Neither self-reported atopy nor IgE-mediated allergy are linked to gastrointestinal symptoms in patients with irritable bowel syndrome.

BACKGROUND: Among patients with irritable bowel syndrome (IBS), atopic disease has been proposed as a common comorbidity increasing the IBS symptom burden. We therefore assessed the prevalence of self-reported atopy among patients with IBS as compared to non-IBS controls, and whether atopy and higher serum IgE levels were associated with increased IBS symptom severity. METHODS: Levels of total and specific IgE in serum were measured and questionnaires assessing the presence of atopic disease (ie, eczema, asthma, rhinoconjunctivitis, and pollen allergy), gastrointestinal symptom burden, food intolerance, somatic, and psychological symptoms were completed. KEY RESULTS: In total, 223 patients with IBS and 47 controls participated. Presence of atopic disease was reported in 55% of patients with IBS compared to 40% of controls (P = .07). IBS patients with atopic manifestations (N = 123) had higher total serum IgE levels (median 31 vs 16 kUA /L, P < .001) and higher prevalence of self-reported food intolerance (28% vs 9%, P = .002) than non-atopic IBS patients (N = 100), respectively, but no major difference in gastrointestinal or psychological symptom burden was noted. However, severe somatic symptoms were more common among atopic than non-atopic patients with IBS (38% vs 27%, P = .028). We found no associations between self-reported atopy and IBS symptom severity using linear regression models. CONCLUSIONS & INFERENCES: Atopic disease is common in patients with IBS, but that is also true for subjects without IBS. The presence of atopic disease in IBS is associated with self-reported food intolerance and somatic symptom severity, but unrelated to IBS symptom severity.

Health-related quality of life in children with objectively diagnosed staple food allergy assessed with a disease-specific questionnaire.

AIM: Among Swedish children of 0-12 years old, we investigated various food allergy-related exposures associated with health-related quality of life using a food allergy-specific questionnaire among children allergic to the staple foods cow's milk, hen's egg and/or wheat, and contextualised worse food allergy-associated health-related quality of life using a generic questionnaire versus controls. METHODS: In total, 85 children with objectively diagnosed allergy to the staple foods were included as cases, and 94 children matched for age and sex were included as controls. We administered a food allergy-specific parent-completed questionnaire originally developed by EuroPrevall to cases only, and a generic health-related quality of life questionnaire (EuroQol Health Questionnaire, 5 Dimensions; EQ 5-D); to both cases and controls. RESULTS: Hen's egg was the most common offending staple food, affecting 76% of cases. Approximately 7% of cases were allergic to all three staple foods. Parent-reported respiratory and cardiovascular symptoms were associated with worse health-related quality of life. Elements of disease severity [previous anaphylaxis (p < 0.001); epinephrine autoinjector prescription (p < 0.003)] were negatively associated with health-related quality of life. Cases had worse health-related quality of life measured by the EQ-5D compared to controls (p < 0.01). CONCLUSION: The use of a disease-specific questionnaire revealed that disease severity in children with objectively diagnosed allergy to the staple foods cow's milk, hen's egg and/or wheat is associated with worse health-related quality of life. The use of a generic questionnaire confirmed that cases have worse health-related quality of life than controls.

Socioeconomic evaluation of well-characterized allergy to staple foods in adults.

BACKGROUND: The aim of the present study was to evaluate if total, direct, indirect, and intangible costs differ between a cohort of adults with well-characterized allergy to staple foods ('cases') and controls. METHODS: Swedish adults with objectively diagnosed food allergy to cow's milk, hen's egg, and/or wheat were recruited at an outpatient allergy clinic. Controls age- and sex-matched to cases were recruited from the same geographic area. For assessing the household costs of food allergy, a disease-specific socioeconomic questionnaire, developed within EuroPrevall, was utilized. RESULTS: Overall annual total costs at the household level were significantly higher among adults with food allergy compared with controls (the difference amounted to 8164 €), whereas direct costs did not differ between cases and controls. However, household healthcare costs and costs for medicines were significantly higher for cases vs controls. Furthermore, indirect costs were significantly higher for households with food-allergic adults vs households without food-allergic adults. Specifically, more time was spent on performing domestic tasks due to a family member's food-allergy-related illness, as well as shopping and preparing food, and seeking food-allergy-related information. Presence of food allergy also affected intangible costs. Adults with food allergy experienced overall lower health status compared with controls. CONCLUSIONS: Swedish adults with allergy to staple foods have higher total costs determined as direct, indirect, and intangible costs using the disease-specific socioeconomic questionnaire. Thus, total costs were 8164 € higher per year in households with at least one adult allergic to staple foods compared with controls.

Identification of galactose-α-1,3-galactose in the gastrointestinal tract of the tick Ixodes ricinus; possible relationship with red meat allergy.

Patients with IgE antibodies against the carbohydrate epitope galactose-α-1,3-galactose (α-Gal) have reported severe allergic reactions after consumption of red meat. Investigations have revealed associations between IgE to α-Gal and tick bites. We provide the first direct evidence that α-Gal is present within ticks thus potentially explaining the relationship between tick exposure and sensitization to α-Gal, with development of red meat allergy as a secondary phenomena. Serum from Swedish patients with delayed severe reactions to red meat was included in the study. A dose-dependent inhibition of IgE responses to α-Gal by the tick Ixodes ricinus is demonstrated. Furthermore, using cryostat-cut sections of I. ricinus, we show that both a monoclonal and a polyclonal antibody against α-Gal stains the gastrointestinal tract of the tick. The same pattern is seen when staining with patient sera IgE positive to α-Gal. These results confirm that the α-Gal epitope is present in I. ricinus and imply host exposure to α-Gal during a tick bite. This provides further evidence that tick bites are associated with IgE responses to α-Gal and red meat allergy.

Responsiveness of eosinophils to aeroallergens may be independent of atopic status.

It has been reported that extracts from common aeroallergens directly activate eosinophils from non-allergic individuals, eliciting chemotaxis and degranulation. The aims of this study were to compare the reactivity of eosinophils from non-atopic and atopic individuals to airborne allergens, and to assess if this reactivity was modulated by natural exposure to birch pollen. Blood-derived eosinophils were stimulated with allergen extracts from birch pollen, cat dander, house dust mite and timothy grass, and their capacity to degranulate (eosinophil peroxidase, EPO; major basic protein, MBP) and produce T helper type 1 and 2 cytokines were evaluated as well as their capacity to migrate in vitro, in and out of the birch pollen season. Eosinophils from atopic and non-atopic individuals responded similarly to stimulation with allergen extracts with respect to directed migration, EPO and MBP release, which was independent of the season when the samples were collected. Interestingly, eosinophils from both study groups were incapable of producing tumour necrosis factor-alpha (TNF-alpha) during the birch pollen season, but could generate interleukin-4. Innate responsiveness of eosinophils to aeroallergens is independent of the atopic status of the individual. In vivo exposure to birch allergen as seen during the birch pollen season downregulates the capacity of eosinophils to produce the cytokine TNF-alpha.

Methodological issues in the diagnostic work-up of food allergy: a real challenge.

The standard of reporting in diagnostic studies has generally been low. Fortunately, this issue has begun to be addressed in recent years through the discussion of important methodological issues in educational series, textbooks, and checklists. Double-blind, placebo-controlled, oral food challenges (DBPCFC) are considered to be the gold standard for diagnosis of food allergy. However, there is no consensus regarding how to interpret the outcome and how to define positive and negative provocations in DBPCFC. Furthermore, since most theories on the diagnosis of food allergy rely on the assumption that the DBPCFC has a high accuracy, this accuracy must be formally statistically evaluated. In this review, we discuss essential methodological issues for diagnostic accuracy studies in general and for oral food challenges in particular and discuss the importance of methodological issues as a guide for forthcoming studies of diagnostic procedures.

Detection of local mast-cell activity in patients with food hypersensitivity.

BACKGROUND: Mast cells play a central role in many inflammatory diseases and assessment of their activation may be of use to provide objective confirmation of the outcome of food challenge in the diagnosis of food hypersensitivity. However, to date, assessment of mast-cell activation using serum markers has been unsuccessful. OBJECTIVE: The aim of this study was to explore whether locally released tryptase could be detected in stool samples from patients with food hypersensitivity. METHODS: Nine patients (median age, 55 years; range, 26 - 68 years) with food hypersensitivity confirmed by double-blind placebo-controlled food challenge were included in the study. Tryptase concentration was assessed in stool samples collected before and after an open food challenge at home and symptoms were recorded throughout the study. Tryptase concentration was also assessed in stool samples from 16 apparently healthy individuals (median age, 44 years; range, 27 - 72 years). RESULTS: Measurement of fecal tryptase levels in 16 healthy control subjects revealed an upper limit of the normal range (mean + 2 SD of log transformed data) of 10 ng/g. Fecal tryptase levels exceeded 10 ng/g in 7 out of 9 patients in one or more samples obtained during the study. The tryptase levels varied between patients in response to the food challenge and the individual mean levels of tryptase correlated with the corresponding levels of the inflammatory marker eosinophil protein X (rho = 0.7500, P = .02). CONCLUSION: Measurement of tryptase levels in stool samples is feasible using the method described here. Our results revealed elevated concentrations of fecal tryptase in patients with food hypersensitivity. However, several factors, including food exposure, may account for the increase in fecal tryptase and further studies are necessary to elucidate the role of mast cells in food hypersensitivity.

IgE cross reactivity between reindeer and bovine milk beta-lactoglobulins in cow's milk allergic patients.

BACKGROUND: Allergic reactions to cow's milk are common in small children. One of the main protein allergens found in cow's milk is beta-lactoglobulin (beta-Lg). Reindeer and bovine milk both contain related beta-Lg proteins, but the allergenicity of reindeer beta-Lg has not previously been studied. The purpose of this study was to analyze the immunological cross-reactivity of IgE antibodies from children with cow's milk allergy to reindeer and bovine beta-Lg. METHODS: Sera from 17 children and a serum pool of 4 patients with elevated cow's milk-specific IgE were investigated. Beta-Lg from bovine and reindeer milk was isolated in native form and an enzyme-linked immunosorbent inhibition assay was developed. Bovine beta-Lg was used as a capturing antigen and the inhibiting effects of reindeer and bovine beta-Lg on the IgE binding were measured. RESULTS: Cross-reactivity patterns of bovine milk beta-Lg specific IgE to reindeer beta-Lg varied among patients. In general, reindeer beta-Lg showed significantly lower inhibition (mean 43%) of IgE binding to the capturing antigen than did bovine beta-Lg (mean 89%). In some patients, even high concentrations of reindeer beta-Lg only partly eliminated the IgE binding to bovine beta-Lg. CONCLUSIONS: The partial cross-reactivity of human anti-bovine IgE with reindeer beta-Lg suggests that it lacks important bovine epitopes and those that are recognized are only weakly bound.

Measurements of eosinophil activation before and after food challenges in adults with food hypersensitivity.

BACKGROUND: Objective assessment of inflammatory reactions in the gastrointestinal tract could be useful in the diagnosis of food hypersensitivity. The aim of the present study was to investigate the involvement of eosinophils and mast cells in the inflammatory response of patients with food hypersensitivity before and after food challenges. METHODS: Eleven patients (4 with IgE-mediated allergy and 7 without) with food hypersensitivity and positive double-blind, placebo-controlled food challenge were subjected to food challenge in a single-blinded fashion. Four subjects with no known food hypersensitivity were recruited as controls. Placebo was given after a 1-week washout period followed by an active dose. Stool, urinary and serum samples were collected and symptoms were recorded in a diary. Fecal samples were analyzed for eosinophil protein X (F-EPX) and tryptase; urinary samples for EPX (U-EPX) and leukotriene E4 (U-LTE4) and serum samples were analyzed for eotaxin and food-specific IgE antibodies. RESULTS: Patients with IgE-mediated food allergy had increased levels of F-EPX compared to controls and tended to have lower serum levels of eotaxin compared to non-allergic patients and controls. U-LTE4 was significantly higher in allergic patients compared to non-allergic patients after challenge. Moreover, F-EPX correlated to U-LTE4 (p = 0.011). Reported symptoms, abdominal pain, distension, flatulence and nausea were similar in the allergic and non-allergic patients. CONCLUSION: The results strongly indicate that eosinophils are activated in the gastrointestinal tract of food-allergic patients but not in patients with non-allergic food hypersensitivity. Due to the inconsistent pattern of symptoms after placebo and active food challenge, it was not possible to relate the levels of inflammation markers to the recorded symptoms.

Double-blind placebo-controlled challenges for peanut allergy the efficiency of blinding procedures and the allergenic activity of peanut availability in the recipes.

BACKGROUND: A firm diagnosis of double-blind placebo-controlled food challenge (DBPCFC) would facilitate the diagnosis in patients with uncertain history of reaction. Guidelines are lacking for an upper provoking dose and how to hide high concentrations of peanuts. AIM: To develop and evaluate a double-blind recipe with minimum 10% of peanut. To compare the recipe with published recipes regarding blindness, taste, texture and immunoglobulin (Ig)E antibody binding to peanut. METHODS: A recipe (I) with 10% of peanut was developed evaluated and used in DBPCFC. The challenges were followed by development of a concentrated recipe (II) (15% peanut, 25% fat). Recipe II was compared with the only published recipe (III) (11% peanut, 7% fat) regarding taste, texture and availability of peanut. Recipe IV (12% peanut, 10% fat) was developed using the same methods. The binding of IgE in the recipes was measured using an inhibition method. RESULTS: During challenges, one patient reacted after 4 g, emphasizing the need for blinding recipes containing high doses of peanut. Evaluation between recipes II and III, only recipe II was regarded as blind by the taste panels. A tenfold lower availability of peanut protein in the recipe II was found at 50% of inhibition. Recipe IV had a better IgE binding that did not differ from the original peanut extract. CONCLUSION: The peanut taste and texture can be hidden in a challenge medium. The fat content was important for the availability of the allergenic protein in challenges. The availability of allergens must be taken into consideration when used for DBPCFC.

Bet v 1 homologues in strawberry identified as IgE-binding proteins and presumptive allergens.

BACKGROUND: No strawberry allergen has so far been identified and characterized. METHODS: Serum samples were collected from patients with a suggestive case history of adverse reactions to strawberry and other fruits. Extracts from fresh and frozen strawberries were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blotting and mass spectrometry. Patient blood samples were analysed for inhibition of IgE binding and basophil degranulation. RESULTS: Several IgE-binding proteins could be detected. In more than half of the patient sera, a 20/18-kDa doublet band was observed in Western blotting. These two bands were excised and analysed by mass spectrometry showing the presence of proteins belonging to the Bet v 1 family of allergens. Inhibition of the IgE binding to the 20/18-kDa doublet was obtained by addition of two recombinantly expressed allergens belonging to the Bet v 1 family (Bet v 1 and Mal d 1) and strawberry protein extract. In a cell-based assay of patient blood samples, basophil degranulation could be induced by strawberry protein extract and by Bet v 1 and Mal d 1. CONCLUSIONS: We conclude that strawberry homologues to Bet v 1 may be allergens of importance for adverse reactions to strawberry.

Specific immunoglobulin E antibodies to peanut over time in relation to peanut intake, symptoms and age.

The clinical outcome of peanut allergy and some factors associated with development of peanut allergy remain unsolved. It has not been clarified to what extent peanut intake affects immunoglobulin (IgE) antibody formation in peanut sensitized individuals. The aim of the study was to investigate the development of peanut hypersensitivity in children and adolescents with specific IgE antibodies to peanut, using questionnaires and current serum tests and comparing it to information obtained 5-6 yr earlier, to investigate how peanut intake during this period related to subject age, IgE antibody levels and symptoms and to investigate what information this patient group was given at the time of diagnosis regarding avoidance of peanut related food. All patients with detectable peanut-specific IgE antibodies investigated during 1994-1996 deriving from two allergy laboratories in the western region of Sweden were traced and reinvestigated (n=132). A total of 111 subjects (63 with peanut allergy and 48 peanut sensitized) participated in the questionnaire. Eighty-six of them consented to be enrolled in a further interview and renewed testing of specific IgE antibody to peanut 5 yr later. All tests were done using the Pharmacia CAP system. Increased IgE antibody levels during follow-up was related to age; subjects 0-6 yr at initial test occasion were more likely to have higher IgE antibody class than the older individuals (p=0.018). Exposure to peanut during the study, i.e. 5-6 yr since diagnosis, did not seem to affect the result. During the follow-up period, 29 out of 86 (34%) increased their IgE antibody class. At the second test occasion the remaining subjects had similar (28%) or lowered (38%) levels of IgE antibodies. Exposure to peanut during follow-up was more common in subjects with IgE antibody class 1-3 compared to subjects with high value (> 3) at the initial test (p=0.003). Reported symptoms during follow-up were also more common in subjects with initially high IgE antibody value. Individuals with initially high IgE antibodies to peanut had been given more information about peanut allergy and cross-reacting allergens than other individuals. The subjects over 6 yr of age showed a decrease in peanut-specific IgE class over a 5-yr period. Together with the literature, our result suggest that follow-up and renewed testing is recommended, since there may be a change in IgE antibody classes and clinical sensitivity over time. Even in Sweden, with a low consumption of peanuts, the youngest individuals with peanut sensitization experienced a similar course of events that has been reported in other countries.

Analysis of ET-A and ET-B receptors using an isolated perfused rat lung preparation.

AIMS AND METHODS: The pulmonary and vascular effects of endothelin-1 receptor activation were studied in isolated perfused and ventilated lung preparations from rat. The responses to endothelin-1 (ET-1) and the endothelin B (ET(B)) receptor agonist sarafotoxin 6c (S6c) were characterized using the endothelin A (ET(A))-receptor antagonist FR 139317, the ET(B)-receptor antagonist BQ 788 and the combined ET(A)/ET(B)-receptor antagonist Bosentan. The respiratory parameter airway conductance (G(aw)) and the vascular parameter perfusion flow were analysed simultaneously. RESULTS: Concentration-response curves for ET-1 administered intra-arterially revealed that its most potent effect was on the vascular side while S6c had a more potent effect on airway conductance. ET-1, given as a bolus dose intra-arterially (100 microL of 0.2 nM), induced a strong- and long-lasting contraction of the vasculature while only a less pronounced contraction was seen in the airways. Neither of the antagonists had a significant effect per se on G(aw) or perfusion flow. FR 139317 reduced the effect of ET-1 on perfusion flow by about 50%, while airway conductance was augmented. BQ 788 enhanced the decrease in perfusion flow by ET-1 while G(aw) was not influenced. The combined ET(A)/ET(B) antagonist Bosentan powerfully prevented the ET-1-induced decrease in G(aw) but did not alter its reduction in perfusion flow. CONCLUSIONS: The potent effect of ET-1 on the vascular side of the lung is mediated mainly through ET(A) receptors, whereas both ET(A) and ET(B) receptors are involved in G(aw) in the rat lung.

Self-reported food hypersensitivity in Sweden, Denmark, Estonia, Lithuania, and Russia.

AIM: The main aim of the study was to describe the differences between some Northern countries regarding what foods, according to the patients, elicit hypersensitivity symptoms. METHODS: At the participating clinics, patients with a history of food hypersensitivity (n = 1139) were asked to fill in a questionnaire in which 86 different foodstuffs were listed. Skin-prick tests (SPT) were performed with common inhalant allergens. RESULTS: The foods that were reported as eliciting symptoms differed between countries. In Russia, Estonia, and Lithuania; citrus fruits, chocolate, honey, apple, hazelnut, strawberry, fish, tomato, egg, and milk were most often reported as causes of hypersensitivity. In Sweden and Denmark; birch pollen (BP) related foods, such as nuts, apple, pear, kiwi, stone fruits, and carrot were the most common causes. In all countries, children, more often than adults, had symptoms of allergic reaction to citrus fruits, tomato, strawberry, milk, egg, and fish. Most patients (95%) reported hypersensitivity to several foodstuffs (median: eight foods). The most common symptoms were oral allergy syndrome and urticaria. Severe symptoms were most common with fish, shellfish, nuts, and milk. Slight symptoms were most common with rice, coriander, poppy seed, lingonberry, corn, caraway red currant, and fig. Earlier well-known correlations, such as that between BP sensitization and some fruits and vegetables, as well as that between mugwort and some spices, were conoborated. Positive correlations were found between self-reported hypersensitivity to crustaceans and SPT with horse. A negative correlation was seen between hypersensitivity to crustaceans and SPT with BP. CONCLUSIONS: The foodstuffs that often are reported to cause food hypersensitivity, differ between Sweden/Denmark on one side and the Baltic States and Russia on the other. BP-related foods dominate in Scandinavia, whereas some mugwort-related foods are of more importance in Russia and the Baltic States.

Interpretation of subjective symptoms in double-blind placebo-controlled food challenges - interobserver reliability.

BACKGROUND: Subjective symptoms after food challenges are difficult to interpret and no standard is available. We discuss a strategy for how to interpret a diary. Furthermore, the interobserver reliability is evaluated. METHODS: Diaries for 32 patients with subjective symptoms were used. The diaries were re-evaluated with a predefined strategy by three independent observers. RESULTS: The proportion of positives was 21.9% among the old diagnoses, according to the new approach 34.4% (observers I and II) and 37.5% (observer III) were positive. The new approach had high interobserver reliability (97 and 100%). CONCLUSIONS: The proportion of positives depends on how subjective symptoms are interpreted. Interpretations of subjective symptoms in diaries could be made with high interobserver reliability.

The hazards of kissing when you are food allergic. A survey on the occurrence of kiss-induced allergic reactions among 1139 patients with self-reported food hypersensitivity.

BACKGROUND: According to a few case reports, kissing can induce symptoms due to food allergy. OBJECTIVE: We wanted to investigate the occurrence of kiss-induced allergic symptoms and other social inconveniences among patients with self-reported food hypersensitivity. METHODS: A questionnaire was answered by 1139 patients (1-84 years old, mean age 29 years, 393 males and 746 females) who considered themselves to be food allergic. RESULTS: 12% of the patients experienced allergic symptoms when in close contact with (e.g., kissing) a person who had eaten a nontolerated food prior to the contact. Some case histories suggested that the symptoms only appeared if the food intake had occurred immediately before the kiss. In addition, the questionnaires showed that 55% had problems in daily life finding tolerable food, 44% were afraid of a severe reaction from eating nontolerated food, 13% could experience symptoms when sitting beside a person who was eating such a food, and 17% could experience symptoms in the kitchen when someone else was preparing such food. CONCLUSIONS: What other people eat can influence the quality of life of food-allergic patients.

A kinetic study in adults with food hypersensitivity assessed as eosinophil activation in fecal samples.

BACKGROUND: Immune-mediated food hypersensitivity affecting the gut is difficult to evaluate, and objective tools to diagnose local gastrointestinal (GI) inflammatory reactions are lacking. OBJECTIVES: To determine whether allergic manifestations in adults with a history of food-related GI symptoms could be assessed in feces during symptomatic and non-symptomatic periods, using the surrogate markers, eosinophil cationic protein (ECP), eosinophil protein X (EPX) and myeloperoxidase (MPO). METHODS: Thirteen subjects with food hypersensitivity-related GI symptoms, confirmed by a positive double-blind placebo-controlled food challenge (DBPCFC), were subjected to an open kinetic food challenge design for 6 weeks. Symptoms were recorded and scored during the 3-week study period and stool samples were obtained every day. The surrogate markers ECP, EPX and MPO were measured in the supernatants from feces samples. RESULTS: A significant increase in abdominal pain, distension and flatulence was observed during challenge, with a gradual decrease during elimination diet. Both between days and subjects, EPX levels were more frequently increased compared to ECP and MPO. Individuals with a history of a short duration of symptoms had significantly higher mean levels of EPX and MPO than those with a longer duration of symptoms. CONCLUSIONS: An overall increase in levels of eosinophil markers, in particular EPX, was observed in feces from patients with food-related GI symptoms. However, rather than being a tool to differentiate symptomatic from non-symptomatic periods, EPX might be used for detecting an ongoing clinical or subclinical chronic inflammation, that may have an impact on the patient's clinical course of GI symptoms.

Enhanced intestinal motility influences absorption in anaesthetized rat.

The subject of this investigation was to study influence of the intestinal motility on absorption of 3-o-methyl-D-glucose (3-OMG), mannitol and polyethylene glycol (PEG 4000), used as absorption route markers, while monitoring cardiovascular parameters in an intestinal in situ model in rats. Rats were anaesthetized with Inactin(R) and Rapinovet(R). A segment of duodenum, approximately 10 cm, was perfused single-pass with saline containing unlabelled and radioactive 3-OMG, PEG 4000 or mannitol. The PEG 4000 was recovered almost completely in the intestinal perfusate suggesting an intact mucosal integrity. Most animals exhibited an intestinal contractile activity resembling fed motility except seven out of 19 given Rapinovet, which showed a 'burst-type' pattern resembling migrating motor complex (MMC). Absorption of 3-OMG in rats with MMC-like motility appears to be lower than in rats with fed-like motility, while no such difference was seen for mannitol. Moreover, there was a positive correlation (r 2=0.75) between intestinal activity (fed) and absorption of 3-OMG, but not with absorption of mannitol. The carrier-mediated absorption of 3-OMG was not only influenced by intestinal motility, but also by its pattern. This was not observed with mannitol, which is passively absorbed.

The role of P-glycoprotein in limiting intestinal regional absorption of digoxin in rats.

The objective of this work was to study the role of regional intestinal efflux activity of P-glycoprotein (Pgp) in situ in anesthetized rats in limiting the absorption of digoxin. A 10-cm portion of duodenum or jejunum, or 5-cm of colon was perfused single-pass with saline containing [(3)H]digoxin while the appearance of radioactivity in the blood was measured. Verapamil in the perfusate was used as a modulator of Pgp in the intestinal mucosa. Net water absorption, mucosal integrity, and intestinal motility of the isolated segment were monitored, as well as heart rate and blood pressure. Excretion of i.v. administered unlabelled digoxin, 1 mg/kg, into the intestine while perfusing the duodenum-proximal jejunum region, was studied for comparison. At a perfusate concentration of 1 mM, verapamil caused a dramatic increase in [(3)H]digoxin absorption rate from duodenum and jejunum, while the effect in colon was insignificant. At concentrations of 0.1, 1, and 2.5 mM in the duodenal perfusate, verapamil increased the absorption rate of [(3)H]digoxin in a dose-dependent manner. The lowest concentration almost doubled the rate without having any significant effects on the cardiovascular system, intestinal motility, or net absorption of water. The excretion rate of unlabelled digoxin from the blood into the gut lumen was found to be halved in the presence of 0.5 mM verapamil in the perfusate. Absorption rate of [(3)H]digoxin in the rat is likely limited by Pgp-mediated efflux. The data indicate that Pgp plays an important role for digoxin efflux in the small intestine only.