Plasma Cholecystokinin Levels Research Articles

Evaluation of plasma cholecystokinin levels and gallbladder functions in hyperemesis gravidarum: a prospective cohort study

This is a prospective cohort study aimed to compare women treated due to hyperemesis gravidarum (HG) (n = 24) to women with normal pregnancy attending regular antenatal outpatient care (n = 22) in terms of fasting and post-prandial cholecystokinin (CCK) levels, and gallbladder (GB) functions. The Pregnancy-Unique Quantification of Emesis (PUQE) scores, fasting and postprandial CCK levels, and ultrasonographic GB parameters were recorded at admission before any treatment. The median PUQE score in the study group was 8. There were no statistically significant differences in GB parameters (p>.05), and fasting and postprandial CCK levels between the groups (p=.851, p=.395, respectively). Fasting CCK levels were positively correlated with postprandial GB volume (PGv) (p=.022, r = 0.464). Although GB contractility is compromised during pregnancy, HG does not cause further GB impairment. The positive correlation between fasting CCK levels and PGv requires further evaluation. Impact Statement What is already known on this subject? The pathophysiology of hyperemesis gravidarum (HG) remains poorly understood. Altered cholecystokinin (CCK) levels may have potential consequences on gastric emptying, which may be related to nausea and vomiting. In this context, alterations in CCK secretion in women diagnosed with HG have been previously reported, and alterations in CCK levels lead to impaired gallbladder (GB) functions. What do the results of this study add? CCK levels and GB functions in pregnant women with HG are not statistically significantly different from those in healthy pregnant women. What are the implications of these findings for clinical practice and/or further research? Further studies designed in patients with different severities of HG and larger sample sizes are required for a better understanding of HG pathophysiology.

Changes in plasma levels of cholecystokinin, neurotensin, VIP and PYY in gastric and colorectal cancer – Preliminary results

Physiological roles of enterohormones such as secretion, absorption and digestion were supported by clinical data. Overexpression of cholecystokinin (CCK), neurotensin (NT) and vasoactive intestinal peptide (VIP) receptors occur in gastrointestinal (GI) malignancies. The aim of the paper was to compare plasma levels of CCK, peptide YY (PYY), VIP and NT in patients with gastrointestinal malignancies and healthy controls. The study included 80 patients (37 men and 43 women) with GI malignancies (20 with gastric and 60 with colorectal cancers). Median age of the patients was 62.9 years (range: 40–85 years). Control group was comprised of 30 healthy persons with median age 59.8 years (range: 40–82 years). Fasting plasma concentrations of CKK, PYY, NT, and VIP were determined at rest, using ELISA kits for automated systems. Comparative analysis of enterohormone levels in patients with various types of gastrointestinal malignancies demonstrated presence of some cancer-specific alterations. Patients with gastric cancers presented with lower plasma concentrations of CCK than healthy controls and individuals from colorectal cancers (p = 0.02). The highest plasma concentrations of neurotensin was found in colorectal cancer patients in comparison to gastric (p = 0.02). The plasma levels of VIP observed in gastric cancer group were lower than in colorectal cancer patients (p = 0.01). Patients with GI malignancies may present with tumor-specific alterations in plasma enterohormone levels.

Effects of Sleeve Gastrectomy on Blood Pressure and the Renal Renin-Angiotensin System in Rats with Diet-Induced Obesity.

Sleeve gastrectomy (SG) has been reported to decrease blood pressure (BP), although the reason has not been revealed. The present study aimed to establish the reason why SG decreases BP. Male Sprague-Dawley rats were subjected to surgical (sham operation or SG) and dietary interventions (fed a normal diet or high-fat diet ad libitum or fed by pair-feeding [PF]). Systolic BP (SBP), urinary sodium excretion, and endocrine parameters were examined 4weeks after surgery. Both SG and PF rats had reduced body weight compared with SO rats fed normal diet or high-fat diet ad libitum. SG rats exhibited a reduction in SBP compared with PF, which was associated with a reduction in renal renin, angiotensin II, and catechol-O-methyltransferase levels (P<0.01 for each). SG increased plasma cholecystokinin (CCK) levels compared with PF (P<0.0001 for each), whereas glucagon-like peptide 1 and peptide YY were not changed in fasting. Exogenous administration of CCK reduced renal catechol-O-methyltransferase (P=0.0233), renin (P<0.0001), and angiotensin II (P<0.0001) levels and SBP (P=0.0053). SG reduced SBP, at least in part, through suppression of sympathetic nerve action by elevation of CCK, which was followed by suppression of the intrarenal renin-angiotensin system.

Role of ghrelin in the pancreatic exocrine secretion via mitogen-activated protein kinase signaling in rats

BackgroundThis study was performed to investigate the impact of exogenous ghrelin on the pancreatic α-amylase outputs and responses of pancreatic proteins to ghrelin that may relate to pancreatic exocrine.MethodsSprague-Dawley male rats (9 weeks old, 300 ± 10 g) were injected with ghrelin via intraperitoneal (i.p.) infusion at dosage of 0, 0.1, 1.0 and 10.0 μg/kg body weight (BW), respectively. The plasma ghrelin and cholecystokinin (CCK) level were determined using enzyme immunoassay kit; the mRNA expression of ghrelin receptor (GHSR-1α) and growth hormone (GH) receptor were assessed by reverse transcription PCR; the expressions of pancreatic α-amylase activity, extracellular-signal-regulated kinases (ERK), phosphorylated extracellular-signal-regulated kinases (pERK) and c-Jun N-terminal kinase (JNK) were evaluated by western blotting; moreover the responses of pancreatic proteins to ghrelin were analyzed using the two-dimensional gel electrophoresis system.ResultsThe exogenous ghrelin (1.0 and 10.0 μg/kg BW) elevated the level of plasma ghrelin (p < 0.05), and suppressed the expression of pancreatic α-amylase at a dose of 10.0 μg/kg BW (p < 0.05). No difference in the level of plasma CCK was observed, even though rats were exposed to any dose of exogenous ghrelin. In addition, a combination of western blot and proteomic analysis revealed exogenous ghrelin (10.0 μg/kg BW) induced increasing the JNK and ERK expressions (p < 0.05) and four proteins such as Destrin, Anionic trypsin-1, Trypsinogen, and especially eukaryotic translation initiation factor 3 in rat pancreas.ConclusionsTaken together, exogenous ghrelin by i.p. infusion plays a role in the pancreatic exocrine secretion via mitogen-activated protein kinase signaling pathway.

Cholecystokinin as a potent diagnostic marker for gastric cancer

There is no early diagnosis marker for gastric cancer even though the gastric cancer is the second cause of deaths in East Asia. The aim of the current research is to develop a new diagnostic marker of gastric cancer. Commercially available ELISA kits were used to evaluate the peptide levels in plasma collected from Korean healthy and gastric cancer patients. About 1.5 fold decreased plasma cholecystokinin levels were measured in gastric cancer patients (n=75) than in healthy controls (n=36). Plasma cholecystokinin has no age, sex, and disease-dependent variation in control and patients sample. Receiver-operating characteristic curve analysis assessing the performance of cholecystokinin levels as the sensitivity of 94.7% and specificity of 100 % compared to healthy controls. These findings suggest plasma cholecystokinin as a useful biomarker for diagnosis of gastric cancer.

Dose-dependent effect of ghrelin on gastric emptying in rats and the related mechanism of action

The aim of this study was to investigate the dose-dependent effect of ghrelin on gastric emptying in rats and the related mechanism of action. Sixty Wistar rats were randomized into control and test groups, which respectively received intraperitoneal injection of normal saline and ghrelin at different doses (0.5 nmol/kg, 1.0 nmol/kg, 1.5 nmol/kg, 2.0 nmol/kg, and 2.5 nmol/kg). After 45 minutes, all rats were gavaged with semisolid paste. The gastric emptying rate was determined 30 minutes later, and the plasma cholecystokinin level was tested by radioimmunoassay. The mean gastric emptying rate in the test groups was significantly higher than in the control group (38.24 ± 7.15% and 27.18 ± 2.37%, respectively, p < 0.05). Medium and high doses of ghrelin (1.0 nmol/kg, 1.5 nmol/kg, 2.0 nmol/kg, and 2.5 nmol/kg), but not low dose (0.5 nmol/kg), accelerated the gastric emptying. In addition, the plasma cholecystokinin level in the test groups was significantly higher than in the control group (p < 0.01). The gastric emptying rate was positively correlated with the plasma cholecystokinin level (p < 0.01). Intraperitoneal injection of ghrelin at medium and high doses significantly accelerated gastric emptying in rats.

Obestatin and Ghrelin May Have a Complementary Function During Acute and Chronic Period in Mice.

Obestatin is described as an anorexigenic peptide, and has adverse effects of ghrelin. It has no inhibitory effects on acute/chronic food intake, and it has been reported by several researchers. The role of obestatin in metabolism is still not clear. In the present study, the purpose is to determine the effects of chronically administrated obestatin. For this purpose, (1 µmol/kg; i.p.) or ghrelin (1 µmol/kg; i.p.) and food restriction (24h fast:24h fed) on plasma obestatin, ghrelin, leptin, insulin, cholecystokinin (CCK) and glucose levels, and body weight gain were investigated for 14 days in mice. Additionally, mice were treated with acute ip (100 nmol/kg) injections of obestatin or ghrelin to investigate the food consumptions, plasma obestatin and ghrelin levels to determine unknown acute effects of obestatin. Plasma ghrelin levels increased significantly in obestatin administered mice when compared with the control group for chronic treatment. This increase is consistent with immunohistochemical findings which claim that the number of ghrelin and obestatin immunopositive cells in fundus tissue of stomach are considerably high in obestatin treated animals. Plasma obestatin and ghrelin levels has shown an increase endogenously in food restricted mice, but plasma leptin and insulin levels have been found to be lower compared to the control group. Acute administration of obestatin caused a decrease in plasma obestatin level at 60 min after injection and had no effect on the reduction of food intake in each treatment time. These results imply that obestatin may not itself be involved in the metabolism regulation; however, obestatin accompanied by ghrelin may play a role in the long-term regulation of metabolism.

Effectual comparison of quinoa and amaranth supplemented diets in controlling appetite; a biochemical study in rats.

The objective of this study was to assess the efficacy of two current cynosure protein substitutes; quinoa and amaranth in controlling short term food intake and satiety in rats. Experimental rats were allotted to three groups (n = 8 per group) and fed with diets containing casein, quinoa and amaranth as major protein sources, with casein diet kept as control. At the end of the experiment it was observed that the rats ingesting quinoa and amaranth supplemented diets exhibited lesser food intake (p < 0.01) and lesser body weight gain significantly in amaranth (p < 0.05) as compared to control. They seemed to bring down plasma ghrelin levels while meliorating plasma leptin and cholecystokinin (CCK) levels postprandially (p < 0.01). Although both quinoa diet and amaranth diet were effective in improving blood glucose response and maintaining plasma free fatty acids (FFA) and general lipid profiles subsequently after the meal, amaranth diet showed significant effects when compared to control and amaranth diets. There was 15% improvement in blood glucose profile in the amaranth group with respect to the control at 90min, where as there was only 3.4% improvement in the quinoa group. These findings provide a scientific rationale to consider incorporation of these modest cereals in a diet meant to fight against growing obesity and poverty.

Mo2054 Preclinical Trial of Gastric Injection of Botulinum Toxin Type a As Weight-Loss-Surgery

Background/aim: Recently, a clinical trial enrolling 60 obese patients failed to show that gastric injection of botulinum neurotoxin type -A (Botox) promotes body weight (BW) loss. The aim of this study was to verify the effectiveness and the underlying mechanism of gastric injection of Botox as weight-loss-surgery (WLS). Methods: 102 male rats (42 normal rats at 500 g BW and 60 high-fat-diet-induced obese rats at 700-800 g BW) were subjected to Botox injection, vehicle injection, or sleeve gastrectomy (SG) followed by Botox injection. Rats on high-fat-diet were continuously fed the high-fat-diet after Botox injection or surgery. Botox was injected at a dose of 20 U/rat into the subserosa layer of pyloric antrum or the remaining antrum post SG, and Botox injection was repeated when rats regained BW. Measurements included BW development, food intake, eating behavior and metabolic parameters (monitored by Comprehensive Laboratory Animal Monitoring System, CLAMS), fasting blood glucose levels, gastric emptying rate (acetaminophen absorption test), gut hormones (RIA), and expression of genes encoding orexigenic and anorexigenic neuropeptides in the hypothalamus (in situ hybridization). Results: There were no mortality, adverse effects and pathological changes in rats subjected to Botox injection. Botox injection reduced BW by 14% in normal rats and 25% in obese rats compared to values before Botox injection (p 0.05). Additional Botox injection led to BW loss of 22% (p<0.01). Botox injection increased satiety ratio (min/g), leading to reduced food intake (g/day), and increased energy expenditure (kcal/h/100g BW). Botox injection reduced fasting blood glucose levels, while gastric emptying rate was unchanged (measured at 3 days, 1, 2 or 3 weeks after Botox injection) in either normal or obese rats. Gene expression in hypothalamus and plasma levels of gut hormones were unchanged at 48 hours after Botox injection. However, 8 weeks after Botox injection, the gene expression for neuropeptide Y and agouti-related peptide was increased, while pro-opiomelanocortin was decreased in arcuate nucleus in hypothalamus, and plasma levels of cholecystokinin, gastrin, and peptide YY, but not glucagon, glucagon-like peptide-1, were reduced, suggesting compensatory changes in the gut hormones-hypothalamus pathway. Conclusions: This preclinical trial demonstrates the safety and efficacy of gastric injection of Botox as WLS when it is performed alone or in combination with SG. Botox reduced food intake and increased energy expenditure, independently of the gastric emptying rate and of the hypothalamusgut hormone pathway.

Long-term effects of evodiamine on expressions of lipogenesis and lipolysis genes in mouse adipose and liver tissues

Evodiamine, the major alkaloid component isolated from the fruit of dried, unripened Evodia rutaecarpa Bentham, affects the plasma levels of cholecystokinin and various biological events such as gastric emptying and gastrointestinal transit; these effects of evodiamine were previously investigated in male rats. In this study, we aimed to investigate the effects of evodiamine on average daily weight gain, rectal temperature, and expressions of genes involved in lipid metabolism in liver and adipose tissues. Evodiamine was added as a supplement, comprising 0.02, 0.04, and 0.06% of the diet fed to mice for 1, 2, 3, and 4 weeks. Results showed that average daily weight gain and rectal temperature decreased significantly over time in a dose-dependent manner. Evodiamine changed expressions of the peroxisome proliferator-activated receptor-g (PPARg) in mouse adipose and liver tissues in time- and dose-dependent manners. We found that evodiamine decreased mRNA expression of the sterol-regulatory element binding protein (SREBP-1c) and fatty acid synthase in adipose tissue. In addition, evodiamine increased expressions of hormone-sensitive lipase in both liver and adipose tissues. Interestingly, evodiamine increased the expression of triglyceride hydrolase only in adipose tissue. In conclusion, evodiamine could influence lipid metabolism through regulation of the expressions of its key genes, as well as reduce body heat and body weight.

Effects of the Addition of Mosapride to Gastroesophageal Reflux Disease Patients on Proton Pump Inhibitor: A Prospective Randomized, Double-blind Study

Background/AimsProton pump inhibitors (PPIs) which are the most effective agents for the treatment of gastroesophageal reflux disease (GERD), have been known to delay gastric emptying. Mosapride has been used as prokinetics by accelerating gastric emptying. We evaluated the efficacy of mosapride to prevent PPI-induced delayed gastric emptying in a prospective randomized, double-blind and placebo-controlled trial.MethodsThirty patients who were diagnosed as GERD and had normal gastric emptying were included in this study. PPI monotherapy group was treated with placebo drug in addition to pantoprazole and PPI plus mosapride group was treated with mosapride in addition to pantoprazole for 8 weeks. Gastric emptying scan and questionnaires about GERD and dyspeptic symptoms were assessed by scoring before and after treatment. To evaluate the changes of gastrointestinal endocrine hormones by PPI which are associated gastric acid secretion and gastric motility, fasting plasma gastrin and cholecystokinin were taken at weeks 0 and 8.ResultsHalf gastric emptying time was increased (P = 0.023) in PPI monotherapy group, and there were no significant changes in PPI plus mosapride group. Plasma gastrin level increased in PPI monotherpay group (P = 0.028) and there were no significant changes in PPI plus mosapride group. Plasma cholecystokinin level was not changed after treatment in both groups. GERD symptoms were improved after treatment in both groups, and postprandial bloating and nausea were improved in PPI plus mosapride group.ConclusionsMosapride showed to be effective in preventing delayed gastric emptying and the increase in plasma gastrin level induced by PPI treatment, but did not show prominent clinical symptom improvements.

The effect of submicron fat droplets in a drink on satiety, food intake, and cholecystokinin in healthy volunteers

Small fat droplets infused into the gut reduce food intake and hunger more than bigger ones, at levels as low as 6 g, and these effects are hypothesized to occur via satiety hormones such as cholecystokinin. It is, however, unknown whether the effect of droplet size would persist after oral consumption. It is also unknown whether an even smaller droplet size can affect hunger and food intake and at what minimum amount of fat. Therefore, the aim of the study was to test the effect of very fine fat droplets on satiety and food intake in two different quantities. In a balanced-order 4-way crossover design, 24 volunteers consumed a fat-free meal replacement drink with either 5 or 9 g oil (rapeseed) and either 3 or 0.1 μm droplet size. Appetite scores and plasma cholecystokinin levels (in n = 12 subset) were measured for 180 min, when food intake was assessed during an ad libitum meal. Data were analyzed by ANCOVA, followed by Dunnett's test and paired t test. The behavior of the emulsions was also characterized in a simulated gastrointestinal model. Despite faster in vitro lipolysis of the smallest droplets, neither droplet size nor fat amount affected satiety or food intake. From t = 45-150 min, cholecystokinin response was 50% higher (P < 0.05) after the 0.1 versus 3 μm, but only with 9 g fat. When this particular fat at these amounts is delivered in a meal replacement drink, droplet size does not influence appetite or food intake. This effect is independent of the amount of fat or plasma cholecystokinin changes.

Continuous Administration of Enteral Lipid- and Protein-Rich Nutrition Limits Inflammation in a Human Endotoxemia Model

An overzealous inflammatory response is an important cause of morbidity and mortality in surgical, trauma, and critically ill patients. Enteral administration of lipid-rich nutrition was previously shown to attenuate inflammation and reduce organ damage via a cholecystokinin-1 receptor-mediated vagovagal reflex in animal studies. The current preclinical study investigates the immunomodulatory potential of a custom-made enteral nutrition during systemic inflammation in man. Double-blind, randomized controlled trial. Intensive care research unit. Male volunteers. After an overnight fast, 18 healthy male subjects received an IV bolus of Escherichia coli lipopolysaccharide (2 ng/kg). Subjects in the fasted group (n = 6) were deprived of food throughout the study, while subjects in the intervention groups were fed either custom-made lipid- and protein-rich nutrition (n = 6) or isocaloric control nutrition (n = 6) via nasojejunal tube, starting 1 hour prior to lipopolysaccharide administration until 6 hours afterward. Bolus lipopolysaccharide administration resulted in a marked inflammatory response. Continuous postpyloric administration of nutrition significantly increased plasma cholecystokinin levels throughout the lipopolysaccharide-induced inflammatory response. Lipid- and protein-rich nutrition attenuated circulating levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and the interleukin-1 receptor antagonist compared with control nutrition (all p < 0.05) and fasted subjects (all p < 0.05). In additional, lipid- and protein-rich nutrition augmented the anti-inflammatory response, reflected by increased plasma levels of interleukin-10 compared with fasted subjects (p < 0.0001). The current preclinical study expands the immunomodulating effects of enteral nutrition as previously observed in rodents to man. Continuous administration of enteral nutrition resulted in a rapid anti-inflammatory effect. Furthermore, enrichment of the nutritional composition with lipid and protein was shown to enhance the anti-inflammatory potential. Therefore, continuous enteral administration of lipid- and protein-rich nutrition is a promising intervention to modulate the immune response in the early course of systemic inflammation in man.

Increasing of Plasma Cholecystokinin Level and Jejunum Histological Changes After Treatment with Soybean Extracts Protein

It is well known that soybean has beneficial health effects. There are lot of active compounds in soybean, like protein and anti nutrition factors (ANF). Trypsin inhibitor and lectin, two kinds of ANF have an adverse effect on the morphology and function of digestive tract in animals. β-conglycinin in soybean protein, has been proven has reducing body weight effect through increasing cholecystokinin (CCK) level. The aim of this study was to measure plasma CCK level and the histological changes of jejunum in Wistar rats after treatment with protein extract of Willis raw soybean (PEWS), protein extract of Detam 1 raw soybean (PEDS) and protein extract of Detam 1 tempeh (PEDT) for 14 days. This study was also to ascertain whether β-conglycinin and ANF contribute to reducing body weight by giving PEWS, PEDS, and PEDT to 4 groups of 6 rats for 14 days. We observed food intake, body weight, CCK level, and histological profile of jejunum. As a conclusion, PEWS, PEDS, and PEDT treatment to Wistar Rats for 14 days caused increasing CCK plasma level and jejunum villi atrophy. The reducing body weight is caused not only by β-conglycinin but probably by ANF as well.

Intestinal fatty acid infusion modulates food preference as well as calorie intake via the vagal nerve and midbrain–hypothalamic neural pathways in rats

The intestine plays important roles in the regulation of feeding behavior by sensing macronutrients. Intestinal fatty acids strongly suppress food intake, but little is known about whether intestinal fatty acids affect food preference. We investigated the effects of jejunal fatty acids infusion on food preference by conducting two-diet choice experiments in rats fed a high-fat diet (HFD) and a high-carbohydrate diet (HCD). Jejunal linoleic acid (18:2) infusion reduced HFD intake dose-dependently, while HCD intake increased with the middle dose of the infusion we examined (100 μL/h) and reduced to the control level with the higher doses (150 and 200 μL/h). α-Linolenic acid (18:3), but not caprylic acid (8:0), altered the food preference and total calorie intake in the same manner as linoleic acid. Linoleic acid infusion dose-dependently increased plasma glucagon-like peptide-1, peptide YY and cholecystokinin levels, but not ghrelin levels. Subdiaphragmatic vagotomy or midbrain transection prevented the change in food preference and total calorie intake by linoleic acid infusion. Jejunal linoleic acid infusion increased norepinephrine turnover in the paraventricular hypothalamic nucleus, while intracerebroventricular injection of idazoxan, an α2-adrenergic receptor (AR) antagonist, suppressed the increased HCD intake, but did not affect the decreased HFD intake. These findings indicated that intestinal long-chain fatty acids modulated food preference as well as total calorie intake via the vagal nerve and midbrain–hypothalamic neural pathways. The effects of the α2-AR antagonist in the brain suggested that the brain distinctly controlled HCD and HFD intake in response to jejunal linoleic acid infusion.

The effect of continuous jejunal interposition on gastrointestinal hormones after distal gastrectomy

The objective of our study was to determine the effect of continuous jejunal interposition on gastrointestinal hormones after distal gastrectomy, and lay a foundation for surgical management.Distal subtotal gastrectomy experimental model were established on 24 adult Beagle dogs. Digestive tract reconstruction of the dogs was randomly divided into continuous jejunal interposition group, Billroth II anastomosis group and isolated jejunum interposition group. The content of serum gastrin, plasma motilin and cholecystokinin after different digestive tract reconstructions was detected and compared by enzyme-linked immunosorbent assay. In the dogs which received continuous jejunal interposition, postoperative serum gastrin level was significantly lower than before surgery either in fasting or postprandial state (all p<0.05). The serum gastrin level of continuous jejunal interposition group was significantly higher than the other groups in postprandial state (all p<0.05), and was significantly higher than Billroth II -type anastomosis group in fasting state (p<0.05). Furthermore, the postoperative plasma motilin and cholecystokinin levels were significantly higher than before surgery either in fasting or postprandial in dogs received continuous jejunal interposition (all p<0.05). The postoperative plasma motilin level of continuous jejunal interposition group was significantly higher than the other groups in postprandial state (all p<0.05), and was significantly higher than Billroth II -type anastomosis group in fasting state (p<0.05). However, the postoperative cholecystokinin level of continuous jejunal interposition group was significantly lower than the other groups (all p <0.05).Continuous jejunal interposition after distal gastrectomy could maintain the postoperative plasma motilin and serum gastrin in a relatively high level, while cholecystokinin in a low level.

The effect of protease inhibitors derived from potato formulated in a minidrink on appetite, food intake and plasma cholecystokinin levels in humans

Protease inhibitor 2 derived from potato (PI2) is claimed to reduce appetite and food intake, stimulate the satiety hormone cholecystokinin (CCK) and lower postprandial glucose peaks when taken before a meal. However, current literature is inconclusive with regard to its efficacy and mechanism. Furthermore, the potential effect of PI2 on appetite motivational ratings without an immediately following meal has not previously been reported. To comprehensively test the effects of 30 mg PI2 in a minidrink on appetite ratings, subsequent food intake, and plasma CCK and glucose responses. Minidrinks with or without 30 mg PI2 were compared in three separate substudies (A, B and C), each using a two-way, placebo-controlled, balanced-order, cross-over design and 23 or 24 subjects (mean over groups: body mass index 25.0 kg m(-2), range 22.5-30.7 kg m(-2); age 41.3, range 18-62 years). The minidrink was given (A) 120 or (B) 30 min before an ad libitum lunch or (C) 30 min before a fixed lunch. Study parameters were self-reported satiety (substudies A and C), ad libitum meal intake (substudies A and B), and (in an n=12 subset) plasma CCK and blood glucose in all substudies. All results were analyzed using analysis of covariance. Protease-inhibitory activity of the PI2-containing minidrinks was assessed under simulated gut conditions. PI2 did not differ from control for any study parameters, in any substudy, despite confirmation of the inhibitory activity of PI2. In this study protease inhibition using PI2 in a minidrink at a dose of 30 mg, as commercially used, had no (functional) efficacy on a range of behavioral and physiological appetite and intake control measures.

Genistein Aglycone is Effective in Reducing Bone Loss and Some Predictors of Cardiovascular Risk in Postmenopausal Women: A 3-Years Study

To investigate the mechanisms controlling human gallbladder contraction, especially to determine the role of neural factors, the gallbladder response to various stimuli was evaluated in eight normal subjects using realtime ultrasonography. In addition, plasma cholecystokinin (CCK) levels were measured using a region-specific antibody (OAL 656). Intramuscular injections of CCK-8 and of cerulein induced mean maximal ejection fractions (EF max) of 50% ± 6% and 58% ± 4%, respectively. The mean EF max after ingestion of a fatty meal was 44% ±3%, while the EF max after a fat- restricted meal was significantly lower (17% ±4%). Oral water and sham feeding also significantly induced gallbladder contractions (EF max; 25% ±4% and 12% ±4% respectively) that were eliminated by premedication with atropine. The plasma CCK rose significantly after exogenous administration of CCK-8 and after ingestion of a fatty meal. The peak CCK concentration released after fatty meals was almost identical to that after exogenous CCK-8 loading. In contrast, plasma CCK levels showed no change after the fat-restricted meal, oral water and sham feeding. These findings suggest that not only CCK but also the cholinergic pathway may play important roles in the control mechanism of human gallbladder contraction.

Circadian variation of rectal sensitivity and gastrointestinal peptides in healthy volunteers

The aim of our study was to identify diurnal variation of perception of rectal distension and the release of gastroenteropancreatic hormones. In 12 healthy male volunteers (25 years, range 22-32), a rectal balloon distension was performed. Rectal perception thresholds (minimal, urge and pain) and rectal compliance were double-measured with a computer-controlled barostat at seven standardized time points during the day (from 16.00 to 14.00 hours the following day). Blood samples were taken 30 min before and after each rectal distension procedure to determine plasma levels of cholecystokinin (CCK), pancreatic polypeptide (PP) and motilin. Sensory thresholds for urge and pain varied significantly with the time of day, with higher threshold levels in the evening than in the morning hours. Bowel wall compliance showed as well-significant variance at pain threshold and was higher during daytime than in the evening or at night. In contrast to motilin, release of CCK and PP also showed a significant variation depending on daytime. Perception of rectal distension stimuli as well as compliance was independent of intake of food and peptide hormone levels, but CCK and PP levels increased with food, and PP levels decreased with rectal distension. Significant differences in the perception of rectal distension stimuli for urge and pain depending on daytime were found, but the release of gastrointestinal peptides seemed not to be involved. This circadian variation needs to be taken into account in patients and volunteer studies.

Bioassay 法による各種疾患における血中 Cholecystokinin 基礎値の検討

Bioassay 法による各種疾患における血中 Cholecystokinin 基礎値の検討