Cholecystokinin-Induced Duodenogastric Bile Reflux Increases the Severity of Indomethacin-Induced Gastric Antral Ulcers in Re-fed Mice.

BACKGROUND/AIMS: We examined the involvement of cholecystokinin (CCK) in the exacerbation of indomethacin (IND)-induced gastric antral ulcers by gastroparesis caused by atropine or dopamine in mice. METHODS: Male mice were fed for 2 h (re-feeding) following a 22-h fast. Indomethacin (IND; 10 mg/kg, s.c.) was administered after re-feeding; gastric lesions were examined 24 h after IND treatment. In another experiment, mice were fed for 2 h after a 22-h fast, after which the stomachs were removed 1.5 h after the end of the feeding period. Antral lesions, the amount of gastric contents, and the gastric luminal bile acids concentration were measured with or without the administration of the pro- and antimotility drugs CCK-octapeptide (CCK-8), atropine, dopamine, SR57227 (5-HT3 receptor agonist), apomorphine, lorglumide (CCK1 receptor antagonist), ondansetron, and haloperidol alone and in combination. RESULTS: IND produced severe lesions only in the gastric antrum in re-fed mice. CCK-8, atropine, dopamine, SR57227 and apomorphine administered just after re-feeding increased bile reflux and worsened IND-induced antral lesions. These effects were significantly prevented by pretreatment with lorglumide. Although atropine and dopamine also increased the amount of gastric content, lorglumide had no effect on the delayed gastric emptying provoked by atropine and dopamine. Both ondansetron and haloperidol significantly inhibited the increase of bile reflux and the exacerbation of antral lesions induced by atropine and dopamine, respectively, but did not affect the effects of CCK-8. CONCLUSIONS: These results suggest that CCK-CCK1 receptor signal increases bile reflux during gastroparesis induced by atropine and dopamine, exacerbating IND-induced antral ulcers.

STAT4 targets KISS1 to inhibit the oxidative damage, inflammation and neuronal apoptosis in experimental PD models by inactivating the MAPK pathway.

BACKGROUND: Oxidative stress and neuroinflammation are proven to play critical roles in the pathogenesis of Parkinson's disease (PD). As reported, patients with PD have lower level of STAT4 compared with healthy subjects. However, the biological functions and mechanisms of STAT4 in PD pathogenesis remain uncertain. This study aimed to investigate the roles and related mechanisms of STAT4 in PD development. METHODS: The intraperitoneal injection of MPTP (20 mg/kg) dissolved in physiological saline was performed to mimic PD-like conditions in vivo. MPP + solution was prepared for cell model of PD. Cell viability was measured by CCK-8. Griess reaction was conducted to measure NO concentrations. The mRNA and protein levels were evaluated by RT-qPCR and western blotting. ROS generation was assessed by DCFH-DA. The levels of inflammatory cytokines were measured by ELISA. Cell apoptosis was examined by flow cytometry and western blotting. Moreover, the SH-SY5Y cells were treated with conditioned medium from LPS-stimulated microglia and subjected to CCK-8 assays and ELISA. Mechanistically, CHIP assays and luciferase reporter assays were performed to verify the binding relationship between KISS1 and STAT4. For in vivo analysis, the histological changes of midbrain tissues of mice were determined by hematoxylin and eosin staining. The expression of tyrosine hydroxylase (TH) was detected by immunohistochemistry staining. Iba-1 positive microglial cells in the striatum were assessed by immunofluorescence staining. RESULTS: For in vitro analysis, STAT4 level was downregulated after MPP+ treatment, and STAT4 upregulation inhibited the oxidative damage, inflammation and apoptosis in SH-SY5Y cells. STAT4 bound at +215-228 region of KISS1, and KISS1 upregulation counteracted the protection of STAT4 upregulation against cell damage. Moreover, STAT4 upregulation inhibited cell viability loss and inflammation induced by conditioned medium from LPS-treated microglia, whereas KISS1 upregulation had the opposite effect. For in vivo analysis, the protective effects of STAT4 upregulation against inflammatory response, oxidative stress, dopaminergic neuronal loss and microglia activation were attenuated by KISS1 upregulation. Moreover, the inactivation of MAPK pathway caused by STAT4 upregulation was reversed by KISS1 upregulation, and MAPK inhibition attenuated the MPP+-induced inflammation, oxidative stress and apoptosis in SH-SY5Y cells. CONCLUSION: STAT4 inhibits KISS1 to attenuate the oxidative damage, inflammation and neuronal apoptosis in PD by inactivating the MAPK pathway.

Irisin inhibits CCK-8-induced TNF-α production via integrin αVß5-NF-κB signaling pathways in Nile tilapia (Oreochromis niloticus).

Irisin, a secreted myokine generated by fibronectin type III domain-containing protein 5, has recently shown the potential to alleviate inflammation. Cholecystokinin-octapeptide (CCK-8) is closely associated with the inflammatory factor TNF-α, a central cytokine in inflammatory reactions. However, the interactions between irisin and CCK-8 in regulating TNF-α production and the underlying mechanism have not yet been elucidated. In the present study, irisin treatment inhibited the basal and the CCK-8-induced TNF-α production in vivo. Additionally, neutralizing circulating irisin using an irisin antiserum significantly augmented the CCK-8-induced stimulation of TNF-α levels. Moreover, the incubation of head kidney cells with irisin or CCK-8 has opposite effects on TNF-α secretion. Notably, irisin treatment inhibited basal and CCK-8-stimulated TNF-α release and gene transcription in head kidney cells. Mechanistically, the inhibitory actions of irisin on basal and CCK-8-induced TNF-α production could be negated by co-administered with the selective integrin αVß5 inhibitor cilengitide. In addition, the inhibitory effect of irisin on basal and CCK-8-triggered TNF-α production could be abolished by the inhibition of the nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, irisin impeded CCK-8-induced phosphorylation and degradation of IκBα, simultaneously inhibiting NF-κB phosphorylation, preventing its translocation into the nucleus, and suppressing its DNA-binding activity induced by CCK-8. Collectively, these results suggest that the inhibitory effect of irisin on TNF-α production caused by CCK-8 is mediated via the integrin αVß5-NF-κB signaling pathways in tilapia.

miR-124-3p Delivered Using Exosomes Attenuates the Keratinocyte Response to IL-17A Stimulation in Psoriasis.

Methods: NHEKs, HaCaT cells, and HEK 293T cells were treated with IL-17A. CCK-8 assays were performed to detect cell activity, and immunofluorescence staining and Western blotting were performed to detect the protein expression of STAT3. After isolation of exosomes via ultracentrifugation, the contents of miR-124-3p and oxidative stress markers such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in keratinocytes were measured. Subsequently, transcriptomic analysis was performed using RNA-seq. Data were analysed by using the "edgeR" package within R. After verifying the abnormally expressed genes stimulated by IL-17A, a dual luciferase reporter assay was used to determine the interaction between miR-124-3p and STAT3. Finally, BALB/c mice were used to establish a psoriasis model for analysis. The effect of elevated miR-124-3p on the psoriasis mouse model was determined by exosomal delivery of miR-124-3p. Results: IL-17 intervention enhanced the cell activity of keratinocytes (P < 0.05). miR-124-3p was identified by RNA-seq as one of the differentially expressed miRNAs stimulated by IL-17A. miR-124-3p overexpression induced decreased STAT3 and MDA levels, increased SOD and GSH-Px levels in keratinocytes, and alleviated emergency responses of sclerosis damage (P < 0.05). The dual luciferase reporter assay results confirmed that STAT3 was regulated by miR-124-3p in a targeted manner (P < 0.05). Finally, miR-124-3p delivered by exosomes effectively alleviated the pathological manifestations and oxidative stress responses of psoriatic mice. Conclusions: miR-124-3p regulates keratinocyte activity via STAT3 in response to IL-17A stimulation. The ectopic expression of miR-124-3p in psoriatic skin reduces IL-17A-induced inflammation and inhibits the STAT3 pathway, thus alleviating the symptoms of psoriasis. The findings of this study suggest that exosomes can be used to therapeutically deliver miR-124-3p to keratinocytes and psoriatic lesions, which may provide novel insight for psoriasis treatment.

Inhibition of KLF6 reduces the inflammation and apoptosis of type II alveolar epithelial cells in acute lung injury

Background: The development of acute lung injury (ALI) into a severe stage leads to acute respi-ratory distress syndrome (ARDS). The morbidity and mortality of ALI and ARDS are very high.Objective: This study is aimed to explore the effect of Krüppel-like factor 6 (KLF6) on lipopoly-saccharide (LPS)-induced type II alveolar epithelial cells in ALI by interacting with cysteine-rich angiogenic inducer 61 (CYR61).Material and Methods: ALI mice model and LPS-induced type II alveolar epithelial cells were conducted to simulate ALI in vivo and in vitro. The messenger RNA (mRNA) and protein expres-sion of KLF6 in lung tissues were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Pathological changes in lung tissues were observed by hematoxylin and eosin (H&E) staining. The viability and KLF6 expression of A549 cells treated with different concentrations of LPS were detected by cell counting kit-8 (CCK-8) assay, RT-qPCR, and Western blot analysis. After indicated treatment, the viability and apoptosis of A549 cells were analyzed by CCK-8 and TUNEL assays, and the inflammation fac-tors of A549 cells were detected by Enzyme-linked-immunosorbent serologic assay, RT-qPCR, and Western blot analysis. The combination of KLF6 and CYR61 was determined by chromatin immunoprecipitation (ChIP)-PCR and dual-luciferase reporter assay.Results: KLF6 expression was increased in lung tissues of ALI mice and LPS-induced A549 cells. Interference with KLF6 improved the viability, reduced the inflammatory damage, and promoted the apoptosis of LPS-induced A549 cells. In addition, KLF6 could bind to CYR61. Interference with KLF6 could decrease CYR61 expression in LPS-induced A549 cells. LPS also enhanced the TLR4/MYD88 signaling pathway, which was reversed by KLF6 interference. The above phenomena in LPS-induced A549 cells transfected with Si-KLF6 could be (AU)

Using cholecystokinin to facilitate endoscopic clearance of large common bile duct stones.

AIM: To evaluate the effect of cholecystokinin (CCK) during extracorporeal shockwave lithotripsy (ESWL) in the clearance of common bile duct (CBD) stones in endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Between January 2007 and September 2012, patients with large CBD stones who were treated with ESWL and ERCP were identified retrospectively. Patients were randomized in equal numbers to cholecystokinin (CCK) and no CCK groups. For each CCK case, a dose (3 ng/kg per min for 10 min) of sulfated octapeptide of CCK-8 was administered intravenously near the beginning of ESWL. ERCP was performed 4 h after a session of ESWL. The clearance rate of the CBD was assessed between the two groups. RESULTS: A total of 148 consecutive cases (CCK group: 74, no CCK group: 74) were tallied. Overall there were 234 ESWLs and 228 ERCPs in the 148 cases. The use of CCK showed a significantly higher rate of successful stone removal in the first ESWL/ERCP procedure (71.6% vs 55.4%, P = 0.035), but resulted in similar outcomes in the second (42.8% vs 39.4%) and third (41.7% vs 40.0%) sessions, as well as total stone clearance (90.5% vs 83.8%). The use of mechanical lithotripsy was reduced in the CCK group (6.8% vs 17.6%, P = 0.023), and extremely large stone (≥ 30 mm) removal was higher in the CCK group (72.7% vs 41.7%, P = 0.038). CONCLUSION: CCK during ESWL can aid with the clearance of CBD stones in the first ESWL/ERCP session. Mechanical lithotripsy usage was reduced and the extremely large stone (≥ 30 mm) clearance rate can be raised.

Metabolic effects of activation of CCK receptor signaling pathways by twice-daily administration of the enzyme-resistant CCK-8 analog, (pGlu-Gln)-CCK-8, in normal mice.

Cholecystokinin (CCK) is a hormone that has important physiological effects on energy balance. This study has used a stable CCK(1) receptor agonist, (pGlu-Gln)-CCK-8, to evaluate the metabolic effects of prolonged administration in normal mice. Twice-daily injection of (pGlu-Gln)-CCK-8 for 28 days resulted in significantly lowered body weights (P<0.05) on days 24 and 28, which was associated with decreased accumulated calorie intake (P<0.01) from day 12 onward. Nonfasting plasma glucose was significantly reduced (P<0.05) on day 28, while plasma insulin concentrations were increased (P<0.05). After 28 days, glucose tolerance and glucose-mediated insulin secretion were not significantly different in (pGlu-Gln)-CCK-8-treated mice. However, following a 15-min refeeding period in 18-h fasted mice, glucose levels were significantly (P<0.05) decreased by (pGlu-Gln)-CCK-8 despite similar food intake and nutrient-induced insulin levels. Insulin sensitivity in (pGlu-Gln)-CCK-8-treated mice was significantly (P<0.01) improved compared with controls. Accumulation of triacylglycerol in liver was reduced (P<0.01) but there were no differences in circulating cholesterol and triacylglycerol concentrations, as well as triacylglycerol content of pancreatic, muscle, and adipose tissue in (pGlu-Gln)-CCK-8 mice. These data highlight the beneficial metabolic effects of prolonged (pGlu-Gln)-CCK-8 administration and confirm a lack of detrimental effects.

Electroacupuncture protects against CCK-induced acute pancreatitis in rats.

OBJECTIVE: Electroacupuncture (EA) has been used to treat myalgia, adiposis and gastroenteropathy in Korea. EA as a complementary and alternative medicine has been accepted worldwide mainly for the treatment acute and chronic pain and inflammation. The aim of this study was to investigate the effects of EA on acute pancreatitis induced by cholecystokinin octapeptide (CCK) in rats. METHODS: Animals were divided into four groups: (1) a normal group; (2) a CCK-induced acute pancreatitis group; (3) a CCK-induced acute pancreatitis group treated with 100-Hz EA, and (4) a CCK-induced acute pancreatitis group treated with 2-Hz EA. High-frequency (100-Hz) and low-frequency EA (2-Hz) stimulations were applied to an acupoint equivalent to Zusanli (ST36) in rats, followed by 75 microg/kg CCK subcutaneously three times, after 1, 3 and 5 h. The entire procedure was repeated over 5 days. Repeated CCK treatment resulted in typical laboratory and morphological changes in experimentally induced pancreatitis. RESULTS: EA significantly decreased the pancreatic weight/body weight ratio in CCK-induced acute pancreatitis, increased the pancreatic levels of HSP60 and HSP72, and decreased the beta-amylase and lipase levels associated with CCK-induced acute pancreatitis. Furthermore, the release of ACTH was increased in the blood serum of the EA-treated group. CONCLUSION: EA may have protective effects against CCK-induced acute pancreatitis through the release of ACTH.

Sincalide in patients with parenteral nutrition-associated gallbladder disease.

OBJECTIVE: To review the role of sincalide in treating and preventing parenteral nutrition (PN)-associated gallbladder disease. DATA SOURCES: A MEDLINE (1996-March 2004) search was performed using the key terms cholecystokinin, sincalide, parenteral nutrition, cholelithiasis, cholestasis, and sludge. DATA SYNTHESIS: Five human studies investigated the safety and efficacy of sincalide in patients with PN-associated gallbladder disease. Sincalide at intravenous doses of 0.04 microg/kg 3 times daily increased bile flow and improved serum bilirubin levels. However, patients with advanced liver disease did not respond to sincalide therapy. Long-term follow-up data on sincalide effects on liver disease progression are not yet available. CONCLUSIONS: Sincalide improved the signs of cholestasis. However, its long-term effects in preventing and treating PN-associated gallbladder disease remain unknown and its routine use for this indication cannot be recommended at this time.

Pulmonary and systemic nitric oxide measurements during CCK-5-induced panic attacks.

Nitric oxide (NO) plays a major role in cardiopulmonary regulation as illustrated by the alterations of the NO system described in cardiopulmonary illnesses. Recent studies have found an association between panic disorder and cardiovascular death and illness, as well as pulmonary diseases. Our objective was to investigate whether pulmonary or systemic NO production was altered during induced panic attacks (PAs). We used a double-blind placebo-controlled crossover design with randomization of the order of an injection of placebo and pentagastrin, a cholecystokinin-B receptor agonist that induces PAs in healthy volunteers (HVs). A total of 17 HVs experienced a PA after pentagastrin challenge. Exhaled NO and NO metabolites were measured by chemiluminescence. During pentagastrin-induced PAs, HVs displayed significant decreases in plateau concentrations of NO exhaled, which were associated with proportional increases in minute ventilation. There were no significant changes in pulmonary or systemic NO production. These results suggest that the decrease in exhaled NO concentration observed during pentagastrin-induced PAs is related to the associated hyperventilation, rather than to any change in lung NO production. This study is the first to evaluate changes in NO measurements during acute anxiety.

Induction of HSP72 by sodium arsenite fails to protect against cholecystokinin-octapeptide-induced acute pancreatitis in rats.

A number of investigators have demonstrated that the preinduction of heat-shock protein (HSP) expression (particularly HSP60 and HSP72) by hyper- or hypothermia may have a protective effect against cerulein-induced acute pancreatitis. The aim of the present study was to induce HSPs in the pancreas and lungs by thermal (hot-water immersion, HWI) and nonthermal methods (injection of sodium arsenite intraperitoneally) and to investigate the potential effects of HSP preinduction on cholecystokinin-octapeptide (CCK) induced acute pancreatitis and pancreatitis-associated lung injury in rats. The dose-response and time-effect curves observed following HWI and sodium arsenite treatments were evaluated. Animals were injected with 3 x 75 microg/kg CCK subcutaneously at intervals of 2 hr at the peak level of HSP synthesis, as determined by Western blot analysis. The rats were killed by exsanguination through the abdominal aorta 2 or 6 hr after the last CCK injection. HWI and the injection of sodium arsenite significantly elevated the expression of HSP72 in the pancreas and lungs, whereas they did not influence the levels of HSP60. Overall, HWI pretreatment had a protective effect against CCK-induced pancreatitis and pancreatitis-associated lung injury. In contrast, the nonthermal preinduction of HSP72 by sodium arsenite did not result in any beneficial effects on the measured parameters of the disease. The findings suggest that the preinduction of HSP72 is not sufficient to protect against CCK-induced acute pancreatitis and pancreatitis-associated lung injury or that the beneficial effect of hyperthermia may not be exclusively related to HSP72 expression.

Time-course changes in serum cytokine levels in two experimental acute pancreatitis models in rats.

Activated leukocytes and cytokines have important roles in the multi-system involvement during acute pancreatitis. The changes in the serum level of tumor necrosis factor-a (TNF-alpha) and interleukin-6 (IL-6) over time were investigated in two experimental acute pancreatitis models in rats. Mild edematous pancreatitis was induced with an overdose of cholecystokinin octapeptide (CCK-8), while a severe hemorrhagic form of pancreatitis was induced by ligation of the common bilio-pancreatic duct. The rats were examined 2, 4, 8, 16, 24 and 48 h after pancreatitis induction. The severity of the inflammation was assessed by measurement of the serum amylase activity, quantification of the edema, and histological examination. Serum TNF-alpha and IL-6 were determined by bioassay, using the TNF-sensitive WEHI 164 and the IL-6-dependent B9 cell lines, respectively. In CCK-8-induced acute pancreatitis, the pancreatic weight/body weight ratio (pw/bw) and amylase level were significantly elevated at 2 h, and the maximum levels were observed at 4 h (8.19 +/- 1.13 mg/g and 69.4 +/- 12.8 x 10(3) U/ml, respectively). Both parameters subsequently decreased continuously during the observation period. The serum IL-6 level was significantly increased at 4 h relative to the controls (123.3 +/- 5.8 vs 37.5 +/- 15 pg/ml), and then decreased continuously. In this model, only a moderate level of serum TNF-alpha was observed at 2 h. In the biliary type of acute pancreatitis, the ratio pw/bw increased continuously during the study and reached the maximum level at 48 h relative to the sham-operated control (8.8 +/- 1.4 vs 5.3 +/- 0.8 mg/g). The serum amylase level was significantly elevated at 2 h (43.2 +/- 13 x 10(3) U/ml), but then decreased continuously. The serum IL-6 reached its maximum level at 16 h (3800 +/- 447 pg/ml). In this model, increased TNF-alpha levels (75-300 U/ml) were measured 8, 16 and 24 h after pancreatitis induction. The results led to correlations between the serum IL-6 levels and the biochemical and morphological severity of acute pancreatitis in both experimental models. The data suggest that IL-6 and TNF-alpha may participate in the pathogenesis of these types of acute pancreatitis.

Treatment of parenteral nutrition-associated cholestasis with cholecystokinin-octapeptide.

The authors investigated whether parenteral nutrition-associated cholestasis (PNAC) in surgical neonates could be alleviated by the administration of cholecystokinin-octapeptide (CCK). Two groups of infants were studied, after major abdominal or cardiac surgery in the newborn period. The low-dose group consisted of three infants with PNAC who received cholecystokinin-octapeptide (Sincalide) at a dose of 0.02 micrograms/kg intravenously (IV), twice daily. The high-dose group comprised eight infants with PNAC who received an initial dose of 0.02 micrograms/kg IV or intramuscularly, three times daily on the first day, followed by a daily doubling of the dose up to as high as 0.32 micrograms/kg. In the low-dose group, direct bilirubin levels declined a mean of 50.2 +/- 14.5%. In the high-dose group, direct bilirubin levels declined a mean of 23.4 +/- 14.3%. In three patients in the high-dose group, no decline occurred. All three had clinical signs of overt liver failure and died of liver failure within 2 months after treatment with CCK. By excluding these patients from the high-dose group, the decline in bilirubin levels increased to 49.6 +/- 10.9%. Side effects from CCK occurred in two patients and consisted of abdominal pain and feeding intolerance. Treatment with CCK appears to be associated with a decline in direct bilirubin levels, provided overt liver failure has not developed.

Gallbladder contraction after hormonal manipulations in normal subjects and patients under total parenteral nutrition.

Total parenteral nutrition (TPN) induces biliary dilatation, sludge and formation of gallstones. Cholecystokinin (CCK) induces gallbladder (GB) contraction. During thyrotropin-releasing hormone (TRH) testing for thyroid function, we observed that patients felt a strong micturition reflex attributable to smooth muscle contraction of the bladder. The possibility of GB contraction after TRH administration was studied compared to cholecystokinin-octapeptide (CCK-OP) and/or fatty meal administration. The effect of intravenous (IV) CCK-OP, TRH and a combination of the two on GB volume was studied in normal volunteers without GB or liver disease and in patients receiving TPN for greater than 2 weeks. Subjects included six normal volunteers who received an oral fatty meal only, 18 other normal volunteers (Group A) and 18 TPN patients (Group B). Gallbladder contraction was estimated by ultrasound prior to and after administration of the fatty meal; in the other 36 subjects, GB contraction was calculated prior to and after administration of CCK-OP, TRH, or both. Results are expressed as a percentage of the GB basal volume using each subject as his or her own control. Group A and Group B were each divided into three equal subgroups receiving IV CCK-OP (A1, B1), TRH (A2, B2), or both (A3, B3).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of a soup preload on reduction of food intake by cholecystokinin in humans.

Cholecystokinin octapeptide (CCK-8) or saline was intravenously infused for 5 min before and 5 min during a meal of macaroni and beef, served 20 min after a preload of either 100 or 500 g of soup to 12 nonobese men. Intake of the test meal was significantly lower when CCK-8 was given, following the larger preload, than after any of the other treatments. There were no significant differences among the other three treatment conditions. These results are consistent with the hypothesis that gastric, but not merely pregastric, stimulation interacts with CCK-8 to reduce food intake in humans. Although gastric filling seems to be the most likely stimulus for the interactive effect with CCK-8, other factors such as activation of nutrient-sensitive sites cannot be eliminated. In addition, hunger ratings were significantly lower immediately after the larger soup preloads than after the smaller. Hunger ratings after the soup also correlated better with test-meal intake after the large soup preloads with and without CCK-8 than after the smaller preloads. Hunger did not correlate significantly with test meal intake after the small soup preload with CCK-8. These results suggest that hunger ratings are more sensitive predictors of intake when the stomach is relatively full (i.e., after a large preload) than when it is relatively empty (i.e., after a small preload) at the time the hunger rating is taken.

Double blind controlled trials of cholecystokinin octapeptide in neuroleptic-refractory schizophrenia.

A group of 14 schizophrenics who remained symptomatic after neuroleptic treatment received either 0.02 mcg/kg CCK-8 or saline placebo intravenously. Thereafter, 13 received the alternative infusion as a crossover treatment. A second group of 16 such patients received 0.04 mcg/kg CCK-8 or saline intravenously and, thereafter, 14 of these received the alternative infusion as a crossover treatment. Psychopathology was rated prior to, 2-3 h post, and on days 3, 5 and 7 after each infusion. Ratings consisted of the BPRS, the Abrams and Taylor Scale for Emotional Blunting, the Hamilton Anxiety Scale and a Schneiderian "Positive" symptom scale abstracted from the President State Examination. Parallel groups and cross over design analyses failed to show efficacy for CCK-8.

The therapeutic potential of cholecystokinin.

A review of the satiating effect of cholecystokinin in humans reveals that the synthetic C-terminal octapeptide of cholecystokinin (CCK-8) inhibits liquid and solid food intake in non-obese men and women, and in obese men. Side effects, such as nausea, slight stomach sickness or abdominal cramps are infrequent and transient, and they are neither necessary nor sufficient for the inhibition of intake. These results demonstrate the efficacy of the satiating effect of CCK-8 in humans. The therapeutic potential of CCK-8 cannot be estimated until further studies are performed that demonstrate the efficacy of CCK-8 for decreasing body weight and that the safety of CCK-8 when it is administered repetitively for prolonged periods is established.