Acquired cow's milk sensitization after liver transplant in an adult: "clinical implications" and future strategies.

BACKGROUND: Identifying the mechanisms responsible for the development of food allergy in liver transplant recipients is more complex as there are several different clinical scenarios related to the immunological function of the liver. CASE PRESENTATION: We describe the first case of Transplant Acquired Food Allergy (TAFA) to cow milk in an adult following LT from a donor dead because of anaphylactic shock. A 67-year-old woman with primary biliary cirrhosis was referred to the Transplant Center of our hospital because of an acute-on-chronic liver failure. The donor was a 15-year-old girl deceased for anoxic encephalopathy due to food induced anaphylaxis after eating a biscuit. In the donor's history food allergies to cow milk and eggs were present. CONCLUSION: This case emphasizes the need for a standardized assessment of both solid-organ donors and recipients including donor allergy history in order to detect recipients at risk for anaphylaxis due to passive IgE transfer. Despite several reports of TAFA after solid organ, especially liver, an appropriate protocol to avoid risk for the recipient doesn't exist at the moment. The SPT (skin prick test) or specific IgE level are not enough to ensure a correct management in these cases and a correct education of the patients and the medical staff involved is absolutely necessary. It is the first case of milk allergy sensitization after solid organ transplant by passive transfer of IgE.

Improvement of quality of life in allergic rhinoconjunctivitis patients using nasal filters, a preliminary study.

BACKGROUND: Allergic rhinoconjunctivitis is a clinical condition that impairs quality of life. The use of traditional drugs in many cases is not enough to improve quality of life in these patients. METHODS: In this pilot study we used the Sanispira Nasal filters in 15 patients (mean age 34,7 years) affected by allergic rhinoconjunctivitis for 18 days. At each follow-up visit, patients were assessed with a specific quality of life questionnaire, a symptoms form and a drugs form that evaluates the use of antiallergic drugs in the last week. Patients sensitive to environmental allergens wore Sanispira nasal filters during the day, while patients sensitive to domestic allergens wore the device during the night. RESULTS: Thirteen patients completed the study. We found an improvement significative (p=0,0241) of the total score of RQLQ of 23,10 points between baseline and 18 days ( total score at baseline prior to nasal filter insertion= 60,60, at 1 week = 42, 28, at 18 days= 34, 10). A significative improvement in the nasal symptoms domain between baseline and 18 days (in particular stuffy nose p=0,047; runny nose p=0,012; sneezing p=0,0021; ) and one item of practical problems domain, the need to repeatedly blow the nose(p=0,082). The total score of symptoms evaluated with the symptoms form improved significantly from baseline to 18 days. Total symptoms score at baseline was 9,7; at 1 week it was 8,1 and at 18 days it was 4,7. The improvement was statistically significant (p=0,0092). Three of the thirteen patients that completed the study eliminated completely the use of drugs during of the study. CONCLUSIONS: The use of SANISPIRA ®, has shown encouraging results, with an improvement in the quality of life in Rhinoconjunctivitis patients specially an improvement in nasal and ocular symptoms.

Lipid transfer proteins: the most frequent sensitizer in Italian subjects with food-dependent exercise-induced anaphylaxis.

BACKGROUND: Specific food-dependent exercise-induced anaphylaxis (S-FDEIAn) is a distinct form of food allergy in which symptoms are elicited by exercise performed after ingesting food to which the patient has become sensitised. Non-specific FDEIAn (NS-FDEIAn) is a syndrome provoked by exercise performed after ingesting any food. OBJECTIVE: We sought to identify the culprit allergenic molecules in patients with FDEIAn, combining 'classic' allergy testing with an allergenic molecule-based microarray approach for IgE detection. METHODS: All subjects were evaluated who reported at least one episode of anaphylaxis in association with physical exercise performed within 4 h after a meal. We performed skin prick tests (SPT) with commercial food extracts, prick plus prick tests (P + P) with fresh foods (P + P), and serum specific IgE assays by means of both the ImmunoCAP (CAP) and the ISAC 89 microarray system (ISAC). RESULTS: Among our 82 FDEIAn patients, the most frequent suspected foods were tomato, cereals, and peanut. SPT, P + P, and CAP displayed different degrees of sensitivity. Each test disclosed some positivities not discovered by others. Seventy-nine subjects were positive to at least one food (49 to more than 20), whereas three were negative. All suspected foods were positive to at least one of SPT, P + P, and CAP. When tested using the ISAC, 64 (78%) subjects were positive to Pru p 3 [peach lipid transfer protein (LTP)], 13 were positive to other food allergen molecules, and five displayed negative results to all food allergenic molecules. Overall, 79 patients probably had S-FDEIAn and the other 3 NS-FDEIAn. CONCLUSIONS: Multiple food hypersensitivity represents a clinical hallmark of a large percentage of FDEIAn patients. The very high prevalence of IgE to the LTP suggests a role of this allergen group in causing S-FDEIAn.

Assessing potential determinants of positive provocation tests in subjects with NSAID hypersensitivity.

BACKGROUND: Provocation tests (PTs) with the suspected compounds are considered the 'gold standard' for establishing or excluding a diagnosis of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). However, only a few studies have evaluated the potential determinants of positive responses to PTs. OBJECTIVE: The aims of this study are to assess the reliability of clinical histories as indicators of NSAID hypersensitivity, as well as the risk factors for a positive PT. METHODS: Two hundred and seventy-five subjects with an unequivocal history of NSAID hypersensitivity reactions underwent PTs with the suspected drugs. To establish the potential determinants of positive PTs, we examined the following variables: gender, age at the time of reaction (<40 or ≥40 years), family and personal histories of atopy, patients who had reacted to one or more NSAIDs, time interval between drug intake and symptom onset (immediate or non-immediate reactions), time interval between the last drug reaction and the allergologic examination (≤12 or >12 months), and inclusion in a category of the Stevenson et al. classification. RESULTS: Two hundred and fourteen (77.8%) subjects tolerated the suspected drugs and 61 (22.2%) reacted. Age <40 years, male gender, immediate reactions, and time interval ≤12 months were significant risk factors for a positive PT. CONCLUSIONS AND CLINICAL RELEVANCE: Our study confirms that clinical histories are not reliable tools for diagnosing NSAID hypersensitivity. Therefore, we recommend that suspected cases should undergo drug PTs. However, further studies on large samples of NSAID-sensitive patients are necessary to establish the risk factors that allow the number of candidates for PTs to be reduced.

Early sexual maturity in local boars of Northeastern India: age-related changes in testicular growth, epididymal sperm characteristics and peripheral testosterone levels.

The present study reports the age related changes in the peripheral testosterone levels, testicular and epididymal growth and development and cauda epididymal spermiogram in local pigs of Northeastern India, which attain sexual maturity around 3 months of age. Local boars (n = 20) were castrated at monthly intervals from 2 to 6 months of age (4 boars per month) to study the testicular growth and development and the epididymal spermiogram. Blood samples, collected from local boars (n = 6) at monthly intervals from 2 to 6 months of age, were analyzed for testosterone levels by radioimmunoassay. Compared to Hampshire boars, significantly (P < 0.05) high testosterone levels were observed in the local boars as early as 2 months of age. The mean (± SEM) level of testosterone in the local boars at 2, 3 and 4 months of age was 11.89 ± 1.52, 20.45 ± 1.33 and 20.38 ± 2.0 ngml(-1), respectively. Though there was consistently significant (P < 0.05) difference in the body weight between Hampshire and local pigs, the same was not observed in case of testicular weight except at 3 and 6 months of age. In line with the above observation, the testis:body weight ratio (gram testis per kg body weight) was significantly (P < 0.05) higher in the local boars compared to the Hampshire boars at any time of observation, which ranged from 0.8 to 1.0 in case of Hampshire and from 2.3 to 3.0 in local boars. The sperm concentration in the cauda epididymal fluid of local boars at 2, 3 and 6 months of age was 2255 ± 186.6, 3685 ± 103.8 and 4325 ± 146.2 million/ml, respectively and the sperm motility, viability and total abnormality was 73.3, 75.2 and 6.2%, respectively at 3 months of age. Taken together, the testosterone level, testicular growth and development and epididymal spermiogram indicate the trait of early sexual maturity in the local pigs as compared to Hampshire.

The very limited usefulness of skin testing with penicilloyl-polylysine and the minor determinant mixture in evaluating nonimmediate reactions to penicillins.

BACKGROUND: The contribution of skin testing with penicilloyl-polylysine (PPL) and the minor determinant mixture (MDM) to the diagnosis of hypersensitivity reactions to penicillins differs greatly according to the type of reaction: immediate (occurring within 1 h after the last drug administration) or nonimmediate (occurring more than 1 h after the last drug administration). OBJECTIVE: To assess the contribution of skin testing with PPL and MDM to the diagnosis of nonimmediate reactions to penicillins. METHODS: We evaluated 162 adults who had had 232 nonimmediate reactions to penicillins, mostly aminopenicillins, and presented positive skin and/or patch tests to one or more penicillin reagents: PPL, MDM, benzylpenicillin, ampicillin, and amoxicillin, as well as any responsible penicillins. RESULTS: A total of 157 subjects (96.9%) displayed patch-test and/or delayed-reading intradermal-test positivity to penicillin reagents, which indicates a cell-mediated hypersensitivity; six of them also presented immediate-reading skin-test positivities. All 157 patients with a cell-mediated hypersensitivity were positive to the responsible penicillins (parent drugs); 16 of them also displayed delayed-reading intradermal-test positivity to MDM. Five (3.1%) of the 162 patients displayed only immediate-reading skin-test positivity (four to PPL and one to amoxicillin). Overall, 158 subjects (97.5%) presented positive responses to the responsible penicillins, while only 9 (5.5%) and 17 (10.5%) were positive to PPL and MDM, respectively. CONCLUSIONS: The contribution of skin testing with PPL and MDM in diagnosing nonimmediate hypersensitivity reactions to penicillins, especially cell-mediated ones, is very limited. This finding could be useful at a time when PPL and MDM are not available in all countries.

Determining the negative predictive value of provocation tests with beta-lactams.

BACKGROUND: The beta-lactam allergic work-up is mostly standardized. However, the negative predictive value of drug provocation tests is not yet well established. METHOD: A historical-prospective multicentre cohort study was conducted in four centres (one in France, one in Portugal, two in Italy) to assess the negative predictive value of provocation tests with beta-lactams in patients initially tested for a suspicion of drug allergy/hypersensitivity. Patients were contacted at least 6 months after the work-up, between 2003 and 2007. A new allergic work-up was proposed to reacting patients. RESULTS: Among the 457 patients included, 365 (79.9%) were followed up (159 [79.1%] from France, 153 [82.7%] from Italy and 53 [74.6%] from Portugal). Only 118 (25.8%) were re-exposed to the negatively tested beta-lactam. Nine (7.6%) reported a non-immediate (occurring more than 1 h after drug administration) reaction: five urticaria, three exanthema and one undefined cutaneous reaction. None were severe. Only four accepted a re-challenge, negative in two cases and positive in the two others. The negative predictive value was 94.1% (89.8-98.3) (111 out of 118 patients). CONCLUSION: Although the negative predictive value of drug provocation tests may not be 100%, none of the false negative patients experienced a life-threatening reaction. This should reassure doctors who might hesitate to prescribe beta-lactams, even in patients with negative allergic work-ups.

Gastrointestinal cytoprotection: from basic science to clinical perspectives.

An essential point of cytoprotection is that the prostaglandins are able to prevent chemical-induced gastric mucosal damage without affecting gastric acid secretion, this being originally suggested as a property specific to prostaglandins. Since then gastrointestinal cytoprotection has been shown with various agents (anticholinergic agents, H(2)RA, growth factors) and retinoids the latter differing from the actions of vitamin A. In examining the various components of gastrointestinal cytoprotection we have performed studies in isolated cells, stable cell lines, animal experiments, healthy human subjects, and in patients with gastrointestinal diseases. Our attention has focused on the effects of cytoprotective agents on cellular viability, mitochondrial and DNA damage, oxygen free radicals, natural antioxidant systems, mucosal biochemistry, vascular events, gastrointestinal mucosal protection as well as in their prevention of different human diseases. This paper gives a short overview on the different approaches for the exploring gastrointestinal cytoprotection.

Allergic reactions to antibiotics, mainly betalactams: facts and controversies.

Allergic reactions to antibiotics are commonly reported. They can be classified as immediate or non-immediate according to the time interval between the last drug administration and their onset. Immediate reactions occur within the first hour and are manifested clinically by urticaria and/or angioedema, rhinitis, bronchospasm, and anaphylactic shock; they may be mediated by specific IgE-antibodies. The main non-immediate reactions (occurring more than one hour after drug administration) are maculopapular exanthems; specific T lymphocytes may be involved in this type of manifestation. The diagnostic evaluation of hypersensitivity reactions to antibiotics is usually complex. The patient's history is fundamental; the allergologic examination includes in vivo and in vitro tests selected on the basis of the clinical features. Prick and intradermal tests are sensitive in evaluating betalactam hypersensitivity. Together with delayed-reading intradermal testing, patch testing is useful in diagnosing maculopapular reactions to systemically administered aminopenicillins. Determination of serum specific IgE is the most common in vitro method for diagnosing immediate reactions, while the lymphocyte transformation test can be performed for evaluating both immediate and non-immediate ones. In selected cases, provocation tests should be performed.

Dual role of endogenous nitric oxide in development of dextran sodium sulfate-induced colitis in rats.

The role of nitric oxide (NO) in the etiology of ulcerative colitis is controversial with reports of the improvement and aggravation of colonic lesions by inducible NO synthase (iNOS) inhibitors. In the present study, we compared the effect of the selective iNOS inhibitor aminoguanidine and the nonselective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on a dextran sulfate sodium (DSS)-induced model of colitis in rats. Experimental colitis was induced by a 3% DSS-solution added to drinking water for 7 days. Aminoguanidine (5 approximately 20 mg/kg) and L-NAME (10 mg/kg) were administered p.o. twice daily for the first 3 days, the last 3 days or all 6 days of DSS treatment. Body weight and severity of colitis (diarrhea, bloody feces) were observed over a period of 7 days. DSS treatment resulted in severe colonic lesions, accompanied by diarrhea, bloody feces, decrease of body weight and colon shortening. All of the parameters investigated improved significantly with aminoguanidine treatment at 20 mg/kg for 6 days or the last 3 days of DSS-treatment, but L-NAME did not significantly affect the colitis during these periods. When L-NAME or aminoguanidine was given in the first 3 days of DSS treatment, the colonic lesions were slightly aggravated by L-NAME but not affected by aminoguanidine. The expression of iNOS mRNA was observed from the 3(rd) day of DSS treatment. These results suggested that endogenous NO exerts a biphasic influence on DSS-induced colitis, depending on the NOS isoenzyme; a beneficial effect of NO derived from constitutive NOS and a detrimental effect of NO produced by iNOS in the development of colitis.

[Light-emitting diodes (LED) technology applied to the photopolymerization of resin composites]. / Tecnologia light-emitting diodes (LED) applicata alla fotopolimerizzazione delle resine composite.

An adequate polymerization of resin composites can significantly contribute to increase the longevity of a restoration. In this field, the choice of the operative technique and the characteristics of the lamp are very important. The aim of this review was to evaluate the effectiveness of cure of the light-emitting diodes (LED) lamps comparing them to the others currently available for resin composites photopolymerization. At present, halogen lamps are the most commonly used light sources, but this technology does not allow further developments; even plasma arc and laser lamps have some drawbacks. The innovative LED technology, based on semiconductors, opened new and interesting views in the field of photopolymerization; to the advantages of a soft-start polymerization they add the safety, efficiency, economy and long lifetime of LED light. A careful review of the literature revealed that, although their lower emission of light, these lamps are capable of a polymerization qualitatively comparable to other light sources. Physical and mechanical properties, degree of conversion, depth of cure and final hardness of the composites cured with a LED light are similar to the values achieved with the halogen lamp, whereas the temperature increase is significantly lower and does not pose a threat to the pulp tissue. Undoubtedly, more tests of the mechanical properties of composites processed with LED units need to be carried out but, as the technology improves, LED curing will become an interesting alternative to existing curing methods.

3-D surface profile analysis: different finishing methods for resin composites.

A microfilled and hybrid resin composites used for esthetic restoration were finished and polished using four methods: Enhance system, Sof-Lex system, Multi-step system and Identoflex points. The tested materials were condensed into cylindrical molds, covered with a Mylar matrix at the surface to be tested and incrementally cured according to manufacturers' instructions. Samples were randomized into four groups of three for each material and were finished/polished using the different methods. The samples were then analyzed by a 3-D surface profiler to obtain roughness average (Ra), root mean square value (rms), greatest distance peak-valley (PV), measure of profile about the center line (Rsk) and measure of steepness of the amplitude density curve of the roughness profile (Rku) directly from the tested area. This method offers the advantage of being error-free. All parameters were determined for each sample and the mean of each parameter was determined for each group. ANOVA and Sheffé's test were employed to determine whether significant differences existed. The Enhance and Multi-step systems gave the best finish and polish for both materials.

Changes of serum carotenoids in patients with esophageal, gastric, hepatocellular, pancreatic and colorectal cancer.

UNLABELLED: The serum levels of carotenoids (vitamin A, lutein, zeaxanthin, alfa- and beta cryptoxanthin, alfa- and beta-carotene) were measured in healthy persons (n=40) and in 98 patients with different malignant gastrointestinal diseases (44 patients with colon adenocarcinoma, 21 with gastric cancer, 15 with hepatocellular adenocarcinoma, 10 patients with pancreas adenocarcinoma and eight patients with esophagus cancer). The serum levels of carotenoids were measured with high-pressure liquid chromatography. The sera of the patients were taken at the time of the diagnosis. RESULTS: the measurements indicated that (1) the serum level of vitamin A and zeaxanthin were significantly lower in all of these groups (except of pancreas adenocarcinoma), but the extent of the A decrease was different in the patients with different types of gastrointestinal malignancy. The serum level of vitamin A was in the healthy subjects 2.072+/-0.332 mmol/l and in the case of gastrointestinal malignancies was 0.77+/-0.14 mmol/l (P<0.001) The serum level of zeaxanthin was in the healthy subjects 0.143+/-0.057 mmol/l and at the malignancies was 0.042+/-0.014 mmol/l (P<0.01). (2) There were no significant differences in the serum levels of other carotenoids in the checked groups. (3) The serum level of cholesterol, total protein, albumin and haemoglobin were in the normal range in these patients. These results indicate that the carotenoids may be responsible nutritional factors (as nutritional scavengers) in the development of different malignant diseases. This supposed role in the carcinogenesis does not depend fully on the vitamin A activity.

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.

Leiden mutation (as genetic) and environmental (retinoids) sequences in the acute and chronic inflammatory and premalignant colon disease in human gastrointestinal tract.

BACKGROUND: Tumor, calor, dolor, pallor and functio laesa are together involved in the different acute and chronic inflammatory processes. The processes involved in the inflammation are determined by differently acquired and hereditary factors. Recently the presence of a new genetic marker (Leiden point mutation) was found in Crohn's disease and ulcerative colitis. On the other hand, the GI mucosal integrity was proven on gastrointestinal mucosal damage to be produced by different chemicals, xenobiotics, drugs. In human observations, the serum level of retinoids (vitamin A, lutein, zeaxanthin, alpha-, beta-carotene) was proven in patients with chronic gastrointestinal inflammatory bowel disease. The aims of this study were (1) to measure the prevalence of Leiden mutation; (2) to identify the changes in the serum retinoid level in patients with Helicobacter pylori infection of the stomach (n=24), hepatitis C infection (n=75), ileitis terminalis (Crohn's disease; n=49), ulcerative colitis (n=35), colon polyposis (n=59) and adenocarcinoma in colon polyps (n=9), and 57 healthy persons were used in the control group; (3) to compare the directions of the changes in the measured parameters in the acute (H. pylori and hepatitis C infections), chronic (ileitis terminalis, ulcerative colitis) GI inflammatory diseases and in colon polyposis without and with malignisation. METHODS: The Leiden mutation was measured by the method of polymerase chain reaction, the retinoid level in the patient's serum was measured by high liquid cromathografic method (HPCL). RESULTS: (1) It has been found that the prevalence of Leiden mutation increased significantly in patients with ileitis terminalis (P<0.001), ulcerative colitis (P<0.001), colon polyposis (P<0.001) and with colon polyps with malignisation (P<0.01). (2) Serum level of vitamin A and zeaxantin were decreased significantly in all group of patients except for the group with H. pylori infections. (3) alpha- and beta-carotenes were found to be practically at the same level as those in the control groups, except in patients of colon polyps with malignisation. (4) The vitamin A, lutein, zeaxantin, alpha- and beta-carotenes were decreased in patients with ileitis terminalis. CONCLUSIONS: (1) The essential role of retinoids (carotenoids) as environmental factors are suggested for keeping GI mucosal integrity in human healthy subjects and patients. (2) Leiden mutation, as a genetic marker, can be used in the screening of patients with ileitis terminalis, ulcerative colitis and colon polyposis (without and with malignisation). (3) An opposite direction can be found between the increased prevalence of Leiden mutation and decrease of serum levels of retinoids in group of patients with ileitis terminalis, ulcerative colitis and colon polyposis (without and with malignisation).

[Effect of retinoic acid on the cytogenetic remission in the first chronic phase of chronic myeloid leukemia treated with interferon]. / Retinsav hatása a citogenetikai remisszióra krónikus myeloid leukaemia interferonnal kezelt elsó krónikus fázisában.

Cytogenetic responses of 11 chronic myeloid leukemic (CML) patients during the first chronic phase, treated with the combination of all-trans retinoic acid (ATRA) + interferon (IFN) were compared to 9 other CML patients of phase one, treated with interferon monotherapy. Metaphase and interphase cytogenetics and a semiquantitative polymerase chain reaction (PCR) were used to evaluate the cytogenetic responses. Two of the 11 patients in the ATRA + interferon treated group were withdrawn, one of them because of interferon intolerance, and the other because of compliance failure. Among the 9 ATRA + interferon treated patients 6 major cytogenetic responses could be detected and 3 of them were complete. Of the 9 patients treated with IFN monotherapy only 2 major cytogenetic responses could be registered. No severe adverse effects were observed. The first results suggest that the ATRA + interferon combination may be superior in achieving cytogenetic remission in the first chronic phase of CML.

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.

[Oxidative stress and antioxidant defense in alcoholic liver disease and chronic hepatitis C]. / Oxidatív stressz és antioxidáns védelem alkoholos májbetegségben és krónikus C hepatitisben.

In the past decade it became accepted that free radicals, lipid peroxidation and antioxidant defense play a role in various tissues damages, thus in certain liver diseases as well. Since only limited data have been reported concerning the oxidative stress in viral hepatitis, a comparative study was performed in patients (pts) with chronic hepatitis C and alcoholic liver disease. In addition, the effects of a flavonolignan drug silymarin were assessed. 10 pts with chronic hepatitis C, 5 pts with alcoholic hepatitis and 13 pts with alcoholic cirrhosis have been investigated. Biochemical liver tests (serum bilirubin, aminotransferases, ALT, AST, lactate dehydrogenase (LDH), pseudocholinesterase, prothrombin), malandialdehyde (MDA) levels in plasma and red blood cell (RBC) hemolysate, superoxide radical generating capacity of stimulated polymorphonuclear granulocytes (PMN), plasma concentrations of reduced (GSH) and oxidized (GSSG) glutathione, vitamin A, luteine and beta carotene, furthermore RBC superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase activities were determined. The level of plasma MDA--as the marker of lipid peroxidation--was highest in alcoholic cirrhosis (five times of normal) (p < 0.05), the RBC hemolysate MDA was most elevated in chronic hepatitis C (p < 0.05). The mean PMNs' superoxide radical generating capacity was 116.6% of normal control in alcoholic hepatitis, where the mean GSH level was the lowest (89.8% of normal). Plasma vitamin A content was lowest in alcoholic cirrhosis (68% of control) (p < 0.05). SOD activity was elevated in both chronic hepatitis C and alcoholic cirrhosis, where GPx activity was decreased (p < 0.05). There was a correlation between LDH and SOD activities (r = 0.77, p = 0.015). Silymarin treatment of one month duration resulted in normalization of serum bilirubin in 55% of treated pts, AST became normal in 45%, and RBC hemolyzate MDA level normalized in similar rate. A significant increase in both GSH and retinoids was found. Alterations in oxidative stress and antioxidant defense system were shown in chronic hepatitis C, not only in alcoholic liver disease. The parameters of lipid peroxidation and antioxidant defense may be useful surrogate markers for monitoring pts with liver disease during hepatoprotective treatment.