Chenodeoxycholic acid stimulated fibroblast growth factor 19 response - a potential biochemical test for bile acid diarrhoea.

BACKGROUND: Bile acid diarrhoea is underdiagnosed and better diagnostic tests are needed. Fasting serum fibroblast growth factor-19 (FGF19) has insufficient diagnostic value, but this may be improved by stimulation. AIM: To explore if an impaired FGF19 response identifies primary bile acid diarrhoea. METHODS: Eight patients with primary bile acid diarrhoea and eight healthy volunteers ingested (i) a meal plus 1250 mg chenodeoxycholic acid (CDCA), (ii) 1250 mg CDCA or (iii) the meal. Blood was sampled at fasting and repeatedly after stimulation. We analysed FGF19 by enzyme-linked immunosorbent assay and bile acids including 7α-hydroxy-4-cholesten-3-one by liquid chromatography-tandem mass spectrometry. RESULTS: Stimulation with the meal plus CDCA increased median FGF19 in healthy volunteers from fasting 62 pg/mL [interquartile range (IQR): 41-138] to 99 pg/mL (IQR: 67-147; P = 0.012) after 90 min and peaked after 150 min at 313 pg/mL (IQR: 54-512). This response was impaired in primary bile acid diarrhoea patients [fasting 56 pg/mL (IQR: 42-79); 90 min: 48 pg/mL [IQR: 37-63); 150 min: 57 pg/mL (48-198)]. Receiver operating characteristics (ROCAUC ) for fasting FGF19 was 0.55 (P = 0.75) and at 90 min 0.84 (P = 0.02). The difference in FGF19 from fasting to 90 min after the meal plus CDCA separated the groups (ROCAUC 1.0; P = 0.001). 7α-hydroxy-4-cholesten-3-one was elevated in primary bile acid diarrhoea (P = 0.038) and not significantly affected by stimulation. CONCLUSIONS: The FGF19 response following chenodeoxycholic acid plus meal is impaired in primary bile acid diarrhoea. This may provide a biochemical diagnostic test.

Azathioprine and mercaptopurine in the management of patients with chronic, active microscopic colitis.

BACKGROUND: Microscopic colitis (MC) is a common chronic diarrhoeal disease, and remission can be induced with budesonide. However, diarrhoea relapses frequently when budesonide is tapered and a few patients become budesonide intolerant. AIM: To examine retrospectively the effect of azathioprine (AZA) and mercaptopurine (MP) in patients with chronic, active MC. METHODS/PATIENTS: Data on all MC patients who received AZA or MP in the years 1997-2011 at three centres representing three countries were pooled for analysis. The indications for thiopurine therapy were frequent relapses after short-term treatment (N = 26), budesonide dependency on 6 mg (N = 15) and budesonide intolerance (N = 5). The response to thiopurine treatment was defined as clinical remission, intolerance or nonresponse. RESULTS: Forty-six MC patients (32 CC and 14 LC), 32 female; median age 59 years (range: 36-83) with a median disease duration of 3 years (range: 0.5-18) were included. Thirteen patients (28%) achieved long-term clinical remission on AZA therapy. AZA failed in 31 patients (67%) due to intolerance and in 2 patients (4%) because of nonresponse. Thirteen of 31 AZA-intolerant patients were switched to MP and 6 patients (46%) obtained clinical remission. Thus, the overall response rate to thiopurines was 19/46 (41%). The main side effects were nausea/vomiting and abnormally elevated liver enzymes. CONCLUSIONS: In this retrospective case series, the majority of chronic, active MC patients were intolerant to AZA leading to cessation of treatment. However, further studies are needed to explore the efficacy, acceptance, tolerance and safety of MP in patients with chronic, active MC refractory to budesonide.

Microscopic colitis: Current status, present and future challenges: statements of the European Microscopic Colitis Group.

Microscopic colitis (MC) is an inflammatory bowel disease presenting with chronic, non-bloody watery diarrhoea and few or no endoscopic abnormalities. The histological examination reveals mainly two subtypes of MC, lymphocytic or collagenous colitis. Despite the fact that the incidence in MC has been rising over the last decades, research has been sparse and our knowledge about MC remains limited. Specialists in the field have initiated the European Microscopic Colitis Group (EMCG) with the primary goal to create awareness on MC. The EMCG is furthermore a forum with the intention to promote clinical and basic research. In this article statements and comments are given that all members of the EMCG have considered being of importance for a better understanding of MC. The paper focuses on the newest updates in epidemiology, symptoms and diagnostic criteria, pathophysiology and highlights some unsolved problems. Moreover, a new treatment algorithm is proposed on the basis of new evidence from well-designed, randomized control trials.

Systematic review: are lymphocytic colitis and collagenous colitis two subtypes of the same disease - microscopic colitis?

BACKGROUND: Despite similar clinical symptoms, collagenous colitis (CC) and lymphocytic colitis (LC) are considered two distinct disease entities. AIM: To compare pathoanatomical findings, clinical presentations, risk factors, course of diseases and response to treatment in CC and LC to establish whether they could be subtypes of the same disease, microscopic colitis (MC). METHODS: The MEDLINE was searched for CC, LC and MC, and clinical studies of >20 patients were included. Pooled results with 95% confidence intervals were calculated based on the number of patients. RESULTS: An abnormal number of intraepithelial lymphocytes are found in 45% (40-50%) with CC, and an abnormal subepithelial collagen band in 16% (13-20%) with LC suggesting a histological overlap. The incidence of CC and LC has increased in parallel. Mean age (CC 63 years; LC 60 years) and clinical presentation are indistinguishable, and females are predominant in CC (77%; 75-79%) as well as LC (68%; 66-70%). Risk factors such as nonsteroid anti-inflammatory drugs consumption CC 39% (36-42%); LC 32% (29-35%) are similar and prevalence of concomitant autoimmune diseases such as coeliac disease (CC 5%; CI: 4-6% and LC 7%; CI: 6-9%) do not differ. Bile acid diarrhoea is highly prevalent in CC (41%; 37-45%) and LC (29%; 24-34%). The effect of budesonide is identical. CONCLUSIONS: CC and LC could be considered histological subtypes of the same disease, MC. To facilitate recruitment to clinical trials, all MC patients could be included in future trials and stratified for subtypes.

Microscopic colitis: clinical findings, topography and persistence of histopathological subgroups.

BACKGROUND: Uncertainty remains on topography and persistence of histological subgroups of microscopic colitis (MC). AIM: To assess longitudinal clinical, endoscopic, histological, and therapeutic description of MC subgroups including patients with incomplete findings of MC (MCi). METHODS: Retrospective review of a consecutive cohort with MC and histological reassessment of MCi. RESULTS: Clinical characteristics of 168 patients with lymphocytic colitis (LC), 270 with collagenous colitis (CC) and 101 with MCi were similar. At colonoscopy 95% (95% CI: 91-98%) of CC and 98% (93-100%) of LC cases had diagnostic histopathology of MC in both left and right colon. Eight and three patients had characteristics of MC only in the left and right colon, respectively. Histology findings resembling coexistence of the other MC subtype was present in 48% (40-55%) with CC and 24% (18-31%) with LC. A first diagnosis of MC was made in 49 (30%) of 164 patients only at repeat endoscopy. Another 34 of 115 (30%) with MC in the first endoscopy did not fulfil the MC criteria at repeat endoscopy. Only seven cases had a primary endoscopy without histopathological abnormalities. Fifteen percentage of MCi were reclassified as MC. Ileal inflammation was present in 33 of 81 patients. Budesonide was efficacious in all MC subgroups irrespective of bile acid malabsorption. CONCLUSIONS: Clinical characteristics of microscopic colitis subgroups are indistinguishable. Biopsies from the left colon suffice to exclude microscopic colitis, and the histological diagnosis of microscopic colitis is inconsistent over time. Ileal inflammation is common. The term microscopic colitis should perhaps be considered one clinical entity and include lymphocytic colitis, collagenous colitis, and incomplete findings of microscopic colitis.

Use of biological molecules in the treatment of inflammatory bowel disease.

The introduction of biological agents (i.e. antitumour necrosis factor-α and anti-integrin treatments) for the treatment of inflammatory bowel disease (IBD) [i.e. Crohn's disease (CD) and ulcerative colitis] has led to a substantial change in the treatment algorithms and guidelines, especially in CD. However, many questions still remain about the true efficacy and the best treatment regimens. Thus, a need for further treatment options still exists as up to 40% of IBD patients treated with the presently available biologicals do not have positive clinical responses. Better patient selection might maximize the clinical benefit for those in most need of an effective therapy to avoid disabling disease whilst also minimizing the complications associated with therapy. Further, the 'trough-level strategy' may help clinicians to optimize therapy and to avoid loss of response and/or immunogenicity. The idea behind this dosage regimen is that correct dosing must ensure that the patient's lowest level of drug concentration (i.e. the trough level) occurring just before the next drug administration is high enough for the full effect to be seen. Controversy continues regarding the appropriate use of biologicals; therefore, in this review, we focus on considerations that might lead to a more rational strategy for antitumour necrosis factor-α agents in IBD, emphasizing the situations in which the risks may outweigh the benefits. Finally, the need for an appropriate strategy for stopping biological treatment is discussed.

Randomized controlled azathioprine withdrawal after more than two years treatment in Crohn's disease: increased relapse rate the following year.

INTRODUCTION: Azathioprine is effective for maintenance of remission in Crohn's disease, however, duration of efficacy and the dose response relationship has not been fully evaluated. AIMS: To investigate whether patients kept in remission by azathioprine treatment for >2 years benefit from further treatment, and to explore dose-response relationship. PATIENTS AND METHODS: In an open 12-month trial, patients with inactive Crohn's disease after >2 years (median 37 months) of azathioprine treatment were randomized to azathioprine withdrawal or continued treatment. Primary end point was relapse defined as: (i) Crohn's disease activity index rise >/= 75, and Crohn's disease activity index >150 or (ii) disease activity requiring intervention. RESULTS: Of 29 patients, 28 completed the observation period or relapsed. Eleven of 13 patients (85%) continuing azathioprine remained in remission compared with seven of 15 (47%) observed without azathioprine (P = 0.043). In patients who had been treated with azathioprine >1.60 mg/kg/day the difference was even more pronounced, eight of nine (89%) vs. four of 12 (33%) respectively (P = 0.017). CONCLUSIONS: Patients with Crohn's disease in remission after >2 years of continuous azathioprine treatment will benefit from further continued treatment. Further controlled studies with azathioprine doses <2.0 mg/kg/day are needed.

Congruence on medication between patients and physicians involved in patient course.

OBJECTIVE: To analyse congruence on medication throughout patient courses, including an acute admission to a medical department. DESIGN: A prospective, observational study. Data were collected from patient records in primary health care, hospital departments, from the Health Insurance database and through patient interviews. SETTING: Departments of internal medicine, general practice and patients' homes. MAIN OUTCOME MEASURES: Number, type and character of discrepancies between paired sources of information on patient medication at predefined time points throughout the complete patient course. Assessment of likelihood and severity of potential untoward effects of discrepancies. RESULTS: Data were obtained for 75 of 99 consecutive patients included. Patients stated use of four drugs (median, range 0-17) at admission, five (0-16) at discharge and four (0-15) 1 month after discharge. At admission, 11 patients used no drugs. A median of one (0-20) to three (0-16) discrepancies per patient were identified in seven paired source comparisons with no improvement along patient course. Full agreement throughout the course was found in six patients (8%; 95% confidence interval: 3-17%). No association was found among source discrepancies and number of drugs and age. Of discrepancies, 4-13% were considered serious and likely to cause untoward effects. Discrepancies due to synonymous and analogous drugs accounted for 2-7% of the discrepancies. CONCLUSION: Congruence between sources of information on medication throughout patient courses cannot be obtained with separate medication charts. Discrepancies among patient, general practitioner and hospital give rise to a definitive risk of serious untoward effects.

Incomplete remission with short-term prednisolone treatment in collagenous colitis: a randomized study.

BACKGROUND: Microscopic colitis is a disease of unknown aetiology characterized by chronic watery diarrhoea and diarrhoea can be eliminated by budesonide but frequently recurs when budesonide is stopped. We studied whether prednisolone could induce remission in patients with disabling, chronic diarrhoea due to microscopic colitis. METHODS: A double-blind, randomized (3:1) trial of oral prednisolone 50 mg daily or placebo for 2 weeks. Remission was defined as stool weight < or = 200 g/day or frequency < or = 2/day; effect was defined as > 50% reduction of either stool frequency or weight. Six centres screened 31 consecutive patients and included 11 with collagenous colitis and 1 with lymphocytic colitis. Median duration of diarrhoea was 9 months. Patients had a normal colonoscopy, and no evidence of coeliac disease, bile acid or lactose malabsorption. Patients with gastrointestinal infection, previous gastrointestinal surgery, abnormal biochemical screening or recent treatment with immunosuppressive agents were excluded. RESULTS: Stool weight (grams) declined in 7 of 9 patients given prednisolone and in 1 of 3 receiving placebo; changes in median weight were from 430 to 278 and from 825 to 489, respectively. Stool frequency (per day) declined from 6 to 3 and from 8 to 5. Remission was obtained in 2 and 0, and effect in 5 and 0, respectively (NS; Fisher exact test). CONCLUSIONS: Prednisolone 50 mg daily for 2 weeks induces incomplete remission in patients with chronic diarrhoea due to collagenous colitis.

[Joint charts in drug handling. Toward increased drug safety]. / Enstrenget medicinhåndtering. På vej mod øget sikkerhed.

INTRODUCTION: Medication errors contribute to 8% of all hospital admissions. Minimalization of the number of information transferrals and improvement in communication may increase the quality of drug treatment. MATERIAL AND METHODS: The effect of introducing joint charts for prescription and administration on the quality of drug handling in a hospital setting is reported. RESULTS: When separate charts were used the prescriptions in the case records and the nurses' charts for administration did not tally for any of 20 patients. One year after introducing the joint charts, prescriptions for the regular medication and medication on demand were correct and signed for 88% and 48%, respectively, on a patient basis. Ninety-five per cent of the regular administrations were correct and signed. Potential interactions were identified in 15% of the prescriptions. Discharge medication was stated in 65% of the discharge letters to the family doctors. Complete agreement on admission medication between the patient and family doctor was found in 39%. DISCUSSION: Joint charts for prescription and administration represent a significant step towards safe and rational medical treatment. It is more time-consuming. Improvement in communication between all parties involved in the treatment of the same patient represents an important potential for further improving the quality of care, including drug treatment.

Transport of neutral, cationic and anionic amino acids by systems B, b(o,+), X(AG), and ASC in swine small intestine.

Amino acid influx across the brush border membrane of the intact pig ileal epithelium was studied. It was examine whether in addition to system B, systems ASC and b(o,+) were involved in transport of bipolar amino acids. The kinetics of interactions between lysine and leucine demonstrates that system b(o,+) is present and accessible also to L-glutamine. D-aspartate (K(1/2) 0.3 mM) and L-glutamate (K(i) 0.5 mM) share a high affinity transporter with a maximum rate of 1.3 micromol cm(-2) h(-1), while only L-glutamate with a K(1/2) of 14.4 mM uses a low affinity transporter with a maximum rate of 2. 7 micromol cm(-2) h(-1), system ASC, against which serine has a K(i) of 1.6 mM. In the presence of 100 mM lysine, L-glutamine (A), leucine (B), and methionine (C) fulfilled the criteria of the ABC test for transport by one and the same transporter. However, serine inhibits not only transport of L-glutamate but also of glutamine (K(i) 0.5 mM), and L-glutamate inhibits part of the transport of glutamine. The test does, therefore, only indicate that the three bipolar amino acids have similar affinities for transport by systems B and ASC. Further study of the function of system B must be carried out under full inhibition by lysine and glutamate.

Effects of pH changes on systems ASC and B in rabbit ileum.

Influx of D-aspartate (D-Asp), L-glutamate (L-Glu), and serine (Ser) across the brush-border membrane of the intact mucosa from rabbit ileum has been examined. L-Glu influx is chloride independent and completely sodium dependent. D-Asp and L-Glu share a transport system with a maximum transport rate of 1 micromol. cm-2. h-1 and an apparent affinity constant (K1/2) of approximately 0.3 mM. The function of this transport system is pH insensitive between pH 5.65 and 8.2, and bipolar amino acids do not affect the way in which the transport system handles D-Asp and L-Glu. The characteristics of this transport system match those of system X-AG. L-Glu and Ser share a transporter for which the inhibitor constant (Ki) of L-Glu against Ser decreases from 54 to 10 mM when pH is reduced from 7.2 to 5.65, while the maximum rate of transport remains unaffected at approximately 10 micromol. cm-2. h-1. The Ki values (5 mM) of Ser against L-Glu influx and the L-Glu-sensitive contribution to Ser influx (0.8 micromol. cm-2. h-1 at 1 mM Ser) are the same at both pH values. The L-Glu-sensitive transport of Ser together with the contribution of system bo,+ account for approximately 50% of Ser influx at pH 7.2. The remaining 50% can be ascribed to system B. Transport of Ser by system B is reduced by >95% at pH 5.65. At pH 7. 2 Ki of Ser against transport of leucine (Leu) by system B is 18 mM and Ki of Leu against transport of Ser is 1.7 mM. The low-affinity transport of L-Glu and the L-Glu-sensitive transport of Ser are performed by an equivalent of system ASC. Supplementary experiments using the jejunum confirm the validity of these results for a major portion of the rabbit small intestine.

Comparative aspects of chloride-dependent amino acid transport across the brush-border membrane of mammalian small intestine.

Chloride-dependent amino acid transport has been described in several tissues. This article briefly reviews the evidence of cotransport of chloride and amino acids across the brush-border membrane of rabbit distal ileum. On the basis of amino acid carriers described in the rabbit and the surveys of chloride-dependence reported, a comparison of amino acid carriers in the mammalian small intestine is performed. Additional characteristics of the carriers in the different species are included in the discussion when necessary. From this comparison the rabbit distal ileum and the pig small intestine emerge as the best models of amino acid transport in the human small intestine.

Regional differences in the effect of mucosal glucose and amino acids on ion transport in normal and cholera toxin-stimulated porcine small intestine.

BACKGROUND: This study explores regional differences in the response to mucosal D-glucose and L-amino acids in both normal intestine and intestine stimulated with cholera toxin. METHODS: Proximal, mid and distal small intestines from 6- to 8-week-old pigs were bathed in Ussing chambers with a buffer containing 15 mM serosal glucose, and the effect of adding a cocktail giving luminal chamber concentrations of 15 mM D-glucose and 20 mM of each L-alanine, L-proline, L-lysine, L-phenylalanine, and L-glutamine on transmucosal Na+ and Cl- transport was measured. RESULTS: In all segments of both normal and cholera toxin-treated intestine, electrogenic Na+ and electroneutral NaCl absorption were promoted. No significant differences in the net increase of Na+ and Cl- absorption between normal and cholera toxin-stimulated intestine were present. Under both conditions no segmental differences were present in the stimulated Cl- absorption, describing identical capacity for stimulated electroneutral NaCl absorption. In contrast the electrogenic Na+ absorption was, compared to the proximal part, doubled in the mid and distal parts under both conditions. CONCLUSIONS: We conclude that mucosal D-glucose and L-amino acids stimulate electroneutral NaCl and electrogenic Na+ absorption to the same degree in normal and cholera toxin-treated small intestine. There is no segmental difference in stimulated electroneutral NaCl absorption, while electrogenic Na+ absorption is highest in mid and distal parts.

Na+-independent transport of bipolar and cationic amino acids across the luminal membrane of the small intestine.

The role of sodium in transport of bipolar and cationic amino acids and their interactions were examined in vitro by measuring unidirectional influx across the brush-border membrane of intact rat jejunal and rabbit ileal epithelia. The chloride-dependent and beta-alanine inhibitable B(0,+) present in rabbit ileum was blocked by combining inhibition by beta-alanine with Na(+)- or Cl(-)-free conditions. Under these conditions, lysine influx across the brush-border membrane is Na+ independent. All Na+-independent influx of cationic and bipolar amino acids is by a system b(0,+) equivalent in the brush-border membrane of both species, where a system y+ is not present. System b(0,+) is shown to be a potent exchanger of intracellular leucine for extracellular lysine and of intracellular lysine for extracellular leucine. The model used to explain leucine stimulation of mucosa to serosa lysine transport can explain Na+ dependence of net lysine absorption. On the assumption that b(0,+) in situ, like the transporter induced by retroperitoneal brown adipose tissue in Xenopus laevi oocytes, acts as an obligatory exchanger, this model can also explain the effects of lysine on short-circuit current and net transport of sodium and the effect on transport capacity by preincubation at Na+-free conditions.

beta-Amino acid transport in pig small intestine in vitro by a high-affinity, chloride-dependent carrier.

This study describes unidirectional influx of amino acids and D-glucose across the small intestinal brush-border membrane of fully weaned eight week old pigs. Influx is minimal in the duodenum and maximal in the distal and/or mid small intestine. Influx of beta-alanine, taurine and N-methyl-aminoisobutyric acid is chloride-dependent. The activation stoichiometry for taurine influx is 1.0 +/- 0.2 chloride/2.4 +/- 0.3 sodium/1 taurine. Influx of D-glucose, lysine, glycine and glutamate is chloride-independent. An ABC test demonstrates a common beta-amino acid carrier: (a) the apparent affinity constant K1/2Taurine is 44 +/- 13 microM (means +/- S.D.) and the inhibitory constant (KiTaurine) against beta-alanine influx is 41 +/- 5 microM (means +/- S.E.). (b) K1/2beta-alanine is 97 +/- 23 microM and Kibeta-alanine against taurine influx is 160 +/- 22 microM. (c) KiHypotaurine against taurine and beta-alanine influx is 43 +/- 4 (n = 7) and 22 +/- 5 microM (n = 7), respectively. In conclusion, a high affinity, low capacity, sodium- and chloride-dependent carrier of beta-amino acids is present in pig small intestine.

Chloride-dependent amino acid transport in the small intestine: occurrence and significance.

The unidirectional influx of amino acids, D-glucose and ions across the brush-border membrane of the small intestine of different species has been measured in vitro with emphasis on characterization of topographic and species differences and on chloride dependence. The regional differences in transport along the small intestine are outlined and shown to be caused by variation in transport capacity, while the apparent affinity constants are unchanged. Rabbit small intestine is unique by exhibiting maximal rates of transport in the distal ileum and a very steep decline in the oral direction from where tissues are normally harvested for preparation of brush-border membrane vesicles. Transport in the guinea pig and rat is much more constant throughout the small intestine. Since the capacity of nutrient carriers is regulated by their substrates it is possible that bacterial breakdown of peptides and proteins in rabbit distal ileum increases the concentration of amino acids leading to an upregulation of the carriers. Chloride dependence is a characteristics of the carrier rather than the transported amino acid, and is used to improve the classification of amino acid carriers in rabbit small intestine. In this species the imino acid carrier, the beta-amino acid carrier, and the beta-alanine carrier, which should be renamed the B0,+ carrier, are chloride-dependent. The steady-state mucosal uptake of classical substrates for these carriers in biopsies from the human duodenum is also chloride-dependent. The carrier of beta-amino acids emerges as ubiquitous and chloride-dependent, and evidence of cotransport with both sodium and chloride is reviewed. A sodium:chloride:2-methyl-aminoisobutyric acid coupling stoichiometry of approx. 2:1:1 is suggested by ion activation studies. Direct measurements of coupled ion fluxes in rabbit distal ileum confirm that sodium, chloride and 2-methyl-aminoisobutyric acid are cotransported on the imino acid carrier with an identical influx stoichiometry. Control experiments and reference to the literature on the electrophysiology of the small intestine exclude alterations of the membrane potential as a feasible explanation of the chloride dependence. Thus, it is concluded that chloride is cotransported with both sodium and 2-methyl-aminoisobutyric acid across the brush-border membrane of rabbit distal ileum.

Transport of glycine and lysine on the chloride-dependent beta-alanine (B0,+) carrier in rabbit small intestine.

Transport of glycine, lysine and beta-alanine in rabbit, guinea pig and rat small intestine has been examined by measurements of the unidirectional influx across the brush border membrane of the intact epithelium. In rabbit distal ileum the chloride-dependent fraction of glycine transport, and all sodium- and chloride-dependent lysine transport is carried on the beta-alanine carrier. Lysine eliminates all saturable, sodium-independent transport of glycine. The saturable, sodium-dependent, and lysine resistant influx of glycine is characterized by a K1/2Gly of 60 mM. Glycine transport in the mid intestine of the guinea pig is chloride-independent and in the rat only a minute fraction may be chloride-dependent. These species do not possess an equivalent of the rabbit beta-alanine carrier. In conclusion, glycine transport in rabbit distal ileum is by the sodium-dependent carrier of neutral amino acids, by the sodium-independent lysine carrier, and by the sodium- and chloride-dependent beta-alanine carrier which closely resembles the B0,+ carrier described in mouse blastocysts. All sodium dependent lysine transport in rabbit distal ileum is by the chloride- and sodium-dependent beta-alanine carrier. It is proposed that the beta-alanine carrier in rabbit distal ileum be renamed the B0,+ carrier.

Chloride dependent amino acid transport in the human small intestine.

Carriers of beta amino acids and imino acids in the small intestine of rabbits and guinea pigs are chloride dependent, and a cotransport of chloride, sodium, and 2-methyl-aminoisobutyric acid has been shown. This study examines the chloride dependence of amino acid transport in the human small intestine. The steady state tissue uptake of amino acids, given as the ratio between substrate concentration in intracellular and extracellular water after 35 minutes incubation at 37 degrees C, was determined in mucosal biopsy specimens from the duodenum of patients undergoing diagnostic upper endoscopy and compared using one way analysis of variance. Uptake of leucine and alpha-methyl-D-glucoside in the duodenum and the distal ileum did not differ. The accumulation of all substrates was sodium dependent. In the absence of mucosal chloride the uptake of taurine, glycine, and 2-methyl-aminoisobutyric acid was significantly reduced while that of leucine and alpha-methyl-D-glucoside was unaffected and the reduction of beta alanine uptake not statistically significant. Uptake of 2-methyl-aminoisobutyric acid and proline showed mutual inhibition. Leucine did not reduce uptake of the beta amino acids. In conclusion, chloride dependent transport processes for 2-methyl-amino-isobutyric acid, taurine, and glycine are present in the human small intestine.