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T T Zittel

Publications and source records attributed to T T Zittel.

At least 37 records · Page 2Linked to original sources
PubMed1998

Calcitonin gene-related peptide and spinal afferents partly mediate postoperative colonic ileus in the rat.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is a widely distributed neuropeptide contained in intrinsic and extrinsic neurons of the gastrointestinal wall that has been shown to be released by noxious stimulation, to be involved in nociception, to inhibit gastrointestinal motility, and to partly mediate postoperative gastric ileus. We hypothesized that abdominal surgery-induced release of CGRP might inhibit postoperative colonic motility and food intake. METHODS: Colonic transit, stool pellet number, stool pellet weight, and food intake were measured for 48 hours after induction of postoperative ileus in rats. CGRP was immunoneutralized by preoperative injection of CGRP monoclonal antibody, or visceral afferent nerve fibers containing CGRP were functionally ablated by topical capsaicin treatment of the vagus nerves or of the celiac/superior mesenteric ganglia before abdominal surgery. RESULTS: Abdominal surgery increased colonic transit time and decreased 24-hour cumulative stool pellet number, stool pellet weight, and food intake. CGRP immunoneutralization reversed postoperative inhibition of colonic transit, 24-hour cumulative stool pellet number, stool pellet weight, and food intake by 77%, 82%, 80%, and 52%, respectively. Whereas ablation of vagal afferent nerve fibers had no effect, spinal afferent nerve fiber ablation reversed postoperative inhibition of 24-hour cumulative stool pellet number, stool pellet weight, and food intake by 41%, 38%, and 19%, respectively. CONCLUSIONS: CGRP and spinal afferent nerve fibers partly mediate postoperative colonic ileus and inhibition of food intake in the rat. By the magnitude of reversal of postoperative ileus, CGRP seems to be an important mediator of postoperative colonic ileus. Our results for the first time show involvement of a neuropeptide and spinal afferents in the mediation of postoperative colonic ileus and postoperative inhibition of food intake in rats.

Abdomen↗
PubMed1998

Blood flow measurements with [(15)O]H2O and [18F]fluoride ion PET in porcine vertebrae.

A dual positron emission tomography (PET) tracer study with [18F]fluoride and the freely diffusible tracer [(15)O]H2O was performed to measure the capillary transport of [18F]fluoride and to evaluate the potential of [18F]fluoride ion PET to quantitate bone blood flow. Under the condition of a high predictable single-pass extraction fraction (E(F)) for [18F]fluoride, the [18F]fluoride ion influx transport constant (K1F), derived from kinetic [18F]fluoride ion PET measurements, can be used to estimate bone blood flow. Bone blood flow was measured in vertebral bodies by dynamic [(15)O]H2O PET during continuous ventilation with N2O, O2, and Isoflurane (FiO2 = 0.3) in seven adult mini pigs, followed by dynamic [18F]fluoride ion PET. The mean blood flow measured by [(15)O]H2O (FlowH2O) was 0.145 +/- 0.047 ml x minute(-1) x ml(-1) and the mean K1F was 0.118 +/- 0.031 ml x minute(-1) x ml(-1), respectively (mean +/- SD). Regional analysis showed excellent agreement between FlowH2O and K1F at low flow and a significant underestimation of flow by K1F relative to FlowH2O in regions of normal and elevated flow. The observed relationship between parameters followed the Renkin-Crone distribution. The permeability-surface product was determined as 0.25 minute(-1) for vertebral bodies consisting of a mixture of trabecular and cortical bone. We conclude that [18F]fluoride ion PET can be used to estimate bone blood flow in low and normal flow regions, as long as the flow dependency of the E(F) is taken into consideration. Above blood flow values of 0.2 to 0.35 ml x minute(-1) x ml(-1), the magnitude of K1F is increasingly independent on blood flow because diffusion limits tracer transport.

Animals↗
PubMed1998

[Postoperative colon tonus after partial resection of the large intestine].

Only limited data are available on postoperative colonic motility in patients. We investigated colonic tone and motility after large bowel resection in 20 patients. A combined barostat/manometry catheter was placed intraoperatively. Postoperative colonic motility increased day by day. Barostat bag volumes were reduced on postoperative day 1 compared to postoperative day 2 and 3 indicating increased colonic tone on the 1st postoperative day. The use of morphine-like analgesics was highest right after surgery but might not explain increased colonic tone on postoperative day 1 since morphine has been shown to decrease colonic tone. Possibly, increased postoperative sympathetic activity which caused reduced splanchnic blood flow may be responsible for the apparent increase in postoperative colonic tone. The recording of colonic motility in the early postoperative period is feasible with a combined manometry/barostat catheter. These investigations may improve the understanding of the pathophysiology of postoperative colonic ileus.

Aged↗
PubMed1998

Strain gauge transducer technique for investigation of the pathophysiology of postoperative colonic ileus in awake rats.

Postoperative inhibition of colonic motility is a major contributor to postoperative ileus, but only limited information is available on its pathophysiology. We developed a model to record perioperative gastrointestinal motility in awake rats and investigated the effect of nitric oxide (NO) synthesis blockade on postoperative colonic ileus in rats. Rats were equipped with an i.v. catheter. Two strain gauge transducers were sutured to the colon, and the effects of NO synthesis blockade on postoperative colonic motility were investigated. NO synthesis blockade slightly increased baseline colonic motility. Abdominal surgery profoundly inhibited colonic motility. Blockade of NO synthesis did not prohibit intraoperative inhibition of colonic motility, but significantly hastened recovery of postoperative colonic ileus compared to vehicle. We established a model to record gastric, small intestinal and colonic motility in awake rats postoperatively. Laparotomy and short manipulation of the cecum produced a prolonged inhibition of colonic motility. Inhibition of NO synthesis improved recovery of postoperative colonic motility, indicating that NO partly mediates postoperative colonic ileus in rats.

Animals↗
PubMed1997

Prolonged intestinal afferent nerve discharge in response to cholecystokinin-58 compared to cholecystokinin-8 in rats.

Intestinal afferents are sensitive to cholecystokinin (CCK) octapeptide. However, CCK-58 may be a more biologically relevant molecule. Therefore, recordings from jejunal mesenteric afferent bundles were secured for extracellular multi-unit recording and the responses to CCK-8 and CCK-58 compared. CCK-8 and CCK-58 (i.v.) evoked a dose-dependent, devazepide sensitive, increase in afferent nerve discharge. Peak discharge frequency was higher for CCK-8 at all doses (P < 0.05). However, response duration was more prolonged for CCK-58 (P < 0.05) at 200 pmol.kg(-1). This resulted in an overall increase in area under the curve of CCK-58 compared to CCK-8 (P < 0.05). CCK-58 stimulates afferent discharge in a different pattern than CCK-8 and, therefore, may have differential biological effects.

Afferent Pathways↗
PubMed1997

[Calcium and bone metabolism after gastrectomy].

Disturbances in calcium and bone metabolism after gastrectomy have long been recognized. It has been suggested that due to impaired calcium absorption after gastrectomy, serum calcium is decreased, being counter-regulated by parathyroid hormone release and 1,25-(OH)2-vitamin D formation. Both parathyroid hormone and 1,25-(OH)2-vitamin D are known to release calcium from bone, resulting in bone mass loss and increased fracture risk in some of the gastrectomized patients. No therapy is currently generally agreed on, although supplementation of vitamin D and calcium has been suggested repeatedly. A review on the current understanding of calcium and bone metabolism after gastrectomy is given.

Aged↗
PubMed1997

High prevalence of bone disorders after gastrectomy.

BACKGROUND: Studies indicate that gastrectomy might alter calcium and bone metabolism, resulting in bone disorders. No data are currently available on the prevalence of bone disorders after gastrectomy. METHODS: Sixty gastrectomy patients were investigated for serum parameters of calcium and bone metabolism 5 to 20 years postoperatively and compared to an age- and sex-matched healthy control population. Forty patients agreed to a radiological investigation of the spine by anterior-posterior and lateral radiographs of the thoracic and lumbar spine and by computed tomography (CT) osteodensitometry. RESULTS: Serum calcium and 25-(OH)-vitamin D were decreased in gastrectomized patients, while parathyroid hormone and 1,25-(OH)2-vitamin D were increased. Serum parameters of calcium metabolism were altered in as many as 68% of patients. We found 31 vertebral fractures in 13 patients, 30 grade 2 vertebral deformities in 18 patients, and osteopenia in 15 patients, corresponding to a prevalence of 33%, 45%, and 37% in gastrectomized patients, respectively. The overall rate of gastrectomy patients having vertebral fractures and/or osteopenia was 55%. The risk of having a vertebral deformity was increased by more than sixfold after gastrectomy. Our study is the first report evaluating vertebral deformities in gastrectomized patients, and the largest series of gastrectomized patients investigated by CT osteodensitometry. CONCLUSION: We found a high prevalence of bone disorders in gastrectomized patients, possibly resulting from disorders in calcium metabolism. Postgastrectomy bone disease might derive from a calcium deficit, which increases calcium release from bone and impairs calcification of newly build bone matrix.

Absorptiometry, Photon↗
PubMed1997

Calcium regulation and bone mass loss after total gastrectomy in pigs.

OBJECTIVE: Total gastrectomy often results in postgastrectomy bone disease with decreased bone mass and increased fracture risk. To further elucidate the mechanisms of postgastrectomy bone disease, the authors investigated calcium metabolism and bone mineral density after total gastrectomy in pigs. SUMMARY BACKGROUND DATA: Postgastrectomy bone disease can present as osteomalacia, osteoporosis in excess of normal aging, or a combination of both. The underlying mechanisms are insufficiently understood and need further investigation. METHODS: Growing minipigs were gastrectomized and compared with fed-matched, sham-operated control p gs for 1 year. Calcium absorption, serum calcium, parathyroid hormone, 25-(OH)-vitamin D, 1,25-(OH)2-vitamin D, alkaline phosphatase, and computed tomography bone mineral density were measured in three monthly intervals. RESULTS: Total gastrectomy resulted in impaired calcium absorption, reduced serum calcium and 25-(OH)-vitamin D, increased parathyroid hormone and 1,25-(OH)2-vitamin, and reduced bone mineral density compared with fed-matched, sham-operated control pigs. CONCLUSIONS: The authors data indicate that a reduced serum calcium activates counter-regulatory mechanisms, resulting in calcium mobilization from the bone. Possibly, calcium and vitamin D supplementation after total gastrectomy might prevent postgastrectomy bone mass loss.

Animals↗
PubMed1997

Pathways of Fos expression in locus ceruleus, dorsal vagal complex, and PVN in response to intestinal lipid.

Exogenous cholecystokinin (CCK) injected peripherally mimics effects of lipid entering the intestine on food intake and gastric motility via vagal afferents and induces c-fos expression in the locus ceruleus complex (LCC), nucleus of the solitary tract (NTS), area postrema (AP), and paraventricular nucleus (PVN). However, the role of peripheral endogenous CCK in induction of c-fos expression in the brain at ingestion of nutrients is controversial. In awake rats, intraduodenal lipid infusion markedly increased Fos protein-like immunoreactivity (FLI) in these brain nuclei. Perivagal capsaicin pretreatment reduced the increase of FLI in the LCC, NTS, and PVN by 66-86% and in the AP by 46%. The CCK-A receptor antagonist MK-329 (0.1 mg/kg i.p.) diminished the FLI increase in LC, NTS, AP, and PVN by 39-100%; the CCK-B receptor antagonist L-365,260 reduced the increased FLI in the AP by 54%. After capsaicin pretreatment, both CCK antagonists had additional inhibitory effects only on FLI in the AP. These findings suggest that entry of lipid into the intestine activates c-fos in the LCC, NTS, and PVN predominantly via CCK-A receptors on vagal afferents and in the AP via vagal and nonvagal pathways, as well as CCK-B and CCK-A receptors.

Animals↗
PubMed1995

Peptide immunoreactivities in the ganglionated plexuses and nerve fibers innervating the human gallbladder.

The mammalian gallbladder is innervated by a well-developed intrinsic neural network. However, little is known about the neurochemistry and organization of the innervation of this organ in humans. The aim of this study was to analyze the distribution of immunoreactivity (IR) for the neuropeptides, vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), tachykinins (TK) and calcitonin gene-related peptide (CGRP) in the human gallbladder by means of immunohistochemistry. Neuropeptide-IRs are found in neurons and processes of the two ganglionated plexuses, i.e., the innermost plexus located in the lamina propria at the base of the mucosal folds, and the outermost plexus situated within the fibro-muscular layer. In these two plexuses, VIP-, NPY- and TK-IRs are present in ganglion cells and varicose fibers, whereas CGRP-IR is confined to nerve processes. VIP-IR is present in most, if not all, neurons. NPY- and TK-IRs are also found in many neurons. The densities of the peptide-IR nerves in the mucosa are NPY and VIP > TK >> CGRP, and in the fibro-muscular layer are NPY > VIP and TK > CGRP. The vasculature is richly innervated by NPY-IR nerves, which are mostly perivascular. CGRP-, VIP- and TK-IR processes are found only occasionally around blood vessels and in a paravascular position. Double-label studies demonstrated that a large number of VIP-containing neurons expresses NPY- or TK-IR. On the other hand, all neurons positive for either NPY- or TK-IR are immunostained for VIP. In agreement with these findings, most of the NPY-IR fibers in the lamina propria and fibro-muscular layer contain VIP-IR, and numerous TK-IR fibers are positive for VIP. However, the perivascular NPY-IR processes do not contain VIP-IR, suggesting an extrinsic origin. In addition, a population of TK-IR processes contains CGRP-IR and presumably originates from extrinsic sources, since CGRP/TK-IR intrinsic neurons could not be detected in the gallbladder. Peptide-IRs have a similar distribution in the neck, body and fundus of the gallbladder. No peptide-containing endocrine/paracrine cells are observed in the epithelium. The presence of peptide-IRs in the ganglionated plexuses and the abundance of peptidergic innervation suggest that peptides exert their effects on gallbladder function by acting directly on tissue targets and influencing intrinsic ganglion cells. Furthermore, the co-localization of more than one peptide in the same neuron raises the possibility that peptides are co-released upon stimulation and might interact at the same target.

Gallbladder↗
PubMed1995

Cholecystokinin is partly responsible for reduced food intake and body weight loss after total gastrectomy in rats.

PURPOSE: To determine the cause of body weight loss after total gastrectomy. METHODS: We evaluated the acute effect of exogenous cholecystokinin (CCK) on food intake and the chronic effect of CCK receptor blockade on food intake and body weight after total gastrectomy in rats. RESULTS: Exogenous CCK significantly reduced food intake in gastrectomized rats; this was blocked by administration of a CCK-A but not a CCK-B receptor antagonist. Chronic treatment with a CCK-A or CCK-B receptor antagonist after total gastrectomy in rats significantly increased postoperative food intake and body weight. CONCLUSION: Our data indicate that endogenous CCK is partly responsible for reduced food intake and body weight loss after total gastrectomy in rats.

Animals↗
PubMed1995

Inhibition of gastric motility induced by intestinal glucose in awake rats: role of Na(+)-glucose co-transporter.

Carbohydrates are a component of chyme that initiate feedback control of gastric emptying. The aim of the study was to investigate the mechanism by which sensors in the intestine are activated by carbohydrate to initiate intestinal feedback of gastric motor function. Intestinal perfusion with D-glucose inhibited gastric motility in awake rats. This response was reproduced by 3-O-methyl glucose, a non-metabolizable analogue of glucose that is absorbed by the Na(+)-glucose co-transporter, but not by 2-deoxy-D-glucose, and was attenuated by perfusion of the intestine with phloridzin, a competitive blocker of the Na(+)-glucose co-transporter. Feeding a high carbohydrate diet to increase the number of co-transporters reduced the response to intestinal glucose. It was concluded that activation of sensors to initiate feedback inhibition of gastric motility may be dependent either on rapid accumulation of glucose within epithelial cells or on activation of the Na(+)-glucose co-transporter.

Animals↗
PubMed1994

Fos protein expression in the nucleus of the solitary tract in response to intestinal nutrients in awake rats.

Nutrients in the intestine inhibit food intake via an action on the vagal afferent pathway. The aim of the present study was to use immunochemical detection of Fos protein-like immunoreactivity (FLI) in the brainstem to trace the neuronal pathways activated by intestinal nutrients. Perfusion of the intestine of awake rats via an indwelling duodenal catheter with iso-osmotic mannitol, hydrochloric acid or casein hydrolysate had no effect on the number of FLI neurons in the nucleus of the solitary tract (NTS). Lipid emulsion (20%) and 2.7 M glucose significantly increased the number of immunopositive cells in the NTS. There was a significant increase in the number of immunopositive cells from caudal to rostral NTS. Nutrients effective at decreasing food intake (carbohydrate and fat) produced significant increases in Fos-like immunopositive cells in the NTS.

Animals↗
PubMed1994

Laser therapy for esophageal cancer. Results and additional endoscopic treatments.

Between 1/1/1988 and 5/31/1991, we treated 96 patients with laser therapy to the esophagus. In 61 inoperable patients, laser therapy has been performed initially. In 64% of these 61 patients, laser therapy alone gave sufficient relief of symptoms until death. However, in 36% of the patients, additional endoscopical interventions had to be performed. In 14 patients (23%), a prosthesis became necessary; 13 patients (21%) needed a percutaneous endoscopical gastrostomy. We conclude that laser therapy has an important role in the treatment of esophageal cancer, but in a significant number of patients, it might not be sufficient alone.

Adult↗
PubMed1994

Gastroduodenal sensory mechanisms and CCK in inhibition of gastric emptying in response to a meal.

The ability of nutrients in the intestinal lumen to exert feedback control over the proximal gastrointestinal tract function is well recognized, yet the control mechanisms are poorly defined. There is evidence that extrinsic sensory pathways from the intestine are required to initiate this regulatory process. Furthermore, CCK appears to be involved in the gastric response to several intestinal stimuli, such as fat, carbohydrate and protein. Our hypothesis is that nutrients release CCK from the intestine, which then stimulates intestinal mucosal afferents to signal reflex changes in gastric motor function and thus inhibit gastric emptying.

Animals↗
PubMed1994

Role of spinal afferents and calcitonin gene-related peptide in the postoperative gastric ileus in anesthetized rats.

OBJECTIVE: The object of this study was to investigate the mechanisms of postoperative gastric ileus in an experimental model of abdominal surgery in anesthetized rats. SUMMARY BACKGROUND DATA: Sensory neurons partly mediate postoperative gastric ileus. Among other neuropeptides, sensory neurons contain calcitonin gene-related peptide (CGRP) and release CGRP in response to noxious stimulation. Because CGRP inhibits gastric motility, it was hypothesized that abdominal surgery stimulates sensory neurons, which then releases CGRP, thereby inhibiting gastric motility. METHODS: Postoperative ileus was induced by abdominal surgery. Gastric corpus motility was measured by an intragastric catheter. CGRP action was blocked by CGRP immunoneutralization or by a CGRP receptor antagonist. Spinal sensory neurons were ablated by application of a sensory neurotoxin (capsaicin) to the celiac and superior mesenteric ganglia. RESULTS: Abdominal surgery decreased gastric corpus motility in the first 5 minutes after abdominal surgery by 59 +/- 5% and by 24 +/- 4% during the 1st postoperative hour. Capsaicin pretreatment of the celiac and superior mesenteric ganglia, CGRP immunoneutralization, or CGRP receptor antagonism reversed the postoperative decrease in gastric corpus motility during the 1st postoperative hour by 50%, 100%, and 59%, respectively. CONCLUSIONS: These data indicate that spinal sensory neurons and CGRP partly mediate postoperative gastric ileus. CGRP may be released from spinal sensory neuron terminals in the celiac and superior mesenteric ganglia as part of an extraspinal intestinogastric inhibitory reflex activated by abdominal surgery.

Abdomen↗
PubMed1994

Small intestinal capsaicin-sensitive afferents mediate feedback inhibition of gastric emptying in rats.

Functional studies have implied the existence of small intestinal receptive mechanisms for components of chyme to mediate feedback inhibition of gastric function. However, it is not known if the sensors are in the wall of the small intestine or located at another site. The present studies evaluated the localization of receptive mechanisms mediating intestinal feedback inhibition of gastric emptying by functional ablation of intestinal capsaicin-sensitive afferents. Perfusion of the small intestine of conscious rats with hydrochloric acid (0.1 N; total amount 50 meq), glucose (1 M; total amount 90 mg), or a lipid emulsion (Intralipid 10%; total amount 50 mg) inhibited gastric emptying. One to 7 days after perfusion of the intestine with capsaicin (3.6 mumol), feedback inhibition of gastric emptying produced by acid, glucose, or lipid was inhibited 100, 59, and 42%, respectively. We conclude that acid-induced inhibition of gastric emptying is mediated entirely by small intestinal capsaicin-sensitive afferent neurons and that a major portion of the glucose-induced inhibition of gastric emptying is mediated by small intestinal afferents. However, only a minor part of the response to lipid is mediated by this pathway.

Animals↗