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Biomedical subjects

L T Ho

Publications and source records attributed to L T Ho.

At least 163 records · Page 9Linked to original sources
PubMed1987

Somatostatin effects in isolated human atrial fibres.

Effects of hypothalamic hormone somatostatin on the action potential and contractile force of 54 human atrial preparations obtained at cardiac surgery were studied with standard microelectrode techniques. In the atrial fibres responding to electrical stimuli with fast response action potentials in 4 mM [K]0 Tyrode solution (maximum rate of phase 0 depolarization greater than 50 V/s), somatostatin (10(-7) to 10(-6) M) reduced slightly the duration of action potential and decreased twitch force dose-dependently. In spontaneously active atrial fibres, somatostatin (10(-7) to 10(-6) M) abolished the action potentials in the preparations with low maximal diastolic potential (MDP, -48 +/- 2.8 mV), but induced only mild suppressive effect in the preparations with high MDP (-70 +/- 2.4 mV). When the fibres were depolarized in 27 mM [K]0 Tyrode solution, somatostatin decreased the maximum rate of depolarization and amplitude of the slow response action potentials induced by electrical stimuli. The delayed afterdepolarizations or triggered action potentials induced by high-frequency electrical drive in the presence of epinephrine were also suppressed by somatostatin. The above findings suggest that somatostatin may suppress the abnormal automaticity and the triggered activity in human atrial fibres through a reduction of cellular calcium.

Action Potentials↗
PubMed1987

The pancreatic glucagon and C-peptide secretion during hyperinsulinemia in euglycemic glucose clamp with or without somatostatin infusion in normal man.

6 normal subjects received two times of 2 hr euglycemic glucose clamp studies (insulin infusion rate 40 mU/M2/min) one with and the other without somatostatin (SRIF) infusion (500 microgram/hr). Serum C-peptide and glucagon levels were measured during clamp to study the sensitivity of pancreatic alpha and beta cells to the suppressive effects of exogenous hyperinsulinemia during normoglycemia in normal subjects and to find whether SRIF had any modulative effects on endocrine pancreas secretion at the status of hyperinsulinemia. The results showed that in normal man the degree of suppression of pancreatic glucagon secretion by hyperinsulinemia (approximately 100 uU/ml) during euglycemic glucose clamp without SRIF infusion was less than that of C-peptide with mean value of 62 +/- 4% of basal glucagon remained at the end of clamp study; while only about 30 +/- 2% of basal C-peptide concentrations remained. But during SRIF infused glucose clamp studies (SRIF was infused from 60 to 120 min), 32 +/- 2% of mean basal C-peptide concentrations and 38 +/- 6% of mean basal glucagon concentrations left at the end of 2 hr clamp studies when serum insulin level was about 100 uU/ml. For the glucose infusion rate (M value), it was significantly greater in our normal subjects in response to insulin + SRIF as compared to insulin alone (12.0 + 0.9 vs 8.8 +/- 1.4; P less than 0.01). We concluded: during hyperinsulinemia (100 uU/ml), the sensitivity of pancreatic alpha cells to insulin seems less than that of beta cells in normal man at normoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Hypothalamic involvement in the hyperglycemia and satiety actions of somatostatin in rats.

To determine whether the anorexic and the hyperglycemia actions of somatostatin were mediated through the hypothalamic nuclei, rats were infused with somatostatin and normal saline through previously implanted hypothalamic cannulae. Administration of somatostatin (0.5-1.5 microgram in 1.0 microliter) into the lateral hypothalamus, but not the ventromedial or the anterior hypothalamus, caused a reduction in food consumption without affecting relative water intake (or water-to-food ratio) in conscious rats in a freely moving state. On the other hand, administration of somatostatin into the lateral hypothalamus, but not the anterior or the ventromedial hypothalamus, caused an increase in blood glucose level in rats. This hyperglycemia was antagonized by vagotomy, but not by spinal transection or adrenalectomy. The data indicate that the lateral hypothalamus is the most sensitive site of the somatostatin-induced anorexia and the action of somatostatin on the lateral hypothalamus-vagus efferent activity is also a possible mechanism mediating hyperglycemia in rats.

Animals↗
PubMed1987

Effects of thyroidectomy and thyroxine replacement on the release of luteinizing hormone and gonadotropin-releasing hormone in vitro.

The effects of thyroidectomy and thyroxine (T4) replacement on the release of luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) in ovariectomized (Ovx) rats were studied. Immediately after ovariectomy, rats were thyroidectomized (Tx) or sham-Tx. The Ovx-Tx rats were injected subcutaneously with either saline or T4 (2 micrograms/100 g body weight) daily for 30 days before sacrifice. Sham-Tx rats were treated with saline only. Twenty hours after the last injection, the blood sample was obtained by decapitation. The excised anterior pituitary gland (AP) was bisected and incubated in vitro with or without 0.1, 0.5, 2.5, and 50 ng GnRH at 37 degrees C for 4 h. The mediobasal hypothalamus (MBH) was bisected and incubated with or without the AP of Ovx donor rat in vitro. Concentrations of LH and GnRH in the medium and that of LH in the serum were measured by radioimmunoassay. LH in the serum of Tx rats was higher than that in the serum of sham-Tx and Tx-T4 rats. Thyroidectomy resulted in an increase of LH release by Ovx rat AP, stimulated with or without 0.1 and 50 ng GnRH, as well as in an increase of immunoreactive GnRH release from MBH of Ovx rats in vitro. After a 4-hour incubation with donor APs, the LH in the medium containing MBH obtained from Tx rats was significantly higher than that obtained from sham-Tx and Tx-T4 rats. LH concentrations, in both sera and media, as well as GnRH concentration in the media of euthyroid and T4-replaced Tx groups were nonsignificantly different. These results suggest that T4 is inhibitory to the basal and GnRH-stimulated LH release as well as to the release of GnRH in the absence of ovarian hormones.

Animals↗
PubMed1987

Selective suppression of insulin-induced proliferation of cultured human hepatoma cells by somatostatin.

The effects of somatostatin (SRIF), insulin, and triiodothyronine (T3) on the growth of human hepatoma cells were investigated on the well-differentiated human hepatoma cell line Hep3B. Results showed that both insulin and T3 can stimulate cell growth of serum starved Hep3B cells at physiological concentrations. SRIF alone showed little growth-promoting activity. When added concurrently with insulin, however, SRIF suppressed the insulin-induced cell proliferation in a dose-dependent manner. On the other hand, SRIF had no inhibitory effect on T3-induced cell proliferation. SRIF is labile in the medium, with a half-life of about 2 h during culture incubation. SRIF did not disturb the insulin binding to its surface receptors nor inhibit the insulin-dependent receptor kinase activity of Hep3B cells in vitro. These results suggest that postreceptor regulation may be involved. The selective suppression by SRIF of insulin-induced cell growth provides an unique approach to the study of insulin actions on proliferation of human hepatoma cells.

Carcinoma, Hepatocellular↗
PubMed1987

Inhibition of somatostatin on glucose-induced release of gastric inhibitory polypeptide in rats.

The effect of somatostatin on glucoseinduced secretion of insulin and gastric inhibitory polypeptide (GIP) in rats was examined. Anesthetized male rats were catheterized via the right carotid artery before gastric infusion of 2 ml of 40% glucose through a syringe pump over 3 min. Ten micrograms somatostatin dissolved in 0.5 ml saline was injected intraperitoneally 10 min before oral glucose administration. Rats receiving 0.5 ml saline were used as controls. Blood samples were collected at -10, 0, 10, 20, 30, 45, 60, and 90 min after glucose infusion. Concentrations of GIP and insulin in rat plasma samples were measured by radioimmunoassay. The level of plasma glucose was determined by YSI glucose analyzer. The results revealed that the rise of plasma insulin and GIP after the glucose load was abolished by a preinjection of somatostatin. It is concluded that somatostatin at 10 micrograms inhibits the effects of oral glucose in stimulating the secretion of GIP from the gut, and insulin from the pancreas in normal fasted rats.

Animals↗
PubMed1986

Somatostatin potentiation of insulin-induced glucose uptake in normal individuals.

The ability of somatostatin (SRIF) to enhance insulin-stimulated glucose uptake was evaluated during clamp studies in normal individuals and patients with non-insulin-dependent diabetes mellitus (NIDDM). The results demonstrated that glucose uptake at insulin levels of approximately 100 microU/ml was significantly greater (P less than 0.001) in normal individuals in response to insulin plus SRIF as compared with insulin alone. In contrast, SRIF did not enhance insulin-stimulated glucose uptake in patients with NIDDM. Measurements were also made of the relative ability of insulin as compared with insulin plus SRIF to suppress C-peptide and glucagon concentrations during the clamp studies. The results of these experiments showed that SRIF did not potentiate the ability of insulin to suppress C-peptide concentrations in normal subjects but did in patients with NIDDM. However, plasma glucagon levels were reduced to a greater degree when SRIF was added to insulin in both normal and diabetic individuals.

C-Peptide↗
PubMed1986

Beta-adrenergic-mediated extrarenal potassium disposal in patients with end-stage renal disease: effect of propranolol.

This study was designed to investigate beta-adrenergic-mediated extrarenal potassium disposal in patients with end-stage renal disease (ESRD). Plasma potassium was measured over a period of 3 months in 20 patients with ESRD who were receiving the nonselective beta-blocker propranolol (n = 10) or not (n = 10). Both groups were virtually anuric and had a comparable plasma BUN, plasma bicarbonate, and red cell Na-K-ATPase activity. Plasma potassium measured before dialysis was higher in propranolol users than in nonusers (5.6 +/- 0.2 and 4.6 +/- 0.1 mEq/l, p less than 0.005). To examine beta-adrenergic-mediated internal potassium disposal more directly, epinephrine and epinephrine plus propranolol were acutely administered to another group of patients with ESRD and to normal subjects. Epinephrine resulted in a similar fall in plasma potassium in both groups (0.69 +/- 0.20 and 0.63 +/- 0.07 mEq/l, respectively), thereby suggesting unimpaired beta-adrenergic-mediated extrarenal potassium handling in patients with ESRD. In patients, however, the response to epinephrine was heterogeneous. In 4 of the 10 patients studied, epinephrine infusion did not result in a decrement in plasma potassium suggesting impaired beta-adrenergic responsiveness and thus blunting of this mechanism of extrarenal potassium disposal. In the remaining 6 patients, epinephrine infusion resulted in a fall in plasma potassium which was greater than that observed in normal subjects (1.13 +/- 0.14 and 0.63 +/- 0.07 mEq/l, respectively, p less than 0.01). In the presence of propranolol, the infusion of epinephrine did not result in a decrement in plasma potassium in these 6 patients or in the 6 normal subjects (0.04 +/- 0.07 and -0.02 +/- 0.06 mEq/l, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1986

Pharmacokinetics and effects of intravenous infusion of somatostatin in normal subjects--a two-compartment open model.

A direct radioimmunoassay of plasma somatostatin-like immunoreactivity (SRIF-LI) was developed and validated. The sensitivity was 16.0 pg/ml, and the specificity was good. The recovery of plasma SRIF-LI was 98.8 +/- 6.3%. The Scatchard plot of the antiserum binding data revealed a straight line, with a binding affinity of 3.52 X 10(-12) M and a binding capacity 4.06 X 10(-10) M. Synthetic SRIF (Stilamin), 250 micrograms, was infused intravenously over a 30-min period in 9 healthy volunteers. Plasma glucose, insulin (IRI), glucagon (IRG) and SRIF-LI were measured. A two-compartment open model was adopted to analyze the pharmacokinetic data of SRIF-LI. The results showed that plasma SRIF-LI rose from 192.2 +/- 16.2 pg/ml to a plateau of 2,129.8 +/- 288.2 pg/ml within 5-10 min after starting the infusion. The half disappearance time from plasma (Ta1/2) was 1.36 +/- 0.18 min, the half disappearance time from the 'remote' compartment (Tb1/2) was 49.6 +/- 10.9 min and the net half disappearance time from the two compartments together (Tn1/2) was 9.19 +/- 1.49 min. The metabolic clearance rate was 50.3 +/- 7.0 ml/kg/min. The plasma IRI, IRG and the IRI/IRG molar ratio were all suppressed during the infusion period. The recovery time of plasma IRG was mildly delayed in comparison to that of IRI. This indicates that there are dissociations between IRI and IRG in the extent and the duration of suppression caused by somatostatin infusion.

Adult↗
PubMed1986

Establishment of a radioimmunoassay of somatostatin in human plasma and in rat hypothalamus.

Synthetic cyclic somatostatin-14 (SRIF-14) was conjugated with carbodiimide onto hemocyanin to immunize rabbits, and anti-sera with high titers (1:5,000-100,000) and good sensitivity and specificity were obtained. 125I-Tyr1-SRIF was made and purified on CM-52 cation exchange column. The immunoreactive specific activity (SP.AC.) of the tracer was around 1013 mCi/mg, which was much higher than the commercial products and other reports. The sensitivity of the assay was around 16 pg/ml, and the detectable range 20-2000 pg/ml. Human plasma was freshly prepared in the presence of aprotinin. Rat hypothalamus was homogenized and extracted with HC1 followed by heating at 95 degrees C then centrifuged, and the supernatant assayed. The standard curves of the acetate buffer (ph 5.2), plasma doses, plasma recovery doses, hypothalamic extract doses, and hypothalamic extract recovery doses were all in good parallelism with each other. The recovery of SRIF from human plasma and from rat hypothalamus were 98.8 +/- 6.3% and 86.9 +/- 6.8%, respectively. The specificity of the antisera were very high, and they only cross-react with H2-SRIF and Tyr1-SRIF at 15% and 170%, respectively, of the immunoreactivity to cyclic SRIF-14. The Scatchard plot of the binding data showed a straight line with a Kd of 3.52 X 10(-12)M and binding capacity of 4.06 X 10(-10)M. The intra- and inter-assay coefficient of variation were 4.5% and 12%, respectively. When the synthetic cyclic SRIF (Stilamin) was infused intravenously into normal volunteers, there were reproducible plasma time-dose curves of SRIF-LI (SRIF Like Immunoreactivity), which revealed its plasma half life around 1.5 minutes, and metabolic clearance rate about 50 ml/kg/min.

Animals↗