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Biomedical subjects

J Kania

Publications and source records attributed to J Kania.

At least 19 recordsLinked to original sources
PubMed2006

Ascorbic acid attenuates aspirin-induced gastric damage: role of inducible nitric oxide synthase.

Aspirin (ASA) represents an important risk factor for gastric mucosal injury. Recently, vitamin C releasing aspirin (ASA-VitC) has been shown to reduce gastric toxicity of ASA in animal model of gastric injury. The aim of the present study was to compare the effect of ASA and ASA-VitC on the gastric mucosal damage before and after Helicobacter pylori (Hp) eradication in 10 young healthy Hp-positive volunteers. All subjects underwent endoscopy at day 0 (before ASA or ASA-VitC treatment) and at day 3 following treatment (1.6 g ASA/day or 1.6 g ASA + 0.96 g Vit C/day). In addition, in vitro experiments were performed in which gastric mucosal cell line (MKN-45 cells) was incubated with ASA or ASA-VitC alone or in combination with H.pylori. Expression of constitutive and inducible NO synthase (cNOS, iNOS) was analyzed by Western blot. Moreover, COX-2 expression was analyzed in gastric biopsies at mRNA and protein level by RT-PCR and Western blot, respectively. In humans, treatment with ASA-VitC induced significantly less gastric mucosal lesions than plain ASA. Furthermore, in comparison to plain ASA, ASA-VitC caused stronger inhibition of cNOS and increase in iNOS expression in the gastric mucosa. In vitro studies demonstrated a significant increase in iNOS expression in MKN-45 cells incubated with Hp. This effect was aggravated by the addition of ASA, but not ASA-VitC, to MKN-45 cells incubated with H.pylori. Both ASA and ASA-VitC stimulated the COX-2 expression in the gastric mucosa. We conclude that ASA-VitC in comparison with ASA induces less gastric mucosal damage and this protective effect may be due to its inhibitory effect on iNOS expression.

Adolescent↗
PubMed2005

Prostaglandins as mediators of COX-2 derived carcinogenesis in gastrointestinal tract.

This review was designed to show the role of expression of cyclooxygenase (COX)-1 and COX-2 in the cancerogenesis of esophagus, stomach and colon. Unlike COX-1, which is expressed in the normal esophago-gastro-colonic mucosa, COX-2 was found to be expressed mainly in the pre-cancer changes in the mucosa including Barrett's esophagus, Helicobacter pylori (H. pylori)-induced gastritis and inflammatory changes in colonic mucosa. In Barrett's esophagus, prostaglandins (PGs) derived from upregulated COX-2 contribute to the progression of low-grade to high-grade dysplasia and finally to cancer. In chronic gastritis induced by chronic H. pylori infection, overexpression of COX-2 is probably induced by inflammatory cytokines, growth factors, especially gastrin and reactive oxygen species leading to mutagenesis and subsequent metaplasia, dysplasia and cancer formation. The imbalance between cell proliferation and apoptosis caused mainly by products of COX-2 leads to cancerogenesis. Similarly, in colorectal cancer the overexpression of COX-2, possibly induced by the action of growth promoting factors including progastrin and gastrin and overexpression of survivin contribute to the colorectal cancerogenesis that could be, at least in part, amended by the treatment with specific COX-2 inhibitors. We conclude that: 1) COX-2-derived PGs play a key role in the tumorigenesis in the gastrointestinal tract; 2) The tumor-promoting effect of PGs may be attributed to their ability to stimulate cell proliferation and migration, to inhibit the apoptosis and to increase angiogenesis and invasiveness; 3) In accordance to the proposed major role of COX-2 in cancerogenesis, selective COX-2 inhibitors have been shown in numerous studies to exhibit strong chemopreventive effect on the development of gastrointestinal cancers.

Animals↗
PubMed2003

Nitric oxide-releasing aspirin protects gastric mucosa against ethanol damage in rats with functional ablation of sensory nerves.

OBJECTIVE AND DESIGN: The aim of the present study was to investigate, whether sensory nerves are involved in the gastroprotection induced by NO releasing non-steroidal anti-inflammatory drugs (NO-NSAID). MATERIAL: Studies were performed in Wistar rats with intact or inactivated sensory nerves by pretreatment with large dose of capsaicin (125 mg/kg sc). TREATMENTS: Acute gastric lesions were induced by 100% ethanol (100% EtOH). 1 h before exposure to 100% EtOH, rats received vehicle, aspirin (ASA) or NO-releasing aspirin (NO-ASA) in the same dose (50 mg/kg). The animals were killed 1 h after exposure to 100% EtOH. METHODS: Determinations were made of gastric mucosal injury, mucosal gastric blood flow, mucosal mRNA expression of glutathione peroxidase (GPx), zinc copper superoxide dismutase (SOD) and heat shock protein (HSP70) by RT-PCR and protein expression for HSP70 by Western blotting. RESULTS: Pretreatment with ASA aggravated the acute gastric injury induced by 100% EtOH, whereas pretreatment with NO-ASA led to a significant reduction in this injury. Administration of 100% EtOH was accompanied by a pronounced upregulation of HSP70, which was reduced by ASA, but enhanced by NO-ASA application. Sensory deactivation with capsaicin enhanced acute ethanol lesions and led to a significant attenuation in HSP70 expression. In contrast to ASA, NO-ASA attenuated gastric mucosal lesions and significantly upregulated HSP70 expression despite blockade of sensory nerves. NO-ASA, but not ASA, caused an upregulation of SOD and GPx mRNA in gastric mucosa with or without sensory denervation. CONCLUSIONS: NO-ASA protects gastric mucosa even after blockade of sensory nerves due to the upregulation of HSP70 expression and attenuation of the oxidative injury resulting from strong upregulation of genes for antioxidant enzymes.

Animals↗
PubMed2003

Expression of survivin and caspase-3 in gastric cancer.

Gastric cancer is one of the most common malignant tumors of the gastrointestinal tract. However, the molecular pathways involved in the regulation of gastric carcinogenesis are not completely elucidated. In the last decade, basic cancer research has been focused on the deregulation of apoptosis as a central event in the process of carcinogenesis. Caspase-3 and survivin are regulators of apoptosis and have been implicated in the development of gastric cancer. The aim of the present study was to compare the expression of mRNA and protein for survivin and caspase-3 in the gastric cancer and in the cancer margin with that in normal human gastric mucosa. Fifteen patients with advanced gastric cancer (all H. pylori-positive) and 15 matched control subjects with normal gastric mucosa were included in this study. The biospy specimens for histology and for molecular analyses were taken from gastric tumor, tumor surrounding gastric mucosa and in normal patients from the mucosa of antrum and corpus. Survivin mRNA expression was very weak, but detectable, in the normal gastric mucosa. However, at the protein level, no expression for survivin was detected in the normal gastric mucosa. In the biopsy specimens from tumor and surrounding gastric mucosa, a significant increase in survivin mRNA and protein expression was observed. The expression of survivin was higher in the tumor than in the tumor margin. The mRNA and protein expression of caspase-3 was detected in the gastric mucosa of normal subjects. In gastric cancer only the expression of procaspase-3 was observed, while the expression of active caspase-3 was completely undetectable. In the gastric mucosa surrounding gastric cancer, no gene and protein expression for caspase-3 was detected. We conclude that the changes in the level of caspase-3 and survivin play an important role in the transformation from normal gastric mucosa to gastric career.

Adult↗
PubMed2003

Influence of COX-2 inhibition by rofecoxib on serum and tumor progastrin and gastrin levels and expression of PPARgamma and apoptosis-related proteins in gastric cancer patients.

Cyclooxygenase-2 (COX-2) expression and certain growth hormones, such as gastrin, have been related to gastric carcinogenesis, but little is known about the factors that enhance this COX-2 expression and whether specific blockade of this enzyme has any influence on tumor growth and progression. Our objective was to determine the influence of a specific COX-2 inhibitor, rofecoxib (Vioxx), on serum and tumor levels of gastrin and its precursor, progastrin, as well as on tumor gene expression of COX-2, peroxisome proliferator-activated receptor gamma (PPARgamma), and apoptosis-related proteins (Bax and Bcl-2, caspase-3, and survivin). Twenty-four gastric cancer (GC) patients entered this study and were examined twice, once before and then following a 14-day treatment with Vioxx at a dose of 25 mg twice daily. For comparison, 48 age- and sex-matched healthy controls and 24 similarly matched Helicobacter pylori (Hp)-positive subjects were enrolled and treated with Vioxx as GC patients. Serum levels of anti-Hp and anti-CagA antibodies as well as IL-8 and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA), while serum and tumor contents of progastrin and amidated gastrin were determined by specific RIA. Tumor gene and protein expressions of COX-2, PPARgamma, Bax and Bcl-2, caspase-3, and survivin were determined by RT-PCR and western blot. The overall Hp and CagA seropositivity in 24 GC patients was significantly higher (82% and 47%) than in 48 controls (61% and 22%) but not in 24 Hp-infected subjects (100% and 38%). Serum IL-8 and TNF-alpha values were significantly higher in GC patients than in controls without GC or Hp-infected controls. Median serum progastrin and gastrin levels were found to be significantly higher in GC than in controls without GC and in Hp-positive subjects. Treatment of GC patients with Vioxx resulted in a significant decrease in plasma and tumor contents of both progastrin and gastrin, and this was accompanied by the increment in tumor expression of COX-2, PPARy, Bax, and caspase-3 with a concomitant reduction in Bcl-2 and survivin expression. We conclude that: (1) GC patients show significantly higher Hp and CagA seropositivity than age- and sex-matched controls, but not Hp-positive subjects, indicating that infection with cytotoxic Hp is linked to GC. (2) Serum progastrin and gastrin levels are significantly higher in GC patients than in matched controls, confirming that both gastrins may be implicated in gastric carcinogenesis. (3) GC patients exhibit significantly higher levels of IL-8 and TNF-alpha than non-GC controls and Hp-positive subjects, probably reflecting more widespread gastritis in GC. (4) COX-2, PPARgamma, Bcl-2, and survivin were overexpressed in gastric tumor, but the inhibition of COX-2 activity by Vioxx resulted in a significant reduction in serum and tumor levels of progastrin and gastrin and serum IL-8 and TNF-alpha levels, suggesting that gastrin and proinflammatory cytokines could mediate the up-regulation of COX-2 in gastric cancerogenesis. (5) Vioxx also enhanced expression of COX-2, PPARy, Bax, and caspase-3, while inhibiting the expression of Bcl-2 and survivin, suggesting that COX-2 blockade might be useful in chemoprevention against gastric cancer possibly due to enhancement of the PPARy- and proapoptotic proteins-dependent apoptosis and the reduction in progastrin/gastrin-induced promotion of tumor growth.

Aged↗
PubMed2003

Influence of gastrin on the expression of cyclooxygenase-2, hepatocyte growth factor and apoptosis-related proteins in gastric epithelial cells.

BACKGROUND: Several studies have shown a link between gastrin and gastric cancer, both in humans and animals, especially infected with Helicobacter pylori (H. pylori). However, the exact role of hypergastrinemia in gastric carcinogenesis remains still undetermined. The aim of the present study was to evaluate the interaction between gastrin, cyclooxygenase-2 (COX-2), hepatocyte growth factor (HGF) and apoptosis-related proteins (Bax, Bcl-2, caspase-3, survivin) in cultured gastric epithelial cancer cells. MATERIAL AND METHODS: In the present study, gastric cultured cancer cells (KATO III cells) were exposed to increasing concentrations of gastrin (1-1000 nM). Cells incubated with culture medium alone, without added gastrin, served as controls. Using RT-PCR and Western blot, we examined the mRNA and protein expression for COX-2, HGF and apoptosis-related proteins (Bax, Bcl-2, caspase-3 and survivin). In addition, the gene expression of gastrin and gastrin receptor (CCK-2) as well as the release of gastrin in culture medium in the unstimulated cells were examined by RT-PCR and RIA, respectively. The apoptosis rate in cells was measured by flow cytometric analysis. RESULTS: The present study shows that the gastric cultured epithelial cells exhibit the expression of gastrin and CCK-2 receptors and release of gastrin into the culture medium. The epithelial gastric cancer cells incubated with gastrin showed a concentration-dependent increase of COX-2 and HGF expression. Although no significant changes in apoptosis rate were observed, the exposure of these cells was associated with a dose-dependent increase in the expression of antiapoptotic proteins Bcl-2 and survivin. CONCLUSIONS: This study demonstrates that 1) gastrin stimulates the gene and protein expression of COX-2 and HGF in human cultured gastric cancer cells and 2) gastrin shows antiapoptotic activity through the upregulation of Bcl-2 and survivin.

Apoptosis↗
PubMed2003

Pioglitazone, a specific ligand of the peroxisome proliferator-activated receptor gamma reduces gastric mucosal injury induced by ischaemia/ reperfusion in rat.

BACKGROUND: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent nuclear receptor that has been implicated in the control of metabolism and numerous cellular processes, including cell cycle control, carcinogenesis, and inflammation. The present study was designed to investigate the effect of the specific PPARgamma ligand, pioglitazone, on the mucosal lesions induced by ischaemia and reperfusion (I/R) in rats. METHODS: I/R lesions were induced in Wistar rats by applying a small clamp to the coeliac artery for 30 min (ischaemic phase), followed by the removal of the clamp for 3 h (reperfusion phase). Vehicle (saline) or increasing doses of pioglitazone (2.5, 10, and 30 mg/kg i.g.) were given 30 min before exposure to I/R. The animals were killed immediately after the end of the reperfusion phase (time 0) and at 12 and 24h after I/R. The area of gastric lesions was measured by planimetry, and the gastric blood flow was determined by the H2 gas clearance method. The gastric mucosal gene expressions of PPARgamma, interleukin-1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha), leptin, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were examined by RT-PCR. In addition, protein expression of COX-2 and leptin was assessed by Western blot. RESULTS: The pretreatment with pioglitazone reduced in a dose-dependent manner the mean lesion area induced by I/R, and this effect was accompanied by a significant increase in the gastric blood flow. The decrease in gastric ulcerations by pioglitazone was also observed 12 and 24 h after the I/R. The PPARgamma mRNA was weakly expressed in the intact gastric mucosa but significantly up-regulated after exposure to I/R at each time interval studied. The expression of IL-1beta was not changed significantly after pioglitazone applied i.g. at doses 2.5 and 10 mg/kg, but it was down-regulated at the dose 30mg/kg. TNFalpha mRNA was strongly increased after the exposure to I/R, but it was down-regulated after pioglitazone pretreatment. In contrast, both leptin and COX-2 mRNA and protein expression were increased in the gastric mucosa after exposure to I/R. The pretreatment with pioglitazone caused a significant up-regulation of mRNA and protein expression of leptin, reaching its peak at the dose 30 mg/kg i.g. In contrast, COX-2 expression did not change significantly after the 2.5 and 10 mg/kg of pioglitazone, but it significantly decreased after pioglitazone at dose 30 mg/kg given to rats before exposure to I/R. CONCLUSIONS: Pioglitazone reduces the acute erosions and deeper gastric lesions induced by I/R. The beneficial effect of this PPARgamma ligand on I/R-induced gastric damage may be due to its anti-inflammatory properties, especially to the reduction in TNF-alpha expression and to up-regulation of leptin mRNA in the gastric mucosa. The inhibition of COX-2 expression by pioglitazone may reflect the anti-inflammatory properties of this compound.

Amino Acid Sequence↗
PubMed1990

Occupational obstructive disorders: nonspecific airways obstruction and occupational asthma.

Airways obstruction as a result of occupational exposure may be divided into two categories on the basis of whether or not occupational asthma is present. The first category, nonspecific airways obstruction, takes place in the absence of occupational asthma, and demonstrates only modest changes in airways responsiveness. The second category, occupational asthma, usually has a causal relationship to exposure, and demonstrates marked changes in airways responsiveness. These distinctions are of use in diagnosis, treatment, and disability assessment.

Asthma↗
PubMed1988

The value of a zero power intraocular lens.

An intraocular lens with a reversed optic and with haptics angulated forward presses the posterior capsule more posteriorly than other types of lenses. This position is thought to be important even in eyes that do not need intraocular lenses for optical reasons, such as eyes with high axial myopia (because of their increased tendency to postoperative retinal detachment) and eyes with postoperative capsular fibrosis. "Zero lenses" were implanted in seven eyes. The lenses had a convex posterior surface and a concave anterior surface which were parallel. The position of the posterior capsule, measured with ultrasound, was 4.9 mm to 5.8 mm (mean 5.5 mm) behind the anterior corneal surface. In two fellow eyes without a lens (after planned extracapsular cataract extraction), the posterior capsule was 4.1 mm and 4.3 mm behind the anterior corneal surface.

Humans↗
PubMed1986

Outpatient treatment of patients with substance abuse and coexisting psychiatric disorders.

Thirty-two patients with coexisting substance abuse and other psychiatric disorders were treated in a unique outpatient pilot program that used techniques drawn from both psychiatric and substance abuse treatment. Eleven patients remained in treatment for 3 or more months, and seven completed a year or more of treatment. Severity of associated psychiatric illness did not affect retention in treatment. Drug-abusing patients and those with personality disorders dropped out quickly; patients with a history of reliable outpatient treatment involvement tended to remain in treatment. Treatment retention was associated with reduced hospital utilization. The authors suggest guidelines for management of patients with coexisting substance abuse and other psychiatric disorders.

Adult↗
PubMed1986

[Insulin secretion and utilization of insulin in piglets after insulin, arginine and glucose loads].

The insulin secretion and utilization dynamics have been investigated in 35 six weeks old healthy piglets in order to find the connection with spontaneous hypoglycemia. The trial to load piglets with insulin showed an average time t1/2 = 4.93 minutes accepted as normal in 10 piglets with the mean increase in body weight equal to 0.19 kg/day, prolonged time t1/2 = 7.56 minutes in 7 piglets with the decreased gain of body weight to 0.108 kg/day, and short time t1/2 = 2.78 minutes with the poor gain of body weight in 6 piglets at the age of 6 weeks. In 10 weeks old piglets the noted time t1/2 was 14.7 minutes. The trial to load piglets with L-arginine--HC1 showed a high insulin secretion amounting to 105.5 microU/ml of plasma in 3 piglets only, assumed as correct, and a low insulin secretion amounting to an average of 20.5 microU/ml of plasma in 10 piglets corresponding, according to the criteria of diagnostics, to the subclinical form of human diabetes mellitus. The glucose tolerance test enabled to distinguish 7 strongly reacting piglets (over 100 microU/ml of plasma), 10 moderately responding piglets (from 20 to 100 microU/ml), and 2 piglets not responding (16 microU/ml) by means of increase in insulin concentration. The differentiated results with the individuals deviations to subclinical values observed in healthy piglets, point to serious difficulties in the maintenance of the equilibrium between insulin secretion and utilization. Excessive secretion lasting over 2 hrs and very fast utilization of insulin as well as the level of glucose not compensated by gluconeogenesis, can be the cause of hypoglycemia.

Animals↗
PubMed1984

Drug use by alcoholics in outpatient treatment.

Although increasing attention has been paid to the problems of combined and sequential alcohol and drug abuse, data about drug use by alcoholics during the course of outpatient treatment are not available. Urine testing for commonly abused drugs was obtained on 112 alcoholic outpatients during a 2-week period. Ten urine samples were positive for abuseable drugs. Patients' age, length of treatment involvement, and history of drug use prior to treatment appeared to affect drug use during treatment. At 4 month follow-up of the 10 patients with positive urine tests, five were drug free, three had discontinued but then returned to drug use, and two had been discharged. Given the limitations of such a cross-sectional study, the incidence of drug use by alcoholics during outpatient treatment seems high enough to warrant further study.

Adult↗
PubMed1983

Comparison of effects of neurotensin and fat on pancreatic stimulation in dogs.

In six conscious dogs with esophageal, gastric, and pancreatic fistulas, the effects of intravenous infusion of neurotensin and intraduodenal instillation of sodium oleate on gastric and pancreatic secretion were determined under basal conditions and after exogenous (secretin and cholecystokinin octapeptides) or endogenous stimulants (feeding and duodenal acidification). Neurotensin given intravenously in graded doses (1.5-200 pmol . kg-1 . min-1) to fasted dogs produced a dose-dependent stimulation of pancreatic bicarbonate and protein secretion reaching, respectively, about 18 and 100% of maximal responses to secretin and cholecystokinin octapeptide (CCK). Duodenal oleate in graded doses (0.5-16 mmol/h) resulted in a similar pattern of bicarbonate and protein secretion but increased plasma neurotensin only to about 10% of that achieved with infusion of exogenous neurotensin producing an equal rate of pancreatic secretion. Neurotensin, like oleate, potentiated the action of secretin and CCK on pancreatic bicarbonate and had additive effects on protein response to these secretagogues. Both neurotensin and oleate increased pancreatic response to liver extract meal kept in the stomach at constant pH (5.5) and the response to sham feeding but decreased the response to ordinary feeding, probably due to the inhibition of gastric acid secretion and reduction of duodenal acidification. Neurotensin given intra-arterially directly to the pancreas or to isolated intestinal segment increased dose dependently the blood flow and oxygen consumption without affecting general circulation. We conclude that 1) neurotensin mimics the pancreatic secretory effects of intestinal fat, 2) neurotensin may contribute in part to fat-induced stimulation of the pancreatic secretion, and 3) the secretory effects of neurotensin are accompanied by a marked stimulation of intestinal and pancreatic circulation and metabolism.

Animals↗
PubMed1983

Prostaglandins and alkaline secretion from oxyntic, antral, and duodenal mucosa of the dog.

Alkaline secretion (AS) measured under basal conditions in oxyntic and antral pouches of conscious dogs averaged about 20 mumol/30 min and was about three times lower than that from the duodenal pouch. Natural prostaglandin E2 and prostaglandin F2 alpha, but not prostaglandin I2, were effective stimulants of AS, mainly when given topically. Stable analogues such as 16,16-dimethyl prostaglandin E2 and prostaglandin I2 were relatively more potent stimulants than their parent prostaglandins (PGs), particularly when applied topically. The highest alkaline response of the oxyntic pouch to PG was about 5% of the maximal acid response of this pouch to histamine. Indomethacin reduced markedly AS from the duodenal but not from the oxyntic or antral pouch. AS from the duodenal pouch was relatively more sensitive than that from gastric pouches to the stimulation by PGs, which were effective also after pretreatment with indomethacin. This study shows that the oxyntic, antral, and duodenal mucosa of conscious dogs is capable of secreting bicarbonate, and this secretion, particularly from the duodenal mucosa, is highly sensitive to the stimulation with certain PGs, mainly of the E and F type and their analogues, and to suppression by indomethacin, a potent inhibitor of PG biosynthesis, suggesting that endogenous PGs are involved in the mechanism of AS.

Animals↗
PubMed1980

Isolation, characterization and implications of anti-TF (Thomsen-Friedenreich) agglutinins from different sources.

Anti-TF agglutinins from peanut (Arachis hypogaea) and from vertebrate sera of different species have been successfully isolated by affinity chromatography on acid-activated Sepharose 4 B. The proteins were characterized by immunoelectrophoresis, polyacrylamide gel electrophoresis in the presence of SDS and with respect to their carbohydrate binding specificities. Anti-TF substances from sera showed one precipitin arc in immunoelectrophoresis, but quantitative immunoprecipitation revealed our human anti-TF to be a mixture of the three Ig-classes IgG, IgA and IgM. This finding was confirmed on SDS gel electrophoresis, where high molecular weight aggregates were found before reduction. Hemagglutination inhibition revealed that all isolated anti-TF compounds exhibit an exceptionally high affinity for the immunodominant group of the TF-antigen, namely the beta-D-galactosyl-(1 leads to 3)-N-acetyl-D-galactosamine disaccharide. On examination of formalin-fixed and neuraminidase treated tissue sections (kidney, mammary gland), fluorescein-labelled anti-TF from horse serum showed a virtually identical pattern when compared with fluorescein labelled peanut lectin. Likewise isolated IgA-class myeloma J 539, which shows specificity against beta-(1 leads to 6)-galactans, only bound to the appropriate Gal-beta-(1 leads to 6)-Gal structures, such as those found on bovine lung or the albumin gland of Helix pomatia. Rabbit anti-VCN (Vibrio cholerae neuraminidase) activity could be selectively abolished by beta-galactosyl-containing inhibitors, whereas papain F(ab) fragments from rabbit anti-VCN immunoglobulin did not compete with anti-TF for binding sites on VCN-treated human red cells. Anti-TF, on the other hand, did not compete with anti-VCN for active VCN.

Agglutinins↗