Rare case of alimentary butylbiphenyl intoxication.

BACKGROUND: Unexpected accidental intoxication by uncommon industrial substances is a rare, but challenging and perilous event. To our best knowledge, this is the first reported case of 3,4',5,6'-tetra-tert-butylbiphenyl-2,3'-diol intoxication. CASE REPORT: A 20-year-old man was referred to the Department of Emergency Medicine after seven days of nausea and vomiting triggered by drinking mead. Very high doses of 3,4',5,6'-tetra-tert-butylbiphenyl-2,3'-diol were detected in mead, blood, and urine samples. To prove the intoxication, gas chromatography - ion trap was performed. Symptoms of intoxication persisted for two weeks without significant organ damage. The case report illustrates the need for a multistep approach, focused mainly on the analysis of possible sources of intoxication.

[Epidemiology of dyspepsia]. / Epidemiologie dyspepsie.

Epidemiology of uninvestigated dyspepsia was studied in the Czech Republic for the first time in 2001. The aim of our current multi-centre prospective study was to evaluate dyspepsia using the same methods in a representative sample of general unselected population from the same geographical areas 10 years later. A total of 22 centres entered the study. A total of 1,836 subjects (aged 5-98 years) were enrolled. The overall prevalence of dyspepsia was 12 %; namely 3.5 % in subjects aged 5-24 years, 18 % among 25-64-year-old persons and 15 % in subjects 65 years. Despite the substantial decrease of Helicobacter pylori infection in the Czech Republic over the past 10 years, the prevalence and basic socio-demographic determinants of uninvestigated dyspepsia did not change significantly.

The Assessment of Serum Drug Levels to Diagnose Non-Adherence in Stable Chronic Heart Failure Patients.

BACKGROUND: The aim of our study was to evaluate the prevalence of drug non-adherence in stable chronic heart failure (CHF) patients using serum drug levels (SDL) assessment. METHODS: CHF patients were prospectively enrolled during scheduled outpatient visit. Except standard procedures an unanticipated blood sampling for the SDL assessment was obtained. Analysis was focused on the prescribed heart failure and antihypertensive medication and was performed by liquid chromatography coupled with mass spectrometry. The patient was labelled as non-adherent if at least one of drugs assessed was not found in the serum. In the first half of patients multiple SDL have been evaluated during the follow-up. RESULTS: Eighty one patients were enrolled. The non-adherence was proven in twenty of them (25%). In the subgroup of thirty eight patients with multiple SDL evaluation the non-adherence raised significantly with increasing number of visits assessed together (21% for single visit, 29% for two of three visits assessed together and 34% for all three visits evaluated together, all p < 0.001). CONCLUSION: The non-adherence was proven in significant part of stable CHF patients using SDL assessment. This method seems to be reliable and effective and should be a part of clinical assessment in selected patients with CHF.

Prevalence and sociodemographic determinants of uninvestigated dyspepsia in the Czech Republic.

OBJECTIVE: There are no data on the epidemiology of dyspepsia in Central Europe. The aim of this study was to evaluate the prevalence of uninvestigated dyspepsia in a representative sample of the Czech population. METHODS: A total of 2509 persons, aged 5-100 years, randomly selected from 30 012 individuals in the general population, entered this multicentre, prospective, questionnaire-based epidemiological study. RESULTS: We found a 17% prevalence of long-lasting (>12 months) dyspeptic symptoms in the general population. Two subgroups were distinguished: (i) persons with dyspepsia as the only one long-lasting symptom and themselves feeling otherwise healthy (9%), mostly among younger patients (subgroup A); and (ii) patients with dyspepsia as part of the complex of previously recognized diseases (8%), mostly in older patients (subgroup B). The prevalence of dyspepsia was significantly higher among women. The excess cases of dyspepsia among the highly educated seemed to be cases of dyspepsia of subgroup A, and the higher prevalence of dyspepsia among the lower social classes was largely dyspepsia of subgroup B. Being a widow/widower had a significant effect on the risk of self-reported dyspepsia among 25-64-year-olds. No association between Helicobacter pylori infection and dyspepsia was found. CONCLUSION: The prevalence of uninvestigated dyspepsia in the Czech Republic is comparable with data from other European countries. Clearly distinct subgroups of dyspeptic patients exist that should be further studied.

Electrogastrography in patients with Roux-en-Y reconstruction after previous Billroth gastrectomy.

BACKGROUND/AIMS: The aim of this prospective study was to characterize gastric myoelectrical activity in patients with Roux-en-Y reconstruction after previous Billroth gastrectomy. METHODOLOGY: Thirteen patients entered the study (6 men and 7 women, aged 35-57). The mean time from Roux-en-Y reconstruction to electrogastrography (EGG) recording was 5 years. Surface cutaneous EGG was recorded using a Digitrapper EGG in the morning both fasting and after a standard solid test meal. All patients assessed their dyspeptic symptoms at the time of EGG in a semi-quantitative subjective scale. RESULTS: EGG was abnormal in all studied patients (but one postprandial recording). Dyspepsia was not meal-related and was not more severe in Helicobacter pylori positive patients. There was a significant negative correlation between time from Roux-en-Y reconstruction to EGG recording and bradygastria percent activity, both fasted and postprandial (r = -0.576; p = 0.0022). There was an inverse trend between severity of dyspepsia and normal slow-wave rhythm percent activity. Older patients tended to have more severe dyspepsia. CONCLUSIONS: The results of this study suggest that abnormal EGG recording is associated with dyspepsia in patients after Roux-en-Y reconstruction.

The New Acetylcholinesterase Inhibitors PC-37 and PC-48 (7-Methoxytacrine-Donepezil-Like Compounds): Characterization of Their Metabolites in Human Liver Microsomes, Pharmacokinetics and In Vivo Formation of the Major Metabolites in Rats.

The objective of this study was to elucidate the pharmacokinetics and metabolite formation of newly developed non-selective AChE/BChE 7-MEOTA-donepezil-like inhibitors for potential therapeutic use in Alzheimer's disease (AD) patients. The chemical structures of metabolites were defined during incubation with human liver microsomes, and subsequently, the metabolization was verified in in vivo study. In vitro metabolic profiling revealed the formation of nine major metabolites in the case of PC-37 and eight metabolites of PC-48. Hydroxylation and the enzymatic hydrolysis of bonds close to the piperazine ring appeared to be the principal metabolic pathways in vitro. Of these metabolites, M1-M7 of PC-37 and M1-M6 of PC-48 were confirmed under in vivo conditions. Pilot pharmacokinetic experiments in rats were focused on the absorption, distribution and elimination of these compounds. Absorption after i.m. application was relatively fast; the bioavailability expressed as AUCtotal was 28179 ± 4691 min.ng/mL for PC-37 and 23374 ± 4045 min.ng/mL for PC-48. Both compounds showed ability to target the central nervous system, with brain concentrations exceeding those in plasma. The maximal brain concentrations are approximately two times higher than the plasma concentrations. The relatively high brain concentrations persisted throughout the experiment until 24 hr after application. Elimination via the kidneys (urine) significantly exceeded elimination via the liver (bile). All these characteristics are crucial for new candidates intended for AD treatment. The principle metabolic pathways that were verified in the in vivo study do not show any evidence for formation of extremely toxic metabolites, but this needs to be confirmed by further studies.

The prevalence and sociodemographic determinants of uninvestigated dyspepsia in the Czech Republic: a multicentre prospective study accomplished 10 years after the first study from the same geographical areas.

OBJECTIVE: The epidemiology of uninvestigated dyspepsia was studied in the Czech Republic for the first time in 2001. The aim of the current multicenter prospective study was to evaluate dyspepsia using the same methods in a representative sample of general unselected population from the same geographical areas 10 years later. PARTICIPANTS AND METHODS: A total of 38 147 individuals comprised the general population for a random two-step selection process. A total of 1836 participants (863 males and 973 females; aged 5-98 years) took part in the questionnaire-based study. Helicobacter pylori status was investigated in all participants by means of C-urea breath test. RESULTS: The overall prevalence of dyspepsia was 2.6% among children and adolescents aged 5-17 years and 16.0% among adults aged 18-98 years. We did not detect any statistically significant sex differences in the prevalence of total dyspepsia or its subtypes. Overall, 2.4% of H. pylori-negative children and adolescents aged less than 18 years reported dyspepsia, and 16.8% of H. pylori-negative adults reported it. Among H. pylori-positive children and adolescents and adults, dyspepsia was present in 8.3 and 15.8%, respectively. Type A dyspepsia (as the only long-lasting symptom) was statistically significantly associated with H. pylori status among children and adolescents. Among adults aged 18 years or older, we noted a lower prevalence of dyspepsia in adults with elementary education compared with university education. Current use of antibiotics was associated with an increased prevalence of dyspepsia in adults. CONCLUSION: Despite the substantial decrease of H. pylori infection in the Czech Republic over the past 10 years, the prevalence and sociodemographic determinants of uninvestigated dyspepsia did not change significantly.

Serum drug levels to diagnose non-adherence in acute decompensated heart failure.

BACKGROUND: The aim of this study was to analyze medication non-adherence by measuring serum drug levels (SDL) in patients presenting with acute decompensated heart failure (ADHF). METHODS: Included in the study were chronic heart failure patients presenting with signs of acute decompensation. Blood sampling for the measurement of SDL was performed shortly after presentation. SDL were measured using liquid chromatography coupled with mass spectrometry. The estimation of SDL was calculated from the recommended chronic cardiac medications with the exception of drugs administered as part of the acute treatment prior to blood sampling. The patients were labeled as non-adherent when any one of the evaluated medications was not found in the serum. RESULTS: Fifty patients with ADHF were prospectively enrolled. All of the evaluated drugs were detected in the sera of 28 (56%) patients. Non-adherence was diagnosed in the remaining 22 (44%) patients. None of the evaluated medications was detected in the sera of 5 (10%) patients. CONCLUSION: The estimation of SDL indicates that non-adherence to the recommended chronic therapy is a common problem among patients presenting with ADHF. This method should be an essential aspect of routine clinical evaluation in these patients.

An HPLC-MS method for the quantification of new acetylcholinesterase inhibitor PC 48 (7-MEOTA-donepezil like compound) in rat plasma: Application to a pharmacokinetic study.

A simple, rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated for the quantitative determination in rat plasma of a new candidate for AD treatment, namely PC 48 (a 7-MEOTA-donepezil like compound) in rat plasma. Sample preparation involved pH adjustment with sodium hydroxide followed by solvent extraction with ethyl acetate:dichloromethane (80:20, v/v). The chromatographic separation was achieved on an Ascentis Express RP-Amide column (75 mm × 2.1mm, 2.7 µm) with a gradient mobile phase consisting of 0.05 M aqueous formic acid and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry on an LTQ XL system using the MS/MS CID (collision-induced dissociation) mode. The method was linear in the range 0.1-1000 ng/ml (r(2)=0.999) with a lower limit of quantitation of 0.1 ng/mL. Extraction recovery was in the range 63.5-72.1% for PC 48 and 70.5% for reserpine (internal standard, IS). Intra- and inter-day precisions measured as relative standard deviation were below 10.8% and accuracy was from -7.2% to 7.4%. The method was successfully applied to a pharmacokinetic study involving intramuscular application of 3.86 mg/kg PC 48 to rats for the first time. Pharmacokinetic parameters for PC 48 include Cmax 39.09 ± 4.45 ng/mL,Tmax 5.00 ± 3.08 min, AUC0-t 23374 ± 4045 min ng/mL and t1/2 1065 ± 246 min.

Influence of dermal exposure to ultraviolet radiation and coal tar (polycyclic aromatic hydrocarbons) on the skin aging process.

BACKGROUND: Ultraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D). OBJECTIVE: To determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs). METHODS: The study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT. RESULTS: Intensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05). CONCLUSION: Dermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP.

Analytical monitoring of trinitrotoluene metabolites in urine by GC-MS. Part I. Semiquantitative determination of 4-amino-2,6-dinitrotoluene in human urine.

A routine procedure for the monitoring of occupational exposure to 2,4,6-trinitrotoluene (TNT) based on the semiquantitative determination of 4-amino-2,6-dinitrotoluene (4A2,6-DNT) in urine samples by gas chromatography (GC-MS) was developed. For calibration purposes, a standard sample of 4-amino-4,6-dinitrotoluene was prepared. Urine samples were collected from munition workers in a military plant in Hradec Kralove district. The samples were extracted into ethyl acetate, and analyzed by GC-MS without previous derivatization. The GC was equipped with a DB1701 column (30 m, 0.25 mm, 0.25 microm) for optimum separation. 4A2,6-DNT was detected at concentrations above the limit of quantitation (0.2 mg/L). This simple method is sufficient for the screening of high degree of TNT exposure and constitutes the first step of a broad project focused on this occupational medicine problem.

Multi-drug intoxication fatality involving atorvastatin: A case report.

Mixed antihypertensive drug intoxication poses a significant risk for patient mortality. In tandem to antihypertensives, hypolipidemic medicines (especially statins) are often prescribed. Among their well-known adverse effects belongs rhabdomyolysis. We report a case of fatal multi-drug overdose in a 65-year-old female alcoholic. The patient was unconscious at admission. Empty blister packs indicated the abuse of 250 tablets of urapidil, 42 tablets of verapamil/trandolapril, 50 tablets of moxonidin, 80 tablets of atorvastatin and 80 tablets of diacerein. Standard measures (gastric lavage, activated charcoal, mechanical ventilation, massive doses of vasopressors, volume expansion, diuretics and alkalinization) failed to provide sufficient drug elimination and hemodynamic support and the sufferer deceased on the fourth day. Dramatic elevations of serum myoglobin (34,020 µg/L) and creatine kinase (219 µkat/L) were accompanied by rise in cardiac troponin I and creatinine. Gas chromatography revealed ethanol 1.17 g/kg (blood) and 2.81 g/kg (urine). Thin layer chromatography and gas chromatography of gastric content and urine verified verapamil, moxonidin and urapidil fragment (diacerein method was unavailable). Atorvastatin and trandolapril concentrations (LC-MS(n)) equaled 277.7 µg/L and 57.5 µg/L, resp. (serum) and 8.15 µg/L and 602.3 µg/L, resp. (urine). Histology confirmed precipitates of myoglobin with acute necrosis of proximal renal tubules in association with striated muscle rhabdomyolysis and myocardial dystrophy. Cardiogenic-distributive shock in conjunction with acute renal failure due to the combined self-poisoning with vasoactive agents and atorvastatin were determined to be this decedent's immediate cause of death. The manner of death was assigned to be suicidal.

Development of gastric emptying in premature infants. Use of the (13)C-octanoic acid breath test.

OBJECTIVE: The non-invasive (13)C-octanoic acid breath test ((13)C-OABT) has recently been used to monitor gastric emptying. We evaluated (13)C-OABT as a method for assessing gastric emptying in relation to the amount of milk ingested in preterm neonates during their first days of life. METHODS: The (13)C-OABT was performed in 16 stable preterm neonates born between weeks 31 and 37 of gestation (mean +/- standard deviation: 34.0 +/- 1.5 wk). Birth weight was 1400 to 2680 g (2076 +/- 350 g); four newborns were small for gestational age. The newborns underwent (13)C-OABT three times according to the amount of (13)C-primed breast milk being fed to them (<7 mL/kg, 7-13 mL/kg, and 10-19 mL/kg per dose). (13)C-primed breast milk (the test meal) was prepared by adding (13)C-octanoic acid to pasteurized breast milk to achieve a concentration of 1 microL of (13)C-octanoic acid/mL of milk. Exhaled air samples were taken through an original nasal mask. Amounts of (13)C and (12)C in the exhaled air samples were measured by mass spectrometry. Results were expressed as delta over baseline and related to the international standard of Pee Dee Belemnite Limestone. To assess the half-life of elimination (t(1/2)E), we modeled the process of elimination with the incomplete gamma-function, which has a convenient form for the empiric plotting of breath test data. We estimated the parameters of the function, f(x) = A x(b) e(-cx), by using the moment method. The curves were determined by the t(1/2)E of (13)CO(2) and characterized by the shape of the elimination curve. The half-time of gastric emptying (t(1/2)GE) was calculated as t(1/2)E reduced by the mean metabolic half-time of octanoic acid. RESULTS: Forty-eight (13)C-OABT results from 16 premature newborns were analyzed. The mean and median of t(1/2)GE calculated from all three tests were 50.3 (+/-29.9) and 43.7 min, respectively. The t(1/2)GE did not change significantly (P = 0.6811) with the administered dose of (13)C-primed breast milk in the stomach. The coefficient of variation among the studied infants was 4.0% to 33.6% (mean, 11.5%). In 12 infants, the characteristic type of elimination curve was the same for all three tests. CONCLUSIONS: In the first hours of gastric feeding, neither the age of the neonate nor the amount of administered (13)C-primed breast milk had any effect on t(1/2)GE. The gastric emptying rate and the evacuation curve shape for individual neonates were similar and independent of milk amount.

Blood pressure and stature in Helicobacter pylori positive and negative persons.

To evaluate vital signs and body indices in Helicobacter pylori (H. pylori) positive and negative persons. A total of 22 centres entered the study. They were spread over the whole country, corresponding well to the geographical distribution of the Czech population. A total of 1818 subjects (aged 5-98 years) took part in the study, randomly selected out of 38147 subjects. H. pylori infection was investigated by means of a 13C-urea breath test. Data on height, weight, systolic and diastolic blood pressure and heart rate were collected at the clinics of general practitioners. The overall prevalence of H. pylori infection was 30.4% (402/1321) in adults (≥ 18 year-old) and 5.2% (26/497) in children and adolescents (≤ 17 year-old). Once adjusted for age and gender, only a difference in body mass index remained statistically significant with H. pylori positive adults showing an increase of 0.6 kg/m(2) in body mass index. Once adjusted for age and gender, we found a difference in height between H. pylori positive and H. pylori negative children and adolescents. On further adjustment for place of residence, this difference became statistically significant, with H. pylori positive children and adolescents being on average 3.5 cm shorter. H. pylori positive adults were significantly older compared to H. pylori negative subjects. Once adjusted for age and gender, H. pylori infection had no impact on body weight, body mass index and vital signs either in adults or children and adolescents. Chronic H. pylori infection appeared to be associated with short stature in children. H. pylori infection did not influence blood pressure, body weight and body mass index either in adults or children and adolescents.

Black esophagus: acute esophageal necrosis in fatal haloperidol intoxication.

Herein, we present a case of 53-year-old psychotic woman with acute esophageal necrosis (black esophagus), who was found lying on the floor in the living room of her flat. Pillboxes of antipsychotic drugs were located in the bin. External examination of the body was unremarkable. On internal examination, we found acute esophageal necrosis. Histologically, there was complete epithelial necrosis with focal involvement of muscularis mucosae, dense infiltrate of leukocytes, and ulcerations without any viable cells. There was no evidence of underlying organic diseases or trauma. Toxicological analysis revealed a fatal blood level of antipsychotics (haloperidol, zotepine, and chlorprothixene). Death of the deceased was attributed to fatal intoxication with three various types of antipsychotics. As far we know, this is the first described association between so-called black esophagus and fatal blood level of neuroleptics.

Significant decrease in prevalence of Helicobacter pylori in the Czech Republic.

AIM: To study possible decrease in prevalence of Helicobacter pylori (H. pylori) infection in the Czech Republic within a 10-year period. METHODS: A total of 22 centres entered the study. The catchment areas of these centres covered cities and towns with more than 20,000 inhabitants, smaller towns (≤ 20,000 inhabitants) with surrounding villages and rural areas, and were spread over the whole country, corresponding well to the geographical distribution of the Czech population. A total of 1,837 subjects (aged 5-98 years) took part in the study, randomly selected out of 38,147 people from the general population. H. pylori infection was investigated by means of a (13)C-urea breath test. Breath samples in duplicates were analysed using isotope ratio mass spectrometry. The cut-off point was 3.5. Social and demographic characteristics were based on data from self-completed questionnaires. RESULTS: The overall prevalence of H. pylori infection was 23.5% (430/1826), and 4.8% (20/420) in children aged 15 or less. There was no statistically significant difference in prevalence between males (24.3%; 208/857) and females (22.9%, 222/969, P = 0.494). H. pylori infection was strongly associated with higher age, among subjects aged 55+ years, prevalence of H. pylori infection was 39.8% (252/633, P < 0.001). The highest prevalence of H. pylori infection was found among persons aged 55-64 years (43.9%, 97/221) and 75+ years (37.9%, 58/153). Among study subjects aged 15+ years, prevalence of H. pylori infection was significantly increased in those with lowest education (odds risk 3.19, 95% CI 1.87-5.47). Compared to never married (14.1%), the prevalence of H. pylori infection was statistically significantly higher among married (35.4%, 246/694, P < 0.001), divorced (36.8%, 49/133, P < 0.001) and widowed study subjects (40.2%, 45/112, P < 0.001), both in minimally and fully adjusted analysis. There was no significant difference in the prevalence of H. pylori infection between married and widowed subjects (35.4%, 246/694 vs 40.2%, 45/112, P = 0.389). There was little variation in smoking prevalence across categories of smoking and there was no evidence of an increased risk of H. pylori infection among current or past smokers in our data (odds risk 1.04 with 95% CI 0.78-1.40 for current smokers; odds ratio 0.83 with 95% CI 0.60-1.16 for former smokers). The current prevalence of H. pylori in 2011 was significantly lower compared to the prevalence reported from identical geographical areas in 2001 (23.5% vs 41.7%, P < 0.001). CONCLUSION: The overall prevalence of H. pylori infection in the general population has fallen substantially in the Czech Republic over the past 10 years.

Difficult-to-control arterial hypertension or uncooperative patients? The assessment of serum antihypertensive drug levels to differentiate non-responsiveness from non-adherence to recommended therapy.

Difficult-to-control arterial hypertension is a common medical problem that may result from severe hypertensive disease or from poor adherence to the recommended medical treatment. The identification of non-adherent patients is challenging, especially when non-adherence is intentional. The current report describes the use of serum levels of prescribed antihypertensive drugs to evaluate the adherence in individuals with difficult-to-control arterial hypertension. Serum drug levels (SDLs) were evaluated by liquid chromatography with mass spectrometry. The chromatographic separation was performed on a reversed-phase column with a gradient flow of the mobile phase. The detection of analyzed substances was accomplished on a linear ion-trap mass spectrometer. The subjects were labeled as non-adherent when the serum level of at least one of the evaluated drugs was below the limit of quantification. The study used data from 84 patients with arterial hypertension who underwent SDL assessment to verify compliance with the recommended treatment. Patients who presented with uncontrolled blood pressure despite the recommended combination of at least three antihypertensives were enrolled in the analysis. Based on the evaluation of the SDLs, all of the evaluated drugs were found in the sera of 29 (34.5%) of the study patients. In the remaining 55 (65.5%) patients, non-adherence was diagnosed. None of the prescribed antihypertensive drugs was detected in the sera of the 29 (34.5%) patients. Our data suggest that an assessment of SDLs might be helpful before an extensive evaluation is initiated for difficult-to-control hypertension.

Bacteriocinogeny in experimental pigs treated with indomethacin and Escherichia coli Nissle.

AIM: To evaluate bacteriocinogeny in short-term high-dose indomethacin administration with or without probiotic Escherichia coli Nissle 1917 (EcN) in experimental pigs. METHODS: Twenty-four pigs entered the study: Group A (controls), Group B (probiotics alone), Group C (indomethacin alone) and Group D (probiotics and indomethacin). EcN (3.5×10(10) bacteria/d for 14 d) and/or indomethacin (15 mg/kg per day for 10 d) were administrated orally. Anal smears before and smears from the small and large intestine were taken from all animals. Bacteriocin production was determined with 6 different indicator strains; all strains were polymerase chain reaction tested for the presence of 29 individual bacteriocin-encoding determinants. RESULTS: The general microbiota profile was rather uniform in all animals but there was a broad diversity in coliform bacteria (parallel genotypes A, B1, B2 and D found). In total, 637 bacterial strains were tested, mostly Escherichia coli (E. coli). There was a higher incidence of non-E. coli strains among samples taken from the jejunum and ileum compared to that of the colon and rectum indicating predominance of E. coli strains in the large intestine. Bacteriocinogeny was found in 24/77 (31%) before and in 155/560 (28%) isolated bacteria at the end of the study. Altogether, 13 individual bacteriocin types (out of 29 tested) were identified among investigated strains. Incidence of four E. coli genotypes was equally distributed in all groups of E. coli strains, with majority of genotype A (ranging from 81% to 88%). The following types of bacteriocins were most commonly revealed: colicins Ia/Ib (44%), microcin V (18%), colicin E1 (16%) and microcin H47 (6%). There was a difference in bacteriocinogeny between control group A (52/149, 35%) and groups with treatment at the end of the study: B: 31/122 (25%, P=0.120); C: 43/155 (28%, P=0.222); D: 29/134 (22%, P=0.020). There was a significantly lower prevalence of colicin Ib, microcins H47 and V (probiotics group, P<0.001), colicin E1 and microcin H47 (indomethacin group, P<0.001) and microcins H47 and V (probiotics and indomethacin group, P=0.025) compared to controls. Escherichia fergusonii (E. fergusonii) was identified in 6 animals (6/11 isolates from the rectum). One strain was non-colicinogenic, while all other strains of E. fergusonii solely produced colicin E1. All animals started and remained methanogenic despite the fact that EcN is a substantial hydrogen producer. There was an increase in breath methane (after the treatment) in 5/6 pigs from the indomethacin group (C). CONCLUSION: EcN did not exert long-term liveability in the porcine intestine. All experimental pigs remained methanogenic. Indomethacin and EcN administered together might produce the worst impact on bacteriocinogeny.

Small intestinal bacterial overgrowth syndrome.

Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacteriostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO.

Caffeine does not modulate nutritive blood flow to rat gastric submucosa--a microdialysis study.

BACKGROUND AND AIMS: Coffee irritates the gastric mucosa disrupting its barrier and increasing the risk of peptic ulcers. However, caffeine's contribution to these effects has not yet been elucidated. In this study we looked at the local effect of caffeine on the microcirculation and nitric oxide production in rats together with systemic marker of oxidative stress malondialdehyde as possible mechanisms whereby caffeine might participate in mucosal barrier impairment. MATERIALS AND METHODS: Four groups of rats were anesthetized and administered as a bolus four different intraperitoneal doses of caffeine (0, 1, 10 and 50 mg kg(-1) b.wt.). The gastric submucosal microcirculation and nitric oxide production were then recorded for 2.5 hours by in situ microdialysis using the flow marker ethanol. At the completion of the experiments, plasma caffeine and malondialdehyde levels as well as morphological mucosal injury were determined. RESULTS: There were no major differences in the macro- or microscopic pictures of the mucosa among the groups. Local microcirculatory (ethanol out/in ratio) and nitric oxide monitoring failed to demonstrate statistically significant changes as did measurement of plasma malondialdehyde in response to caffeine injections. CONCLUSIONS: Caffeine per se seems unlikely to contribute to the gastric mucosal barrier injury associated with coffee consumption by alterations in nutritive blood flow, nitric oxide production or aggravation of systemic oxidative stress. This information is relevant for better understanding of the mechanisms involved in caffeine-mediated influences on gastric physiology in relation to the irritant effects of coffee.