Hydrolyzable tannins from Poincianella (Caesalpinia) microphylla fruits: Metabolite profiling and anti-Trichomonas vaginalis activity.

Poincianella (Caesalpinia) microphylla fractions were analyzed by LC-DAD-MS and by statistical tools to determine the possible bioactive compounds against T. vaginalis. Tannins enriched-fractions toxicity (M5 and M10) were analyzed in in vitro against human red cells and in in vivo model of Galleria mellonella. Twenty-six compounds were detected from the P. microphylla fractions. The main compounds identified were hydrolyzable tannins (gallotanins and ellagitannis), such as O-digalloyl hexoside, O-digalloyl HHDP -hexoside, tri-O-galloyl HHDP-hexoside, O-galloyl HHDP-DHHDP-hexoside and their isomers. In addition, procyanidin dimer, epicatechin, ellagic acid and O-(digalloyl) quinic acid were also identified. Based on univariate statistical analyses, stronger correlations with the anti-T. vaginalis properties were observed for the compounds 7 (O-galloyl HHDP-DHHDP-hexoside - Geraniin isomer), 3 (O-digalloyl HHDP -hexoside - mallotinic acid), 2 (O-digalloyl) quinic acid), 1 (O-digalloyl hexoside) and 9 (unknown). Tannins enriched-fractions (M5 and M10) presented anti-Trichomonas activity (IC50 70.41 µg/mL and 142.1 µg/mL, respectively) and no toxicity in the in vivo model of G. mellonella. This innovative approach allowed us to identify likely bioactive compounds in the extracts, although the mechanism(s) underlying anti-trichomonal activity encompass a complex trait.

Comparison of three different risk scoring systems in non-variceal upper gastrointestinal bleeding.

BACKGROUND AND AIMS: To prospectively validate in patients with non-variceal upper gastrointestinal bleeding three risk scoring systems (the Baylor College scoring system, the Rockall's risk scoring system and the Cedars-Sinai Medical Centre predictive index) previously proposed to be predictive of rebleeding/death after upper gastrointestinal bleeding. PATIENTS AND METHODS: We calculated values of the scores for 343 patients, who underwent endoscopy after non-variceal upper gastrointestinal haemorrhage during the years 1997-1999. We compared the observed outcomes with the ones expected upon the original series contributed by the authors. Discriminative ability was evaluated by calculating the area under the receiver operating characteristic curve. RESULTS AND CONCLUSIONS: Rockall's score accurately predicted rebleeding in low- and intermediate-risk categories (< 6), but not in high-risk patients. The rates of rebleeding were significantly higher than the ones predicted by the low-risk categories of either Cedars-Sinai index (< or = 2) or Baylor score (< or = 6). The predicted and the observed mortality was not significantly different throughout all the categories of Rockall's score, except for patients with a score of 4. All the scores had better discriminative ability for mortality than for rebleeding. The Rockall's score identifies a low-risk group of patients (Rockall's score < or = 2) for rebleeding and mortality.

What is the utility of selected clinical and endoscopic parameters in predicting the risk of death after caustic ingestion?

BACKGROUND AND STUDY AIMS: Despite the increasing use of early esophagogastroduodenoscopy, the prognostic evaluation and triage of patients who have ingested caustic material is challenging. We evaluated the usefulness of selected clinical and endoscopic parameters in predicting the risk of death after ingestion of caustic substances. PATIENTS AND METHODS: Clinical and endoscopic parameters were obtained from the records of all the patients admitted to our endoscopy unit because of ingestion of caustic material between 1 March 1982 and 30 June 1999. Parameters significantly associated with the risk of death by univariate analysis were entered into a multivariate logistic model. The independent predictors of death by multivariate analysis were used to build a risk score system. RESULTS: Out of 210 patients, 13 underwent emergency surgery (6.2 %) and 25 died (11.9 %). Multivariate analysis identified the following as independent predictors of death: age (10-year intervals; odds ratio [OR] 2.4; 95 % confidence interval 1.4 - 4.1), ingestion of strong acids (OR 7.9; 1.8 - 35.3), white blood cell count at admission > or = 20 000 units/mm3 (OR 6.0; 1.3-28), deep gastric ulcers (OR 9.7; 1.4 - 66.8), and gastric necrosis (OR 20.9; 4.7 - 91.8). The values of the risk score system devised from the results of the multivariate analysis ranged from 1 to 16. No patient scoring < 10 points died and just one of the patients scoring > 14 points survived. CONCLUSION: Age, ingestion of a strong acid, leucocytosis, deep gastric ulcers, and gastric necrosis are predictive of death after caustic ingestion. A risk score system including these predictors may be useful in prognostic evaluation.

Effects of amphetamine on the plus-maze discriminative avoidance task in mice.

RATIONALE: The contradictory amphetamine effects on memory could be due to different protocols of amphetamine administration or the well-known anxiogenic effect of the drug. OBJECTIVE: The effects of different protocols of administration of amphetamine were investigated on mice tested in the plus-maze discriminative avoidance task (DAT), which provides simultaneous information about memory and anxiety. METHODS: Acutely pre- or post-training, 0.3, 1.0, or 3.0 mg/kg amphetamine-treated, 10-day chronically 3.0 mg/kg amphetamine-treated, 0.3 mg/kg amphetamine plus 0.25 mg/kg scopolamine and 3.0 mg/kg amphetamine plus 3.0 mg/kg tacrine-treated mice were conditioned to choose between two enclosed arms (one of which was aversive) while avoiding two open arms. Learning/memory was evaluated by the percentage time in the aversive enclosed arm (PTAV), and anxiety by the percentage time in the open arms (PTO). RESULTS: Given acutely before conditioning, amphetamine significantly decreased PTO in training, suggesting an anxiogenic effect, and significantly increased PTAV in the test, suggesting an amnestic action. Given acutely after the conditioning, no action of this drug on memory was found. After repeated treatment, the anxiogenic effect disappeared, while the amnestic effect remained. While no effects of subeffective doses of amphetamine and scopolamine co-administration were detected, tacrine attenuated the amnestic effect of amphetamine. CONCLUSIONS: Amphetamine has different effects on DAT when given pre- or post-training. While acute pre-training amnestic action is temporally correlated with an anxiogenic effect, there is tolerance to the anxiogenic but not to the amnestic effect after repeated administration. Because this acute amnestic effect of amphetamine is attenuated by tacrine, a possible relationship with cholinergic system cannot be discarded as a mechanism to amphetamine-induced amnesia in DAT.

Risk of inflammatory bowel disease attributable to smoking, oral contraception and breastfeeding in Italy: a nationwide case-control study. Cooperative Investigators of the Italian Group for the Study of the Colon and the Rectum (GISC).

BACKGROUND: Using data from a case-control study carried out in Italy 1989-1992, we estimated the odds ratios (OR) and the population attributable risks (AR) for inflammatory bowel diseases (IBD) in relation to smoking, oral contraception and breastfeeding in infancy. METHODS: The study focused on 819 cases of IBD (594 ulcerative colitis: UC; 225 Crohn's disease: CD) originating from populations resident in 10 Italian areas, and age-sex matched paired controls. RESULTS: Compared with non-smokers, former smokers were at increased risk of UC (OR = 3.0; 95% confidence interval [CI]: 2.1-4.3), whereas current smokers were at increased risk of CD (OR = 1.7; 95% CI: 1.1-2.6). Females who reported use of oral contraceptives for at least one month before onset of symptoms had a higher risk of CD (OR = 3.4; 95% CI: 1.0-11.9), whereas no significant risk was observed for UC. Lack of breastfeeding was associated with an increased risk of UC (OR = 1.5; 95% CI: 1.1-2.1) and CD (OR = 1.9; 95% CI: 1.1-3.3). Being a 'former smoker' was the factor with the highest attributable risk of UC both in males (AR = 28%; 95% CI: 20-35 %) and in females (AR = 12%; 95% CI: 5-18%). Smoking was the factor with the highest attributable risk for CD in males (AR = 31%; 95% CI: 11-50%). Lack of breastfeeding accounted for the highest proportion of CD in females (AR = 11%; 95% CI: 1-22%). Oral contraceptive use accounted for 7% of cases of UC and for 11% of cases of CD. CONCLUSIONS: Taken together, the considered factors were responsible for a proportion of IBD ranging from 26% (CD females) to 36% (CD males). It is concluded that other environmental and genetic factors may be involved in the aetiology of IBD.

[Advantages of the echographic staging of intestinal Crohn's disease. Correlations of echographic patterns and histological findings]. / Vantaggi della stadiazione ecografica del Morbo di Crohn intestinale. Correlazioni tra quadri ecografici e reperti istopatologici.

PURPOSE: Technical improvements in real-time scanners have revalued the importance of abdominal US for gastrointestinal (GI) tract studies, particularly to investigate chronic inflammatory disease. It is now possible to evaluate intestinal wall thickness accurately, to depict changes in the layers and to study bowel wall motility. Some authors proposed a US classification of Crohn disease into three stages. To investigate the usefulness of this US staging in clinical practice, US findings were compared with the corresponding histologic patterns of the full thickness of the bowel wall. MATERIAL AND METHODS: We examined 58 patients with radiography, endoscopy and US and classified them by Limberg's stage. We compared in vivo and in vitro US findings with the corresponding histologic pattern in seven Crohn patients submitted to ileocolic resection for complications. We performed the US studies with an Acuson 128 XP/10 and 5- or 7-MHz linear probes. RESULTS AND DISCUSSION: We found five Crohn 2 and two Crohn 3 cases. In Crohn 2, US showed moderate wall thickening and the presence of all five layers, with corresponding inflammatory infiltration, mainly in the submucosa, at histology. In Crohn 3, US showed marked wall thickening and no layers at all; no layers and wall necrosis areas were found at histology. In Crohn 2, correct drug treatment can stop or reduce intestinal wall lesion progression, which is not possible in Crohn 3 where fistulae and stenoses are likely to develop. CONCLUSIONS: We found the same patterns at abdominal US and histology of the surgical specimens: US accurately showed the characteristics and the extent of bowel wall inflammatory lesions. US is a simple and cost-effective method with no side-effects playing a major role in Crohn disease staging because it permits to study the bowel wall characteristics--an important piece of information for treatment planning.

[Roxatidine in the treatment of gastroduodenal mucosal lesions in hepatic cirrhosis]. / La roxatidina nel trattamento del danno mucoso gastroduodenale in corso di cirrosi epatica.

In about 50% of patients with liver cirrhosis, upper digestive bleeding is not due to oesaphageal varices rupture, but to a group of peculiar mucosal lesions usually referred as "congestive gastropathy" and "hepatogenic ulcer". The pathogenesis of such mucosal damage is still unclear: an important causative role is commonly thought to be played by portal hypertension, but the role of peptical pathway and of the mucosal barrier impairment must not be underscored as well. Aim of this study was to evaluate the effect of roxatidine in the long-term treatment of mucosal damage in 19 patients with liver cirrhosis. Patients showed a good tolerance and no side effects. The improvement of endoscopic pattern after a three months period of roxatidine therapy was statistically significant; moreover there was no occurrence of digestive bleeding. In conclusion, H2 antagonist may be considered as the drug of choice for the treatment of mucosal damage in patients with liver cirrhosis, for both its safety and effectiveness.

[The activity of misoprostol on the gastric and duodenal mucosal damage in patients with liver cirrhosis]. / Attività del misoprostol sul danno mucoso gastrico e duodenale in pazienti con cirrosi epatica.

Twenty-five liver cirrhosis patients with endoscopically demonstrated gastro-duodenal mucosal damage (microhemorrhages, erosions, ulcers) were treated with misoprostol (prostaglandin E1) 400 mg/die. Eleven patients (44%) had abdominal pain and diarrhea and stopped treatment. Three months later, a new endoscopy was performed in the 11 patients that completed the study (3 patients were lost at follow up). Mucosal damage was stable in 5 patients (45%) and improved in 6 patients (55%), with complete absence of mucosal lesions in 2 patients (P = 0.027, Wilcoxon Ranks test). No case of worsening was observed and no patient had digestive bleeding during treatment. Digestive bleeding is a common complication of liver cirrhosis, originating in about 50% of cases from gastro-duodenal mucosal damage. Misoprostol suggests itself as a possible alternative therapy to the drugs usually utilized in these lesions (beta-blockers, H2-inhibitors), but individual intolerance is frequent and must be preliminary excluded.

A prospective study of the ability of three endoscopic classifications to predict hemorrhage from esophageal varices.

Hemorrhage from esophageal varices in cirrhotics is a frequent event with high mortality in spite of therapy. Preventive sclerotherapy seems to be beneficial only if the patient's bleeding risk is higher than 40 to 50% a year. A series of 320 patients with esophageal varices without previous bleeding was studied prospectively; the varices were classified according to three widely used endoscopic classifications. During follow-up (6 to 36 months, average 14 months), hemorrhage occurred in 49 patients (15.3%) of whom 30 (61.2%) bled from varices (8.2 and 11.0% at 12 and 24 months, respectively). At the same time intervals, mortality of the entire population studied was 18.0 and 23.8%, respectively, of which one third was directly due to hemorrhage. With all three classifications, the higher the degree of bleeding risk, the greater the actual percentage of hemorrhages recorded; however, it never reached 40% a year. In predicting the bleeding event, Dagradi's classification proved more sensitive than JRSPH or NIEC, but the latter classifications were more specific and assessed a higher predictive value for a positive test. Endoscopic observation probably needs integration with other methods if a reliable bleeding prediction is to be made.

Regulation of transferrin, transferrin receptor, and ferritin genes in human duodenum.

To gain insights at the molecular level into the expression of iron-regulated genes [transferrin (Tf), transferrin receptor (TfR), and ferritin H and L subunits] in human intestinal areas relevant to iron absorption, the steady-state levels of specific messenger RNAs (mRNAs) were analyzed in gastric and duodenal samples obtained from 6 normal subjects, or 10 patients with anemia, 14 patients with untreated iron overload, and 8 patients with various gastrointestinal disorders. No Tf mRNA was detected in human gastroduodenal tissue, confirming earlier findings in the rat. In normal subjects, although higher levels of ferritin H- and L-subunit mRNAs were consistently found in duodenal than in gastric samples, no differences in the content of TfR transcripts were detected. However, a dramatic increase in TfR mRNA levels was specifically found in duodenal samples from subjects with mild iron deficiency but severe anemia. This response of the TfR gene is presumably secondary to decreased cellular iron content due to its accelerated transfer into the bloodstream, as also indicated by the low levels of ferritin subunit mRNAs found in the same tissue samples, and is not linked to faster growth rate of mucosal cells because no changes in duodenal expression of histone, a growth-related gene, were detected. In patients with secondary iron overload, a down-regulation of duodenal TfR gene expression and a concomitant increase in ferritin mRNA content were documented. On the contrary, a lack of TfR gene down-regulation and an abnormally low accumulation of ferritin H- and L-subunit mRNAs were detected in the duodenums of subjects with idiopathic hemochromatosis. Whether these molecular abnormalities in idiopathic hemochromatosis are relevant to the metabolic defect(s) of the disease is presently unknown.

Seroepidemiology of pertussis in Italy.

During 1988 and 1989 the prevalence of serum IgG antibodies to pertussis toxin in a sample of 3,875 unvaccinated, apparently healthy persons between the ages of 1 year to 19 years was estimated by enzyme-linked immunosorbent assay. The participants were recruited by means of systematic cluster sampling from public and private schools in five geographic areas of Italy. The overall prevalence of IgG antibodies was 80.8%, with a steady increase from 33.5% among 1- to 3-year-old children to 95% among 17- to 19-year-old individuals. The prevalence of natural immunity was 50% and 75% at the ages of 4 and 6 years, respectively. No gender-related difference in immunity was observed. For children greater than 10 years of age, the seroprevalence of pertussis antibodies was significantly higher in northern regions than in southern regions until the age of 17-19 years, when the pattern reversed. There was no association of a child's immune status with the father's number of years of schooling or with family size. For children aged 1-3 years, serologic studies showed that the history of pertussis reported by parents in questionnaires was highly specific (97.6%) in predicting antibody status, with positive and negative predictive values of 90.5% and 79.2%, respectively. However, 20.8% of children had antibodies to pertussis toxin even though they had no history of whooping cough.

Immunity to diphtheria in the 3-19 year age group in Italy.

In Italy, immunization with diphtheria toxoid has been compulsory for all newborns since 1939. The last two clinical cases of diphtheria were reported in 1987. During the period 1987-1989, immunity against diphtheria was assessed by neutralization test in a random sample of 1740 healthy subjects 3-19 years old, from five geographical areas of Italy. Of the total population, 76.5% showed antibody levels considered to be protective (greater than or equal to 0.1 IU ml-1), 17.2% had a relative degree of protection (0.01-0.09 IU ml-1), and 6.3% lacked immunity (less than 0.01 IU ml-1). The percentage of unprotected subjects increased from 6.1% in the age group of 3-5 years to 11.4% in the age group of 18-19 years (p less than 0.01). A smaller proportion of males (5.3%) than of females (7.2%) was unprotected, but this difference was not statistically significant. Subjects residing in the south and the islands were more likely to be unprotected than those residing in the north (7.4 versus 4.1%, p less than 0.01). No association was found between lack of protective antibodies and family size (odds ratio 1.35, confidence interval 95% = 0.77-2.36). However, paternal education of less than 12 years was associated with a higher prevalence of non-responders. In order to maintain a high degree of immunity in the adult population, a routine adult booster dose of diphtheria toxoid is advisable.

Prevalence of cytomegalovirus infection in Italy.

Between 1987 and 1989, the prevalence of antibody to cytomegalovirus (CMV) was determined, by the ELISA method, in serum samples from 1494 apparently healthy subjects, 3-18 years old. Subjects were selected by a systematic cluster sampling from five geographical areas in Italy. The overall prevalence of antibody was 64.2%, increasing from 54.4% in 4-6-year-olds to 73.3% in subjects 17-18 years old (P less than 0.01). Prevalence of antibody was significantly higher in females (P less than 0.05) and in subjects residing in the South of Italy (P less than 0.01). A significant association was found with sociodemographic factors. Subjects belonging to a household with six or more persons had a 1.5-fold risk (C.I. 95% = 1.11-2.04) and subjects whose fathers had less than 6 years of schooling had a 1.4-fold risk (C.I. 95% = 1.1-1.87) of previous exposure to CMV infection. The high prevalence (74.4%) of young women who are naturally immune when entering childbearing years does not guarantee that there will be a low risk of fetal infection.

Prevalence of Toxoplasma gondii antibodies among children and teenagers in Italy.

Between 1987 and 1989, the prevalence of antibodies to Toxoplasma gondii was determined by ELISA in serum samples from 1,494 apparently healthy subjects, 3-18 years old. Subjects were selected by a systematic cluster sampling from five geographical areas in Italy. The overall prevalence of antibodies was 17.9%, increasing from 4.7% in 4-6 year olds to 28.4% in 17-18 year olds (P less than 0.01). A slight predominance was observed among males (18.2% vs. 17.5% in females), as well as among subjects residing in Southern Italy and the Islands (21.9% vs. 19.2% in subjects residing in the North), but neither difference was statistically significant. Toxoplasma infection was associated with sociodemographic factors. Subjects belonging to a household with six or more persons had a 1.8-fold risk (C.I. 95% = 1.3-2.6) and subjects whose fathers had less than six years of schooling had a 2.7-fold rosk (C.I. 95% = 1.8-3.9) of previous exposure to toxoplasma infection. Considering the large proportion (70%) of young women entering childbearing age without toxoplasma antibodies, it appears that the risk of congenital toxoplasmosis will not be negligible in Italy in forthcoming years.

Baseline sero-epidemiology of hepatitis B virus infection in children and teenagers in Italy. A survey before mass hepatitis B vaccination.

During the period May 1987 to November 1989, the prevalence of hepatitis B virus (HBV) markers was determined by ELISA in serum samples of 7405 (55% male, 45% female) apparently healthy persons 3-19 years of age in Italy. Earlier studies of adults there had shown an intermediate degree of HBV endemicity (hepatitis B surface antigen carrier rate greater than 2%). Persons were selected by systematic cluster sampling in five different geographical areas of Italy. The overall prevalence of hepatitis B surface antigen (HBsAg) was 0.6%. The overall prevalence of at least one marker of HBV was 2.8%; it increased from 1.7% among children 3-5 years of age to 4.5% in teenagers 17-19 years of age (P less than 0.001). The prevalence of any HBV marker was higher in southern then in northern areas (3.5% vs. 1.8%, P less than 0.001). A significant association was found with sociodemographic features. Persons whose fathers had less than 6 years of schooling had a 2.3-fold risk (C.I. 95% = 1.5-3.4) while those belonging to a household of six or more under one roof had a 1.7-fold risk (C.I. 95% = 1.2-2.4) of previous exposure to HBV infection. These findings indicate that, today in Italy, exposure to HBV infection at a young age is very low and suggest a shift towards a low degree of endemicity following improvements in socio-economic conditions, decreased family size and increasing use of disposable syringes during recent years.(ABSTRACT TRUNCATED AT 250 WORDS)

Baseline seroepidemiology of hepatitis A virus infection among children and teenagers in Italy.

During the period from May 1987 through November 1989, the prevalence of antibodies to hepatitis A virus infection (anti-HAV) was assayed by the ELISA method in the serum samples of 5,507 (54% males, 46% females) apparently healthy subjects three to 19 years old in Italy. Subjects were selected by a systematic cluster sampling in five different geographical areas of Italy. The overall prevalence of anti-HAV was 9.5%; it increased from 2.3% among children three to five-years-old to 16.3% in teenagers 17 to 19 years old (p less than 0.001). A slight preponderance of females was observed (10% versus 9.1%), but the difference was not statistically significant. The prevalence was significantly higher in Southern Italy than in Northern Italy (27.4% versus 4.8%; p less than 0.01). The prevalence of anti-HAV was inversely related to the fathers' years of schooling (O.R. 3.3; 95% C.I. = 2.5-4.2) and positively related to the family size (O.R. 2.4; 95% C.I. = 1.9-3.1). These findings indicate that, today, exposure to HAV infection at a young age in Italy is very low. However, sociodemographic factors are still important determinants in the spread of this infection.

Prevalence of hepatitis B markers among teen-agers in Friuli.

In 1989, the prevalence of hepatitis B virus (HBV) markers was studied by Elisa in 421 healthy teen-agers, 17-19 year old, in Udine, Friuli. The prevalence of any HBV marker was 2.4%, with a male predominance (3.8% vs. 0.5%). The prevalence of hepatitis B surface antigen (HBsAg) was 0.5% (2/421); both subjects were anti-Hbc IgM negative, with AST/ALT values in the normal levels, and males. The prevalence of any HBV marker was not associated with largest family size, nor with lowest father's years of schooling. These findings suggest a very low exposure to HBV infection in such area.

Hemodynamic changes after ruthenium irradiation of Hippel's angiomatosis.

The authors report a case of Hippel's angiomatosis successfully treated with contact beta irradiation. The area of the multiplex retinal angioma and the accompanying retinal detachment was irradiated with a 106Ru/106Rh radioactive applicator. Hemodynamic changes due to irradiation were followed up in the ipsilateral ophthalmic artery with transcranial Doppler sonography. Scarring was also demonstrated by fluorescein angiography and A- and B-scan ultrasonography. Irradiation caused the narrowing and later the occlusion of the precapillaries and capillaries (i.e. the resistance vessels) and that of the shunts inside the angioma; consequently, vascular resistance increased. Transcranial Doppler sonographic recordings showed a decrease in blood flow velocity as compared to pathologically increased blood flow velocity in angiomas, and a gradual increase in vascular resistance which was lower before treatment.