Infusion Of Cholecystokinin Research Articles

Heterosynaptic plasticity of the visuo-auditory projection requires cholecystokinin released from entorhinal cortex afferents.

The entorhinal cortex is involved in establishing enduring visuo-auditory associative memory in the neocortex. Here we explored the mechanisms underlying this synaptic plasticity related to projections from the visual and entorhinal cortices to the auditory cortex in mice using optogenetics of dual pathways. High-frequency laser stimulation (HFS laser) of the visuo-auditory projection did not induce long-term potentiation. However, after pairing with sound stimulus, the visuo-auditory inputs were potentiated following either infusion of cholecystokinin (CCK) or HFS laser of the entorhino-auditory CCK-expressing projection. Combining retrograde tracing and RNAscope in situ hybridization, we show that Cck expression is higher in entorhinal cortex neurons projecting to the auditory cortex than in those originating from the visual cortex. In the presence of CCK, potentiation in the neocortex occurred when the presynaptic input arrived 200 ms before postsynaptic firing, even after just five trials of pairing. Behaviorally, inactivation of the CCK+ projection from the entorhinal cortex to the auditory cortex blocked the formation of visuo-auditory associative memory. Our results indicate that neocortical visuo-auditory association is formed through heterosynaptic plasticity, which depends on release of CCK in the neocortex mostly from entorhinal afferents.

Kinetics of Gallbladder Emptying During Cholecystokinin Cholescintigraphy as an Indicator of In Vivo Hormonal Sensitivity.

Cholecystokinin cholescintigraphy is used clinically to quantify gallbladder ejection fraction as an indicator of functional gallbladder disorder. It can also provide the opportunity to quantify an individual's responsiveness to the physiologic stimulant of gallbladder contraction, cholecystokinin, which is a major regulator of appetite and postprandial satiety. Methods: In the current work, we use cholecystokinin cholescintigraphy to quantify the kinetics of gallbladder emptying, including average and peak rates, in response to a standard cholecystokinin infusion. Results: We demonstrated that patients with no gallstones or biliary obstruction who empty their gallbladders completely in response to cholecystokinin, having an ejection fraction greater than 80%, exhibit a broad range of sensitivity to this hormone. Three distinct kinetic profiles were observed, with those most sensitive to cholecystokinin achieving the earliest peak and the fastest rate of gallbladder emptying, whereas those least sensitive to cholecystokinin have the latest peak and the slowest rate of emptying. Conclusion: Patients can have abnormal cholecystokinin stimulus-activity coupling as an effect of endogenous negative allosteric modulation by membrane cholesterol. This was predicted in ex vivo studies but has not, to our knowledge, previously been demonstrated in vivo. This type of kinetic analysis provides a tool to quantify cholecystokinin responsiveness in patients and identify patients who might benefit from a drug that would positively modulate cholecystokinin action to improve their appetite regulation and to better control their weight.

Role of capsaicin-sensitive peripheral sensory neurons in anorexic responses to intravenous infusions of cholecystokinin, peptide YY-(3-36), and glucagon-like peptide-1 in rats.

Cholecystokinin (CCK)-induced suppression of feeding is mediated by vagal sensory neurons that are destroyed by the neurotoxin capsaicin (CAP). Here we determined whether CAP-sensitive neurons mediate anorexic responses to intravenous infusions of gut hormones peptide YY-(3-36) [PYY-(3-36)] and glucagon-like peptide-1 (GLP-1). Rats received three intraperitoneal injections of CAP or vehicle (VEH) in 24 h. After recovery, non-food-deprived rats received at dark onset a 3-h intravenous infusion of CCK-8 (5, 17 pmol·kg⁻¹·min⁻¹), PYY-(3-36) (5, 17, 50 pmol·kg⁻¹·min⁻¹), or GLP-1 (17, 50 pmol·kg⁻¹·min⁻¹). CCK-8 was much less effective in reducing food intake in CAP vs. VEH rats. CCK-8 at 5 and 17 pmol·kg⁻¹·min⁻¹ reduced food intake during the 3-h infusion period by 39 and 71% in VEH rats and 7 and 18% in CAP rats. In contrast, PYY-(3-36) and GLP-1 were similarly effective in reducing food intake in VEH and CAP rats. PYY-(3-36) at 5, 17, and 50 pmol·kg⁻¹·min⁻¹ reduced food intake during the 3-h infusion period by 15, 33, and 70% in VEH rats and 13, 30, and 33% in CAP rats. GLP-1 at 17 and 50 pmol·kg⁻¹·min⁻¹ reduced food intake during the 3-h infusion period by 48 and 60% in VEH rats and 30 and 52% in CAP rats. These results suggest that anorexic responses to PYY-(3-36) and GLP-1 are not primarily mediated by the CAP-sensitive peripheral sensory neurons (presumably vagal) that mediate CCK-8-induced anorexia.

Ultrasound Evaluation of Gallbladder Dyskinesia: Comparison of Scintigraphy and Dynamic 3D and 4D Ultrasound Techniques

The purpose of this study was to determine the efficacy of 3D and 4D ultrasound in correlation with hepatoiminodiacetic acid (HIDA) scanning for calculating gallbladder ejection fraction (EF). A prospective study was conducted with 40 adult patients with suspected gallbladder dyskinesia. Cholecystokinin-provoked (99m)Tc-HIDA scintigraphy was performed, and concurrent 3D and 4D ultrasound images of the gallbladder were obtained before cholecystokinin infusion and 20, 30, and 40 minutes after infusion. The EF values calculated from the ultrasound images and HIDA scan were compared. The gallbladder EF values (mean ± standard error of the mean) calculated 20 minutes after cholecystokinin infusion from HIDA scans and 3D and 4D ultrasound images were 54.1% ± 5.0%, 58.9% ± 6.3%, and 62.8% ± 5.5%. Thirty minutes after infusion the EF values were 56.3% ± 4.7%, 56.9% ± 5.7%, and 59.1% ± 4.6%. The numbers of patients with an EF less than 50% were 14, 12, and 13, and the numbers with an EF less than 35% were 10, seven, and eight. For the patients with an EF less than 50%, the kappa agreement between HIDA scanning and 3D ultrasound was 0.89 (95% CI, 0.73-1.00), between HIDA scanning and 4D ultrasound was 0.83 (95% CI, 0.65-1.00), and between 3D and 4D ultrasound was 0.83 (95% CI, 0.64-1.00). Both 3D and 4D ultrasound techniques correlate well with HIDA scanning for calculating gallbladder EF in patients with suspected biliary dyskinesia.

Block by Nitrate Tolerance of Meal-Induced Insulin Sensitization in Conscious Rabbits

Hemodynamic nitrate tolerance has been shown to result in an insulin-resistant state. We studied whether nitrate tolerance induced by a 7-day continuous exposure to transdermal nitroglycerin influenced the meal-induced insulin sensitization phenomenon in rabbits. Changes in insulin sensitivity in response to feeding in conscious rabbits were determined by rapid insulin sensitivity test, in both nitrate-tolerant and nitrate-intolerant animals. In a separate series of experiments with anesthetized rabbits with or without nitrate tolerance, the hyperinsulinemic euglycemic glucose clamping methods was used to study the effect of intraportal infusion of cholecystokinin (CCK) on whole-body insulin sensitivity. Rabbits with normal feeding exhibited a 46 ± 6% increase in insulin sensitivity as compared with their matching fasting controls. A 7-day period of treatment with patches releasing 0.07 mg of nitroglycerin per hour yielded nitrate tolerance and a state of insulin resistance and no increase in insulin sensitivity in response to food. Intraportal infusion of CCK8 (0.3-3.0 μg/kg over 20 minutes) resulted in a dose-dependent increase in insulin sensitivity in normal but not in nitrate-tolerant, fasted anesthetized animals. Nitrate tolerance blocks both the meal-induced insulin sensitization phenomenon and the insulin-sensitizing effect of intraportal CCK.

Circulating GLP-1 and CCK-8 reduce food intake by capsaicin-insensitive, nonvagal mechanisms

Previous reports suggest that glucagon-like peptide (GLP-1), a peptide secreted from the distal small intestine, is an endocrine satiation signal. Nevertheless, there are conflicting reports regarding the site where circulating GLP-1 acts to reduce food intake. To test the hypothesis that vagal afferents are necessary for reduction of food intake by circulating GLP-1, we measured intake of 15% sucrose during intravenous GLP-1 infusion in intact, vagotomized, and capsaicin-treated rats. We also measured sucrose intake during intravenous infusion of cholecystokinin, a peptide known to reduce food intake via abdominal vagal afferents. We found that reduction of intake by GLP-1 was not diminished by capsaicin treatment or vagotomy. In fact, reduction of sucrose intake by our highest GLP-1 dose was enhanced in vagotomized and capsaicin-treated rats. Intravenous GLP-1 induced comparable increases of hindbrain c-Fos immunoreactivity in intact, capsaicin-treated, and vagotomized rats. Plasma concentrations of active GLP-1 in capsaicin-treated rats did not differ from those of controls during the intravenous infusions. Finally, capsaicin treatment was not associated with altered GLP-1R mRNA in the brain, but nodose ganglia GLP-1R mRNA was significantly reduced in capsaicin-treated rats. Although reduction of food intake by intraperitoneal cholecystokinin was abolished in vagotomized and capsaicin-treated rats, reduction of intake by intravenous cholecystokinin was only partially attenuated. These results indicate that vagal or capsaicin-sensitive neurons are not necessary for reduction of food intake by circulating (endocrine) GLP-1, or cholecystokinin. Vagal participation in satiation by these peptides may be limited to paracrine effects exerted near the sites of their secretion.

Nuclear medicine hepatobiliary imaging (cholescintigraphy)

Nuclear medicine hepatobiliary imaging (cholescintigraphy)

Effect of feeding fat or intrajugular infusion of glucagon-like peptide-1 and cholecystokinin on dry matter intake, digestibility, and digesta rate of passage in growing wethers1

A cause and effect relationship between glucagon-like peptide 1 (7, 36) amide (GLP-1) and cholecystokinin (CCK) and DMI regulation has not been established in ruminants. Three randomized complete block experiments were conducted to determine the effect of feeding fat or infusing GLP-1 or CCK intravenously on DMI, nutrient digestibility, and Cr rate of passage (using Cr(2)O(3) as a marker) in wethers. A total of 18 Targhee × Hampshire wethers (36.5 ± 2.5 kg of BW) were used, and each experiment consisted of four 21-d periods (14 d for adaptation and 7 d for infusion and sampling). Wethers allotted to the control treatments served as the controls for all 3 experiments; experiments were performed simultaneously. The basal diet was 60% concentrate and 40% forage. In Exp. 1, treatments were the control (0% added fat) and addition of 4 or 6% Ca salts of palm oil fatty acids (DM basis). Treatments in Exp. 2 and 3 were the control and 3 jugular vein infusion dosages of GLP-1 (0.052, 0.103, or 0.155 µg•kg of BW(-1)•d(-1)) or CCK (0.069, 0.138, or 0.207 µg•kg of BW(-1)•d(-1)), respectively. Increases in plasma GLP-1 and CCK concentrations during hormone infusions were comparable with increases observed when increasing amounts of fat were fed. Feeding fat and infusion of GLP-1 tended (linear, P = 0.12; quadratic, P = 0.13) to decrease DMI. Infusion of CCK did not affect (P > 0.21) DMI. Retention time of Cr in the total gastrointestinal tract decreased (linear, P < 0.01) when fat was fed, but was not affected by GLP-1 or CCK infusion. In conclusion, jugular vein infusion produced similar plasma CCK and GLP-1 concentrations as observed when fat was fed. The effects of feeding fat on DMI may be partially regulated by plasma concentration of GLP-1, but are not likely due solely to changes in a single hormone concentration.

Nuclear Medicine Hepatobiliary Imaging

Nuclear medicine hepatobilary imaging (HIDA) is a time proven imaging methodology that uses radioactive drugs and specialized cameras to make imaging diagnoses based on physiology. HIDA radiopharmaceuticals are extracted by hepatocytes in the liver and cleared through the biliary system similar to bilirubin. The most common indication for HIDA imaging is acute cholecystitis, diagnosed by nonfilling of the gallbladder due to cystic duct obstruction. HIDA can detect high grade biliary obstruction prior to ductal dilatation; images reveal a persistent hepatogram without biliary clearance due to the high backpressure. HIDA also aids in the diagnosis of partial biliary obstruction due to stones, biliary stricture, and sphincter of Oddi obstruction. It can confirm biliary leakage postcholecystectomy and hepatic transplantation. Calculation of a gallbladder ejection fraction after cholecystokinin infusion is commonly used to diagnose chronic acalculous gallbladder disease. Diseased gallbladders do not contract. There are many other less common but valuable diagnostic indications for HIDA imaging.

Evaluation and management of functional biliary pain in patients with an intact gallbladder

The diagnosis and management of suspected functional biliary pain in patients with an intact gallbladder remains contentious. Major issues include the lack of a clear definition of what constitutes biliary pain, a poor understanding of its natural history and pathophysiology, and the all too common scenario of the patient who has persistent pain despite surgical removal of the gallbladder. As a consequence, symptoms alone have generally been considered to be unreliable in the diagnosis of gallbladder dysfunction, and this has led to a search for a reliable test to help confirm a clinical suspicion of gallbladder dysfunction prior to the definitive treatment, cholecystectomy. At present, cholecystokinin-cholescintigraphy with a calculation of the gallbladder ejection fraction is the most commonly used test; however, its utility in predicting symptom outcome after cholecystectomy has been questioned. The use of cholecystokinin-cholescintigraphy to determine the appropriateness for cholecystectomy appears to be most useful when performed using a slow infusion of cholecystokinin in a well-selected patient population. However, for reasons explained herein, consideration of cholecystectomy on the basis of high clinical suspicion after adequate follow-up with trials of pharmacological therapies and exclusion of other disease entities, together with counseling the patient on postoperative expectations, may be a reasonable alternative.

Sphincter of Oddi dysfunction in children with recurrent abdominal pain: 5‐year follow‐up after endoscopic sphincterotomy

Sphincter of Oddi (SO) dysfunction has not been reported as a cause of recurrent abdominal pain (RAP) in children. We present a 5-year follow-up of a group of children with RAP and manometry proven SO dysfunction. Retrospective chart review of children who underwent SO manometry and endoscopic sphincterotomy (ES) for recurrent abdominal pain. Long-term follow-up was obtained by telephone survey. Eleven of the 12 children had abdominal pain; one had reproducible postprandial discomfort. Five children localized the pain to the upper abdomen. The same number of children had associated nausea or vomiting. On hepatobiliary scintigraphy study, three children had SO dysfunction type curve, four had low ejection fraction and nine had reproduction of symptoms on cholecystokinin (CCK) infusion. SO manometry revealed elevated pressure in 11 children. The remaining child had paradoxical contraction of the SO. On short-term follow-up, eight children had resolution of symptoms after ES, three did not respond and one had recurrence of symptom in 6 months. Children symptomatic for less than 1 year were more likely to respond to ES (P < 0.01). All children with upper abdominal pain with nausea and/or vomiting, postprandial pain and SO type scintiscan curve responded to ES. On long-term follow-up, seven of the eight responders to ES remained symptom free, one recurred with irritable bowel syndrome-like symptoms. One child with recurrent symptoms had resolution after cholecystectomy and another non-responder improved after an appendectomy. SO dysfunction is an uncommon but treatable cause of RAP in children. Awareness of this condition may help a segment of children with RAP.

Cholecystokinin- and gastrin-induced protein and amylase secretion from the parotid gland of the anaesthetized rat

I.V. infusion of pentagastrin (20 μg/kg/h) or cholecystokinin (CCK)-8 (1 μg/kg/h) for 10 min caused secretion of salivary proteins from the parotid gland in the anaesthetized rat without any accompanying overt fluid secretion. This “occult” response was revealed by a subsequent wash-out injection of methacholine (5 μg/kg, I.V.) 10 min after the end of the infusion period (aiming at avoiding synergistic interactions). While the fluid response to methacholine was unaffected by the preceding infusion of pentagastrin and CCK-8, the output of protein increased by 147% (pentagastrin) and 74% (CCK-8) and that of amylase by 45% (CCK-8) compared to the responses to methacholine upon saline infusion. Those increases were abolished by the CCK-A receptor blocker (lorglumide), but not by the CCK-B receptor blocker (itriglumide). Evisceration, combined sympathetic and parasympathetic denervation of the glands and assay under adrenoceptor blockade excluded contribution from the gastro-intestinal tract, central or ganglionic mechanisms and circulating catecholamines to the increase in protein/amylase. Furthermore, Western blot demonstrated CCK receptors for both A and B subtypes in normal and chronically denervated glands. In the submandibular gland, both pentagastrin and CCK-8 evoked a trace secretion of saliva but, under the present experimental set-up, no statistically significant increase in protein output. Thus, in addition to the autonomic nervous system, gastrointestinal hormones may, in some types of glands, be involved in the secretion of salivary gland proteins.

IV Hypertonic Glucose Stimulates the Exocrine Pancreas in Rat

Pancreatic atrophy and dysfunction resulting from parenteral nutrition (PN) may be explained by several mechanisms; one of the important factors is the nutrient in the circulation, which affects the pancreatic growth and secretion. The effect of nutrients on the pancreatic exocrine still has controversies. The aim of the present study is to better understand the effect of i.v. glucose on the exocrine pancreas stimulated by cholecystokinin during the parenterally fed condition. Two mixed solutions consisting of 30% and 50% glucose, respectively, were used. Thirty male Sprague-Dawley rats were randomly divided into 5 groups, including a control group; a freely fed group received cholecystokinin; 2 groups were infused with 30% and 50% glucose, and a group was infused with 50% glucose with cholecystokinin. The body weight and pancreatic contents were measured after 10 days. The body weight in all groups was increased but lower than in the freely fed rats. I.v. glucose caused a decrease in the pancreatic weight, the amount of the pancreatic protein and DNA, and the level of amylase but elevated the level of trypsin in all treated groups. The enzymes were elevated after infusion of cholecystokinin with glucose, but they were lower than in freely fed animals with cholecystokinin. Compared with 30% glucose, 50% glucose elevated the level of amylase but did not affect the level of trypsin. I.v. glucose results in atrophy of the exocrine pancreas, elevates the amylase in pancreas, but suppresses the stimulatory effect of cholecystokinin on the exocrine pancreas.

Controversies Concerning Pathophysiology and Management of Acalculous Biliary-Type Abdominal Pain

Acalculous biliary-type abdominal pain is a commonly encountered clinical problem whose pathophysiology is unclear and evaluation and management are controversial. Cholecystokinin cholescintigraphy to measure the gallbladder ejection fraction (GEF) has been advocated as a criterion for cholecystectomy. However, there is no consensus regarding the dose and rate of infusion of cholecystokinin, both of which can alter the GEF, and the definition of an abnormal ejection fraction varies among studies. Many but not all studies have concluded that a low GEF predicts good outcomes after cholecystectomy, but most studies suffer from poor methodology and there is only one prospective randomized controlled trial. Also, some patients with a normal GEF have responded to cholecystectomy. Another controversial area has been the role of sphincter of Oddi dysfunction (SOD) in patients with biliary-type pain and gallbladder in situ. Some reports suggest an overlap between SOD and low GEF, although a causal relationship has not been established. Yet another subject of interest is the role of visceral hyperalgesia in patients with acalculous biliary-type pain. We have reviewed the relevant literature relating to these issues and have highlighted the controversial aspects. In the absence of high-quality studies, an evidence-based treatment algorithm is difficult to design but will be proposed. More prospective controlled trials are warranted to better define the appropriate evaluation and management of patients with this syndrome.

The role of luminal gastrin in the regulation of pancreatic juice secretion in preruminant calves

The effect of luminal gastrin on the secretion of pancreatic juice was studied in seven conscious preruminant calves employing luminal infusions of gastrin and cholecystokinin (CCK)-9 and pharmacological CCK 1 and CCK 2 receptor blocks with antagonists. The study was performed in the preprandial and prandial states. Pharmacological blocking of the CCK 2 receptor, like that of the CCK 1 receptor, resulted in reduction of pancreatic postprandial secretion and increased the duration of the prandial pattern of duodenal electrical activity. Exogenous luminal gastrin, like luminal CCK-9, enhanced the secretion of pancreatic juice proteins, though the overall effect of gastrin was weaker than that of CCK-9. The effect was inhibited by infusion of CCK 2 but also by CCK 1 receptor antagonist. In conclusion, duodenal luminal gastrin can stimulate exocrine pancreatic secretion by a mechanism that depends on CCK 2 receptors in calves. Involvement of the CCK 1 receptor in this mechanism needs further investigation. Prandial pancreatic secretory and duodenal motility cycles can be regulated by endogenous gastrin release.

Does gallbladder ejection fraction predict outcome after cholecystectomy for suspected chronic acalculous gallbladder dysfunction? A systematic review.

The clinical utility of cholecystokinin-cholescintigraphy with calculation of a gallbladder ejection fraction (GBEF) in patients with suspected chronic acalculous gallbladder dysfunction (CAGD) remains controversial. It was our aim to critically evaluate the literature on the utility of the GBEF to predict outcome of patients with suspected CAGD. We performed an electronic search of the MEDLINE database for articles published between 1980 and 2002 and a manual search of references from bibliographies of identified articles. Only articles in English that concerned adults were screened. Data extracted included both qualitative and quantitative data reported on the study groups, cholescintigraphic technique, interventions, treatment outcomes, and trial methodologic characteristics. Twenty-three publications met the inclusion criteria. All were considered of poor methodologic quality. All but three studies were retrospective case series, only one was randomized, and none were adequately blinded, used adequate controls, or enrolled a sufficient number of patients. Five studies used a cut-off value for an abnormal GBEF that was different than the value used by the others, one study did not provide a cut-off value, and several did not report details of the cholescintigraphic technique (namely, the rate of cholecystokinin infusion). Studies varied in their outcome measures and the criteria for success. The overall assessment of outcome in 19 studies concluded that calculation of a GBEF was useful in patients with suspected CAGD. The low methodologic quality of the studies precluded a meta-analysis approach to the data. Use of a calculated GBEF to diagnose and predict treatment outcome in suspected CAGD has not been adequately studied. Although most studies report utility of GBEF in predicting symptom outcome after cholecystectomy in patients with suspected CAGD, quality evidence is lacking, thereby precluding a definitive recommendation regarding its use. More high quality trials are needed.

Elevated plasma cholecystokinin and appetitive ratings after consumption of a liquid meal in humans

Objective This study had two objectives. The first was to evaluate the possibility that, in a previous study, a soup preload augmented the reduction of food intake in a test meal induced by an exogenous infusion of cholecystokinin (CCK) because the soup also endogenously released CCK. The second was to compare CCK release by soup between men and women to determine whether the increased satiating effectiveness of soup in women as opposed to men could have been partly attributable to differences in CCK release. Methods By using a bioassay that measures all of its known isoforms, we determined plasma CCK levels at baseline and at several times postprandially in eight healthy, non-obese men and women (four of each sex). Each subject ingested 800 g of tomato soup, which was followed 30 min later by 300 g of a yogurt shake. Appetitive ratings were also collected and related to CCK levels. Results Ingestion of tomato soup significantly increased plasma CCK levels by 3.81 pmol/L (± 1.21 standard error, P = 0.016) over baseline within 30 min in all subjects combined. When CCK concentrations at 5 min after soup and 5 min after yogurt were averaged, the women’s mean averaged concentration was 5.58 pmol/L (± 1.994, t = 2.80, P = 0.0073) higher than the men’s. The elevated levels persisted but did not rise further upon consumption of the yogurt shake. Hunger ratings declined and fullness ratings increased after eating, although patterns of ratings did not match exactly patterns of CCK release. Conclusions A large quantity of tomato soup stimulates significant CCK release; therefore, some of the satiating effects of soup preloads could have been mediated by an elevation in endogenous CCK.

Second harmonic imaging improves trans-abdominal ultrasound detection of biliary sludge in 'idiopathic' pancreatitis.

Recently, biliary sludge has been strongly correlated with 'idiopathic pancreatitis'. It is often diagnosed by trans-abdominal ultrasonography, despite the low sensitivity of this investigation. New scanners, using second harmonic imaging, may improve the quality of the echographic picture. To verify the impact of this methodology on the detection of biliary sludge in patients with 'idiopathic' pancreatitis. Fifty patients with 'idiopathic' pancreatitis observed over a 18-month period entered the study. Exclusion criteria were gall-bladder stones, polyps, clinical conditions related to biliary sludge development and haemolytic disorders. Patients were assessed blind by two operators using either conventional ultrasonography or second harmonic imaging. The parameters of diagnostic quality of both examinations were evaluated using, as the gold standard, microscopic examination of the gall-bladder content collected at endoscopy after cholecystokinin infusion. An improvement in sensitivity, specificity, efficiency and negative predictive value was obtained by second harmonic imaging compared with conventional ultrasonography. Second harmonic imaging, in our experience, is a reliable non-invasive tool for the diagnosis and follow-up of biliary sludge in the course of 'idiopathic' pancreatitis.

Effects of acute cholecystokinin infusion on hemispheric EEG asymmetry and coherence in healthy volunteers

This study investigated the effects of continuous slow infusion of cholecystokinin tetrapeptide (CCK-4), a neuropeptide with panicogenic properties, on functional hemispheric differences, as indexed by quantitative electroencephalographic (EEG) asymmetry and coherence measures. Twenty-four adult volunteers (15 females and 9 males) were assigned to infusion with either placebo or CCK-4 in a randomized, double-blind, parallel-group design, with EEG being recorded before and during (10 and 40 min) a 60-min infusion period. No significant treatment differences were observed for absolute EEG power but, compared to placebo, CCK-4 infusion increased asymmetry and reduced coherence of slow-wave activity at midtemporal recording sites. These findings support the contention that functional imbalance of the temporal cortex, perhaps mediated by CCK-4, is involved in panic disorder (PD).

Impaired renal D(1)-like and D(2)-like dopamine receptor interaction in the spontaneously hypertensive rat.

D(1)-like (D(1), D(5)) and D(2)-like (D(2), D(3), D(4)) dopamine receptors interact in the kidney to produce a natriuresis and a diuresis. Disruption of D(1) or D(3) receptors in mice results in hypertension that is caused, in part, by a decreased ability to excrete an acute saline load. We studied D(1)-like and D(2)-like receptor interaction in anesthetized spontaneously hypertensive rats (SHR) by the intrarenal infusion of Z-1046 (a novel dopamine receptor agonist with rank order potency of D(3)> or =D(4)>D(2)>D(5)>D(1)). Z-1046 increased glomerular filtration rate (GFR), urine flow, and sodium excretion in normotensive Wistar-Kyoto rats but not in SHRs. The lack of responsiveness to Z-1046 in SHRs was not an epiphenomenon, because intrarenal cholecystokinin infusion increased GFR, urine flow, and sodium excretion to a similar extent in the two rat strains. We conclude that renal D(1)-like and D(2)-like receptor interaction is impaired in SHRs. The impaired D(1)-like and D(2)-like receptor interaction in SHRs is not caused by alterations in the coding sequence of the D(3) receptor, the D(2)-like receptor expressed in rat renal tubules that has been shown to be involved in sodium transport. Because the diuretic and natriuretic effects of D(1)-like receptors are, in part, caused by an interaction with D(2)-like receptors, it is possible that the decreased Z-1046 action in SHRs is secondary to the renal D(1)-like receptor dysfunction in this rat strain.