Biomedical subjects

L T Ho

Publications and source records attributed to L T Ho.

At least 73 records · Page 4Linked to original sources

PubMed1997

Amelioration of insulin resistance and hypertension in a fructose-fed rat model with fish oil supplementation.

In type II diabetic patients, one can detect several pathologic changes including insulin resistance and hypertension. Sprague-Dawley rats fed a fructose-rich diet (group F) exhibited these characteristic abnormalities within 2 weeks and were an excellent laboratory animal model for research on insulin action and development of hypertension. Since fish oils containing omega-3 fatty acids have a beneficial effect in preventing atherosclerotic diseases, we performed repeated experiments to test the effects of fish oil supplementation in group F rats. Compared with control rats on a normal diet (group C), group F consistently developed hypertriglyceridemia without elevated plasma free fatty acid (FFA), fasting hyperinsulinemia together with fasting hyperglycemia (insulin resistance syndrome), and systolic hypertension within 3 weeks. Insulin-stimulated glucose uptake and insulin binding of adipocytes were significantly reduced. Rats fed the same high-fructose diet but supplemented with fish oil (group O) had alleviation of all of these metabolic defects and a normalized insulin sensitivity and blood pressure. beta-Cell function as shown by plasma glucose and insulin responses to oral glucose remained intact in group F and group O. The plasma endothelin-1 (ET-1) level and ET-1 binding to adipocytes were not different among the three groups. Based on these results, we suggest that dietary high fructose induced hypertriglyceridemia and insulin resistance with normal islet function, and that the induced hypertension was not associated with plasma ET-1 abnormalities and was probably caused by other undefined pathologic changes that can be prevented by dietary omega-3 fatty acids.

Adipocytes↗

PubMed1997

Acipimox attenuates hypertriglyceridemia in dyslipidemic noninsulin dependent diabetes mellitus patients without perturbation of insulin sensitivity and glycemic control.

Hyperlipidemia, hypertriglyceridemia in particular, is a common feature in patients with noninsulin dependent diabetes mellitus (NIDDM) and may associate with insulin insensitivity. Acipimox, being widely prescribed for treating hypertriglyceridemia, is also used in NIDDM patients for their dyslipidemia. In the present study, we evaluated the effect of acipimox in Chinese NIDDM patients with hypertriglyceridemia. A total of 16 patients enrolled in a double-blind, randomized, placebo-controlled and two-period crossover study. After an 8 week run-in period, patients were randomly assigned into two groups receiving either acipimox (250 mg, twice daily) or placebo treatment. A total of 12 weeks later, these two groups switched their treatment for an additional 12 weeks. Blood samples were collected at the end of the run-in period and then at 4-week intervals in the whole study for lipid profile. A modified insulin suppression test was performed at the ends of the run-in period, 12-week and 24-week treatment to assess changes in insulin sensitivity. Our results showed that acipimox significantly lowered serum total triglyceride while compared to those by placebo. However, no difference was observed in serum non-esterified fatty acid, low-density lipoprotein cholesterol, total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C) and HDL-C/ TC ratio between the two groups. Furthermore, glycemic indices and insulin sensitivity were similar during the base-line, placebo or acipimox periods. Taken together, our data suggest that acipimox significantly lowered TG without perturbation of insulin sensitivity in hypertriglyceridemic NIDDM patients.

Adult↗

PubMed1997

Soluble macrophage factors trigger apoptosis in cultured hippocampal neurons.

It is not clear whether macrophages which can phagocytose dead cells, may also contribute to death of potentially viable neurons when they enter brain lesion sites after insult. We have initially examined the effects of macrophage-conditioned medium on the integrity of hippocampal neurons in culture. We assessed qualitative and quantitative changes in neuronal status in terms of nuclear morphology, internucleosomal cleavage, cell membrane integrity and process density. Cell morphology with manual counts to quantitate findings showed that macrophage conditioned medium significantly increased the percentage of neurons with abnormal nuclei. Aurintricarboxylic acid attenuated this effect. Demonstration of laddering of DNA on agarose gels suggested an apoptosis-like event. A commercially available kit used to detect high concentrations of 3'-OH DNA ends showed marked increase in labelled cells. These combined findings confirmed that apoptosis was the main event triggered by conditioned medium. Although the number of cells with incompetent membranes also increased with conditioned medium application the majority of cells with apoptotic nuclei maintained membrane integrity. Conditioned medium also resulted in significant loss of cell processes. Conditioned medium from stimulated microglia showed a similar pattern of injury. The response of stressed neurons to conditioned medium was also tested. Exposure of cultures to mild hypoxia resulted in injury but did not significantly alter their subsequent vulnerability to macrophage-conditioned medium. Early experiments suggest that the documented changes in neuronal status are caused by relatively large and stable secreted macrophage proteins.

Animals↗

PubMed1997

Growth hormone (GH) replacement reduces total body fat and normalizes insulin sensitivity in GH-deficient adults: a report of one-year clinical experience.

The effects of GH replacement on body fat composition and insulin sensitivity were assessed in GH-deficient adults. The patients were randomized into a double-blind, placebo-controlled study of human recombinant GH replacement therapy for 6 months (period 1), followed by an open phase of GH for another 6 months (period 2). Anthropometric variables, body fat composition (fat %), and biochemical parameters were measured during the trial. Measurements of in vivo insulin sensitivity were carried out at the commencement of the study and on completion of the trial by modified insulin suppression test. The modified insulin suppression test was performed both in the morning (AM) and in the afternoon (PM) to further evaluate the PM-AM steady-state plasma glucose (SSPG) pattern. We found that the GH-deficient adults had more body fat and were insulin resistant. Significant reduction in fat % and total body fat mass was found in the active arm of period 1 without alteration of body weight. Besides, we demonstrated, for the first time, the GH replacement for 6 months did not alter the insulin sensitivity, but replacement for a longer period (12 months) normalized not only the AM SSPG level but also the PM-AM SSPG pattern. We also found a positive correlation between SSPG (regardless of AM vs. PM) and fat % and total body fat mass. In conclusion, normalization of insulin sensitivity in GH-deficient adults after replacement of GH may be related to the reduction of total body fat.

Adipose Tissue↗

PubMed1997

Inhibition of corticosterone secretion by thyroxine in male rats.

The effects of thyroxine (T4) on the secretion of corticosterone both in vivo and in vitro in male rats were studied. Rats were thyroidectomized (Tx) or sham Tx. The Tx rats were subcutaneously with T4 (20 micrograms/kg) or saline once daily for two weeks. In an in vitro experiment, adrenal glands were incubated with ACTH, T4, or ACTH plus T4 in the presence or absence of 0.5 mM 3-isobutyl-1-methylxanthine (IBMX) at 37 degrees C for 60 min. Medium and ether-extracted plasma samples were analyzed for corticosterone by radioimmunoassay (RIA). The accumulation of cyclic adenosine monophosphate (cAMP) in adrenal tissues after incubation with IBMX was measured by RIA. The levels of plasma corticosterone in Tx rats were significantly increased as compared with euthyroid rats. T4 replacement in Tx rats restored plasma corticosterone to euthyroid level. Administration of T4 in vitro resulted in an inhibition of both basal and ACTH-stimulated release of corticosterone. Both basal and ACTH-stimulated generations of cAMP in adrenal tissues were decreased by T4. These results suggest that T4 inhibits the spontaneous and ACTH-stimulated secretion of corticosterone by acting directly at adrenal glands via a decrease in cAMP production.

Adrenal Glands↗

PubMed1996

Endothelin-1 induces insulin resistance in conscious rats.

Since endothelin-1 (ET-1) might regulate insulin secretion and glucose metabolism, we carried out experiments to study the effect of ET-1 in conscious rats by injecting ET-1 (0.5 or 1.0 microgram/100 g body weight, i.p.) and examining the plasma glucose (PG) and insulin (PI) concentrations and PG/PI ratios continuously for 3 hours after the injection. Compared to the saline controls, ET-1 increased PG and PG/ P1 ratios in a dose-dependent manner. Oral glucose tolerance test (OGTT) performed at 30 min after the injection showed that PG levels stayed significantly higher in rats preinjected with ET-1 than rats with saline injection, although the change in PI levels was not different. Simultaneous infusion of glucose and insulin to somatostatin-primed rats with ET-1 or saline injection resulted in significantly higher steady state plasma glucose (SSPG) levels and SSPG/PI ratios in rats injected with ET-1 than control rats with saline. These results unequivocally indicated that intraperitoneally administered ET-1 induces insulin resistance in conscious rats.

Animals↗

PubMed1996

Neurocognitive function in chronic hemodialysis patients.

We administered a comprehensive neuropsychological test battery, including measures of intelligence, immediate and delayed memory, attention and mental processing speed, language abilities, complex problem solving, motor skills, and depression, to 16 well-dialyzed (Kt/Vurea = 1.46 +/- 0.24) patients with end-stage renal disease (ESRD) and 12 age- and education-matched medical controls. We observed no clear neuropsychological deficits in these ESRD patients who had low average intelligence and limited educational achievement, and hypothesize that previously observed apparent deficits resulted either from very low dialysis delivery or comparison with poorly-matched historical controls. There were significant deficits in language ability and intelligence in ESRD patients with higher than median scores on the Beck Depression Inventory compared with less-depressed ESRD patients. However, this effect of depression did not result in differences between dialysis and non-ESRD patient groups.

Adult↗

PubMed1996

Heterogeneous responses to the long-term treatment of active acromegaly with octreotide.

To study GH response to the long-acting somatostatin analogue, we treated 11 actively acromegalic patients with octreotide (Sandostatin), 100 micrograms, sc, tid, for six months. Their endocrinological outcomes and clinical improvements varied. The 11-h GH secretory profiles on pretreatment day confirmed the hypersecretion of GH in all patients. Three hours after the first dose of octreotide, serum GH declined rapidly to levels below 5 ng/ml in all but two patients who failed to normalize their serum GH. In spite of the subsequent doses, there was no further suppression in serum GH. Drug resistance with GH rebound developed in some patients after three months of continued treatment. The paradoxical serum GH rises in response to oral glucose or iv TRH detected before the treatment in all patients attenuated or disappeared after the 6-month octreotide therapy; an exceptional case was one of the above-mentioned two patients, whose serum GH was stimulated more than before by glucose and TRH at the end of therapy. Serum insulin-like growth factor I (IGF-I) levels of all patients showed a significant reduction after 6-month treatment, but their mean values remained abnormally high. There were no intolerable adverse side effects; some patients, however, experienced pain at the injection site, passage of loose stool, and incidence of new gall stone or intrahepatic lesions on octreotide therapy. We concluded that octreotide was a useful long-term adjunctive therapeutic agent for patients with active acromegaly, but that a high degree of response heterogeneity including total refractoriness would be expected.

Acromegaly↗

PubMed1996

Lovastatin lowers serum cholesterol levels in non-insulin-dependent diabetes mellitus patients without altering their insulin sensitivity.

BACKGROUND: Lovastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in the treatment of hypercholesterolemia. It is also applied to dyslipidemia in patients with diabetes mellitus. The influence of lovastatin on insulin sensitivity was evaluated in twelve Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients with hypercholesterolemia. METHODS: This double-blind, randomized, placebo-controlled, and two-period cross-over experiment enrolled 12 patients. After a run-in period of two months, the patients were randomized into 2 groups to receive either lovastatin (20 mg once daily) or placebo treatment. Eight weeks later, two groups of patients exchanged their treatment for another 8 weeks. Blood samples were collected at the end of the run-in period and at 4-week intervals during the study to observe serum lipid profiles. A modified insulin suppression test was made to assess insulin sensitivity three times: at the end of run-in period, in week 8 and week 16, respectively. Wilcoxon signed rank test was used for analysis of statistical significance of the difference between lovastatin and placebo treatments. RESULTS: As compared with the placebo, lovastatin reduced serum total cholesterol (TC) levels significantly. Serum total triglyceride (TG) concentrations decreased slightly by lovastatin. The ratio of TC to high density lipoprotein-cholesterol (HDL-C) also decreased significantly in lovastatin period. No difference was found in serum apolipoprotein A1 levels. A significant reduction of serum apolipoprotein B concentrations was also noted in lovastatin period. No difference in glycemic indices and insulin sensitivity was observed in the base-line, placebo or lovastatin periods. CONCLUSIONS: The results demonstrated that lovastatin significantly lowered the serum TC levels without perturbation of insulin sensitivity in hypercholesterolemic NIDDM patients.

Aged↗

PubMed1995

Alterations with age of the T3-stimulated release of atrial natriuretic peptide and its effect on water and sodium metabolism in rats.

The influence of age on urinary excretion of sodium and water and in vitro release of atrial natriuretic peptide (ANP) were studied in rats. Older rats had increased daily water intake and urine output. They also had increased plasma ANP, decreased right atrial contents of ANP and increased ANP release in response to 10 nM T3. The ageing process may have altered the regulatory mechanisms of water metabolism and secretion of ANP.

Aging↗

PubMed1995

Gastric inhibitory polypeptide and gastric acid secretion in pregnant rats.

The effects of pregnancy on the basal and pentagastrin-stimulated gastric acid secretion and the level of plasma gastric inhibitory polypeptide (GIP) in rats were studied on pentobarbital-anaesthetized non-pregnant rats and rats in the 1st, 2nd, or 3rd week of gestation. Acid output was determined by titration of the gastric perfusate. Basal secretion was collected for 45 min before a 30 min infusion of pentagastrin (8 micrograms/ml/300 g body weight). Concentration of plasma GIP was measured by a radioimmunoassay (RIA). The immunoreactivity of GIP-like substance in the extract of the rat placenta collected from the rat at day 21 of gestation was examined by RIA. The biological activity of GIP-like substance in the rat placenta extract was tested by the reduction of pentagastrin-stimulated gastric acid secretion in male rats. The basal level of gastric secretion was higher in late pregnancy as compared with the non-pregnant rats. Pentagastrin induced a greater increase of gastric acid secretion in early but not late pregnant rats as compared with the non-pregnant animals. The basal and post-pentagastrin level of plasma GIP was higher in rats in late pregnancy. Both immunoreactivity and biological activity of GIP exist in the rat placenta extract. These results suggest that the normalization of gastric acid secretion in late pregnant rats is at least in part due to the production of GIP-like substance from placenta.

Animals↗

PubMed1995

Evidence for CGRP accumulation and activity in experimental neuromas.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and widely distributed neuropeptide that may participate in the injury response of peripheral nerve. We examined evidence for the presence of CGRP immunoreactivity (IR) and its activity in experimental neuromas of Sprague-Dawley rats created by sectioning the midsciatic nerve with resection of 2-3 cm of its distal portion and branches. CGRP activity was evaluated by measuring local blood flow in neuromas using hydrogen polarography and laser-Doppler flowmetry. At all time points studied after nerve section (24 h, 48 h, 7 days, 14 days) there was a rise in local blood flow in the neuroma stumps. At 48 h the hyperemia was maximum but was reversed by topical application of human CGRP(8--37), a specific CGRP-receptor antagonist. CGRP presence was evaluated by immunohistochemistry and radioimmunoassay (RIA). At 24 and 48 h, CGRP IR was intense and distributed in a globular and diffuse pattern apparently not confined to discrete axonlike profiles. At 7 and 14 days, CGRP IR remained prominent and was associated with disorganized axonlike profiles, sometimes directed in a circumferential pattern around the outside of the neuroma. RIA confirmed rises in CGRP content at 24 and 48 h that accompanied the changes in local blood flow and altered distribution of CGRP IR. CGRP accumulates in a time-related fashion within experimental neuromas, where it induces among other possible actions prominent local vasodilatation. CGRP may be important in the regenerative milieu of injured nerves.

Animals↗

PubMed1995

Regulatory patterns of plasma pituitary-adrenal and pituitary-thyroid hormone secretions: indication for adrenal factor inhibiting adrenal response to ACTH.

Although organization and hormonal regulation of the hypothalamic-pituitary-adrenocortical (HPA) and the hypothalamic-pituitary-thyroid (HPT) axes share a remarkable degree of similarities, distinctive patterns of their plasma hormone secretions are observed. We measured plasma levels of ACTH-cortisol (PA) and hTSH-T3 (PT) pairs of hormones in 24-hour sequential blood specimens sampled at 30-minute intervals from 3 patients with suspected adrenal disorders and 4 normal volunteers and found the same percentage of discordant secretions of the PA and PT hormones but significantly greater coefficients of variations of the PA values than the PT values (p < 0.002). This confirms that plasma PT hormones are more tightly self-regulated between themselves than plasma PA hormones. Moreover, cluster analysis of the 24-hour plasma hormonal fluctuations revealed one or more ACTH-cortisol hyposecretory clusters only in subjects with a normal status of adrenal function. There was no similar hTSH-T3 hyposecretory cluster detected in any one of the 7 subjects. Based on these results, we postulate that there is some adrenal factor normally exerting a subtle antagonistic action against ACTH and causes the incidence of such ACTH-cortisol hyposecretory cluster.

Adrenocorticotropic Hormone↗

PubMed1995

Inhibition of cortisol production by aldosterone secretion-inhibitory factor and brain natriuretic peptides.

Circumstantial evidence has indicated that the adrenal gland may produce certain factors regulating its own corticoid production through a paracrine pathway. The putative factors play only a subtle role modulating adrenocortical function in response to ACTH. Aldosterone secretion-inhibitory factor (ASIF) and brain natriuretic peptides (BNP) are among the attractive candidates. ASIF was tested in a primary culture system of guinea-pig adrenal zona fasciculata (ZF) cells and found to be effective in suppressing both the basal and ACTH-stimulated cortisol production in a dose-dependent manner. At the effective doses, ASIF was not toxic to the cells in culture morphologically but attenuated the growth-stimulating action of ACTH. Tested with three types of natriuretic peptides in the same cell culture system, we found that BNP was as effective as ASIF. Studies on the relationship between peptide primary structures and activities revealed that the inhibitory activity of ASIF on cortisol production required an intact Cys-Cys loop with both N- and C-terminal extensions from Cys residues of not less than 2 amino acids.

Adrenal Glands↗

PubMed1994

Rhabdomyolysis in diabetic emergencies.

Rhabdomyolysis (RM) is a clinical and laboratory syndrome resulting from leakage of muscle cell contents into plasma. The increased plasma concentration of the substances released such as creatine kinase (CK) permits the clinician to diagnose this syndrome. Non-traumatic RM has occasionally been reported in patients with diabetic decompensation. We encountered about 44 cases of RM in 265 diabetic emergencies (including DKA or hyperosmolar, or both) during the period from 1984-1 to 1990-6, diagnosed based on (1) serum creatine kinase (CK) > 1000 IU/l and (2) the absence of acute myocardial infarction, stroke and end-stage renal disease. On admission, those who presented with RM had significantly higher concentration of blood urine nitrogen (BUN) (83.3 +/- 5.9 vs. 58.8 +/- 2.4 mg/dl, P < 0.05), creatine (4.45 +/- 0.4 vs. 2.97 +/- 0.1 mg/dl, P < 0.05) and serum osmolarity (386.5 +/- 5.2 vs. 351.6 +/- 2.4 mOsm/kg, P < 0.05). The mortality within 1 week of diabetic emergencies (38.5% for DKA, 35.5% for HHNK) was higher in patients with RM than those without RM (9.7% for DKA, 26.7% for HHNK). There was a correlation (r = 0.49, P < 0.05) between the levels of serum creatinine and CK in patients with RM.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Dorsal root ganglia microenvironment of female BB Wistar diabetic rats with mild neuropathy.

Abnormalities in the microenvironment of dorsal root ganglia (DRG) might play a role in the pathogenesis of sensory abnormalities in human diabetic neuropathy. We examined aspects of DRG microenvironment by measuring local blood flow and oxygen tension in the L4 dorsal root ganglia of female BB Wistar (BBW) diabetic rats with mild neuropathy. The findings were compared with concurrent measurements of local sciatic endoneurial blood flow and oxygen tension. Diabetic rats were treated with insulin and underwent electrophysiological, blood flow and oxygen tension measurements at either 7-11 or 17-23 weeks after the development of glycosuria. Nondiabetic female BB Wistar rats from the same colony served as controls. At both ages, BBW diabetic rats had significant abnormalities in sensory, but not motor conduction compared to nondiabetic controls. Sciatic endoneurial blood flow in the diabetic rats of both ages was similar to control values, but the older (17-23 week diabetic) BBW diabetic rats had a selective reduction in DRG blood flow. Sciatic endoneurial oxygen tensions were not significantly altered in the diabetic rats. DRG oxygen tension appeared lowered in younger (7-11 week diabetic) but not older (17-23 week diabetic) BBW rats. Our findings indicate that there are important changes in the DRG microenvironment of diabetic rats with selective sensory neuropathy.

Animals↗

PubMed1994

Endothelin-1 inhibits insulin-stimulated glucose uptake in isolated rat adipocytes.

A single class of high affinity endothelin-1 (ET-1) binding sites with an apparent Kd of 350 pM and a binding capacity of 69,000 sites/cell was found in isolated rat adipocytes. Whereas ET-1 had no effect on basal glucose uptake, it inhibited insulin-stimulated glucose uptake in both a dose- and time-dependent manner. Insulin binding, however, was not altered. Thus, the present study demonstrates the presence of ET-1 receptor in isolated rat adipocytes and the inhibition of insulin-stimulated glucose uptake by ET-1 via a post-receptor mechanism.

Adipocytes↗

PubMed1994

Neonatal guanethidine treatment alters endoneurial but not dorsal root ganglion perfusion in the rat.

In previous work, we suggested that there were differences in vasoregulation between dorsal root ganglia (DRG) and the endoneurium of peripheral nerve trunks. To investigate sympathetic control of both microvessel beds, we compared local perfusion in the sciatic nerve endoneurium and lumbar DRG of adult Sprague-Dawley rats treated from neonatal day 5 with guanethidine monosulfate to induce adrenergic sympathectomy. Control rats were injected with normal saline. Local blood flow and microvascular resistance were measured using microelectrodes sensitive to the clearance of hydrogen. Guanethidine-sympathectomized rats had higher sciatic endoneurial blood flow and lower endoneurial microvascular resistance than saline-injected controls. In contrast, DRG blood flow was not increased by sympathectomy and was comparable to control values despite the hypotension induced by sympathectomy. The results suggest that sympathetic control of local blood flow and may be less apparent in DRG than endoneurium and that local autoregulation may protect DRG from hypotension.

Animals↗