Plasma carnitine ester profiles in Crohn's disease and ulcerative colitis patients with different IGR2230a_1 genotypes.

An association has been repeatedly demonstrated between inflammatory bowel disease (IBD) and the IBD5 locus in the 5q31 chromosomal region. The aim of the present study was to examine the prevalence of the IGR2230a_1 intronic nucleotide polymorphism of the slc22a5 gene (coding for the OCTN2 carnitine transporter protein) lying within this region, and its possible relationship with the carnitine metabolism in Hungarian IBD patients and controls. We genotyped by restriction fragment length polymorphism 200 Crohn's disease (CD) and 246 ulcerative colitis (UC) patients, as well as 187 healthy controls. From plasma samples we determined detailed carnitine ester profiles of 76 CD, 43 UC patients and 45 control persons using electrospray ionization triple quadruple tandem mass spectrometry. The distribution of the genotypes was not significantly different in the CD or the UC group compared with the controls. We found no significant alterations of the carnitine profile in the carrier/non-carrier or the homozygote/non-homozygote comparisons in both the CD and the UC groups, stratified by IGR2230a_1 genotype. Our data suggest that this polymorphism alone is not associated with CD and UC in the Hungarian population, and has no effect on the carnitine metabolism.

Microalbuminuria in inflammatory bowel diseases using immunoturbidimetry and high-performance liquid chromatography.

BACKGROUND AND STUDY AIMS: To measure urinary albumin excretion using immunoturbidimetry (IT) and high-performance liquid chromatography (HPLC) in inflammatory bowel diseases. PATIENTS AND METHODS: A cross-sectional study was carried out on 60 selected patients with Crohn's disease (CD), 57 with ulcerative colitis (UC) and 22 healthy volunteers, as controls. Urinary albumin excretion was measured by IT and HPLC, and albumin-creatinine ratio was calculated. This ratio was compared in patients with active and inactive CD and UC and in healthy volunteers. RESULTS: Patients with CD and UC had higher albumin-creatinine ratio compared to controls using both IT and HPLC (p < 0.05). We measured higher albumin-creatinine ratio in patients with active compared to inactive CD (p < 0.05). Albuminuria did not correlate with disease duration of CD or UC, but patients with more extended CD according to the Montreal classification had higher HPLC-albumin-creatinine ratio. In CD, we found a significant correlation between HPLC-albumin-creatinine ratio and some inflammatory markers i.e. white blood cells (p < 0.05) and erythrocyte sedimentation rate (p < 0.05). In UC, there was no significant correlation between HPLC-albumin-creatinine ratio and the above markers of systemic inflammation or activity of UC. Albumin-creatinine ratio measured by HPLC was higher in both active and inactive CD and UC groups than albumin-creatinine ratio measured by IT. Using a receiver operating characteristics curve analysis, in case of HPLC-albumin-creatinine ratio cut-off values of the activity of CD were 2.46 mg/mmol for men, 5.30 mg/mmol for women. CONCLUSIONS: HPLC-urinary albumin-creatinine ratio is associated with the clinical and laboratory disease activity indices in CD, but not in UC. Using HPLC we found a more sensitive method compared to IT to measure albuminuria that would be a sensitive activity marker in CD.

Results of nutritional risk screening of patients admitted to hospital.

INTRODUCTION: To identify malnutrition, nutritional risk screening and assessment should be performed. A number of nutritional screening and assessment tools have been developed. MATERIALS AND METHODS: Authors monitored the nutritional state of 1266 patients using the MUST (Malnutrition Universal Screening Tool) method. Measurements and questioning were done at admission. The study was cross-sectional, presenting a snapshot about nutritional risk of patients. RESULTS: In this study 21% of the patients had a BMI smaller than 20.29% patients admitted to hospital lost at least 5% of their body weight in the 3 to 6 months before the admission. Altogether in this survey 41% of the patients are considered to be endangered concerning malnutrition! There is a statistically visible difference at BMI values between the disease groups. DISCUSSION: If only body weight of patients is measured, the rate of malnutrition is about 20%. Using MUST the number of endangered patients is doubled. In these patients it is more likely that any complication would develop. Since there is no significant relation between the age and the risk group, MUST screening can be carried out on all patients. We intended to emphasize the necessity of nutritional risk assessment and nutritional therapy at all levels of health care.

The key-role of vagal nerve and adrenals in the cytoprotection and general gastric mucosal integrity.

BACKGROUND: Our laboratory group observed earlier that the gastric mucosal cytoprotective effect of prostacyclin (PGI(2)) disappeared after surgical vagotomy in rats. Similarly to this, the beta-carotene induced gastric cytoprotection disappeared in adrenalectomized rats too. AIMS: In these studies we aimed to investigate the possible role of vagal nerve and adrenals in the development of gastric mucosal lesions induced by exogenously administered chemicals (ethanol, HCl, NaOH, NaCl and indomethacin), and on the effects of cytoprotective and antisecretory drugs (atropine, cimetidine), and scavengers (vitamin A and beta-carotene). METHODS: The observations were carried out in fasted CFY strain rats. The gastric mucosal lesions were produced by intragastric (i.g.) administration of narcotising agents (96% ethanol; 0.6 M HCl; 0.2 M NaOH; 25% NaCl) or subcutaneously (s.c.) administered indomethacin (20 mg/kg) in intact, surgically bilaterally vagatomized, and adrenalectomized rats without or with glucocorticoid supplementation (Oradexon, 0.6 mg/kg given i.m. for 1 week). The gastric mucosal protective effect of antisecretory doses of atropine (0.1-0.5-1.0 mg/kg i.g.) and cimetidine (10-25-50 mg/kg i.g.), and vitamin A and beta-carotene (0.01-0.1-1.0-10 mg/kg i.g.) was studied. The number and severity of mucosal gastric lesions was numerically or semiquantitatively measured. In other series of observations the gastric acid secretion and mucosal damage were studied in 24 h pylorus-ligated rats without and with acute bilateral surgical vagotomy. RESULTS: It was found that: (1) the chemical-induced gastric mucosal damage was enhanced in vagotomized and adrenalectomized rats, meanwhile the endogenous secretion of gastric acid, and the development of mucosal damage can be prevented by surgical vagotomy; (2) the gastric cyto- and general protection produced by the drugs and scavengers disappeared in vagotomized and adrenalectomized rats; (3) the gastric mucosal protective effects of drugs and of scavengers returned after sufficient glucocorticoid supplementation of the rats. CONCLUSION: It has been concluded that the intact vagal nerve and adrenals have a key role in the gastric mucosal integrity, and in drugs- and scavengers-induced gastric cyto- and general mucosal protection.

Prevalence of the factor V Leiden mutation in human inflammatory bowel disease with different activity.

BACKGROUND: the developmental mechanism of inflammatory bowel disease (IBD) in patients is unknown, but it may be influenced by different environmental and genetical factors. AIMS of this study were: (1) to classify the IBD patients according the disease activity; and (2) to determine the presence of factor V Leiden mutation in IBD patients. PATIENTS AND METHODS: the observation was carried out in 49 patients with Crohn's disease (CD) and 29 patients with ulcerative colitis (UC). None of them had a history of thrombotic episodes. IBD was diagnosed by conventional clinical, endoscopic, radiological and histological criteria. The factor V Leiden mutation was detected by the polymerase chain reaction (PCR) method. Crohn's disease activity index (CDAI) was evaluated using the method of the National Cooperative Crohn's Disease Study. We determined the UC disease activity according to Truelove-Witts classification. RESULTS: The prevalence of factor V Leiden mutation was increased in both populations of the patients to compare it with healthy persons (14.28 and 27.58% vs. 5.26%, n=7/49 and 8/29 vs. 3/57). The statistical analysis did not show a significant relationship between the CDAI or the Truelove-Witts grade in UC and the presence of Leiden mutation. CONCLUSION: the presence of factor V Leiden mutation probably has a role in the development of IBD. Our results suggest a higher prevalence of this mutation in Central European patients than in Southern, Northern Europe or America, may be due to the genetical differences of these populations.

Mechanisms of action of retinoids in gastrointestinal mucosal protection in animals, human healthy subjects and patients.

UNLABELLED: Retinoids prevent chemically induced gastric mucosal damage without inhibiting gastric acid secretion ("nutritional gastric cytoprotection"). The gastroprotective effects of retinoids do not depend on 1) vitamin A activity; 2) number of unsaturated double bonds; 3) the presence of a characteristic chemical structure of their terminal components; however, they depend on 1) intact vagal nerve and 2) adrenals in experimental animals. The gastric cytoprotective effect of retinoids produces a dose-dependent inhibition of ATP-transformation into ADP. It also increases the transformation of ATP into cAMP. Other features of these gastric cytoprotective effects of retinoids include: 1) The retinoid-induced gastric mucosal protection differs from that of PGs; 2) The cAMP is an intracellular signal in the development of gastric mucosal damage produced by chemicals (e.g., ethanol, HCl, indomethacin) and in the protection of gastric mucosa induced by retinoids (but not by PGs); 3) The gastric mucosal protection induced by retinoids and gastric mucosal permeability can be separated in time. The existence of gastric mucosal protection can be demonstrated in healthy persons (against indomethacin treatment), in patients with gastric ulcer (GU) and duodenal ulcer (DU) without any inhibition of gastric acid secretion. The serum levels of vitamin A and zeaxanthin were significantly decreased in patients with chronic gastrointestinal (GI) inflammatory diseases (e.g., terminal ileitis, ulcerative colitis), colorectal polyposis, and different (e.g., esophageal, gastric, pancreatic, hepatocellular and colorectal) malignant diseases. The serum levels of vitamin A provitamins were unchanged and their GI mucosal protective effects do not depend on vitamin A activity. CONCLUSIONS: 1) Abundant experimental and human observations clearly proved the defensive role of retinoids in the GI tract; 2) There is a correlation between the a) scavenger properties of retinoids vs. intact vagal nerve; b) scavenging properties vs. intact adrenals. 3) The GI mucosal protective effect of retinoids is correlated with biochemical changes in the GI mucosa.

Effects of exogenous serotonin on a motor behavior and shelter competition in juvenile lobsters (Homarus americanus).

Three experiments were conducted to determine (1) the pharmacodynamics of 5-hydroxytryptamine in juvenile lobsters; (2) the effects of 5-hydroxytryptamine, using a range of dosages, on a motor behavior used to escape an aversive situation; and (3) the effect of doses that did and did not inhibit this motor behavior on measures of dominance and shelter competition. The fate of 5-hydroxytryptamine in hemolymph over a 60-min post-injection period showed that the concentration fell rapidly to a low plateau that was maintained for at least 1 h. Low doses of 5-hydroxytryptamine did not affect locomotor behavior, but higher doses inhibited it. Dominance and subsequent possession of a shelter were unaffected by a low dose of 5-hydroxytryptamine but a higher dose that inhibited locomotion resulted in lobsters that lost fights and did not secure or retain possession of the shelter. In the context of dominance and shelter competition, we were unable to demonstrate any advantage of the low dose of exogenous 5-hydroxytryptamine and a severe disadvantage with the higher dose. Previous reports of transient increases in aggression in 5-hydroxytryptamine-treated subordinate lobsters did not take into account motor inhibition as a possible critical variable in aggression.

Membrane-bound, ATP-dependent energy systems and tissue hypoxia in human gastric mucosa.

1. The biochemical measurements of gastric mucosal ATP, ADP, AMP and cAMP offer excellent information on the extent of tissue oxygenation, when the observations are taken simultaneously from the same tissue sample. 2. Adenosine triphosphate is split by membrane-bound enzymes in two directions (to ADP and cAMP), while ADP and cAMP transform to AMP, supplying further energy liberation. 3. The liberated free energy modifies physiologically or pathophysiologically the functions of target organ cells. 4. Different drugs, hormones and mediators, have different effects on the regulation of ATP breakdown (into ADP vs cAMP). 5. The actual tissue level of ATP is a consequence of the equilibrium between the directions of ATP-ADP and ATP-cAMP breakdown, as well as of ATP resynthesis. 6. The biochemical measurement of the reduction in gastric mucosal ATP alone is not enough proof for the existence of tissue hypoxia, because demonstration of the simultaneous elevation of tissue lactate is also necessary.

Effects of pectin-induced passive linkage of gastric H+ on the gastric acid secretion on the development of ethanol- and salicylate-induced gastric mucosal lesions in rats.

The aim of this study was to evaluate the effects of intragastrically given pectin-induced physicochemical properties and actions on active gastric acid secretion and on the development of ethanol- and aspirin-induced gastric mucosal lesions. The observations were carried out on CFY-strain rats, fasted for 24 h before the experiments with water ad libitum. The observations were carried out in two experimental series. A) The gastric mucosal lesions were produced by intragastrically given 96% ethanol or aspirin prepared with 0.2 M HCl. Different doses of pectin (100, 50 and 25 mg x kg(-1), respectively) were administered intragastrically 30 min before giving necrotizing agents. The number of gastric lesions was noted 1 h after the administration, while the severity of gastric mucosal lesions was scored by semi-quantitative scale. B) The effects of pectin were studied on the volume and H+ secretion of the stomach in 4-h pylorus-ligated rats. It has been found that: 1) the gastric mucosal lesions could be produced in 100% of rats by the application of both necrotizing agents. 2) Pectin in doses of 50-100 mg x kg(-1) increased the number of gastric mucosal lesions in both models, while no increase was produced by the application of 25-mg x kg(-1) dose. 3) The severity of mucosal lesions increased significantly after the administration of all doses of pectin. 4) The pectin-induced increase of gastric lesions (number) showed a dose-response effect. 5) The pectin produced a significant increase in the volume of gastric secretion and gastric H+ secretion. It has been concluded that: a) pectin-induced physicochemical changes are able to enhance the aggression to gastric mucosa produced by ethanol and aspirin; b) a positive correlation exists between the linkage of H+ to pectin and significant active metabolic response in the rat stomach; c) pectin alone stimulates the active metabolic process of the gastric H+ secretion.

Small doses of capsaicin given intragastrically inhibit gastric basal acid secretion in healthy human subjects.

Although the direct inhibitory effect of small dose of capsaicin on gastric secretory responses was proved in animal observations, the role of capsaicin-sensitive afferent nerves (CSAN) and the effect of capsaicin applied in small and high doses on gastric secretion in human has not been clarified yet. In this study we investigated the influence of different small doses (100-800 microg) of capsaicin given intragastrically through an orogastric tube on gastric basal secretory responses in 10 healthy human subjects. Gastric basal secretory responses (volume, H+-concentration, H+-output) were measured from the suctions of gastric juice for a 1-h period. It has been found that: a) capsaicin dose-dependently inhibited the volume and H+-output of gastric juice; b) ID50 was found to be about 400 microg for capsaicin on gastric acid secretion; c) the time interval for capsaicin-induced gastric inhibition existed for about 1 h indifferently from the higher dose (800 microg) of capsaicin given after. It has been concluded that the capsaicin (given in small doses) inhibits the gastric basal acid output via stimulation of the inhibition of capsaicin sensitive afferent nerves.

Capsaicin increases gastric emptying rate in healthy human subjects measured by 13C-labeled octanoic acid breath test.

The role of capsaicin-sensitive primary afferent sensory nerves in the regulation of gastrointestinal motility in human is not clarified yet. In this study, we investigated the effect of 400 microg capsaicin given intragastrically on gastric emptying measured by 13C-octanoic acid breath test in ten healthy human subjects. Four parameters of gastric emptying curves were taken into consideration: 1) maximum value of the curve, 2) time belonging to this maximum, 3) slope of the rising part of the curve and 4) time belonging to the 50% of the area under the curve. Administration of 400 microg capsaicin significantly increased the slope of gastric emptying curve (from 0.1 +/- 0.01 to 0.139 +/- 0.014 U x min(-1), P < 0.05) and significantly decreased the time belonging to the maximum value of emptying curve (from 150 +/- 18 to 75 +/- 12 min, P < 0.05) and the time belonging to the 50% of the area under the curve (from 112 +/- 15 to 99 +/- 14 min, P < 0.05). According to our results 400 microg capsaicin enhances gastric emptying rate in healthy human subjects.

Effects of indomethacin, with vitamin A or beta-carotene, on the rat gastric mucosa: extra-and intracellular membrane-bound ATP mechanisms.

BACKGROUND: Indomethacin (IND) is a widely used non-steroidal anti-inflammatory agent in the treatment of various inflammatory disorders, which causes gastrointestinal injury in humans and animal experiments. Vitamin A and beta-carotene prevent the IND-induced gastric mucosal injury. These compounds modify the membrane-bound ATP-dependent energy systems. The aims of this investigation were: (1) To study the IND-induced gastric mucosal damage and its prevention by vitamin A and beta-carotene; (2) to measure the biochemical compounds of the gastric mucosa ATP, ADP, ATP/ADP, AMP, ATP+ADP+AMP, 'energy charge' (ATP + 0.5 ADP)/(ATP+ADP+AMP), cAMP, lactate under the circumstances mentioned above; (3) to analyze the extra- and intracellular regulatory mechanisms between the membrane-bound ATP-dependent energy systems. METHODS: The observations were carried out with CFY (Sprague-Dawstrein rats, weighing 180-210 g). The gastric mucosal damage was produced by IND (20 mg/kg sc. administration) and it was prevented by vitamin A (or beta-carotene), given in doses of 0.01-0.1 to 1.0-10.0 mg/kg ig. Different biochemical compounds (ATP, ADP, AMP, cAMP, lactate) and parameters (ATP/ADP, adenylate pool, 'energy charge') were measured and calculated. RESULTS: (1) Vitamin A and beta-carotene prevented dose-dependently the IND-induced gastric mucosal damage; (2) the extent of ATP-ADP transformation was increased significantly, while the ATP-cAMP decreased in the gastric mucosa after IND-treatment; (3) vitamin A and beta-carotene enhanced the extent of ATP-cAMP transformation, while the ATP-ADP transformation was inhibited (the actions were dose-dependent responses); (4) No change was found in 'energy charge' by IND, while its value decreased significantly with vitamin A and beta-carotene. CONCLUSIONS: (1) A very complex extra- and intracellular feedback mechanism system exists in the gastric mucosa during IND, IND + vitamin A, and IND + beta-carotene treatments; (2) The gastric mucosal preventive effect of vitamin A and beta-carotene only partly depend on their scavenger properties.

Leiden mutation in patients with Crohn's disease.

BACKGROUND: Inherited resistance to activated protein C is a common risk factor of venous thrombosis. In a majority of patients the defect is caused by single-point mutation in the gene for factor V. This mutated form of factor Va is more stable against proteolytic attack by activated protein C. The prevalence of this inherited defect in the European population is at least 5%. The risk of thrombosis is increased in the case of heterozygosity 5- to 10-fold, in homozygous subjects 50- to 100-fold, but even homozygous individuals will not necessarily suffer from thrombosis. The aim of our study was to determine whether the presence of Leiden mutation might play a role in the pathophysiology and clinical manifestation of Crohn's disease. MATERIALS AND METHODS: Thirty-four patients with Crohn's disease (mean age 34 years, range 21-72 years) were studied. None of them had a history of thrombotic episodes. We examined the case history for risk factors: use of oral contraceptive, steroids, cigarette smoking. Levels of fibrinogen, APTT, lupus anticoagulant and levels of IgG and IgM class anticardiolipin (ACL) antibodies were determined. The Leiden mutation was detected by PCR method (Denninger et al., 1995). RESULTS: Fibrinogen was elevated in five cases, lupus anticoagulant in one case, but none of the patients had ACL antibodies in the serum. Molecular analyses showed heterozygosity for the Leiden factor V gene mutation in the case of 30 patients (25%). CONCLUSION: Thromboembolic events frequently complicate the clinical course of patients with Crohn's disease; however, we do not have enough knowledge about its role in manifestation of the disease. These results suggested the high frequency of Leiden mutation among our patients and suggest a new genetic background of Crohn's disease.

Effects of alcohol, congeners, and acetaldehyde on aggressive behavior of the convict cichlid.

Ethanol and three beverage alcohols were examined for their effects on the aggressive responses of the convict cichlid. At an ethanol concentration that gave negligible effects on the basal level of these responses, rum was observed to depress aggression. As its concentration of acetaldehyde was significantly higher than that of the other beverage alcohols, we assessed the effects of acetaldehyde on the aggressive responses, as well as the locomotor activity of the fish. At 4 mg/l, acetaldehyde completely inhibited aggressive responses, without affecting locomotor activity. It is likely, however, that acetaldehyde does not explain the entire inhibitory effect of rum on the aggressive responses of the cichlid.

Modulation of aggressive behavior in fish by alcohol and congeners.

Studies of alcohol and congener effects on the aggressive behavior of fish have been reviewed. It is clear that alcohol has both depressing effects at very low and very high doses and a facilitating effect at moderate doses. Congener effects as they are present in bourbon and in rum appear to have aggression-inhibiting effects. A study of the most prevalent congener in rum and some bourbons, acetaldehyde, demonstrated that it is psychoactive and has a depressing effect on aggressive behavior at doses that do not cause locomotor decrements.

Pentobarbital sodium and attack behavior in male Siamese fighting fish.

An experiment was undertaken to determine the effects of pentobarbital sodium on intraspecific attack behavior in male Siamese fighting fish in an attempt to extend earlier findings with chlordiazepoxide and secobarbital sodium. Pairs of fish fought while immersed in 20 microgram/ml or 40 microgram/ml pentobarbital sodium or plain water. The 40 microgram/ml group showed significantly less attack (e.g., biting, jaw locking) than either control or low dose groups without producing a change in general arousal. Quasisexual behavior, seen in an earlier chlordiazepoxide study, did not occur in the present study.

Chlordiazepoxide (librium)-induced changes in intraspecific attack and selected non-agonistic behaviors in male Siamese fighting fish.

Two experiments were undertaken to determine the effects of chlordiazepoxide on intraspecific attack behavior and selected non-aggressive behaviors in male Siamese fighting fish. In Exp. 1, pairs of fish fought while immersed in either 15 mug/ml or 30 mug/ml of chlordiazepoxide, or plain water. The drug groups showed significantly less attack (e.g., biting, jawlocking) than the control group, without noticeable behavioral toxicity. Also, in the drug groups alone, some variants of the copulatory clasp, seen in normal mating, occurred in many pairs. In Exp. 2, individual fish were isolated in one of the same doses or plain water for a period equivalent to that of Exp. 1. These doses produced no changes in measures of arousal, locomotion, and feeding behavior, as compared to the control condition. The drug-related appearance of the intermale mating-like behavior is discussed in terms of a theoretical formulation postulating a mutually inhibitory relationship between sex and aggression in fish.