Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0000729 (abdominal cramps)
 531 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In search of new practical diagnostic methods for the early diagnosis of hereditary medullary carcinoma of the thyroid (MCT) calcitonin release has been studied following induction by pentagastrin, cholecystokinin-pancreozymin (the C-terminal octapeptide, C8-CCK, and the native swine extract), and ethanol in eighteen cases of MCT (all but one clinically occult), three 'borderline cases', seven first degree relatives of patients with hereditary MCT and thirty-five healthy controls. Pentagastrin, subcutaneous (s.c.) or intravenous (i.v.), induced a pronounced and rapid increase of serum calcitonin within 2-5 min. The elevation was roughly proportional to the tumour mass as estimated at operation. Seventeen out of eighteen MCT patients responded to s.c. pentagastrin with a significant increase in serum calcitonin and the response correlated well with that induced by calcium infusion test. Only two blood samples, at times 0 and 5 min, were necessary for diagnosis. In the MCT patients, i.v. pentagastrin produced more pronounced elevations of serum calcitonin than did s.c. pentagastrin, whereas no increase was seen in the control group. The subjective discomfort caused by i.v. pentagastrin was somewhat more intense but lasted shorter than that induced by s.c. administration. No serious complications were seen. All of nine MCT patients responded to C8-CCK with increments in serum calcitonin exceeding those of the control group and both of two responded similarly to the native cholecystokinin-pancreozymin extract. Generally the serum calcitonin response was lower and more variable after C8-CCK than after s.c. or i.v. pentagastrin, and the subjective discomfort was also more pronounced with abdominal cramps during the injection. Ethanol in the dose used was the least effective stimulator for serum calcitonin release. Clinically suspected MCT carriers with palpable tumours can be diagnosed by determination of the basal, i.e. non-stimulated serum calcitonin levels. Other possible Sipple genome carriers, who are at the time clinically healthy with normal basal serum calcitonin, should be subjected to a s.c. or i.v. pentagastrin stimulation test at each examination. These tests are much simpler to perform than a calcium infusion, test, but seem to have about the same sensitivity.
 ...
PMID:Screening for medullary carcinoma of the thyroid in families with Sipple's syndrome: evaluation of new stimulation tests. 40 80

MK-329 is a nonpeptidal, highly specific cholecystokinin (CCK) receptor antagonist, with affinity for pancreatic and gallbladder CCK receptors similar to CCK itself. MK-329 and its progenitor, asperlicin, can inhibit the growth of CCK receptor-positive human pancreatic cancer in athymic mice. Based on these activities and the ability of MK-329 to transiently increase food intake and enhance morphine analgesia in murine models, we conducted an open trial of MK-329 in 18 patients with advanced pancreatic cancer in whom the CCK receptor status of the tumors was unknown. Tumor response, pain control, and nutritional parameters (hunger rating, caloric intake, body weight, and anthropometrics) were serially assessed. The results of the study failed to demonstrate any impact of MK-329 on tumor progression, pain, or nutrition. Toxicity was mild and limited to nausea, vomiting, diarrhea, and abdominal cramps, with 17 of 18 patients able to tolerate treatment. While a role for MK-329 in the management of patients with advanced pancreatic cancer cannot be supported by the results of this trial, additional studies of this agent in patients with known CCK receptor-positive tumors, at escalated doses, and possibly in conjunction with other growth antagonists, appear warranted.
 ...
PMID:A pilot clinical trial of the cholecystokinin receptor antagonist MK-329 in patients with advanced pancreatic cancer. 155 66

Hunger and satiety appear to reflect the postabsorptive and absorptive phases of caloric homeostasis, respectively. However, only some of the signals that inhibit food intake can be related to caloric homeostasis. For example, decreases in food intake also are observed after administration of nauseogenic chemical agents, treatment with cholecystokinin (CCK), or dehydration. In each case, inhibition of food intake is correlated with induced decreases in gastric motility and increases in secretion of pituitary oxytocin in rats; in primates, including humans, vasopressin but not oxytocin is secreted. In contrast, meal-induced satiety increases gastric contractions and has little or no effect on neurohypophyseal hormone secretion in rats or human subjects. Nauseogenic toxins, CCK, and dehydration stimulate very different subjective states from satiety: LiCl elicits abdominal cramps, nausea, and vomiting, as does exogenous CCK in high doses, whereas dehydration elicits thirst. Thus, inhibition of eating may not be associated with satiety or reflect changes in caloric flux; noncaloric controls of food intake exist and may be accompanied by distinctive increases in neurohypophyseal hormone secretion and loss of gastric function.
 ...
PMID:Caloric and noncaloric controls of food intake. 195 22

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.
 ...
PMID:The therapeutic potential of cholecystokinin. 610 Jan 12

The present study was undertaken to compare the effects of equimolar amounts of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) on plasma cholecystokinin (CCK) concentrations and gallbladder contraction in man. On separate mornings and in random order six healthy volunteers ingested either 60 mmol LCT or 60 mmol MCT. Plasma CCK concentrations were measured by a sensitive and specific radioimmunoassay and gallbladder contraction by ultrasonography. Ingestion of LCT induced significant increases in plasma CCK from 2.8 +/- 0.5 to 6.5 +/- 0.7 pmol/l (p less than 0.005) and decreases in gallbladder volume from 33.4 +/- 5.9 to 13.2 +/- 4.2 cm3 (p less than 0.005). On the other hand, no significant changes in plasma CCK and gallbladder volume were found after MCT. Ingestion of MCT was followed by abdominal cramps and diarrhea, while LCT were without side effects. It is concluded that, in contrast to LCT, MCT do not induce CCK release and gallbladder contraction.
 ...
PMID:Effect of equimolar amounts of long-chain triglycerides and medium-chain triglycerides on plasma cholecystokinin and gallbladder contraction. 669 35

Cholecystokinin (CCK) is known to have a short biological half-life. In order to prolong the half-life and create a new investigative tool, we previously PEGylated the peptide, yielding PEG-CCK(9), and demonstrated that it had a dose-dependent prolonged anorectic effect. The aim of this study was to investigate whether PEG-CCK(9) reduces food intake by inducing satiation or by abnormal physiological effects, such as pain, malaise, or nausea. An observational study was performed to examine the effects of different doses of PEG-CCK(9) (1, 2, 4, 8, or 16 microg kg(-1)) on feeding and other behaviors. The behavioral sequence associated with satiety (BSS), i.e. the orderly progression from eating, through grooming and activity, to resting, was analyzed. From the lowest dose tested (1 microg kg(-1)), PEG-CCK(9) caused a dose-dependent reduction in food intake due to a dose-related reduction in both the duration and frequency of eating and a dose-dependent increase in duration of rest. A dose-dependent acceleration in the temporal profile of the BSS was observed, while the normal structure of feeding behaviors was well preserved, except at the dose of 16 microg kg(-1) of PEG-CCK(9), at which a decrease in eating rate and grooming behavior was observed, together with the occurrence of a significant number of abdominal cramps. These findings suggest that the hypophagic response to PEG-CCK(9) is mainly induced by natural mechanisms of satiety, although abnormal physiological effects, such as abdominal cramps, might reinforce the food inhibitory effect, especially at high doses of PEG-CCK(9) (>8 microg kg(-1)).
 ...
PMID:Dose-response effects of PEGylated cholecystokinin on the behavioral satiety sequence. 1946 39