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R C Ritter

Publications and source records attributed to R C Ritter.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cholecystokinin and leptin act synergistically to reduce body weight.

Leptin, the product of the obese gene, reduces food intake and body weight in rats and mice, whereas administration of the gut-peptide CCK reduces meal size but not body weight. In the current experiments, we report that repeated daily combination of intracerebroventricular leptin and intraperitoneal CCK results in significantly greater loss of body weight than does leptin alone. However, leptin plus CCK treatment does not synergistically reduce the size of individual 30-min sucrose meals during this period, and the effect of leptin-CCK combination on daily chow intake, while significant, is small compared with the robust effects on body weight loss. This synergistic effect on body weight loss depends on a peripheral action of CCK and a central action of leptin. These data suggest a previously unsuspected role for CCK in body weight regulation that may not depend entirely on reduction of feeding behavior and suggest a strategy for enhancing the effects of leptin in leptin-resistant obese individuals.

Adipose Tissue↗
PubMed2000

NMDA receptor participation in control of food intake by the stomach.

We previously reported that MK-801 (dizocilpine), an antagonist of N-methyl-D-aspartate (NMDA)-type glutamate receptors, increased meal size and duration in rats. MK-801 did not increase sham feeding or attenuate reduction of sham feeding by intraintestinal nutrient infusions. These results suggested that the MK-801-induced increase in meal size did not depend on antagonism of postgastric satiety signals. Consequently, we hypothesized that the NMDA antagonist might increase food intake by directly antagonizing gastric mechanosensory signals or by accelerating gastric emptying, thereby reducing gastric mechanoreceptive feedback. To test this hypothesis, we recorded intake of 15% sucrose in rats implanted with pyloric cuffs that could be closed to prevent gastric emptying. Sucrose intake was increased when the pyloric cuffs were open, allowing the stomach to empty. However, intake was not increased when the pyloric cuffs were inflated, causing gastric retention of all ingested sucrose. Direct measurements of gastric emptying revealed that MK-801 accelerated the emptying of 5-ml loads of 0.9% NaCl and 15% sucrose. Furthermore, MK-801 also accelerated the rate of emptying of freely ingested sucrose regardless of the volume ingested. Taken together with our previous findings, these results indicate that blockade of NMDA receptors with MK-801 does not increase food intake by antagonizing gastric mechanosensation. Rather, it accelerates gastric emptying, and thereby may indirectly reduce gastric mechanoreceptive cues, resulting in prolongation of eating. Modulation of gastric emptying rate by NMDA receptors could play an important role in the control of meal sizes.

Animals↗
PubMed2000

Experimental study of the magnetic stereotaxis system for catheter manipulation within the brain.

OBJECT: The magnetic stereotaxis system (MSS) is a device designed to direct catheter tips through magnetic forces. In this study the authors tested the safety and performance of the MSS in directing catheters through a nonlinear path to obtain biopsy specimens in pig brains. METHODS: Sixteen pigs underwent biopsy of the frontal brain region with the aid of an MSS (11 pigs) or a standard stereotactic biopsy tool (five pigs). Surgical preparation consisted of placement of six fiducial markers in the skull and the creation of a burr hole for attachment of a cranial bolt and passage of the biopsy catheter. The pigs underwent magnetic resonance (MR) imaging of the head to define a biopsy target and to plan a nonlinear path. Guided by the MSS, which used nearly real-time fluoroscopic imaging fused to the preoperative MR image, the authors advanced a catheter to the biopsy target. A biopsy tool was passed through the catheter and a tissue sample was obtained. The animals were observed for 3 to 5 days postoperatively, when they were assessed for neurological abnormalities or other signs of morbidity. Actual catheter placement was within 1.5 mm of the planned path to the biopsy site, using a minimum path radius of 30 mm. The registration error associated with the use of the MSS x-ray fluoroscopy and MR imaging averaged 1.7 mm. Tissue disruption caused by the MSS was similar to that of standard stereotactic procedures. CONCLUSIONS: The MSS affords accurate and safe guidance of brain catheters in animals. The application tested here, brain biopsy, is one of a number of potential catheter-guided procedures.

Animals↗
PubMed1999

Cholecystokinin: proofs and prospects for involvement in control of food intake and body weight.

Evidence that CCK participates in the control of meal size is compelling, but the avenues by which CCK may affect daily food intake and body weight regulation are still uncertain. Although participation of brain CCK in control of food intake is acknowledged, our focus here is on participation of peripheral CCK in the control of food intake. Therefore, in this article we (1) review evidence for CCK's participation in control of meal size, (2) document involvement of CCK-A receptors located on vagal sensory neurons in control of food intake by exogenous and endogenous CCK, (3) point out apparent discrepancies in the experimental record, which auger for non-endocrine sources of CCK and non-vagal sites of CCK action, and (4) summarize recent observations, suggesting mechanisms by which CCK could participate in the control of daily food intake and body weight regulation.

Animals↗
PubMed1999

Measurement of the force required to move a neurosurgical probe through in vivo human brain tissue.

The advent of high-precision magnetic and robotic computer-controlled neurosurgery systems makes it necessary to determine the range of forces that will be encountered by the probes of such devices as they are guided through the brain tissues to intraparenchymal targets. We have measured the penetration forces on 2.5-mm spheres and the drag forces on 3.0-mm ventricular shunt catheters advanced 2.0-3.5 cm deep into in vivo human brain tissues (in patients about to have those tissues resected during epilepsy surgery) at rates of approximately 0.33 mm s-1. Penetration forces of (8 +/- 2) grams were found for the spherical probe once it passed 0.5 cm below the cortical surface, and frictional drags of (2.8 +/- 0.3) grams cm-1 were exerted on the catheters. The variable nature of these forces is discussed and the results are compared with earlier studies on experimental animal tissues and brain phantom gelatins. The implications of these results for magnetic and robotic surgery systems are considered.

Biomechanical Phenomena↗
PubMed1999

Long-term CCK-leptin synergy suggests a role for CCK in the regulation of body weight.

The gut peptide CCK is a nutrient-related signal important to the control of food intake. In the present studies, we observed that a single intraperitoneal injection of CCK (1-2 microgram/kg) given 2-3 h after intracerebroventricular leptin (2-5 microgram) reduced body weight and chow intake over the ensuing 48 h more than did leptin alone. CCK alone had no effect on either 48-h chow intake or body weight but significantly reduced feeding during a 30-min sucrose test. However, reduction of 30-min sucrose intake by CCK was not enhanced by prior intracerebroventricular leptin. The present data suggest that CCK can contribute to the regulation of body weight when central leptin levels are elevated.

Animals↗
PubMed1999

Reduced sensitivity to the satiation effect of intestinal oleate in rats adapted to high-fat diet.

When rats are maintained on high-fat diets, digestive processes adapt to provide for more efficient digestion and absorption of this nutrient. Furthermore, rats fed high-fat diets tend to consume more calories and gain more weight than rats on a low-fat diet. We hypothesized that, in addition to adaptation of digestive processes, high-fat maintenance diets might result in reduction of sensitivity to the satiating effects of fat digestion products, which inhibit food intake by activating sensory fibers in the small intestine. To test this hypothesis we measured food intake after intestinal infusion of oleic acid or the oligosaccharide maltotriose in rats maintained on a low-fat diet or one of three high-fat diets. We found that rats fed high-fat diets exhibited diminished sensitivity to satiation by intestinal infusion of oleic acid. Sensitivity to the satiation effect of intestinal maltotriose infusion did not differ between groups maintained on the various diets. Reduced sensitivity to oleate infusion was specifically dependent on fat content of the diet and was not influenced by the dietary fiber or carbohydrate content. These results indicate that diets high in fat reduce the ability of fat to inhibit further food intake. Such changes in sensitivity to intestinal fats might contribute to the increased food intake and obesity that occur with high-fat diet regimens.

Adaptation, Physiological↗
PubMed1999

Purification of two equine pepsinogens by use of high-performance liquid chromatography.

OBJECTIVES: To purify and characterize pepsinogens in equine gastric mucosa. SAMPLE POPULATION: Stomachs collected from 2 healthy horses at necropsy. PROCEDURE: After collection, stomachs were placed immediately in ice before storage at -48 C. After slow thawing, the mucosa was scraped off while the tissue was immersed in 0.1M potassium phosphate (pH 7.4) at 4 C, then was homogenized. The filtered extract was subjected to anion-exchange chromatography. Fractions that were found to contain pepsin or pepsinogen were further chromatographed. Individual fractions were tested for pepsinogen or pepsin content by monitoring proteolytic activity at pH 2 and 3, respectively. Fractions from all columns were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to confirm molecular weight of pepsinogens and pepsin. RESULTS: Two pepsinogens and at least 1 pepsin were purified from equine gastric mucosa. CONCLUSIONS: On the basis of molecular mass, equine gastric mucosa contains 2 pepsinogens. CLINICAL RELEVANCE: Results of this study will enable future development of an ELISA or radioimmunoassay for use in the diagnosis of equine gastric ulceration.

Animals↗
PubMed1998

Visceral afferent participation in delayed satiation following NMDA receptor blockade.

We previously reported that rats increase their food intake, but not water intake, following intraperitoneal (i.p.) injection of MK-801, a noncompetitive antagonist of N-methyl-D-aspartate (NMDA)-activated ion channels. The drug appears to specifically interfere with signals that participate in satiation, thereby prolonging the meal and increasing its size. The mechanism by which delayed satiation occurs is not known. However, some well-studied satiety signals are carried by visceral sensory fibers that innervate the abdominal viscera. We hypothesized that MK-801 might increase food intake by interfering with satiety signals transmitted by visceral afferent neurons. To test this hypothesis, we examined MK-801's effect on food intake in rats systemically treated with capsaicin, a neurotoxin that destroys small unmyelinated visceral afferent neurons. Capsaicin treatment significantly attenuated increased sucrose intake following MK-801. We also investigated whether the effects of MK-801 on food intake would persist in rats treated with total subdiaphragmatic vagotomies. MK-801 increased the intake of 15% sucrose by sham-vagotomized rats, while vagotomized rats did not increase their intake following MK-801. Taken together, these results support the hypothesis that capsaicin-sensitive visceral sensory neurons are involved in increased food intake following systemic NMDA receptor blockade. This, in turn, suggests that NMDA receptor activation may be an important component of the neural circuitry involved in satiation.

Animals↗
PubMed1998

Delay in meal termination follows blockade of N-methyl-D-aspartate receptors in the dorsal hindbrain.

We have reported that rats increased their intake of food, but not water, following an intraperitoneal injection of MK-801, a non-competitive antagonist of N-methyl-d-aspartate (NMDA)-activated ion channels. The antagonist appears to specifically interfere with signals that participate in meal termination (satiety), thereby prolonging the meal and increasing its size. The anatomical site at which MK-801 acts to increase food intake is not known. However, vagal sensory neurons are known to participate in satiation for food. Furthermore, NMDA receptor immunoreactivity is present in the caudal nucleus of the solitary tract (NTS) where vagal sensory fibers terminate. Therefore, we hypothesized that MK-801 might increase food intake by blocking NMDA receptors in the NTS. To test this hypothesis, we microinjected MK-801 directly into the hindbrain, immediately prior to a deprivation-induced meal of 15% sucrose. We found that sucrose intake was significantly increased following injection of MK-801 (2 microgram/3 microliter) into the fourth ventricle. When MK-801 was injected directly into the caudomedial NTS, intake was increased significantly by doses as small as 198 ng/30 nl, while equivalent injections into other hindbrain areas or the fourth ventricle did not increase food intake. These data are consistent with control of food intake by endogenous glutamate and NMDA-type glutamate receptors located in the caudomedial NTS.

Animals↗
PubMed1998

Intracerebroventricular cholecystokinin A-receptor antagonist does not reduce satiation by endogenous CCK.

Suppression of sham feeding by exogenous CCK-8 or intraintestinal oleate infusion is attenuated by peripheral administration of the CCK-A receptor antagonist, devazepide, but not by the CCK-B antagonist, L365260. Likewise, systemically administered devazepide increases food intake by real feeding rats. These results suggest that endogenous CCK participates in the reduction of food intake by intestinal oleate and ingested food. Although originally categorized as a "peripheral" receptor subtype, the CCK-A receptor is also present in the brain. In an effort to examine whether devazepide acts in the brain or in the periphery to attenuate suppression of food intake by intraintestinal oleate, we injected devazepide into the lateral or fourth cerebral ventricles of intraintestinally infused, sham-fed rats. We also compared the ability of intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) devazepide to elicit increased food intake in real feeding rats. Doses of devazepide that were sufficient to attenuate or abolish oleate-induced suppression of sham feeding, when administered i.p., failed to attenuate suppression of intake when administered i.c.v., i.p. devazepide also was more effective than i.c.v. devazepide for attenuation of the suppression of sham feeding by i.p. injection of exogenous CCK-8. Finally, i.c.v. devazepide was ineffective for increasing real food intake, whereas the same dose administered i.p. significantly increased food intake. Our results do not support participation of brain CCK-A receptors in the suppression of food intake by exogenous CCK, or by endogenous CCK released after intraintestinal oleate infusion, or food intake.

Animals↗
PubMed1998

Rats maintained on high-fat diets exhibit reduced satiety in response to CCK and bombesin.

Rats maintained on high-fat diets often exhibit increased food intake and weight gain. We hypothesized that high-fat diets might result in reduced sensitivity to hormonal signals responsible for terminating food intake--satiety signals. The intestinal hormone cholecystokinin (CCK) and the gastrointestinal neuropeptide, bombesin (BBS) both have been proposed as satiety signals. To determine whether maintenance on high-fat diets alters sensitivity to satiating effects of CCK and bombesin (BBS), rats were maintained on a low fat diet (LF), a high-fat diet that was isocaloric with the low-fat diet (HF), or one of two hypercaloric high-fat diets (HF-1, HF-2) that differed from HF and LF in fat, fiber, and total caloric content. CCK and bombesin reduced food intake significantly less in rats maintained on high-fat diets, compared to those on the low fat diet. Neither high caloric intake, which was associated with increased body weight gain on the two hypercaloric diets, nor fiber content of the diet accounted for the reduced response of HF rats to CCK. Rather, reduced sensitivity to CCK was related only to the high proportion of calories taken as fat. We also determined whether reduced CCK sensitivity was due to the maintenance on a particular diet or to the diet eaten during a CCK test. After CCK, rats maintained on LF reduced food intake more (49%) than rats maintained on HF (22%), regardless of whether they ate HF or LF during the CCK test itself. These findings indicate that maintenance of rats on high-fat diets reduces sensitivity to some peptide satiety signals. Reduced sensitivity to satiety signals might contribute to overeating and obesity often observed when rats are maintained on high-fat diets.

Animals↗
PubMed1998

Measurement of friction on straight catheters in in vitro brain and phantom material.

As part of our studies on the magnetic stereotaxis system (MSS), a means of delivering therapies to the bulk brain, we have measured the frictional forces on a thin, straight tube used to simulate a catheter. Experiments were done with a spring-loaded, stainless steel tube of 1.9-mm diameter which was passed through 5.5 cm of gelatin phantom or, alternatively, through in vitro calf brain. The dynamic response of the tube to sudden displacement of the outer end of the spring yields estimates of the tube's friction per unit length. Twenty-three runs in the two media were analyzed for the static and dynamic frictional forces exhibited. In these series the static frictional forces were found to be (0.0132 +/- 0.0012) N cm-1 [(1.32 +/- 0.12) g cm-1] of length in the gelatin phantom and (0.0079 +/- 0.0008) N cm-1 [(0.79 +/- 0.08) g cm-1] of length in brain. The kinetic friction coefficient, b, was found to be (8.4 +/- 2.1) N s m-1/cm length of catheter in brain and (16.3 +/- 7.6) N s m-1/cm length of catheter in the phantom material. Based on these figures, the MSS will be capable of moving straight catheters of similar friction that are 20-cm long at rates of displacement of 0.02 to 0.05 cm s-1 in the white and grey matter of the brain. Future studies will evaluate the forces arising from curved paths. Unanswered questions remain as to the mechanical difference between in vivo and in vitro brain, between animal and human brain, and the involvement of sulci in practical paths of motion.

Biomechanical Phenomena↗
PubMed1997

Reduced vagal sensory innervation of the small intestinal myenteric plexus following capsaicin treatment of adult rats.

To determine whether capsaicin treatment damages small intestinal vagal sensory nerve endings, we made intra-nodose injections of wheat-germ agglutinin-horseradish peroxidase conjugate (WGA-HRP) to label peripheral and central vagal endings in control and capsaicin-treated rats. Labeled intraganglionic laminar endings (IGLEs), characteristic of vagal sensory endings of the myenteric plexus, were counted. In controls IGLEs were numerous in the duodenum, less numerous in the jejunum and scarce in the ileum. In capsaicin-treated rats, IGLEs were significantly diminished in all areas of the small intestine. Capsaicin also reduced WGA-HRP activity in the medial and commissural nucleus of the solitary tract. Systemic capsaicin produces a long-lasting loss of vagal IGLEs in the small intestinal myenteric plexus. Such loss is consistent with capsaicin-induced impairment of intestinal reflexes and controls of food intake.

Analysis of Variance↗
PubMed1997

Intraintestinal capsaicin transiently reduces CGRP-like immunoreactivity in rat submucosal plexus.

Intraintestinal infusion of the sensory neurotoxin, capsaicin, transiently abolishes behavioral responses to chemical stimulation of the intestine. This desensitizing action of capsaicin may be due to an action on CGRP-containing nerve terminals, which are postulated to serve a sensory function in the enteric plexuses. To determine whether intraintestinal capsaicin treatment alters CGRP-like immunoreactivity (CGRP-li) in the enteric plexuses, we performed immunohistochemical analyses of the small intestinal submucosal and myenteric plexuses of rats at various times after intestinal infusion of capsaicin (5 mg) or its vehicle. Intestinal capsaicin treatment, but not vehicle treatment, reduced CGRP-li, but not substance-P-like immunoreactivity (SP-li), in nerve fibers of the submucosal plexus. CGRP-li was reduced in submucosal interganglionic connectives and in nerve fibers associated with submucosal blood vessels. CGRP-li of submucosal connectives was reduced by 1 h post-infusion. Reduction of CGRP-li in the submucosal fibers also was pronounced 24 h after intraintestinal capsaicin treatment. By 48 h after intestinal capsaicin infusion, CGRP-li was not distinguishable from vehicle-treated animals. There were no consistent immunohistochemical changes in CGRP-li or SP-li in the myenteric plexus at any time. These results indicate that intestinal capsaicin selectively induces transient reduction of CGRP-li in nerve fibers of the submucosal plexus. The chronology of depletion and reappearance of CGRP-li is congruent with previously reported, transient impairment of sensory function observed following intestinal capsaicin infusion.

Animals↗
PubMed1997

Preloads of corn oil inhibit independent ingestion on postnatal day 15 in rats.

The ontogenetic development of postingestive inhibitory control of ingestion by an oil preload was examined in preweaning rats. Gastric preloads (5% b.wt) of water, mineral oil or corn oil were administered 5 min before a 30-min intake test in which pups licked milk from the floor of a test chamber. Preloads of corn oil decreased intake significantly compared with preloads of mineral oil or water on Postnatal Days 15 and 18, but not on Postnatal Day 12. Because preloads of corn oil reduced intake ore than preloads of mineral oil, it is possible that the inhibitory effect of corn oil is due to its fats rather than to its oily texture. Cholecystokinin (CCK), presumably released from the small intestine, apparently mediates part of this inhibitory effect because pretreatment with devazepide, a specific CKKA antagonist, significantly reduced the inhibition produced by corn oil.

Age Factors↗
PubMed1997

The non-competitive NMDA antagonist MK-801 increases food intake in rats.

A role for excitatory amino acids in the control of feeding behavior has not been extensively investigated. Nevertheless, there is direct and circumstantial evidence to indicate that some circuits involved with feeding behavior include glutamatergic elements. To test the hypothesis that endogenous glutamate participates in the control of food intake, we performed experiments to determine whether MK-801, a non-competitive N-methyl-D-aspartate (NMDA) ion channel antagonist, is capable of altering intake of liquid and solid foods in hungry or satiated rats. Following a 16 h fast, intake of 15% sucrose was significantly enhanced by systemic treatment with MK-801. Water intake was not altered by the NMDA antagonist. Rats did not ingest more rat chow after MK-801, unless they had been fasted. When a more palatable food (cookies) was offered, MK-801 did increase intake. Thus MK-801 enhanced food intake only when feeding was initiated by food-deprivation or increased palatability. In conclusion, our results support the hypothesis that endogenous glutamate plays a role in the control of food intake. Blockade of NMDA receptor function by MK-801 may diminish or delay satiety signals, rather than initiate feeding behavior per se.

Animals↗