the gastroprotective effect of CCK and may be implicated in the protective and hyperemic actions of this peptide against mucosal damage evoked by I/R.

Animals↗