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Biomedical subjects

C McIntosh

Publications and source records attributed to C McIntosh.

At least 55 records · Page 3Linked to original sources

Increased somatostatin secretion from pancreatic islets of streptozotocin-diabetic rats in response to glucose.

Glucose stimulates somatostatin release from perifused pancreatic islets of diabetic rats 42-47 days after the induction of diabetes, and 48 h after withdrawal of insulin replacement therapy. The glucose effect is augmented by theophylline or glucagon. Basal somatostatin release and glucose-induced secretion are significantly higher in diabetic islets than in controls. It is suggested that glucose promotes somatostatin release by directly interacting with islet D cells but not via indirect pathways. Glucose-induced stimulation appears to be modulated by a D-cell adenylate cyclase/phosphodiesterase system. Reasons responsible for increased somatostatin secretion by diabetic islets include reduction in B-cell mass, suggesting that B cells may normally suppress the secretory activity of D cells.

Animals↗

Growth hormone cell antibodies and partial growth hormone deficiency in a girl with Turner's syndrome.

Growth hormone (GH) cell auto-antibodies have been demonstrated in the serum of a girl with an iso-chromosome variant of Turner's syndrome. On two occasions she showed an abnormal response of GH release during insulin induced hypoglycaemia. Her response to GH treatment was poor, but this was commenced at a very late bone-age. It is possible that autoimmunity is a new aetiological factor for GH deficiency in some cases.

Adolescent↗

Somatostatin and gastrin release from canine stomach.

Somatostatin and gastrin release into the veins draining the stomach was studied in 27 anaesthetized dogs. Basal somatostatin-like immunoreactivity (SLI) in corpus veins (136 +/- 36 pg/ml) was significantly higher than in antrum veins (83 +/- 20 pg/ml; p less than 0.05) and the femoral artery (58 +/- 15 pg/ml; p less than 0.02). During peptone, pH 6.5, perfusion of the stomach, SLI concentration increased significantly in the corpus veins to approximately four times basal and in the antrum veins to three times basal, whereas SLI levels in the peripheral circulation remained constant. Peptone, pH 3.5, and sodium oleate did not stimulate gastric SLI. Gastric distension increased significantly SLI release from the corpus. In gel filtration studies 50%--70% of SLI from gastric vein plasma samples but greater than 90% from femoral artery samples eluted in the void volume of Sephadex G-25 columns. Gastrin secretion was stimulated significantly only by peptone, pH 6.5.

Animals↗

Effect of fasting on the release of insulin and somatostatin from perifused islets of Langerhans.

Release of somatostatin and insulin from perifused islets of fasted and control rats was compared. After a fasting period of 48 h glucose-induced insulin release but not somatostatin release was diminished. Islets from fasted rats released significantly more somatostatin in the presence of 3.3 mM glucose than islets from controls. Simultaneously, the somatostatin content of isolated islets from fasting rats was significantly decreased. The results indicate that the low secretory activity of islet B cells in the fasting state is associated with a high secretory activity of islet D cells.

Animals↗

[Calcium and phosphate metabolism in hemofiltration (author's transl)].

In 10 patients undergoing hemofiltration treatment acute changes of parameters in the calcium-phosphate metaboism were investigated. Balance studies were also performed in all patients. Control studies were conducted after a 3-month interval in 7 patients. Whereas ionized calcium and 25-HCC remained constant, there was a significant decrease in phosphate, magnesium, fluoride and parathyroid hormone. Corresponding to these results, negative balances could be seen during the course of a hemofiltration treatment: for phosphate a mean value of -593 mg, for magnesium -8.4 mEq and for fluoride -458 microgram. When a calcium content of 3.75 mEq/l was used in the substitution solution, an only slightly positive calcium balance of +1.51 mEq/l (mean value) was found. A significant correlation between calcium and fluid balance was demonstrated by means of 197 filtration treatments of one patient: the calcium balance became negative whenever the fluid loss was greater than 3.86 liters. After a 3-month period no significant changes in the above parameters were found, which indicates, that disturbances in the calcium-phosphate-parathyroid hormone metabolism do not only lie in a reduced renal elimination. Even though our results do not indicate that hemofiltration treatment induces or increases the chances of renal osteodystrophy, the calcium concentration of the substitution solution should be increased to 4.0 mEq/l, in order to guarentee a positive calcium balance even by forced filtration.

Adolescent↗

Comparison of alpha-ketoisocaproic acid and glucose in rats: effects on insulin and somatostatin release and on islet cAMP content.

The insulinotropic effects of alpha-ketoisocaproic acid and glucose reveal many common characteristics in vivo and in vitro. They qualify as initiators of insulin release, their action is amplified by potentiators of insulin release, and they have a similar potency at equimolar concentrations. The dynamics of insulin release evoked by alpha-ketoisocaproic acid and glucose are similar. Epinephrine completely inhibits the insulinotropic effect of glucose and alpha-ketoisocaproic acid. Mannoheptulose exhibits a complete, immediate and reversible blockade of glucose-induced insulin release. In contrast, inhibition of alpha-ketoisocaproic acid-induced insulin release occurs after a lag period and is not reversed by removal of the inhibitor. alpha-ketoisocaproic acid, at equimolar concentrations, is several-fold more effective than glucose in elevating cAMP content in islet. alpha ketoisocaproic acid and glucose are about equally effective in stimulating somatostatin release from isolated rat pancreatic islets. This stimulation is inhibited by epinephrine. Mannoheptulose inhibits only somatostatin release induced by glucose but not by alpha-ketoisocaproic acid. It suggested that the insulinotropic characteristics of glucose and alpha-ketoisocaproic acid reveal many common features, while their mode of action appears to be different.

Animals↗

Assessment of hormone loss through hemofiltration.

The concentrations of testosterone, cortisone, gastrin, insulin, gastric inhibitory polypeptide (GIP), somatomedin B, parathyroid hormone (PTH), human growth hormone (HGH) and thyroid stimulating hormone (TSH) have been determined in the plasma and the ultrafiltrate of five uremic patients undergoing intermittent hemofiltration treatment. There was a considerable loss of gastrin, insulin, GIP, somatomedin B and PTH by hemofiltration treatment. The plasma concentrations, however, did not decrease except for immunoreactive-PTH (IR-PTH) which returned from elevated to normal levels. Cortisone, HGH and TSH concentrations in the ultrafiltrate were below the measureable range. A significant elimination of 11-hydroxylated androstans by hemofiltration may have a positive effect on the disturbed steroid metabolism. Results indicate that hemofiltration does not cause a hormone deficiency syndrome. On the contrary, the loss of degradation products of hormones with disturbing biological activity may be a favorable effect of the hemofiltration treatment.

Cortisone↗

Gastrointestinal somatostatin: extraction and radioimmunoassay in different species.

A radioimmunoassay capable of detecting 300 fg somatostatin has been developed and levels of the polypeptide in gastrointestinal tissues from man, dog, and rat have been measured. Rapid freezing of collected samples and careful control of extraction is necessary. Concentrations in different regions of dog antrum (425 +/- 50 to 773 +/- 254 ng/g tissue) are similar to those in antrum from duodenal ulcer patients and control subjects: 614 +/- 125 and 465 +/- 104 ng/g tissue respectively. Levels in histologically normal human pancreas (253 +/- 43 ng/g tissue) are comparable with those in dog pancreas (333 +/- 66 ng/g tissue), whereas in two cases of neonatal hypoglycaemia the concentration exceeded 3000 ng/g tissue. On gel chromatography the majority of immunoreactive somatostatin elutes as the synthetic tetradecapeptide and a small fraction as a larger species.

Animals↗

The radioimmunoassay and physiology of somatostatin in the pancreas and gastrointestinal tract.

Radioimmunoassays for somatostain have demonstrated that high concentrations of the polypeptide are present in the pancreas and gastrointestinal tract of a number of species. Although measurement in tissue extracts is relatively unproblematic, detection and characterization of somatostatin-like material in plasma has proved technically difficult. Studies of pancreatic somatostatin release in vitro suggest a possible function in the regulation of islet hormone secretion, but the mode of action remains to be elucidated. Although, at present, no clinical relevance can be attributed to the somatostain radioimmunoassay reports of somatostatin secreting tumors and changes in stomach tissue content in patients with ulcer disease indicate a contributory role in the pathophysiology of certain disease states.

Animals↗

[Pancreatic polypeptide (PP) (author's transl)].

Pancreatic polypeptide (PP) can be reproducible measured in serum and tissue extracts by mean of a standardized radioimmunoassay. Dispite extensive investigations into the biological actions of the polypeptide and a range of radioimmunological measurements in serum and tissue the physiological significance of PP is, at present, unclear. The normal postprandial increase of serum PP levels has been reported to be lacking after vagotomy and reduced in patients with chronic pancreatitis. If these observations can be confirmed then PP measurement may be a clinically usefull criterion as to the effectiveness of vagotomy and as an indicator for chronic pancreatic disease.

Digestion↗

Plasma digoxin levels in anuric patients and normal subjects taking digitoxin.

Plasma digoxin suspected to be elevated in anuric patients taking digitoxin was determined by radioimmunoassay in 15 anuric patients and 15 normal persons subjected to 0.1 mg digitoxin therapy per day. All plasma digoxin values from the anuric patients and the normal subjects were far below the lower limit of the therapeutic range of plasma digoxin. There existed no difference between the digoxin values determined in anuric patients and subjects with normal renal function; in both groups there was a scatter of digoxin values about the cross reaction line between digitoxin and digoxin antibody. It is concluded from the results that digoxin retention in anuric patients taking digitoxin plays an insignificant role; thus, the pharmacological effect is mediated by digitoxin itself.

Anuria↗

Metabolic and clinical studies on patients with acromegaly treated with bromocriptine over 22 months.

In twenty-two patients with active acromegaly who were untreated or unsuccessfully operated or irradiated (mean growth hormone (GH) values greater than 4 ng/ml) the following investigations were performed: routine laboratory tests, tomography of pituitary fossa, oral glucose tolerance tests, TRH and other pituitary function tests and GH profiles over 5-10 h before and during bromocriptine treatment with daily doses between 7.5 and 50 mg. In seventeen patients GH was suppressed to less than 50% by bromocriptine, in thirteen of them it was normalized on at least one occasion. A TRH induced GH release was observed in all but two responders to bromocriptine before therapy. This effect of TRH was not blunted during treatment with bromocriptine and also in the two patients with negative tests before therapy a significant GH increase was observed. In no non-responder to bromocriptine was a significant increase of GH after TRH observed. One patient showed a secondary resistance to bromocriptine during a period of treatment with griseofulvin. In the remaining sixteen patients the GH suppression has been consistent for between 3 and 22 months. A single dose of pimozide abolished the bromocriptine effect on GH totally in one patient; in others a slight or no significant effect was observed. Tissue swelling and sweating decreased in all bromocriptine responders and glucose tolerance improved in five patients. In four diabetic patients a partial or full remission of diabetes occurred. Apart from postural hypotension after the first administration in two patients no other severe side effects have been observed. Sella size and the other pituitary functions did not change during the time of the study. It seems that a high percentage of acromegalics may be successfully treated with bromocriptine.

Acromegaly↗

Parathyroid hormone, calcium and phosphate balance in hemofiltration.

The acute changes in calcium, phosphate and parathyroid hormone have been examined in chronic renal failure patients under-going hemofiltration therapy and the results compared to a similar group treated by hemodialysis. In both groups there was a significant increase in Catot (0.32 mEq/1 for hemodialysis; 0.56 m Eq/1 for hemofiltration) with Ca++ remaining constant. Plasma phosphate and parathyroid hormone decreased during hemofiltration. Calcium balances were slightly positive and phosphate balances distinctly negative in all cases. To date there is no indication of induced osteodystrophy during hemofiltration therapy, although long-term studies are needed. However, the present results indicate, that hemofiltration more closely approaches the physiological situation than conventional hemodialysis.

Calcium↗