Intracellular mechanisms involved in short-term regulation of net protein synthesis in pancreatic acini.

The mechanisms regulating the net synthesis of digestive enzymes during short-term stimulation by agonists were examined in pancreatic acini isolated from the rat. Dispersed pancreatic acini were stimulated for up to 60 min with various concentrations of cholecystokinin octapeptide (CCK-OP), carbachol, A23187, 4 beta-phorbol 12-myristate 13-acetate (PMA). The effects of these agonists on net protein synthesis was determined by measuring the incorporation of [3H]leucine or [35S]methionine into protein. Carbachol, PMA, A23187 and concentrations of CCK-OP of 100 pM and greater caused inhibition of protein synthesis. Fluorography of [35S]methionine labeled acinar cell proteins separated by one-dimensional SDS-polyacrylamide gel electrophoresis demonstrated that the agonists inhibited the synthesis of the digestive enzymes. Northern blot analysis using cDNA probes revealed that CCK-OP, carbachol and PMA did not alter the cellular content of amylase, lipase and elastase mRNA. The protein kinase C inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and staurosporine failed to reverse the inhibitory effects of CCK-OP, carbachol and PMA on protein synthesis. CCK-OP and PMA activated phospholipase A (PLA) which liberated lysophosphatidylcholine (LPC) and free fatty acids from membrane phosphatidylcholine. Exogenously added PLA2 (Naja naja venom) inhibited protein synthesis and increased LPC to a similar extent as CCK and PMA. The results suggest that the inhibitory effects of CCK and carbachol on net protein synthesis are due to their effects on intracellular calcium and PLA-mediated breakdown of phosphatidylcholine rather than protein kinase C activation.

Acupuncture in the prophylactic treatment of migraine headaches: pilot study.

This study was planned as a pilot study to determine to what extent acupuncture might help in severe cases of migraine and, if possible, to see whether the mechanism was endorphin mediated. The study was carried out on 16 subjects who had severe and regular migraine for more than five years (mean duration 24 years). The study lasted eight months and was divided into four blocks of two months each: pre-treatment, treatment block I, treatment block II, and post-treatment. It was double-blind and cross-over in design. Acupuncture was found to cause a significant change in the number of headaches and their duration, with 40% of the subjects showing a 50%-100% reduction. Although pain sensation was not altered, attacks were less severe and less often accompanied by nausea and vomiting. At no stage was there any difference between subjects receiving saline or naloxone so that the possibility of a non-endorphin mechanism must be considered.

The interaction of lithium and time-of-day on calcium, magnesium, parathyroid hormone, and calcitonin in rats.

Effects of lithium on the concentrations and temporal patterns of serum and cerebellar calcium and magnesium, parathyroid hormone, and calcitonin were studied in 186 rats sacrificed around 24 hours of clock time. Serum calcium, serum and cerebellar magnesium, and parathyroid hormone were increased and calcitonin decreased in lithium-fed animals. Lithium-fed rats also showed different temporal patterns in serum calcium, parathyroid hormone, cerebellar magnesium, and calcitonin. Data support the hypothesis that lithium competes for calcium receptor sites, causing a compensatory increase in parathyroid hormone and decrease in calcitonin until a new, higher set-point for calcium is established. Lithium strongly affected biological rhythms, an effect which may account in part for the diverse literature on lithium's influence on calcium and magnesium regulation.

Adenohypophyseal hormones in the CSF.

The presence of adenohypophyseal hormones in human cerebrospinal fluid (CSF) had been firmly established by radioimmunoassay procedures. The hormones can originate from the adenohypophysis itself and from brain, as well as from peripheral sites of production. These peptide hormones enter the CSF through the choroid plexus or by direct secretion. The hormones entering by direct secretion into the CSF have a higher CSF-blood ratio than the hormones entering through the choroid plexus. Elevated CSF levels of adenohypophyseal hormones are most likely to occur in the presence of hormone-producing pituitary tumors with suprasellar extension. Although the CSF concentrations of adenohypophyseal hormones may merely reflect their blood concentrations, it is more likely that these hormones also have paracrine as well as endocrine effects.

Coping with a stressful sigmoidoscopy: evaluation of cognitive and relaxation preparations.

Sigmoidoscopy involves the insertion of a small scope into the anal cavity to inspect for abnormalities in the colon. Although the procedure is not believed to be painful, it is often noxious for patients because it produces embarassment and discomfort. We examined the effectiveness of two brief interventions designed to enhance coping: self-instructional training and relaxation. In the self-instructional conditions patients were given brief training to focus their attention on either their own (internal) or the doctor's (external) ability to regulate the situation. A third (control) group received attention but did not experience self-instructional training. Half of each of these three groups also received relaxation training, while the other half did not. Planned comparisons demonstrated that subjects in the self-instructional strategies rated themselves as less anxious, had fewer body movements during the exam, and emitted fewer verbalization than those in an attention control group. Patients in the external condition estimated that the exam took less time but tended to have elevated heart rates during the procedure. Those experiencing relaxation training tended to overestimate the duration of the exam, but made fewer requests to stop the exam and rated themselves as less anxious than patients who did not receive relaxation training.

Immunoreactive calcitonin in human cerebrospinal fluid.

The cerebrospinal fluid (CSF) of 123 male subjects was studied by RIA for the presence of immunoreactive calcitonin (CT). The hormone could be detected in the CSF of 75% of 63 subjects at a mean (+/- SE) concentration of 11.1 +/- 1.3 pg/ml, with a range of less than 2 to 55 pg/ml. In 31 subjects, simultaneous measurements were made of CSF and plasma CT and there was not significant correlation between them. Column chromatography of a lyophilized pool of CSF from 60 of the subjects demonstrated that most of the CT immunoreactivity eluted with or after radioiodinated human CT. Our studies demonstrate the presence of immunoreactive CT in human CSF but do not provide any direct evidence regarding the source of the immunoreactivity.