ObjectiveTo investigate the olfactory/gustatory functions of patients with inflammatory bowel disease (IBD) by smell/taste tests, and to determine if disease activity or medication might influence the olfactory/gustatory functions of patients.Patients and MethodsIn total, 59 IBD patients (37 Crohn's disease (CD) and 22 ulcerative colitis (UC) patients) were studied using “Sniffin' sticks” and “taste strips” for olfactory and gustatory tests, respectively, and compared to healthy controls and published normative data.ResultsAmong IBD (CD and UC) patients, the values for odor threshold, but not for odor identification or discrimination, were significantly lower than that of the normative data. Further, these patients showed lower values than the normative taste values and the control group for all tastes, except sour; 57.6% of the IBD patients were hyposmic, while 30.5% were hypogeusic. Subjective self-assessments showed that the patients were not aware of their reduced olfactory/gustatory functions. There were no relevant differences in taste and smell abilities between the CD and UC patients. Disease activity and treatment did not influence the olfactory/gustatory functions.ConclusionIBD (CD and UC) patients exhibited significant reductions in the olfactory and gustatory functions. Therefore, patients should be tested by smell/taste tests, in order to be adequately informed of their olfactory/gustatory functions and provided an understanding of how to overcome their limitations, and thus improve their quality of life.

The expression and functional role of ether-à-go-go-related gene (erg) K+ channels were examined in the bovine epididymal duct. Sperm transit through the epididymal duct relies on spontaneous phasic contractions (SC) of the peritubular smooth muscle wall. Isometric tension studies revealed SC-enhancing effects of the erg channel blockers E-4031, dofetilide, cisapride, and haloperidol and SC-suppressing effects of the activator NS-1643. In the corpus epididymidis, EC50 values of 32 nM and 8.3 microM were determined for E-4031 and NS-1643, respectively. E-4031 was also able to elicit contraction in epithelium-denuded corpus segments, which lacked SC. In the cauda region, E-4031 and NS-1643 exerted effects on agonist-induced contraction similar to those observed in the proximal duct. Experiments with nifedipine and thapsigargin suggested that the excitatory effects of E-4031 depended mainly on external calcium influx and not on intracellular calcium release. Western blot and RT-PCR assays revealed the expression of both, erg1a and erg1b, in all duct regions. Because erg1b appears to predominate in the epididymal duct, patch-clamp experiments were performed on heterologously expressed erg1b channels to investigate the sensitivity of this splice variant to NS-1643. In contrast to its effects on erg1a, NS-1643 induced a concentration-dependent current increase mainly due to a marked leftward shift in erg1b channel activation by approximately 30 mV at 10 microM, explaining the inhibitory effect of the drug on epididymal SC. In summary, these data provide strong evidence for a physiological role of erg1 channels in regulating epididymal motility patterns.

Two different mechanisms leading to increased current have been described for the small-molecule human ether-à -go-gorelated gene (herg) activator NS1643 [1,3-bis-(2-hydroxy-5-trifluoromethylphenyl)-urea]. On herg1a channels expressed in Xenopus laevis oocytes, it mainly acts via attenuation of inactivation and for rat (r) erg1b channels expressed in human embryonic kidney (HEK)-293 cells, it strongly shifts the activation curve to the left. We now investigated the NS1643 effects on erg1b channels in more detail and performed comparative experiments with rat and human erg1a in different expression systems. Significant differences were observed between expression systems, but not between the rat and human isoform. In HEK-293 or Chinese hamster ovary (CHO) cells, activation of rat erg1b channels occurred in a dose-dependent manner with a maximum current increase of 300% obtained with 10 M NS1643. In contrast, the NS1643-induced strong leftward shift in the voltage dependence of activation further increased with higher drug concentration, needed more time to develop, and exhibited use dependence. Coexpression of KCNE1 or KCNE2 did not attenuate this NS1643 effect on erg1 channel activation and did thus not mimic the lower drug potency on this parameter observed in oocytes. NS1643 (10 M) slowed erg1b channel deactivation and recovery from inactivation without significant changes in activation and inactivation kinetics. With the exception of accelerated activation, NS1643 affected erg1a channels similarly, but the effect was less pronounced than in erg1b or erg1a/1b channels. It is noteworthy that rerg1b and herg1a inactivation estimated from fully activated current voltage relationships were unaltered in the continued presence of 10 M NS1643 in the mammalian expression systems, indicating qualitative differences from NS1643 effects in X. laevis oocytes.