Small intestine in lymphocytic and collagenous colitis: mucosal morphology, permeability, and secretory immunity to gliadin

There is a recognised association between the "microscopic" forms of colitis and coeliac disease. There are a variety of subtle small intestinal changes in patients with "latent" gluten sensitivity, namely high intraepithelial lymphocyte (IEL) counts, abnormal mucosal permeability, and high levels of secretory IgA and IgM antibody to gliadin. These changes have hitherto not been investigated in microscopic colitis. Nine patients (four collagenous, five lymphocytic colitis) with normal villous architecture were studied. Small intestinal biopsies were obtained by Crosby capsule; small intestinal fluid was aspirated via the capsule. IEL counts were expressed per 100 epithelial cells, and intestinal IgA and IgM antigliadin antibody levels were measured by ELISA. Small intestinal permeability was measured by the lactulose:mannitol differential sugar permeability test. IEL counts were normal in all cases, median 17, range 7-30. Intestinal antigliadin antibodies were measured in six cases and were significantly elevated in two patients (both IgA and IgM). Intestinal permeability was measured in eight cases and was abnormal in two and borderline in one. These abnormalities did not overlap: four of nine patients had evidence of abnormal small intestinal function. Subclinical small intestinal disease is common in the two main forms of microscopic colitis.     

Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease

The functional integrity of the small bowel is impaired in coeliac disease. Intestinal permeability, as measured by the sugar absorption test probably reflects this phenomenon. In the sugar absorption test a solution of lactulose and mannitol was given to the fasting patient and the lactulose/mannitol ratio measured in urine collected over a period of five hours. The sugar absorption test was performed in nine patients with coeliac disease with an abnormal jejunum on histological examination, 10 relatives of patients with coeliac disease with aspecific symptoms but no villous atrophy, six patients with aspecific gastrointestinal symptoms but no villous atrophy, and 22 healthy controls to determine whether functional integrity is different in these groups. The lactulose/mannitol ratio (mean (SEM) is significantly higher in both coeliac disease (0.243 (0.034), p < 0.0001)) and relatives of patients with coeliac disease (0.158 (0.040), p < 0.005)) v both healthy controls (0.043 (0.006)) and patients with aspecific gastrointestinal symptoms (0.040 (0.011)). The lactulose/mannitol ratio in relatives of coeliac disease patients was significantly lower than in the coeliac disease patient group (p = 0.04). The lactulose/mannitol ratio was the same in healthy controls and patients with aspecific gastrointestinal symptoms. It is concluded that the sugar absorption test is a sensitive test that distinguishes between patients with coeliac disease and healthy controls. The explanation for the increased permeability in relatives of patients with coeliac disease is uncertain. Increased intestinal permeability may be related to constitutional factors in people susceptible to coeliac disease and may detect latent coeliac disease. The sugar absorption test may therefore be helpful in family studies of coeliac disease.     

Forefront of lung cancer therapy

The differential urinary excretion of orally administered lactulose and mannitol is used to evaluate intestinal permeability. This test usually involves a 5- to 6-hr urine collection. We hypothesized that a shorter collection time would give an equivalent result. Forty-three patients with a variety of gastrointestinal symptoms and diagnoses (group 1) and 42 patients with Crohn's disease (group 2) had a standard lactulose/mannitol permeability test. The lactulose and mannitol urinary excretion was calculated using the first urine (group 1) or the 1-hr and 2-hr urine (group 2) and was compared to the values calculated from the routine 5- or 6-hr collection. Lactulose excretion kinetics, expressed as the percent of the total urinary excretion within a given time period, were as follows: 21% in first hour (group 2), 29% in second hour (group 2), and 46% in first 2.5 hr (group 1). Mannitol urinary excretion kinetics were 16%, 31%, and 44%, respectively. The lactulose/mannitol ratio based on a standard urine collection correlated well with the ratio based on just the first urine produced by the patient (R2 = 0.94; P < 0.001; group 1) and the 2-hr urine (R2 = 0.464; P < 0.001; group 2). Future use of the lactulose/mannitol ratio to assess intestinal permeability may be able to be simplified by shortening the urine collection time.     

Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver damage

OBJECTIVE: Only 30% of alcoholics develop cirrhosis, suggesting that the development of alcohol-induced liver injury requires one or more additional factors. Animal studies have shown that gut-derived endotoxin is one such factor. Because increased intestinal permeability has been shown to cause endotoxemia, we hypothesized that increased gastrointestinal permeability contributes to the pathogenesis of alcoholic liver disease. This study aimed to measure gastroduodenal and intestinal permeability in alcoholics with and without chronic liver disease and in nonalcoholic subjects with chronic liver disease. METHODS: Gastroduodenal permeability was assessed by measurement of urinary excretion of sucrose after oral administration. Intestinal permeability was assessed by measurement of urinary lactulose and mannitol after oral administration of these sugars. RESULTS: Alcoholics with no liver disease showed a small but significant increase in sucrose excretion. Alcoholics with chronic liver disease demonstrated a marked and highly significant increase in urinary sucrose excretion relative to the controls, to the alcoholics with no liver disease, and to the nonalcoholics with liver disease. Alcoholics with chronic liver disease demonstrated a marked and highly significant increase in both lactulose absorption and in the urinary lactulose/mannitol ratio (alcoholics 0.703 vs controls 0.019, p = 0.01). In contrast, alcoholics with no liver disease and nonalcoholics with liver disease showed normal lactulose absorption and normal lactulose/mannitol ratio. CONCLUSION: Because only the alcoholics with chronic liver disease had increased intestinal permeability, we conclude that a "leaky" gut may be a necessary cofactor for the development of chronic liver injury in heavy drinkers.     

Increased gastric and intestinal permeability in patients with Crohn's disease

OBJECTIVES: Patients with Crohn's disease exhibit marked changes in intestinal permeability that can be assessed by lactulose and mannitol. Sucrose is a novel marker for gastric permeability. We combined these three sugars to investigate whether patients with Crohn's disease demonstrate changes in gastric permeability and if so, whether these changes are matched with altered intestinal permeability. METHODS: Fifty patients with Crohn's disease and 30 healthy subjects each drank a solution containing 20 g of sucrose, 10 g of lactulose, and 5 g of mannitol. Patients' and subjects' 5-h sugar urinary excretion levels were determined by high performance liquid chromatography and an enzymatic method (sucrose). Furthermore, patients with Crohn's disease underwent endoscopy of the upper GI tract and were grouped according to endoscopic and histological findings. RESULTS: Patients with Crohn's disease showed higher gastric and intestinal permeability compared with healthy control subjects. Gastric permeability was correlated with intestinal permeability. Patients with granuloma had more pronounced changes in both gastric and intestinal permeability than patients with various endoscopic and histological lesions. Patients with normal mucosa had normal permeability. CONCLUSIONS: Alterations in gastric mucosa caused by Crohn's disease are reflected by changes in gastric permeability and can be used to noninvasively screen for Crohn's disease involvement of the upper GI tract.     

Atrophy of the corpus callosum associated with cognitive impairment and widespread cortical hypometabolism in carotid artery occlusive disease

BACKGROUND: The independent influences of small-intestinal bacterial overgrowth and old age on mucosal immunoglobulin production and secretion have not been assessed. This is an important issue, since luminal IgA deficiency may exacerbate small-intestinal bacterial overgrowth, the prevalence of which is high in selected elderly populations. METHODS: Proximal small-intestinal aspirates were obtained from 33 subjects for bacteriologic analysis and measurement of total IgA, IgM, total IgG. IgG subclass, and IgD concentrations. IgA subclasses were measured in 24 unselected subjects. Serum immunoglobulin and salivary IgA concentrations were measured in all subjects. RESULTS: IgA2 and IgG3 were predominant IgA and IgG subclasses in proximal small-intestinal luminal secretions. Luminal concentrations of IgA2 and IgM, but not IgG3 or any other IgG subclass, were significantly increased in small-intestinal bacterial overgrowth, which was present in 19 of 33 (57.6%) subjects. Old age did not influence these levels. Luminal immunoglobulin concentrations did not correlate significantly with either serum or salivary values. IgD was not measureable in proximal small-intestinal secretions. CONCLUSIONS: Increased luminal concentrations of the secretory immunoglobulins, IgA2 and IgM, occur in small-intestinal bacterial overgrowth. Local investigation is mandatory when assessing the mucosal immunopathology of this disorder. Luminal IgG3 is unlikely to be predominantly derived from serum. Old age does not independently influence luminal immunity.     

Glutamine dipeptide attenuate mucosal atrophic changes and preservation of gut barrier function following 5-FU intervention

Traditional parenteral nutrition (PN) and chemotherapy may lead to changes mucosal morphology and gut barrier function. To investigate the effects of alanyl-glutamine on intestinal mucosal morphology and gut barrier function in PN-fed rats challenged with 5-FU male Wistar rats were central catheterized and randomily divided into two groups: PN group (n = 10) that received traditional parenteral nutrition solution only, and Ala-Gln group (n = 10) that received glutamine dipeptide enriched nutritional solution (3% Ala-Gln). The rats were maintained on their respective diets for 7 days. 5-FU (75 mg/kg) was injected intraperitoneally at 8 am on day 4. All rats were gavaged with lactulose (100 mg) and mannitol (50 mg) in 2ml before and three days after administration of 5-FU. Ala-Gln group maintained serum glutamine concentration, intestinal mucosal morphology. While bacterial translocation rates in ala-Gln group was 30%, in PN group was 90% (P < 0.05). Similar intestinal permeability was observed on day 3 in both groups. The control group had a significantly increased intestinal permeability on day 7 (P < 0.05), while Ala-Gln group maintained the intestinal permeability. It was suggested that alanyl-glutamine maintained intestinal morphology and gut barrier function in PN-fed rats challenged with 5-FU.     

The lactulose breath hydrogen test and small intestinal bacterial overgrowth

OBJECTIVES: To i) document the sensitivity and specificity of a combined scintigraphic/lactulose breath hydrogen test for small intestinal bacterial overgrowth and ii) investigate the validity of currently accepted definitions of an abnormal lactulose breath hydrogen test based on "double peaks" in breath hydrogen concentrations. METHODS: Twenty-eight subjects were investigated with culture of proximal small intestinal aspirate and a 10-g lactulose breath hydrogen test combined with scintigraphy. Gastroduodenal pH, the presence or absence of gastric bacterial overgrowth, and the in vitro capability of overgrowth flora to ferment lactulose were determined. RESULTS: Sensitivity (16.7%) and specificity (70.0%) of the lactulose breath hydrogen test alone for small intestinal bacterial overgrowth were poor. Combination with scintigraphy resulted in 100% specificity, because double peaks in serial breath hydrogen concentrations may occur as a result of lactulose fermentation by cecal bacteria. Sensitivity increased to 38.9% with scintigraphy, because a single rise in breath hydrogen concentrations, commencing before the test meal reaches the cecum, may occur in this disorder. Sensitivity remained suboptimal irrespective of the definition of small intestinal bacterial overgrowth used, the nature of the overgrowth flora, favorable luminal pH, the presence of concurrent gastric bacterial overgrowth, or the in vitro ability of the overgrowth flora to ferment lactulose. CONCLUSIONS: Definitions of an abnormal lactulose breath hydrogen test based on the occurrence of double peaks in breath hydrogen concentrations are inappropriate. Not even the addition of scintigraphy renders this test a clinically useful alternative to culture of aspirate for diagnosing small intestinal bacterial overgrowth.     

Increased formation of distinct F2 isoprostanes in hypercholesterolemia

BACKGROUND: F2 isoprostanes are stable, free radical-catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo. METHODS AND RESULTS: Specific assays were developed by use of mass spectrometry for the F2 isoprostanes iPF2alpha-III and iPF2alpha-VI and arachidonic acid (AA). Urinary excretion of the 2 F2 isoprostanes was significantly increased in hypercholesterolemic patients, whereas substrate AA in urine did not differ between the groups. iPF2alpha-III (pmol/mmol creatinine) was elevated (P<0.0005) in homozygous familial hypercholesterolemic (HFH) patients (85+/-5. 5; n=38) compared with age- and sex-matched normocholesterolemic control subjects (58+/-4.2; n=38), as were levels of iPF2alpha-VI (281+/-22 versus 175+/-13; P<0.0005). Serum cholesterol correlated with urinary iPF2alpha-III (r=0.41; P<0.02) and iPF2alpha-VI (r=0. 39; P<0.03) in HFH patients. Urinary excretion of iPF2alpha-III (81+/-10 versus 59+/-4; P<0.05) and iPF2alpha-VI (195+/-18 versus 149+/-20; P<0.05) was also increased in moderately hypercholesterolemic subjects (n=24) compared with their controls. Urinary excretion of iPF2alpha-III and iPF2alpha-VI was correlated (r=0.57; P<0.0001; n=106). LDL iPF2alpha-III levels (ng/mg arachidonate) were elevated (P<0.01) in HFH patients (0.32+/-0.08) compared with controls (0.09+/-0.02). The concentrations of iPF2-III in LDL and urine were significantly correlated (r=0.42; P<0.05) in HFH patients. CONCLUSIONS: Asymptomatic patients with moderate and severe hypercholesterolemia have evidence of oxidant stress in vivo.     

Mucosal injury and disruption of intestinal barrier function in HIV-infected individuals with and without diarrhea and cryptosporidiosis in northeast Brazil

The effects of AIDS-related diarrhea--with and without cryptosporidiosis and microsporidiosis--on intestinal function and injury were studied in 40 AIDS patients and 13 healthy volunteers from Fortaleza, Brazil. The differential urinary excretion of ingested lactulose and mannitol was used as a marker of barrier disruption and overall villous surface area. HIV-infected patients with diarrhea had a 2.8-fold higher lactulose to mannitol excretion ratio than HIV-positive patients without diarrhea and a 10.4-fold higher ratio than healthy volunteers. Moreover, those with crypotosporidial infection had a lactulose to mannitol ratio almost 6-fold greater than those without diarrhea and nearly 3-fold higher than those with non-cryptosporidial diarrhea. This effect involved both decreased mannitol excretion (decreased intestinal absorptive area) and increased lactulose excretion (mucosal barrier disruption). The single patient with microsporidial infection had a nearly 3-fold higher ratio than healthy volunteers. Alpha1-antitrypsin tests were positive in two of five (40%) HIV-positive patients with cryptosporidial infections compared with none of 12 HIV-infected patients with non-cryptosporidial diarrhea. These findings confirm that HIV infection is associated with profound intestinal dysfunction and injury, even in those without diarrhea. Disruption of the intestinal barrier is even greater, however, in HIV-infected patients with cryptosporidial diarrhea, with potential nutritional consequences.     

An evaluation of methods to assess the effect of antimicrobial residues on the human gut flora

1. Barrier effect. Relevant models should include an anaerobic dominant flora that antagonizes minor bacterial populations such as drug resistant E. coli. 2. Anaerobes vs. aerobes. Aerobe counts are more precise and much less time consuming than anaerobe counts. Minor populations of drug resistant aerobes are sensitive markers of the ecosystem balance, and are directly relevant to the potential risk of antimicrobial residues. 3. MIC vs. plate counts. The determination of minimum inhibitory concentrations (MIC) of selected clones in time consuming, does not detect subdominant resistance (less than 1%), and the MIC shift is difficult to test statistically. In contrast, direct counts of bacteria on drug supplemented media allows a rapid measure of minor resistant populations. 4. Statistics: Most published designs do not include adequate statistical evaluation. This is critical for trials made in conventional humans and animals, where data are highly variable. 5. Human trials: The lowest concentration of antibiotic tested in human volunteers (2 mg oxytetracycline/d for 7d in 6 subjects) significantly increased the proportion of resistant fecal enterobacteria (P = 0.05). However, the huge day-to-day and interindividual variations of human floras make this evidence rather weak. 6. Gnotobiotic mice inoculated with human flora are living isolated models in which the effect of any antimicrobial on the human gut flora can be tested. This in vivo model does include the barrier effect of dominant anaerobes. Interindividual and day-to-day variations of bacterial populations are lower in those mice than in humans. 7. Most resistant enterobacteria in the human gut of untreated people come from bacterial contamination of raw foods. The relative contribution of residues in selecting antibiotic resistance seems to be low when compared to bacterial contamination.     

Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects

OBJECTIVES: The HIV-infected population is known to be oxidatively stressed and deficient in antioxidant micronutrients. Since in vitro replication of HIV is increased with oxidative stress, this study assessed the effect of antioxidant vitamin supplementation on lipid peroxidation, a measure of oxidative stress, and viral load in humans. DESIGN: A randomized placebo-controlled, double-blind study. METHODS: Forty-nine HIV-positive patients were randomized to receive supplements of both DL-alpha-tocopherol acetate (800 IU daily) and vitamin C (1000 mg daily), or matched placebo, for 3 months. Plasma antioxidant micronutrient status, breath pentane output, plasma lipid peroxides, malondialdehyde and viral load were measured at baseline and at 3 months. New or recurrent infections for the 6-month period after study entry were also recorded. RESULTS: The vitamin group (n = 26) had an increase in plasma concentrations of alpha-tocopherol (P < 0.0005) and vitamin C (P < 0.005) and a reduction in lipid peroxidation measured by breath pentane (P < 0.025), plasma lipid peroxides (P < 0.01) and malondialdehyde (P < 0.0005) when compared with controls (n = 23). There was also a trend towards a reduction in viral load (mean +/- SD changes over 3 months, -0.45 +/- 0.39 versus +0.50 +/- 0.40 log10 copies/ml; P = 0.1; 95% confidence interval, -0.21 to -2.14). The number of infections reported was nine in the vitamin group and seven in the placebo group. CONCLUSION: Supplements of vitamin E and C reduce oxidative stress in HIV and produce a trend towards a reduction in viral load. This is worthy of larger clinical trials, especially in HIV-infected persons who cannot afford new combination therapies.     

Major determinants of hyperhomocysteinemia in peritoneal dialysis patients

The mechanisms leading to elevated total homocysteine concentrations in peritoneal dialysis patients are only partially understood. We show that a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T transition) results in increased total homocysteine levels in peritoneal dialysis patients compared to age- and sex-matched healthy individuals. The allelic frequency of the C677T transition in the MTHFR gene in peritoneal dialysis patients (0.29) was comparable to the frequency in healthy individuals (0.34). Separate comparison of the total homocysteine plasma levels between non-carriers of the MTHFR polymorphism (C/C), heterozygous (C/T) and homozygous (T/T) subjects was performed by analysis of covariance in the patient and the control group. In the patient group the mean total homocysteine level was 61.7 +/- 40.1 mumol/liter in individuals with the (T/T) genotype, which was significantly higher than the total homocysteine concentration of 23.1 +/- 15.8 mumol/liter in (C/T) patients and 22.2 +/- 11.1 mumol/liter for non-carriers (P = 0.0001). Vitamin B12 (P = 0.0001), folate (P = 0.0005), serum creatinine (P = 0.016), albumin (P = 0.0157) and dialysis center (P = 0.0173) significantly influenced total homocysteine plasma levels in peritoneal dialysis patients, whereas this was not the case for age, gender, weekly Kt/V, weekly creatinine clearance, residual renal function, duration of dialysis, mode of peritoneal dialysis and vitamin intake. Folate levels in peritoneal dialysis patients were significantly affected by the MTHFR genotype (P = 0.016). Elevated total homocysteine levels in diabetic patients with cardiovascular disease were associated with increased cardiovascular morbidity. In summary, the present study provides evidence that homozygosity for the C677T transition in the MTHFR gene, low vitamin B12 and low folate levels result in elevated total homocysteine levels in peritoneal dialysis patients.     

Suppression of inward-rectifying K+ channels KAT1 and AKT2 by dominant negative point mutations in the KAT1 alpha-subunit

Na(+)-glucose transport and transepithelial permeability were investigated during symptomatic acute cryptosporidiosis in newborn rats. The infection resulted in a significant (P < 0.01) decrease in the ileal short-circuit current and a nonsignificant fall in the transepithelial potential difference and conductance. In glucose-stimulated conditions, the rise in ileal short-circuit current and transepithelial permeability were significantly lower in Cryptosporidium parvum-infected rats than in controls (delta Isc = 3.24 +/- 1.21 microA.cm-2 vs delta Isc = 5.09 +/- 2.23 microA.cm-2 in infected and control animals, respectively; P < 0.001; delta PD = -0.35 +/- 0.13 mV vs delta PD = -0.44 +/- 0.14 mV for infected and control animals, respectively; P < 0.01). Electrical parameters were not affected by addition of the cyclooxygenase inhibitor indomethacin in either Cryptosporidium-infected newborn rats or controls. Horseradish peroxidase and mannitol flux studies demonstrated a significant decrease (P < 0.05) in transepithelial molecular permeability in infected enterocyte rats, HRP flux = 380, range 68-5570 ng.cm-2, and mannitol flux = 1.06, range, 0.34-1.44%.cm-2.min-1, compared with controls rats, HRP flux = 4446 range, 1121-124,363 ng.cm-2, and mannitol flux = 1.99, range, 0.57-5.09%.cm-2.min-1; P < 0.05. These effects could originate from C. parvum-induced alteration of intracellular trafficking of pinocytosis vesicles and therefore account for the decrease in permeability to solute and macromolecules, together with impaired transcellular nutrient transport, in suckling rats.     

Absence of gaseous symptoms during ingestion of commercial fibre preparations

BACKGROUND: While fibre is believed to cause gaseous symptoms, a study in healthy volunteers showed no increase in flatulence when the diet was supplemented with fermentable (psyllium) or non-fermentable (methylcellulose) fibre. However, extrapolation of this observation to subjects who use fibre is arguable since these individuals may have a propensity to gaseousness. In the present study, gaseous complaints during fibre ingestion were assessed in subjects who believed that a previous exposure to fibre induced gas. METHODS: In a double-blind protocol, subjects were randomized to one of four treatment periods, during which the regular diet was supplemented for 1-week periods with two daily doses of: placebo 10 g, psyllium 3.4 g, methylcellulose 2 g or lactulose 5 g. A symptom diary was maintained for 1-week periods on or off treatment. RESULTS: During treatment, the lactulose group passed gas significantly more often than did the psyllium or the methylcellulose group (P = 0.01). No other symptom was significantly different among the treatment groups. CONCLUSIONS: (1) psyllium and methylcellulose did not cause greater gaseous symptomatology than did placebo in subjects who believed that these preparations caused gas; and (2) subjects commonly misidentify dietary components that cause gaseous symptoms.     

Breath hydrogen excretion by healthy cats after oral administration of oxytetracycline and metronidazole

Breath hydrogen excretion over a period of three hours was measured to evaluate carbohydrate malassimilation in healthy cats treated orally with antibiotics. Both an absorbable carbohydrate (xylose) and a non-absorbable carbohydrate (lactulose) were administered during the tests to evaluate the changes in the intestinal mucosa and the population of bacteria within the intestinal lumen. Overall, the effects of oxytetracycline and metronidazole on breath hydrogen excretion were not significantly different. However, the treatment effect with an antibiotic did significantly change breath hydrogen excretion after xylose administration (P < 0.05) within groups. Similarly, with each antibiotic, breath hydrogen excretion was affected significantly (P < 0.001) by the time after the administration of the carbohydrate. Treatment with each antibiotic also interacted significantly with this time effect (P < 0.05) within groups. After lactulose administration, there was a trend within groups for the type of antibiotic to interact with the treatment effect on breath hydrogen excretion (P = 0.09). After oxytetracycline treatment, more hydrogen was exhaled during the first 120 minutes after lactulose administration than in the pre-antibiotic test, whereas after metronidazole treatment, less hydrogen was exhaled between 60 and 180 minutes after lactulose, administration. After treatment with either oxytetracycline or metronidazole, more hydrogen was exhaled after xylose administration. Obligate anaerobes could be isolated from samples of small intestinal fluid obtained endoscopically after oxytetracycline treatment, but they could not be isolated after treatment with metronidazole.     

Increased intestinal permeability in bronchial asthma

T lymphocytes are a major component of bronchial inflammatory processes in asthma. Because lymphocytes have the ability to migrate from one mucosal site to another, we initiated this prospective study to demonstrate mucosal abnormalities of the digestive barrier in asthma. To establish this we studied intestinal permeability in a group of 37 patients with asthma (21 allergic and 16 nonallergic) by measuring chromium 51-labeled ethylenediaminetetraacetatic acid (CrEDTA) urinary recovery. The results were compared with those obtained in a group of 13 nonasthmatic patients with chronic obstructive pulmonary disease and 26 healthy control subjects. Urinary recovery of CrEDTA was significantly higher in patients with asthma (2.5% +/- 1.95%) than in patients with chronic obstructive pulmonary disease (1.16% +/- 0.48%) and healthy control subjects (1.36% +/- 0.14%). There was no significant difference in intestinal permeability between patients with allergic asthma (2.94% +/- 2.4%) and those with nonallergic asthma (1.92% +/- 0.9%). Intestinal permeability was not correlated with the severity of asthma as measured by FEV1. Similarly, intestinal permeability did not significantly vary according to Aas score or steroid treatment. Serum IgE values and eosinophil blood count were not correlated with intestinal permeability. Intestinal permeability was evaluated sequentially in seven patients with asthma (4 allergic and 3 nonallergic) with a mean interval of 7.6 months (range, 2 to 13 months) and did not significantly change. Our results support the hypothesis that a general defect of the whole mucosal system is present as a cause or a consequence of bronchial asthma.     

Study of the inhibitor of the crayfish neuromuscular junction by presynaptic voltage control

We demonstrate that rhamnose, 3-O-methyl-D-glucose, D-xylose and lactulose may be quantified accurately in blood by HPLC and pulsed amperometric detection, thus enabling studies of intestinal permeability and function to be carried out using plasma samples. Prior to HPLC, the endogenous glucose was enzymatically modified to gluconic acid and the protein precipitated. The precision of the quantification of the sugars in plasma (CV: 2.2-5.7%; 8.7-10.6% at very low concentrations) compared well with the quantification in urine. The results for groups of 8 dogs with small intestinal bacterial overgrowth and 12 dogs with inflammatory bowel disease were shown to be significantly different from a group of 20 normal control dogs (P < 0.001), demonstrating the test's value as a diagnostic tool. The normal ranges in blood 2 h post oral administration were determined to be 0.05-0.17 for the lactulose/rhamnose ratio and 0.45-0.65 for the xylose/3-O-methylglucose ratio. This method may be employed advantageously when the collection of urine in intestinal permeability and function tests is difficult.     

Bifidobacterium longum and lactulose suppress azoxymethane-induced colonic aberrant crypt foci in rats

Bifidobacterium longum has been shown to afford protection against colon tumorigenesis. Lactulose, a keto analog of lactose, serves as a substrate for preferential growth of Bifidobacterium. It is not known whether feeding lactulose along with B. longum will have any advantage over feeding of B. longum alone. To test this combination effect, 61 male Fisher 344 weanling rats were divided into four groups of 15 rats each (16 in the control group) and assigned to one of the following four diets for 13 weeks: (i) AIN76A (control, C); (ii) C + 0.5% B. longum (C+Bl, containing 1 x 10(8) viable cells/g feed); (iii) C + 2.5% lactulose (C+L); (iv) C + 0.5% B. longum + 2.5% lactulose (C+Bl+L). All animals received a s.c. injection of azoxymethane at 16 mg/kg body wt at 7 and 8 weeks of age. Colons of 10 rats from each dietary group were analyzed for aberrant crypt foci (ACF), which are preneoplastic markers. Colonic mucosa and livers from five rats were analyzed for glutathione S-transferase (GST, a Phase II enzyme marker). Results indicate that feeding of lactulose and B. longum singly and in combination reduces the number of ACF (P = 0.0001) and the total number of aberrant crypts significantly (P = 0.0005). The total number of ACF in diets C, C+Bl, C+L and C+Bl+L were 187 +/- 9, 143 +/- 9, 145 +/- 11 and 97 +/- 11 respectively. There was no significant difference in weight gain among treatments. Colonic mucosal GST levels were significantly (P = 0.05) higher in the Bl and L groups compared with group C. Initially there was a mild diarrhea in lactulose-fed rats. There was a positive correlation between higher cecal pH and number of ACF. Results of the study indicate that Bifidobacterium and lactulose exert an additive antitumorigenic effect in rat colon.     

A study of the anaerobic bacterial flora of the female genital tract in health and disease

Semi-quantitative and qualitative bacterial assessment of the vaginal and cervical flora of a total of 202 women was carried out over a period of six months to determine the bacterial flora in three groups of women and changes caused by prior use of antibiotics. The number was made up of 32 healthy volunteers, 80 women with gynaecological problems and 90 women with gynaecological infections who had had antibiotic treatment prior to this study. Standard methods were used for the investigations. Five main genera of anaerobic bacteria were isolated from all patients. They included, the Bacteroides spp., Prevotella spp., Porphyromonas spp., Peptostreptococcus spp. and Clostridium spp. Five non-sporing gram negative anaerobic bacteria constituted the bulk of the flora including Prevotella bivia, P. disiens, P. melanogenica, P. asaccharolytica and B. fragilis. The predominant flora was P. bivia occurring in 61 pc of cervical swab specimens of the 80 women with proven gynaecological infections who had not used antibiotics and accounting for 27 pc of the total number of Gram-negative anaerobic bacteria isolated. Escherichia coli and Staphylococcus epidermidis were the most frequently encountered aerobic bacteria. The semi-quantitative counts of the different bacterial species in the patient group were significantly higher than in the control group of healthy individuals (p < 0,025). Similarly, prior antibiotic administration significantly reduced the population and quantitative count of the anaerobic bacteria.