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H D Allescher

Publications and source records attributed to H D Allescher.

At least 73 records · Page 4Linked to original sources
PubMed1999

Evidence for a feedback inhibition of NO synthesis in enteric synaptosomes via a nitrosothiol intermediate.

The exact mechanisms controlling nitric oxide synthase (NOS) activity within enteric neurons are largely unknown. In this study, the effect of exogenous nitric oxide (NO) on NOS activity was investigated in enteric synaptosomes of rat ileum. 3-Morpholinosydnonimine (SIN-1; 10(-4) M) and S-nitroso-N-acetylpenicillamine (SNAP; 10(-4) M) significantly inhibited NOS activity by 53% and 48%, respectively. However, superoxide dismutase (SOD; 160 U/ml) as well as the NO scavenger oxyhemoglobin (10(-3) M) did not influence NO donor-induced inhibition. In contrast, the inhibitory effect was antagonized by diethyldithiocarbamate (3 x 10(-4) M), an inhibitor of endogenous Cu/Zn SOD. Inhibition of NOS by exogenous NO was dependent on glutathione (GSH), since the inhibitory effect was augmented in the presence of GSH (5 x 10(-4) M) and antagonized by the GSH-depletor DL-buthionine-SR-sulfoximine (5 x 10(-4) M), suggesting that NO might be protected from extracellular breakdown by reaction with GSH. The reaction product of SIN-1/SNAP and GSH was identified as a nitrosothiol. In the presence of the Cu(+)-chelator neocuproine (10(-5) M), inhibition of NOS by SNAP/SIN-1 was reversed, suggesting that nitrosothiol formation is intermediary. These findings are indicative of a feedback inhibition of enteric NOS, presumably via formation of a nitrosothiol intermediate.

Animals↗
PubMed1999

Characterization of prejunctional and postjunctional muscarinic receptors of the ascending reflex contraction in rat ileum.

The ascending reflex contraction of the small intestine involves predominantly cholinergic neurotransmission. The orally projecting neural excitatory pathway of the myenteric reflex was studied in an in vitro model of rat ileal segments. The contractile response elicited by aboral field stimulation was significantly inhibited by a range of muscarinic receptor antagonists. Methoctramine and tripitramine (both M(2) selective, pIC(50) = 9.3 and 8.8, respectively), darifenacin and hexahydrosiladifenidol (both M(3) selective, pIC(50) = 7.3 and 7.7, respectively), and pirenzepine (M(1) selective, pIC(50) = 7.0). In radioligand binding experiments on synaptosomal and smooth muscle plasma membrane fractions, we examined whether prejunctional or postjunctional muscarinic receptors exist that could potentially contribute to the reflex contraction. In the synaptosomal fraction, the muscarinic ligand [(3)H]N-methylscopolamine labeled a homogeneous population of receptors (Hill coefficient = 1) with a K(d) value of 0.31 +/- 0.09 nM and a B(max) value of 185 +/- 16.6 fmol/mg protein. The ratio of potency of subtype-selective muscarinic receptor antagonists in competition studies was tripitramine (pK(i) = 8.7 +/- 0.3) > 1/6 x methoctramine (pK(i) = 7.9 +/- 0.02) > 1/25 x darifenacin (pK(i) = 7. 3 +/- 0.2) > 1/316 x hexahydrosiladifenidol (pK(i) = 6.2 +/- 0.1) > 1/2511 x pirenzepine (pK(i) = 5.3 +/- 0.1). In the smooth muscle plasma membrane fraction, the K(d) value was 0.29 +/- 0.05 nM and the B(max) value was 770 +/- 29 fmol/mg. The competition studies revealed a similar ratio of potency of the respective antagonists. These data suggest that muscarinic M(2) receptors, located at prejunctional and postjunctional sites, are predominantly involved in the ascending reflex contraction.

Animals↗
PubMed1999

Teleconsultation for endoscopic diagnosis of gastrointestinal diseases--concepts and architecture of the service ENDOTEL.

This paper introduces ENDOTEL as a new project in telemedicine, aiming to reduce local disadvantages in medical health care in rural areas. The progressing specialization in medicine results in a concentration of experts in few medical centers and to deficits of expert knowledge in rural areas, which remain as a domain of unspecialized physicians. ENDOTEL expands the conventional synchronous telemedical communication, which usually means videoconference, by an asynchronous multimedia communication and its resulting advantages. ENDOTEL breaks up with the need that participants have to be present simultaneously.

Computer Systems↗
PubMed1998

Effect of interleukin-1beta on the ascending and descending reflex in rat small intestine.

Acute inflammation of the intestine is associated with motility changes. We investigated the acute effect of inflammatory mediators such as interleukin-1beta, interleukin-2 and tumor necrosis factor-alpha (TNF-alpha) on electrically stimulated ascending and descending reflex responses of the rat small intestine. Exogenous application of interleukin-1beta caused a concentration-dependent inhibition of the oral contraction (0.1 ng/ml: -22.9+/-3.8%, 10 ng/ml: -57.0+/-7.4%, P < 0.05, n=10) but had no effect on anal relaxation. The interleukin-1 receptor antagonist alone had no significant effect on the reflex response, but prevented the inhibitory effect of interleukin-1beta (10 ng/ml: -3.9+/-11.4%, n=8). Interleukin-2 and TNF-alpha had no significant effect on the oral contractile and the anal inhibitory response (n.s., n=10). Using reverse transcriptase polymerase chain reaction (RT-PCR) the presence of mRNA of the interleukin-1 receptor was demonstrated in the rat small intestine. Preincubation of the preparation with indomethacin (10(-6) M), the histamine H1 receptor antagonist, pyrilamine (10(-8) M), and the histamine H3 receptor antagonist, clobenpropit (10(-8) M), decreased the oral contraction by 60.1+/-7.7%, 42.8+/-6.9% and 44.4+/-14.2% as well as the anal relaxation. These data suggest that acute administration of interleukin-1beta inhibits the ascending and descending contractile reflex pathway and this effect seems not to be mediated by prostaglandins or histamine receptors.

Animals↗
PubMed1998

Effect of capsaicin-containing red pepper sauce suspension on upper gastrointestinal motility in healthy volunteers.

Afferent nerves play a major role in the regulation of gastrointestinal motility. The questions remains if specific food ingredients can selectively activate such fibers. The aim of the study was to investigate the effect of intraesophageal application of a capsaicin-containing red pepper sauce (Tabasco) suspension on upper gastrointestinal motility in a controlled trial. After a baseline recording [esophageal motility, balloon distension, electrogastrogram (EGG)], red pepper or saline solution was infused intraesophageally in seven healthy volunteers. At 30 min gastric emptying and orocecal transit time were determined using a [13C]acetate and H2-lactulose breath test. Infusion of red pepper sauce suspension significantly increased the amplitudes (65.8 +/- 3 to 78.5 +/- 4.7 mm Hg, P < 0.05) and propagation velocity (2.9 +/- 0.3 to 4.25 +/- 0.3 sec, P < 0.05) of esophageal pressure waves and LES pressure (17.8 +/- 1.4 to 23.7 +/- 2.6 mm Hg, P < 0.05). It significantly decreased perception and discomfort threshold of intraesophageal balloon distension, reduced the percentage of normal electrical activity in the EGG, and delayed gastric emptying (saline: T(1/2) 42.9 +/- 12.0 min vs red pepper: T(1/2) 66.8 +/- 19.0 min, P < 0.05). Despite the prolongation of gastric emptying, orocecal transit time was not altered, indicating an actual increase of intestinal transit. Esophageal application of capsaicin-containing red pepper sauce suspension had profound changes on upper gastrointestinal motility, which could improve clearance and protection of the esophagus and could lead to retention of the irritant in the stomach and faster transit through the small bowel.

Adult↗
PubMed1998

Biomagnetic 3-dimensional spatial and temporal characterization of electrical activity of human stomach.

Biomagnetic measurements are based on the noninvasive recording of magnetic signals produced by biological sources such as nervous system and muscle. The aim of this study was to obtain multichannel magnetic field recordings from the human gastrointestinal tract and to localize the sources of these signals three-dimensionally. The magnetic field was recorded in eight human healthy subjects using a sensor array with 37 superconducting quantum interference devices (SQUIDs); an electrogastrogram was recorded simultaneously. Biomagnetic source localization was carried out with an iterative nonlinear optimization algorithm using the model of an equivalent current dipole (ECD) and correlated to magnetic resonance imaging (MRI) in four volunteers. Magnetogastrograms and electrogastrograms demonstrated a similar frequency distribution with a peak at 3/min. In all subjects the centers of the calculated dipoles plotted vs time showed a characteristic migration across the stomach area. One volunteer demonstrated tachygastric episodes, during which his magnetic field amplitudes increased fivefold and his dipole migration disappeared. In absence of an attack his recordings changed to normal. This demonstrates multichannel magnetic recordings can be used to localize the sources of the biomagnetic field, which could be useful for the understanding of motility disturbances.

Adult↗
PubMed1998

Long-term results of percutaneous transhepatic biliary drainage for benign and malignant bile duct strictures.

BACKGROUND: Long-term percutaneous transhepatic biliary drainage (PTBD) is a valid alternative to surgery in patients with benign or malignant bile duct strictures in whom endoscopic drainage has failed. However, few data are available on the long-term outcome with percutaneous drainage, specially when the application of Yamakawa-type prostheses is considered. METHODS: During 1996, 48 patients who were either treated with primary PTBD insertion followed by PTBD exchanges (n = 15) or who presented only for exchange of an earlier PTBD (n = 33) were included in the study. Thirty-one patients had malignant strictures, and 17 had benign ones. The PTBD catheters were scheduled for exchange every 3 months or earlier if signs and symptoms of obstruction or other problems were present. The data were collected prospectively during each follow-up visit and included both symptoms and the status and function of the PTBD at the time of exchange. RESULTS: Although PTBD was highly effective in relieving jaundice (progression of cholestasis was observed in only 2 cases), 73 of the 157 PTBD exchanges (47%) had to be carried out earlier than scheduled. Premature exchange was needed for clinical reasons, such as fever indicating PTBD dysfunction, in only 19% of these cases. The other reasons were related to the PTBD catheter and consisted of bile leakage alongside the drain (33%), PTBD disconnection or complete dislocation (30%), or occlusion suspected during regular flushing of the drain (15%). In most cases exchanging the drain was sufficient to solve the problem; in cases of complete dislocation, dilation of the same tract (n = 6) or fresh puncture and establishment of a new drainage site (n = 2) were necessary. Reducing the PTBD exchange interval from 3 to 2 months would have decreased the number of premature stent exchanges by 26%. CONCLUSIONS: Although PTBD is an effective method of biliary drainage, there are frequently minor problems-mostly catheter-related-which require premature exchange of the drain in almost half of the cases, and this may affect the patients' quality of life. Improvements in PTBD materials and catheter design are therefore needed. The effectiveness of reducing the intervals between PTBD exchanges should also be examined.

Adult↗
PubMed1998

Involvement of intracellular Ca2+ stores in inhibitory effects of NO donor SIN-1 and cGMP.

We investigated the role of K+ channels and intracellular Ca2+ stores in the relaxations induced by the NO donor 3-morpholinosydnonimine (SIN-1) and 8-bromo-cGMP (8-BrcGMP), 8-(4-chlorophenylthio)-cGMP (pCPT-cGMP), and alpha, beta-methylene-ATP in isolated segments of rat ileum. The inhibitory responses to SIN-1 and the cGMP analogs were not influenced by the K+ blockers apamin, charybdotoxin, iberiotoxin, or glibenclamide, whereas relaxations induced by alpha,beta-methylene-ATP were abolished by apamin and tetraethylammonium. The NO-donor SIN-1 and the cGMP analogs were able to inhibit contractions induced by activation of L-type Ca2+ channels (BAY-K-8644), by carbachol (CCh), and by cyclopiazonic acid (CPA), a blocker of sarcoplasmic Ca2+-ATPase. However, the inhibition of the combined CPA and CCh response was reduced and the dose-response curve of SIN-1 shifted to the right. Intracellular Ca2+ stores were emptied by incubation in Ca2+-free buffer and repetitive stimulation with CCh or BAY-K-8644. After restoration of extracellular Ca2+, the inhibitory effect of SIN-1 and pCPT-cGMP was only attenuated, whereas in the additional presence of CPA, the inhibitory effect of SIN-1 was blocked and the effect of 8-BrcGMP reduced. Thus depleting intracellular Ca2+ stores attenuated the effect of SIN-1 and 8-BrcGMP, suggesting an involvement of functional Ca2+ stores.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Protein kinase G expression in the small intestine and functional importance for smooth muscle relaxation.

In functional experiments, the nitric oxide (NO) donor N-morpholino-N-nitroso-aminoacetonitrile or the cGMP analog 8-(4-chlorophenylthio)-cGMP caused a concentration-dependent, tetrodotoxin-resistant relaxation of precontracted strips from rat small intestine. The inhibitory effect of both substances was completely blocked at lower concentrations and was significantly attenuated at higher concentrations by the selective cGMP-dependent protein kinase (cGK) antagonist KT-5823 (1 microM). cGK-I was identified by immunohistochemistry in circular and longitudinal muscle, lamina muscularis mucosae, and smooth muscle cells of the villi and in fibroblast-like cells of the small intestine. Additionally, there was staining of a subpopulation of myenteric and submucous plexus neurons. Double staining for neuronal NO synthase (nNOS) and cGK-I demonstrated a colocalization of these two enzymes. Western blot analysis of smooth muscle preparations and isolated nerve terminals demonstrated that these structures predominantly contain the cGK-Ibeta isoenzyme, whereas the cGK-Ialpha expression is about threefold less. The isoform cGK-II was entirely confined to mucosal epithelial cells. These results show that cGK-I is expressed in different muscular structures of the small intestine and participates in the NO-induced relaxation of gastrointestinal smooth muscle. The presence of cGK-I in NOS-positive enteric neurons further suggests a possible neuronal action site.

Alkaloids↗
PubMed1998

Characterization and splice variants of neuronal nitric oxide synthase in rat small intestine.

The aim of this study was to characterize neuronal nitric oxide synthase (nNOS) activity and 5'-end splice variants in rat small intestine. nNOS was predominantly expressed in the longitudinal muscle layer, with attached myenteric plexus (LM-MP). The biochemical properties of NOS activity in enriched nerve terminals resemble those of nNOS isolated from the brain. Western blot analysis of purified NOS protein with an nNOS antibody showed a single band in the particulate fraction and three bands in the soluble fraction. Rapid amplification of 5' cDNA ends-PCR revealed the presence of three different 5'-end splice variants of nNOS. Two variants encode for nNOSalpha, which has a specific domain for membrane association. The third variant encodes for nNOSbeta, which lacks the domain for membrane association and should therefore be soluble. nNOS is predominantly expressed in LM-MP and can be enriched in enteric nerve terminals. We present the first evidence that three 5'-end splice variants of nNOS encoding two different proteins are expressed in rat small intestine. These two nNOS enzymes exhibit different subcellular locations and might be implicated in different biological functions.

Alternative Splicing↗
PubMed1996

Influence of the L-arginine-nitric oxide pathway on vasoactive intestinal polypeptide release and motility in the rat stomach in vitro.

Endogenous nitric oxide (NO) plays an important role as non-adrenergic, non-cholinergic inhibitory transmitter in the gastrointestinal tract, especially in sphincter regions. The aim of this study was to investigate the influence of NO on pyloric motility and on the release of vasoactive intestinal polypeptide (VIP) in the isolated perfused rat stomach in vitro. Therefore, pyloric motility was continuously recorded by a special sleeve manometry catheter placed in the pyloric region and the concentration of VIP was determined in the venous effluent of the portal vein. Arterial perfusion with the nitrate agonist sodiumnitroprusside led to a dose-dependent reduction of the pyloric motility index (basal 166 +/- 48 mm Hg/min: sodiumnitroprusside 10(-6) M 30 +/- 20 mmHg/min: sodiumnitroprusside 10(-4) M 0: n = 8. P < 0.001) while VIP release was not influenced significantly. Inhibition of endogenous NO production by the NO-synthase inhibitor NG-nitro-L-Arg (L-NNA) significantly increased pyloric motility (basal motility index 175 +/- 28 mmHg/min: L-NNA 10(-4) M 348 +/- 48 mmHg/min: n = 8, P < 0.05). This effect was completely blocked by addition of L-Arg 10(-3) M (125 +/- 45 mm Hg/min: n = 8, P < 0.01), L-NNA and L-Arg both did not influence VIP release. Stimulation of the vagal nerve (VS: 20 V, 20 Hz, 1 ms) led to a significant decrease of the pyloric motility index (basal 181 +/- 15 mmHg/min; n = 7, P < 0.05), which was consistent even after addition of L-NNA 10(-4) M (basal 338 +/- 58 mmHg/min; VS 228 +/- 30 mmHg/min; n = 7, P < 0.05). Vagal stimulation increased VIP release significantly (basal 14.9 +/- 1.4 pmol/l; VS 20.1 +/- 2.6 pmol/l; n = 7, P < 0.05) while L-NNA had no influence on vagally induced VIP release. From these data, we conclude that the pylorus of the rat is under a tonic inhibition by endogenously released NO. Under the conditions studied. NO seems not to mediate the inhibitory effect of vagal stimulation exclusively and there seems to be no interaction between NO and VIP in the rat pylorus.

Animals↗
PubMed1996

Presynaptic modulation by VIP, secretin and isoproterenol of somatostatin release from enriched enteric synaptosomes: role of cAMP.

The release of somatostatin-like immunoreactivity was studied in isolated synaptosomes. A significant release of somatostatin-like immunoreactivity was observed in the presence of vasoactive intestinal polypeptide (VIP) (10(-6) M: 53.0 +/- 12.4 pg/mg, basal: 14.3 +/- 1.7 pg/mg, n = 5, P < 0.05), secretin (10(-6) M: 56.1 +/- 3.8 pg/mg, basal: 25.8 +/- 1.6 pg/mg, n = 6, P < 0.01) and isoproterenol (10(-5) M: 54.0 +/- 13.4 pg/mg, basal: 20.0 +/- 3.4 pg/mg, n = 8, P < 0.05). Forskolin, an unspecified activator of the adenylate cyclase, caused a significant release of somatostatin-like immunoreactivity (10(-6) M: 57.3 +/- 13.2 pg/mg, basal: 30.0 +/- 5.8 pg/mg, n = 13, P < 0.01) which was further augmented in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX 10(-4) M) (77.0 +/- 17.8 pg/mg, n = 13, P < 0.01). 3-Isobutyl-l-methylxanthine and N6, 2'-O-dibutyryladenosine-3',5'-cyclic monophosphate mimicked at effect of forskolin and VIP. The release of somatostatin was paralleled by an increase of cAMP immunoreactivity in the presence of VIP (10(-6) M: 37.1 +/- 9.4 pmol/mg, basal: 19.8 +/- 4.2 pmol/mg, n = 10, P < 0.05), isoproterenol (10(-5) M: 42.4 +/- 9.8 pmol/mg basal: 16.7 +/- 2.4 pmol/mg, n = 12, P < 0.01) and forskolin (10(-6) M: 47.1 +/- 12.4 pmol/mg, basal: 19.8 +/- 4.2 pmol/mg, n = 10, P < 0.01). The effect of nitric oxide (NO) which acts as an inhibitory neurotransmitter in the enteric nervous system was studied. NO is known to activate guanylate cyclase to induce transmitter release. The NO-generating compound sodium nitroprusside and bromoguanosine-3',5'-cyclic monophosphate (8-Br-cGMP) had no effect on the release of somatostatin-like immunoreactivity. These data demonstrate the stimulatory effect of VIP, secretin and isoproterenol on release of somatostatin-like immunoreactivity from enteric synaptosomes, which is presumably mediated by cAMP-dependent mechanisms. cGMP-dependent mechanisms seem to be of minor relevance.

Adrenergic beta-Agonists↗
PubMed1996

Regulation of VIP release from rat enteric nerve terminals: evidence for a stimulatory effect of NO.

The basal release of vasoactive intestinal polypeptide (VIP) from freshly prepared enriched synaptosomes was 159.1 +/- 17.3 fmol/mg protein (100%), which constituted 2.5% of the total VIP content. Basal VIP release was reduced by 65% by removal of external Ca2+. Release of VIP was stimulated by depolarization with KCl (65 mM, 143%) and in the presence of veratridine (10(-6) M, 184%), monensin (10(-5) M, 131%), and the Ca2+ ionophore A-23187 (10(-6) M, 160%). Stimulation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent mechanisms using isoproterenol (10(-6)-10(-4) M) and forskolin (10(-6) and 10(-5) M) had no stimulatory influence on VIP release. In contrast, sodium nitroprusside (10(-4) M, 198%), the nitric oxide (NO) donor 3-(morpholino)sydnonimine (10(-4) M, 155%), and the guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-bromo cGMP (10(-4) M, 196%) caused a significant release of VIP. L-Arginine (10(-3) M, 246%) also caused a significant increase of VIP release that was antagonized by the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (5 x 10(-4) M, 131%), which had no effect when given alone. The results demonstrate that VIP can be released from enriched synaptosomes by Ca(2+)-dependent mechanisms by NO agonists or NO-dependent mechanisms. It is speculated that this VIP release is induced by a presynaptic stimulatory mechanism of NO and this effect could enhance or contribute to the action of NO.

Animals↗