Treatment with the ghrelin-O-acyltransferase (GOAT) inhibitor GO-CoA-Tat reduces food intake by reducing meal frequency in rats.

The ghrelin acylating enzyme ghrelin-O-acyltransferase (GOAT) was recently identified and implicated in several biological functions. However, the effects on food intake warrant further investigation. While several genetic GOAT mouse models showed normal food intake, acute blockade using a GOAT inhibitor resulted in reduced food intake. The underlying food intake microstructure remains to be established. In the present study we used an automated feeding monitoring system to assess food intake and the food intake microstructure. First, we validated the basal food intake and feeding behavior in rats using the automated monitoring system. Afterwards, we assessed the food intake microstructure following intraperitoneal injection of the GOAT inhibitor, GO-CoA-Tat (32, 96 and 288 µg/kg) in freely fed male Sprague-Dawley rats. Rats showed a rapid habituation to the automated food intake monitoring system and food intake levels were similar compared to manual monitoring (P = 0.43). Rats housed under these conditions showed a physiological behavioral satiety sequence. Injection of the GOAT inhibitor resulted in a dose-dependent reduction of food intake with a maximum effect observed after 96 mg/kg (-27%, P = 0.03) compared to vehicle. This effect was delayed in onset as the first meal was not altered and lasted for a period of 2 h. Analysis of the food intake microstructure showed that the anorexigenic effect was due to a reduction of meal frequency (-15%, P = 0.04), whereas meal size (P = 0.29) was not altered compared to vehicle. In summary, pharmacological blockade of GOAT reduces dark phase food intake by an increase of satiety while satiation is not affected.

Pregnancy-specific glycoprotein 1 (PSG1) activates TGF-ß and prevents dextran sodium sulfate (DSS)-induced colitis in mice.

Transforming growth factor-ßs (TGF-ßs) are secreted from cells as latent complexes and the activity of TGF-ßs is controlled predominantly through activation of these complexes. Tolerance to the fetal allograft is essential for pregnancy success; TGF-ß1 and TGF-ß2 play important roles in regulating these processes. Pregnancy-specific ß-glycoproteins (PSGs) are present in the maternal circulation at a high concentration throughout pregnancy and have been proposed to have anti-inflammatory functions. We found that recombinant and native PSG1 activate TGF-ß1 and TGF-ß2 in vitro. Consistent with these findings, administration of PSG1 protected mice from dextran sodium sulfate (DSS)-induced colitis, reduced the secretion of pro-inflammatory cytokines, and increased the number of T regulatory cells. The PSG1-mediated protection was greatly inhibited by the coadministration of neutralizing anti-TGF-ß antibody. Our results indicate that proteins secreted by the placenta directly contribute to the generation of active TGF-ß and identify PSG1 as one of the few known biological activators of TGF-ß2.

[Chronic musculoskeletal pain syndrome in primary hyperparathyroidism]. / Chronisches muskuloskelettales Schmerzsyndrom bei primärem Hyperparathyreoidismus.

Chronic somatic pain disorders with somatic and mental factors (ICD-10: F45.41) are common among psychosomatic patients. In the present case, due to the close temporal association with a trauma and the subsequent development of symptoms including depressive symptoms, a chronic pain disorder with a relevant somatoform component was suspected. However, after a period of several months without significant somatic findings, targeted diagnostic approaches resulted in the diagnoses of primary hyperparathyroidism and a papillary thyroid carcinoma. Surgical therapy resulted in an almost complete decline of symptoms within a short period of time.

Living donor liver transplantation and its effect on the donor-recipient relationship--a qualitative interview study with donors.

An important aspect in the preoperative evaluation and a legal precondition for an living donor liver transplantation (LDLT) is a family or emotionally close relationship between donor and recipient. We investigated the development of the donor-recipient relationship after LDLT. We conducted semi-structured clinical interviews with 18 donors as part of a regular postoperative follow-up and analyzed them using the method of Grounded Theory. The donation does not lead to any major changes in the donor-recipient relationship, probably due to careful pre-selection. It does however enhance the existing positive or conflicting character of the relationship. Donors sometimes downplay negative aspects in the relationship and emphasize the improvement as a way of dealing with a major life event. A donation cannot fulfill expectations linked to it and it is unfavorable to be used to improve the relationship. Potential misuse or instrumentalization of the donation by the donor are possible. Postoperative feelings of gratitude are an issue after surgery. A good relationship enhances a better management of the postoperative course. The preoperative donor-recipient relationship should be as free of conflict as possible. A thorough preoperative evaluation of the donor-recipient relationship is particularly important to assess the donors' suitability and clarify conflicts and unrealistic expectations.

Intraperitoneal immune cell status in infertile women with and without endometriosis.

Endometriosis is a widespread chronic disease characterized by endometrial tissue located outside the uterine cavity. Clinical signs are chronic pelvic pain and infertility. Emerging evidence indicates that the immune system is profoundly involved in the onset and/or progression of endometriosis. However, mechanistic pathways have not yet been conclusively specified. In this study, women undergoing diagnostic laparoscopy due to infertility were recruited, and classified as early-stage endometriosis (n=30), advanced-stage endometriosis (n=8) or no endometriosis (n=31). The frequency and phenotype of leukocytes were evaluated in peritoneal fluid. While the frequency of lymphocytes was not significantly different, neutrophils were increased in endometriosis. Flow cytometry analysis revealed an increased frequency of CD4(+) and CD8(+) cells in peritoneal fluid of endometriosis patients. In addition, the frequency of CD4(+)CD25(+)CD103(+) cells and lineage(-)HLA-DR(+)CD11c(+)CD123(+) dendritic cells was decreased in peritoneal fluid in endometriosis, whereas CD57(+) NK cells and CD8(+)CD28(-) T suppressor cells remained largely unaltered. We conclude that therapeutic approaches in endometriosis might focus on peritoneal leukocytes as a target or surveillance marker; however, immune alterations in peritoneal fluid are subtle and their analysis will require highly standardized and harmonized protocols.

Social support during pregnancy: effects on maternal depressive symptoms, smoking and pregnancy outcome.

BACKGROUND: The goal was to study the effects of social support during pregnancy on maternal depressive symptoms, quality of life and pregnancy outcomes. METHODS: Eight hundred ninety-six women were prospectively studied in the first trimester of pregnancy and following completion of the pregnancy. The sample was divided into quartiles yielding groups of low, medium and high social support based on perceived social support. RESULTS: Pregnant women with low support reported increased depressive symptoms and reduced quality of life. The effects of social support on pregnancy outcomes were particularly pronounced in women who had smoked during pregnancy, with significant main effects of social support in a two-way analysis of variance (smoking status and social support) for child body length (F = 4.26, P = 0.04; 50.43 +/- 2.81 cm with low support versus 51.76 +/- 2.31 cm with high support) and birthweight (F = 11.35, P = 0.001; 3175 +/- 453 g with low support versus 3571 +/- 409 g with high support). In smokers, pregnancy complications occurred more frequently when given low support {34 versus 10.3% with high support, chi(2) = 5.49, P = 0.019; relative risk (RR) = 3.3 [95% confidence interval (95% CI) = 1.1-10.2]}, and the proportion of preterm deliveries was greater given low support (10.0 versus 0% with high support, chi(2) = 3.84, P = 0.05, odds ratio = 8.1). CONCLUSIONS: Lack of social support constitutes an important risk factor for maternal well-being during pregnancy and has adverse effects on pregnancy outcomes.

Gene and protein expression of protease-activated receptor 2 in structural and inflammatory cells in the nasal mucosa in seasonal allergic rhinitis.

BACKGROUND: Protease-activated receptor 2 (PAR 2) has been shown to be responsible for trypsin and mast cell tryptase-induced airway inflammation. Here, the present study aimed to explore the expression of PAR 2 in the nasal mucosa of seasonal allergic rhinitis (SAR). METHODS: Study subjects were recruited for the study by medical history, physical examination and laboratory screening tests. Using immunohistochemistry, laser-assisted cell picking and subsequently real-time PCR, nasal mucosa biopsies of SAR patients were investigated for PAR 2 gene and protein expression in complex tissues of the nasal mucosa. RESULTS: Gene and protein expression of PAR 2 was firstly detected in nasal mucosa of SAR patients. The relative gene expression level of PAR 2 was significantly increased in complex tissues of the nasal mucosa of SAR (6.21+/-4.02 vs. controls: 1.38+/-0.86, P=0.004). Moreover, PAR 2 mRNA expression in epithelial cells (SAR: 4.78+/-4.64 vs. controls: 0.84+/-0.61, P=0.003) but not in mucus (SAR: 1.51+/-1.15 vs. controls: 1.35+/-1.02, P=0.78) and endothelial cells (SAR: 1.20+/-0.57 vs. controls: 1.73+/-1.30, P=0.5) was found to be significantly changed in the nasal mucosa in SAR. Using double immunohistochemistry the present study demonstrated that the total numbers of mast cells (P=0.0003) and eosinophils (P=0.03) and the numbers of eosinophils expressing PAR 2 (P=0.006) were significantly elevated in the nasal mucosa of SAR compared with the controls. CONCLUSION: The abundant presence and distribution of gene and protein expression of PAR 2 in different cell types in the nasal mucosa under normal situation, the increased expression of PAR 2 in epithelial cells and the increased number of eosinophils with PAR 2 suggest that PAR 2 may contribute to the pathogenesis of allergic diseases such as SAR.

[Airway sensory nerve and tachykinins in asthma and COPD]. / Die sensible Atemwegsinnervation und die Tachykinine bei Asthma und chronisch-obstruktiver Lungenerkrankung (COPD).

The airway nerve has gained importance in the field of respiratory research as it is known to have the capacity to release numerous mediators which can cause pulmonary effects in the airways. Meanwhile, a broad range of stimuli including capsaicin, bradykinin, hyperosmolar saline, tobacco smoke, allergens, ozone, inflammatory mediators and cold dry air have been shown to activate sensory nerve fibres to release neuropeptides such as the tachykinins substance P (SP) and neurokinin A (NKA) to mediate neurogenic inflammation. SP is synthesized in cell bodies of airway neurons of the trigeminal, jugulare and nodose ganglia. Following their release, tachykinins are degraded by neutral endopeptidase (NEP) and an angiotensin-converting enzyme. Tachykinins have been proposed to play an important role in human respiratory diseases such as bronchial asthma und chronic obstructive diseases (COPD) as they have been shown to have potent effects on the tone of airway smooth muscle, airway secretions, bronchial circulation and on inflammatory and immune cells by activation of the neurokinin-1 (NK-1) and neurokinin-2 (NK-2) receptors. Recently, new tachykinins such as virokinin and hemokinin were identified and characterised. Different aspects of the neurogenic inflammation have been well studied in animal models of allergic airway inflammation, but only little is known about the role of neurogenic airway inflammation in human diseases. To address the precise role of tachykinins and airway sensory nerves in human asthma und COPD, experiments on sensory nerve sensitisation and neuro-immune interaction have to be carried out in future studies.

Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats.

BACKGROUND AND AIMS: Ghrelin, the natural ligand of the growth hormone secretagogue receptor 1a, is the most powerful peripherally active orexigenic agent known. In rodents, ghrelin administration stimulates growth hormone release, food intake, and adiposity. Because of these effects, blocking of ghrelin has been widely discussed as a potential treatment for obesity. Spiegelmer NOX-B11 is a synthetic l-oligonucleotide, which was previously shown to bind ghrelin. We examined the effects of NOX-B11 on ghrelin induced neuronal activation and food intake in non-fasted rats. METHODS: Animals received various doses of NOX-B11, inactive control Spiegelmer, or vehicle intravenously. Ghrelin or vehicle was administered intraperitoneally 12 hours later and food intake was measured over four hours. Neuronal activation was assessed as c-Fos-like immunoreactivity in the arcuate nucleus. RESULTS: Treatment with NOX-B11 30 nmol suppressed ghrelin induced c-Fos-like immunoreactivity in the arcuate nucleus and blocked the ghrelin induced increase in food intake within the first half hour after ghrelin injection (mean 1.13 (SEM 0.59) g/kg body weight; 4.94 (0.63) g/kg body weight versus 0.58 (0.58) g/kg body weight; p<0.0001). Treatment with NOX-B11 1 nmol or control Spiegelmer had no effect whereas treatment with NOX-B11 10 nmol showed an intermediate effect on ghrelin induced food intake. CONCLUSIONS: Spiegelmer NOX-B11 suppresses ghrelin induced food intake and c-Fos induction in the arcuate nucleus in rats. The use of an anti-ghrelin Spiegelmer could be an innovative new approach to inhibit the biological action of circulating ghrelin. This may be of particular relevance to conditions associated with elevated plasma ghrelin, such as the Prader-Willi syndrome.

Transcriptional up-regulation of histamine receptor-1 in epithelial, mucus and inflammatory cells in perennial allergic rhinitis.

BACKGROUND: Histamine receptors play an important role in the pathogenesis of nasal allergy. Activation of histamine receptor 1 (H1R) and 2 (H2R) can cause allergic symptoms which can be blocked effectively by antihistamines. H1R and H2R transcript levels have been found to be up-regulated in perennial - but not in seasonal - allergic rhinitis (AR). The present study aimed to explore H1R and H2R expression in complex tissues of the nasal mucosa of perennial allergic rhinitis (PAR). METHODS: Ten patients with PAR and 13 non-AR subjects were recruited for the study by medical history, physical examination and laboratory screening tests. In this study, we have analysed single cells dissected from the nasal mucosa biopsies by laser-assisted microdissection. H1R mRNA expression was analysed in different cell types such as epithelial, endothelial, mucus and inflammatory cells isolated from the nasal mucosa of PAR in comparison with non-AR subjects. RESULTS: H1R mRNA gene expression level was significantly increased in the nasal mucosa of PAR in comparison with non-AR (P<0.0001). H1R mRNA was significantly elevated in epithelial (P<0.001) and mucus cells (P<0.05) of PAR in comparison with non-AR whereas H1R gene expression levels in endothelial cells between both groups were not changed (P=0.23). Interestingly, inflammatory cells in the nasal mucosa of PAR patients were also strongly expressed H1R mRNA (P<0.001). CONCLUSION: The present study indicates that PAR alters the expression of H1R mRNA in epithelial, mucus and inflammatory cells of the nasal mucosa and but not in endothelial cells. Therefore, epithelial, mucus and inflammatory cells may play an important role in histamine-mediated allergic airway inflammation in PAR.

[Psychological and somatic aspects of living liver donors: preoperative assessment and postoperative course]. / Psychische und somatische Aspekte der Leberlebendspende: Präoperative Evaluation und postoperativer Verlauf.

BACKGROUND AND OBJECTIVE: Living donor liver transplantation (LDLT) has been gaining importance in the treatment of end-stage liver disease in adults as a partial solution to the growing organ shortage. Thus far, only few empirical studies have been published on the situation of donors who are faced with the risk of medical complications after resection of the right hepatic lobe. PATIENTS AND METHODS: 87 potential donors were preoperatively assessed in the years 2000 and 2001 at the Charité Berlin. 41 potential donors were excluded, 46 donors (31 women, 15 men, mean age 41 [19 - 67] years) underwent liver surgery and were re-assessed 6 months after the operation. The frequency of postoperative complications and the course of psychosocial parameters were investigated. Donors' moods were analysed with the Berlin Mood Questionnaire, the physical complaints were assessed with the Giessen Complaint Questionnaire. The preoperative interviews of 20 potential donors were analysed according the current social qualitative research methods. RESULTS: In 11 % (n = 10) of potential donors transplantation was not recommended for psychosocial reasons because they showed a marked ambivalence towards the operation. After operation, 22 % (n = 12) of donors had postoperative complications. Most relevant single causes of severe impairment were temporary and reversible biliary leakages from the cutting edge. There were no long- term complications. 26 % (n = 10) of donors showed postoperative high values for anxious depression and physical complaints. CONCLUSIONS: The resection of the right hepatic lobe holds promise of a good psychosocial outcome for most donors, irrespective of donation-related complications. The psychosocial impairment and physical complaints of some donors after transplantation are yet not clearly understood. Further psychosocial studies will be necessary to develop criteria for an evidence based medical care of living donors.

Patients with haematological malignancies show a restricted body image focusing on function and emotion.

The diagnosis of cancer threatens the psychological and bodily integrity. Based on this assumption, we aimed to explore how newly diagnosed patients cope with special regard to the body image (BI). In total, 40 patients (32 haematological malignancies) were assessed by questionnaires on mood, complaints, self-regulation and quality of life (QOL). The BI was assessed by the 'Body Grid' which reveals the constructs patients choose to characterize the body. The constructs were categorized using a model of six predefined categories comprising: emotion, control, activity, strength, function and appearance. Tinnitus sufferers and medical students served as comparison groups. Cancer patients showed significantly more anxious depression and a significantly lower QOL than controls. Their BI was restricted, focusing the functional status of body organs (e.g. opposing healthy vs. ill organs) as well as emotional aspects (e.g. trust vs. fear). The data convey fundamental psychological distress in newly diagnosed cancer patients. Restriction of BI and use of functional constructs may help to buffer the threat to body integrity. The emotional constructs reflect the existential impact. The data give a clear indication for the need for early psychosocial support which should aim at stabilizing the psychological and bodily integrity of the patient.

Willingness to donate: an interview study before liver transplantation.

OBJECTIVES: The introduction of the living donation in organ transplantation introduces important new psychological conflicts and ethical questions in the transplantation process. Operation related risks, as well as dependencies in the family structure, generate considerable pressure on potential donors. The aim of the study was to reconstruct the determinants of willingness to donate before transplantation. METHODS: Evaluation of 20 taped and transcribed interviews oriented to current approaches in qualitative interview research. The approach used is based on grounded theory, qualitative content analysis, and the concept of the ideal type. RESULTS: Before surgery, "openly motivated" donors push for an operation, leaving no room for ambivalence in the evaluation process. They idealise the relationship with the recipient, and link their donation with the individual-partly in subconscious expectations and wishes. In contrast, "openly ambivalent" donors formulate their anxieties and express arguments against donation. CONCLUSIONS: Statements that claim ambivalence towards donation or utterance of arguments against donation indicate earlier coercion. Before transplantation, potential donors should have the opportunity to discuss their emotional situation to help their decision making process.

Nerve growth factor-induced substance P in capsaicin-insensitive vagal neurons innervating the lower mouse airway.

BACKGROUND: Nerve growth factor (NGF) is elevated in allergic diseases such as bronchial asthma and can lead to an induction of substance P (SP) and related neuropeptides in guinea-pigs large-diameter, neurofilament-positive airway neurons. OBJECTIVE: In the present study, the effect of NGF on tyrosine kinase receptor trkA and the capsaicin receptor TRPV1 expression in airway-specific vagal sensory neurons located in the jugular-nodose ganglia complex (JNC) of mice was investigated. METHODS: Using retrograde neuronal tracing in combination with double-labelling immunohistochemistry, SP, trkA- and TRPV1-receptor expression was examined in airway-specific sensory neurons of BALB/c mice before and after NGF treatment. RESULTS: NGF injected into the lower airway was able to induce SP (13.0+/-2.03% vs. 5.9+/-0.33%) and trkA expression (78+/-2.66% vs. 60+/-2.11%) in larger diameter (>25 microm), capsaicin-insensitive and trkA-positive vagal sensory neurons that were retrograde-labelled with Fast Blue dye from the main stem bronchi. CONCLUSION: Based on the extent of SP and trkA co-expression in airway-specific neurons by NGF treatment, the present study suggests that, following a peripheral activation of trkA receptor on SP afferent by NGF which is elevated in allergic inflammation, there may be trkA-mediated SP induction to mediate neurogenic airway inflammation.

Heme oxygenases in pregnancy II: HO-2 is downregulated in human pathologic pregnancies.

PROBLEM: We previously reported a diminished expression of the heme-degrading enzymes heme oxygenases (HO)-1 and HO-2 in decidua and placenta from mice undergoing Th1-mediated abortion, strongly indicating the protective effect of HO in murine pregnancy maintenance. Here we investigated whether the expression of HO-1 and HO-2 is also reduced at the feto-maternal interface of pathologic human pregnancies. METHOD OF STUDY: Immunohistochemistry was used to detect HOs expression in placental and decidual first-trimester tissue from patients with: spontaneous abortion (n = 14), choriocarcinoma (n = 14), hydatidiform mole (H-mole) (n = 12), compared with normally progressing pregnancies (n = 15). Further, we investigated early third-trimester decidual and placental tissue from patients with pre-eclampsia (n = 13) compared with fetal growth retardation (n = 14) as age-matched controls. RESULTS: In first trimester tissue, we observed a significant reduction of HO-2 expression in invasive trophoblast cells, endothelial cells, and syncytiotrophoblasts in samples from patients with spontaneous abortion compared with normal pregnancy. H-mole samples showed a diminished expression of HO-2 in invasive trophoblast cells and endothelial cells in comparison with NP, whereas choriocarcinoma samples showed no significant differences compared with the control. In third trimester tissue, HO-2 was also reduced in syncytiotrophoblasts and invasive trophoblast cells from pre-eclampsia compared with samples from fetal growth retardation. HO-1 expression was diminished in all pathologies investigated; however, the differences did not reach levels of significance. CONCLUSIONS: Our data indicate that HOs play a crucial role in pregnancy and low expression of HO-2, as observed in pathologic pregnancies, may lead to enhanced levels of free heme at the feto-maternal interface, with subsequent upregulation of adhesion molecules, allowing enhanced inflammatory cells migration to the feto-maternal interface.

[Acute liver failure following the use of ecstasy (MDMA)]. / Akutes Leberversagen nach dem Konsum von Ecstasy (MDMA).

The use of "ecstasy" (Methylenedioxymethamphetamine) as a recreational drug is increasing in europe since the 1980's. Aside intended psychological effects the use of ecstasy can be followed by symptoms of intoxication; complications include toxic hepatic damage up to acute hepatic failure. This case-report is about a 17-year old female patient who regularly used "ecstasy" over a six-month period. Two days after the last use of "ecstasy", she reported to her general practitioner with nausea, vomiting, abdominal pain and jaundice. Within 10 days the patient developed acute liver failure. With criteria for liver transplantation fulfilled she was listed for orthotopic liver transplantation of high urgency which was carried out only one day later. Histological examination of the explanted liver showed evidence for a toxic fulminant hepatitis. After transplantation the patient made a full recovery and was released from hospital on day 26 after transplantation. At the first control after six months the patient was in good physical and nutritional condition, serological parameters were normal and ultrasound examination of the transplanted liver was unremarkable. The ethiopathology of "ecstasy"-induced hepatotoxicity, which can occur dose-independently with a symptom-free period from days to weeks after ingestion is not yet fully understood. Possible mechanisms of hepatic damage include influence of MDMA on body temperature regulation, harmful effects of the substance or further components of the "ecstasy"-tablets on the liver cell or a genetic vulnerability of some individuals against amphetamines and amphetamine derivates. There are no parameters existing which could predict the course and severity of "ecstasy"-induced hepatopathy. Especially in young patients with symptoms of hepatic damage frequent controls of clinical status and relevant laboratory parameters are of great importance. Patient transfer to a specialised centre should follow as early as possible; at the latest, when coagulopathy occurs.

Indications for a 'brain-hair follicle axis (BHA)': inhibition of keratinocyte proliferation and up-regulation of keratinocyte apoptosis in telogen hair follicles by stress and substance P.

It has long been suspected that stress can cause hair loss, although convincing evidence of this has been unavailable. Here, we show that in mice sonic stress significantly increased the number of hair follicles containing apoptotic cells and inhibited intrafollicular keratinocyte proliferation in situ. Sonic stress also significantly increased the number of activated perifollicular macrophage clusters and the number of degranulated mast cells, whereas it down-regulated the number of intraepithelial gd T lymphocytes. These stress-induced immune changes could be mimicked by injection of the neuropeptide substance P in nonstressed mice and were abrogated by a selective substance P receptor antagonist in stressed mice. We conclude that stress can indeed inhibit hair growth in vivo, probably via a substance P-dependent activation of macrophages and/or mast cells in the context of a brain-hair follicle axis.

Dipeptidyl peptidase IV (DP IV, CD26) in patients with inflammatory bowel disease.

BACKGROUND: Dipeptidyl peptidase IV (DP IV, CD26), a serine protease with broad tissue distribution and known activity in serum, participates in T cell activation and promotes a Th1 cytokine response, a function in part attributable to its enzymatic activity. We hypothesized that the activity of DP IV in serum and expression of CD26/DP IV in lymphocytes may be altered in patients with inflammatory bowel disease (IBD). METHODS: Serum DP IV activity and CD26 (DP IV)-positive peripheral blood lymphocytes were measured in 110 patients with IBD (Crohn disease (CD): n = 63, ulcerative colitis (UC): n = 47). Additionally, T cell activation antigens (CD25, CD95) and costimulatory molecules (CD28) were evaluated. The same analyses were carried out in healthy volunteers (HC, n = 28). Thirty-nine patients with CD and 28 patients with UC were reassessed 3-6 months after the first visit. RESULTS: In patients with IBD, the DP IV activity in serum was reduced (mean +/- s (standard deviation): 52.8 U/l +/- 16.9 (CD) and 55.7 +/- 15.1 U/l (UC) versus 71.9 +/- 18.4 (HC), P < 0.001). Furthermore, patients with IBD had higher numbers of CD26-positive cells coexpressing CD25 and a higher surface expression of CD26 (DP IV) (mean fluorescence intensity, mean 57.1 (CD) and 59.8 (UC) versus 29.9 (HC), P < 0.001). The DP IV activity in serum showed an inverse correlation with known disease activity scores as well as with the concentrations of orosomucoid in serum. CONCLUSION: The changes of DP IV in patients with IBD highlight alterations at an interface between immune function and metabolism of peptide hormones, with potential importance for the pathophysiology of IBD. Furthermore, these changes may help to refine the assessment of IBD activity.