Biomedical subjects

L T Ho

Publications and source records attributed to L T Ho.

At least 55 records · Page 3Linked to original sources

PubMed1999

Propentofylline protects neurons in culture from death triggered by macrophage or microglial secretory products.

We recently demonstrated that conditioned medium (CM) from peritoneal macrophages or activated microglia triggers a predominantly apoptotic death in hippocampal neurons in culture. We tested the effects of propentofylline (ppf), an agent that is neuroprotective in focal ischemia and is also associated with reduced microglial antigen expression after insult. Ppf had no impact on the secretion of neurotoxin from microglia. However, ppf significantly attenuated the effects of macrophage and microglial conditioned medium on neurons. Ppf did not attenuate neuronal hypoxic injury but did reverse the exaggeration of hypoxic injury exerted by subsequent addition of macrophage CM. A1 and A2 adenosine receptor inhibitors and an inhibitor of adenosine uptake each mimicked the effect of ppf. Neither ATP nor a deaminase inhibitor blocked the effect of microglial CM. These findings may be relevant to the neuroprotective effects of ppf in ischemia and dementia.

Adenine↗

PubMed1999

Exogenous hyperinsulinemia causes insulin resistance, hyperendothelinemia, and subsequent hypertension in rats.

In many clinical and animal studies, hypertension and insulin resistance coexist, but their mechanistic relationship is unclear. We explored the causal link between these two parameters in a rat model with chronic hyperinsulinemia induced with human insulin (1 U/d) released from subcutaneously implanted minipumps. Rats with saline minipumps served as a control. During the first experiment, plasma levels of insulin and glucose and the systolic blood pressure of the two groups were continuously monitored for 17 days. In the subsequent four experiments, rats were killed on days 10 and 13 to measure plasma endothelin-1 (ET-1) levels and the glucose transport into and insulin and ET-1 binding of isolated adipocytes. In one experiment, rats were tested for oral glucose tolerance on days 10 and 13. In another experiment, ET-1 binding to the aortic plasma membrane was also determined. The results showed that rats became hyperinsulinemic throughout the experimental period by the instillation of exogenous insulin. Hyperinsulinemic rats were consistently hypoglycemic during the first day, but they became euglycemic thereafter, indicating an insulin-resistant state. Glucose intolerance was obvious by day 10, but significant hypertension was not detected until the 11th day on insulin infusion. Compared with the saline controls, insulin-infused rats had an increase of plasma ET-1 levels but a decrease of both basal and insulin-stimulated glucose transport into adipocytes. ET-1 binding to adipocytes of the insulin-infused group was elevated significantly from day 10 through day 13. ET-1 binding to the aortic membranes, supposedly downregulated by the increased plasma ET-1 and hypertension, was similar to that found in the controls on day 13. These results imply that hyperinsulinemia in rats could lead to hypertension via the elevation of plasma ET-1 levels together with an unaltered vascular binding of ET-1, which was probably unrelated to the insulin resistance.

Adipocytes↗

PubMed1999

Inhibition of aldosterone production by testosterone in male rats.

In vivo and in vitro experiments were designed to assess the effect of testosterone on aldosterone secretion in male rats. Orchidectomized rats were injected subcutaneously with oil or testosterone propionate ([TP] 2 mg/kg) for 7 days. Intact rats were injected with oil only. The results indicate that the plasma aldosterone level was higher in orchidectomized versus intact and TP-replaced rats. In the in vitro study, testosterone caused a marked decrease of aldosterone secretion by zona glomerulosa (ZG) cells, but failed to alter the accumulation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP). Testosterone significantly decreased the corticotropin (ACTH)-stimulated production of aldosterone and accumulation of cAMP in rat ZG cells. The conversion of corticosterone to aldosterone and of 25-OH-cholesterol to pregnenolone, as well as angiotensin II (ANG II)-stimulated production of aldosterone, were decreased by testosterone. These results suggest that testosterone inhibits the basal and ANG II- and ACTH-stimulated release of aldosterone, via inhibition of aldosterone synthase activity and cytochrome P-450 side-chain cleavage (P450scc) activity, and ACTH-stimulated cAMP accumulation in rat ZG cells.

1-Methyl-3-isobutylxanthine↗

PubMed1999

Lack of effect of simvastatin on insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia: results from a double-blind, randomized, placebo-controlled crossover study.

AIMS: To evaluate the effects of simvastatin on serum lipids and insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia. METHODS: A double-blind, randomized, placebo-controlled and two-period crossover study. After a 2-month run-in, 19 eligible Type 2 diabetic patients with hypercholesterolaemia were randomized to receive either simvastatin or placebo for 3 months, exchanging their treatment thereafter for another 3 months. Blood samples were taken in month 0 and at monthly intervals to measure serum lipids and indices of glycaemic control. An euglycaemic insulin clamp was performed in months 0, 3 and 6 to assess change of insulin sensitivity. The amount of glucose infused during 90-120 min of the clamp (M), and the mean values of serum insulin during 90-120 min (I) were measured. The M and M/I ratio were used to represent the in vivo insulin sensitivity of the subject. RESULTS: Simvastatin significantly reduced serum total cholesterol (TC) by 23+/-18% and low density lipoprotein-cholesterol (LDL-C) by 30+/-26%. It did not alter glycaemic control. The M-values and M/I ratios were similar in both groups in each period and no drug effect on insulin sensitivity could be identified. CONCLUSIONS: Simvastatin significantly reduced the serum TC and LDL-C levels without alteration of insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia.

Adult↗

PubMed1999

Carboxyfullerene prevents iron-induced oxidative stress in rat brain.

Carboxyfullerene, a water-soluble carboxylic acid derivative of a fullerene, was investigated as a protective agent against iron-induced oxidative stress in the nigrostriatal dopaminergic system of anesthetized rats. Intranigral infusion of exclusive carboxyfullerene did not increase lipid peroxidation in substantia nigra or deplete dopamine content in striatum. Infusion of ferrous citrate (iron II) induced degeneration of the nigrostriatal dopaminergic system. An increase in lipid peroxidation in substantia nigra as well as decreases in K+-evoked dopamine overflow and dopamine content in striatum were observed 7 days after the infusion. Co-infusion of carboxyfullerene prevented iron-induced oxidative injury. Furthermore, tyrosine hydroxylase-immunoreactive staining showed that carboxyfullerene inhibited the iron-induced loss of the dopaminergic nerve terminals in striatum. The antioxidative action of carboxyfullerene was verified by in vitro studies. Incubation of brain homogenates increased the formation of the Schiff base fluorescent products of malonaldehyde, an indicator of lipid peroxidation. Both autooxidation (without exogenous iron) and iron-induced elevation of lipid peroxidation of brain homogenates were suppressed by carboxyfullerene in a dose-dependent manner. Our results suggest that intranigral infusion of carboxyfullerene appears to be nontoxic to the nigrostriatal dopaminergic system. Furthermore, the potent antioxidative action of carboxyfullerene protects the nigrostriatal dopaminergic system from iron-induced oxidative injury.

Animals↗

PubMed1999

The antioxidative effect of carboxyfullerenes (C3/D3) on iron-induced oxidative injury in CNS.

Carboxyfullerenes, including two regioisomers C3 and D3, were investigated as antioxidants against iron-induced oxidative stress in vivo and in vitro. Both C3 and D3 dose-dependently inhibited autoxidation and iron-elevated lipid peroxidation in cortical homogenates. The antioxidative property of C3 was compared to Trolox (a water-soluble analogue of vitamin E) and glutathione. C3 was more effective than glutathione but was less effective than Trolox in inhibiting iron-induced elevation in lipid peroxidation. In urethane-anesthetized rats, intranigral infusion of iron degenerated the nigrostriatal dopaminergic system, including as elevation in lipid peroxidation in the infused substantia nigra (SN) and reductions in K(+)-evoked dopamine overflow and dopamine content in the ipsilateral striatum 7 days after the infusion. Local application of iron with C3 or D3 prevented iron-induced oxidative injuries. Our data suggest that carboxyfullerenes have a neuroprotective effect in preventing iron-induced oxidative injury in CNS.

Animals↗

PubMed1999

Clinical response and patient acceptance of a prefilled, disposable insulin pen injector for insulin-treated diabetes.

BACKGROUND: The aim of this study was to evaluate the clinical response and patient acceptance of a prefilled, disposable insulin pen injector (Novolet, Novo-Nordisk, Bagsvaerd, Denmark) for treating insulin-dependent diabetic patients. METHODS: After a run-in period of six weeks, 19 patients participated in an open, randomized, controlled, crossover study with two 12-week periods using insulin pens or conventional syringes. Clinical responses were assessed every 12 weeks, including glycosylated hemoglobin (HbA1c), seven-point blood glucose profiles and hypoglycemic reactions. At the end of the trial, patients completed questionnaires about their acceptance of the insulin delivery device. RESULTS: Neither of the regimens rendered significant changes in HbA1c, blood glucose profiles or hypoglycemic episodes. Most of the study subjects reported that the prefilled, disposable devices were convenient and easy to use, and many of them wished to continue using the device for insulin delivery. CONCLUSIONS: The clinical response was the same for both treatment regimens, but most subjects preferred the prefilled disposable pen injector for insulin delivery because it was more convenient for daily use.

Adult↗

PubMed1999

Octreotide effect on hypersecretion of growth hormone in a patient with fibrous dysplasia: a case report.

We report the case of a 17-year-old adolescent boy with polyostotic fibrous dysplasia and hypersecretion of growth hormone (GH). The fasting serum GH, insulin-like growth factor-I (IGF-I), alkaline phosphatase activity and osteocalcin levels were all elevated. The GH secretion was stimulated by thyrotropin-releasing hormone and was not suppressed by an oral glucose test. Magnetic resonance imaging of the sella turcica showed no abnormal findings. The patient was treated with octreotide, 100 micrograms subcutaneous injection three times a day for two weeks to observe the effects of octreotide on growth hormone secretion. GH and IGF-I secretions were suppressed by octreotide therapy, while alkaline phosphatase activity and osteocalcin secretion were partially suppressed. We suggest that the high bone turnover states in this patient may be attributed to both hypersecretion of growth hormone and the polyostotic fibrous dysplasia itself.

Adolescent↗

PubMed1998

The antioxidative property of green tea against iron-induced oxidative stress in rat brain.

The antioxidative property of green tea against iron-induced oxidative stress was investigated in the rat brain both in vivo and in vivo. Incubation of brain homogenates at 37 degrees C for 4 hours in vitro increased the formation of Schiff base fluorescent products of malonaldehyde, an indicator of lipid peroxidation. Auto-oxidation (without exogenous iron) of brain homogenates was inhibited by green tea extract in a concentration-dependent manner. Moreover, incubation with iron (1 microM) elevated lipid peroxidation of brain homogenates after 4-hour incubation at 37 degrees C. Co-incubation with green tea extract dose-dependently inhibited the iron-induced elevation in lipid peroxidation. For the in vivo studies: ferrous citrate (iron, 4.2 nmoles) was infused intranigrally and induced degeneration of the nigrostriatal dopaminergic system of rat brain. An increase in lipid peroxidation in substantia nigra as well as a decrease in dopamine content in striatum was observed seven days after the iron infusion. Intranigral infusion of green tea extract alone did not increase, and in some cases, even decreased lipid peroxidation in substantia nigra. Co-infusion of green tea extract prevented oxidative injury induced by iron. Both iron-induced elevation in lipid peroxidation in substantia nigra and iron-induced decrease in dopamine content in striatum were suppressed. Oral administration of green tea extract for two weeks did not prevent the iron-induced oxidative injury in nigrostriatal dopaminergic system. Our results suggest that intranigral infusion of green tea extract appears to be nontoxic to the nigrostriatal dopaminergic system. Furthermore, the potent antioxidative action of green tea extract protects the nigrostriatal dopaminergic system from the iron-induced oxidative injury.

Administration, Oral↗

PubMed1998

Evidence that endothelin-1 (ET-1) inhibits insulin-stimulated glucose uptake in rat adipocytes mainly through ETA receptors.

The specificity of endothelin (ET) receptors involved in the inhibition of insulin-stimulated glucose uptake (ISGU) in rat adipocytes was investigated. Adipocytes were isolated from the epididymal fat pads of Sprague-Dawley rats. To determine receptor subtypes, we used three ET isopeptides, ET-1 and ET-2, both of which are nonselective agonists, and ET-3, a selective agonist for ETC receptors, to displace [125I]ET-1 binding from the fat cells. The efficiency of displacement was ET-1 > ET-2 >> ET-3, indicating that the primary receptors involved belonged to the ETA subtype. At an equal concentration of 1 micromol/L, BQ-610, a selective ETA antagonist, displaced [125I]ET-1 from binding to fat cells, whereas IRL-1038, a selective ETB antagonist, did not. Using [3H]2-deoxy-D-1-glucose ([3H]2-DG) as a tracer in studies of glucose uptake, we found that equimolar BQ-610 completely reversed the inhibitory effect of ET-1 on ISGU, whereas IRL-1038 was ineffective. Northern blot analysis of adipocyte receptors showed abundant mRNA for ETA, but no ETB subtype. These results clearly demonstrate that ETA is the predominant receptor in rat adipocytes.

Adipocytes↗

PubMed1998

Effects of parathyroid hormone infusion on glucose tolerance and glucose-stimulated insulin secretion in normal and uremic rats.

We used thyroparathyroidectomized (TPTX) rats with hypocalcemia to evaluate the effects of parathyroid hormone (PTH) infusion on glucose tolerance and glucose-stimulated insulin secretion in normal and uremic rats. Animals were subjected to oral glucose tolerance test (OGTT) and glucose-stimulated insulin secretion before and after TPTX or after their plasma calcium level was normalized by PTH infusion, vitamin D injection or calcium load. In both normal and uremic groups, TPTX produced a significant increase in area under the cure (AUC) of plasma glucose from 0 to 6 h in response to an oral glucose challenge and decrease plasma insulin level in response to glucose-stimulated insulin secretion. Before TPTX, uremic animals have a normal basal plasma insulin level (29 +/- 3 versus 31 +/- 2 microU/ml) and a normal glucose-stimulated insulin secretion, but significantly increase plasma glucose AUC in response to OGTT as compared with normal rats. TPTX worsen the response of glucose intolerance in uremic rats. After PTH infusion, vitamin D injection or calcium load, all rats in the response of OGTT and glucose-stimulated insulin secretion are recovered to the level before TPTX including normal and uremic rats, but uremic rats still have an abnormal glucose tolerance in response to OGTT. Uremic rats have a low basal plasma glucose level as compared with normal rats. TPTX significantly increase basal plasma glucose level in normal and uremic rats, but the uremic rats with TPTX have been found to elevate basal plasma glucose level to the range of normal rats. The basal plasma glucose level of normal rats with TPTX was recovered to the range before TPTX by PTH infusion, vitamin D injection or calcium load, but PTH infusion, vitamin D injection or calcium load did not decrease the level of basal plasma glucose in uremic rats with TPTX. All TPTX rats, including intact kidney or five-sixths Nx rats, were treated three times weekly by subcutaneous injection of 8 micrograms/kg L-thyroxin. These results indicate that uremia may produce thyroid dysfunction and PTH infusion did not affect the glucose tolerance in OGTT and glucose-stimulated insulin secretion in normal and uremic rats. In addition to PTH, other uremic toxins may be responsible for the glucose intolerance of uremia.

Animals↗

PubMed1998

Technical and clinical evaluation of an electrochemistry glucose meter: experience in a diabetes center.

The Sensorex (Metertech, Taipei, Taiwan), an electrochemical blood glucose meter, is designed for self-monitoring of blood glucose (BG) concentrations in capillary blood through the use of an electrochemical test strip. The intra-assay coefficients of variation of Sensorex were 5.2, 5.4, and 4.7% at BG levels of 46, 154 and 302 mg/dl respectively. The BG concentrations tested by Sensorex were correlated well with those by YSI method (r approximately/= 0.85, P < 0.0001). The intraclass correlation coefficients (rI) between the results obtained by Sensorex and YSI were 0.84 in capillary blood and 0.69 in venous whole blood, which indicated good agreement between both methods. The Sensorex was evaluated by error grid analysis and revealed 'acceptance' results. In field test, the Sensorex results obtained by lay users were in concordance with those by trained technicians (rI = 0.87). Our data show that the Sensorex glucometer is reliable and easy to use. We also demonstrate a practical clinical approach for the evaluation of a novel SMBG system.

Adolescent↗

PubMed1998

Arachidonic acid and protein synthesis inhibitor act synergistically to suppress insulin-stimulated glucose transport in 3T3-L1 adipocytes.

The effect of arachidonic acid (AA) on insulin-stimulated glucose transport by 3T3-L1 adipocytes was examined in the presence of cycloheximide. We found that AA acted synergistically with cycloheximide to suppress insulin-stimulated glucose transport, although it alone was without effect. Similar phenomena were observed while protein synthesis inhibitors other than cycloheximide were employed. Immunoblot analysis indicated that the increase in plasma membranes of the insulin-regulated glucose transporter (GLUT4) in response to insulin was decreased in cells pretreated with cycloheximide for a prolonged time, while total amount of GLUT4 was not altered. Simultaneous presence of AA with cycloheximide had no further effect on the amount of GLUT4 in either total or plasma membranes. Thus the present study suggests that AA in the presence of a protein synthesis inhibitor seems to decrease the intrinsic activity of GLUT4.

3T3 Cells↗

PubMed1998

Overexpression of vascular endothelin-1 and endothelin-A receptors in a fructose-induced hypertensive rat model.

OBJECTIVE: To examine the temporal relationship between hyperinsulinemia and hypertension in the fructose-hypertensive rat model and to study the function of endothelin-1 (ET-1) in fructose-induced hypertension. DESIGN: Since ET-1 induces insulin resistance in conscious rats, we tested the hypothesis that both hyperinsulinemia and hypertension developed in the fructose-hypertensive rat model might be the sequelae of an elevated tissue content of ET-1 and ET(A) receptors. MATERIALS AND METHODS: Systolic hypertension was induced within 3 weeks in male Sprague-Dawley rats fed on a fructose-rich diet. After continual monitoring of blood pressure and plasma insulin concentrations, the animals were killed at the end of experiment to determine plasma levels of ET-1, the contractile response of aortic rings to ET-1, and ET-1 and ET(A) receptor gene expressions. In a separate experiment, BQ-610 was administered to lower the effect of ET-1 in rats with fructose-induced hypertension. RESULTS: Compared with control rats given normal chow, the fructose-fed rats developed systolic hypertension after 3 weeks of the diet (127+/-3.7 versus 110+/-5.5 mmHg, P < 0.01) and hyperinsulinemia both before (1 07.1+/-32.5 versus 48.5+/-14.3 pmol/l, P < 0.005) and after (96.6+/-63.7 versus 50.4+/-5.6 pmol/l, P< 0.05) they became hypertensive. Although plasma ET-1 levels did not differ between the rat groups, aortic ring contraction-concentration curves, indicating vessel contractility in response to ET-1, were significantly greater in these rats than in controls (F1,72 = 12.34, P< 0.00077). Messenger RNA extracted from the tail arteries and blotted with both ET-1 and ET(A) probes showed that fructose-fed rats had greater ET-1 and ET(A)-receptor gene expression than control rats. Concomitant administration of BQ-610 to rats fed on a fructose diet significantly reduced the hypertension. Conclusions These findings suggest that elevated vascular expression of ET-1 and ET(A) receptor genes may mediate the development of hypertension and hyperinsulinemia in rats fed a fructose-rich diet

Animals↗

PubMed1998

Acute effects of thyroid hormones on the production of adrenal cAMP and corticosterone in male rats.

The acute effects of thyroid hormones on glucocorticoid secretion were studied. Venous blood samples were collected from male rats after they received intravenous 3,5,3'-triiodothyronine (T3) or thyroxine (T4). Zona fasciculata-reticularis (ZFR) cells were treated with adrenocorticotropic hormone (ACTH), T3, T4, ACTH plus T3, or ACTH plus T4 at 37 degrees C for 2 h. Corticosterone concentrations in plasma and cell media, and also adenosine 3',5'-cyclic monophosphate (cAMP) production in ZFR cells in the presence of 3-isobutyl-1-methylxanthine, were determined. The effects of thyroid hormones on the activities of steroidogenic enzymes of ZFR cells were measured by the amounts of intermediate steroidal products separated by thin-layer chromatography. Administration of T3 and T4 suppressed the basal and the ACTH-stimulated levels of plasma corticosterone. In ZFR cells, both thyroid hormones inhibited ACTH-stimulated corticosterone secretion, but the basal corticosterone was inhibited only with T3 > 10(-10) M or T4 > 10(-8) M. Likewise, T3 or T4 at 10(-7) M inhibited the basal- and ACTH-stimulated levels of intracellular cAMP. Physiological doses of T3 and T4 decreased the activities of 3 beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11 beta-hydroxylase. These results suggest that thyroid hormones counteract ACTH in adrenal steroidogenesis through their inhibition of cAMP production in ZFR cells.

1-Methyl-3-isobutylxanthine↗

PubMed1998

Pharmacological effects of propylthiouracil on corticosterone secretion in male rats.

BACKGROUND: We investigated the direct effects of propylthiouracil (PTU) on corticosterone secretion both in vivo and in vitro. METHODS: Male rats were divided into 4 groups and then injected subcutaneously with saline, PTU, PTU plus thyroxine (T4), or T4 once daily for 2 weeks. After 2 weeks, rats were decapitated or received adrenocorticotropic hormone (ACTH), intravenously. Zona fasciculata-reticularis (ZFR) cells from normal, saline-, PTU-, PTU plus T4-, or T4-treated rats were incubated with ACTH, forskolin, 8-Br-cAMP, deoxycorticosterone (DOC) +/- PTU (1, 2, or 5 mg/mL) at 37 degrees C for 2 hours. Corticosterone concentrations in plasma and cell media, and 3':5'-cyclic adenosine monophosphate (cAMP) production in ZFR cells were determined by radioimmunoassay. The effects of PTU on the activities of steroidogenic enzymes in ZFR cells were measured by the amounts of intermediate steroidal products separated by thin-layer chromatography. RESULTS: The basal and ACTH-stimulated levels of plasma corticosterone in PTU-treated rats were lower as compared to saline-treated animals. Both basal and ACTH-stimulated corticosterone secretion were inhibited by PTU > 2 mg/mL in rat ZFR cells. The cAMP production induced by forskolin was lower in PTU, PTU plus T4, or T4-treated rats than in saline-treated animals. Chronic administration of PTU or PTU plus T4 inhibited the 3 beta-hydroxysteroid dehydrogenase, 21 beta-hydroxylase, and 11 beta-hydroxylase activities. Administration of PTU (1, 2, and 5 mg/mL) suppressed the basal, ACTH, 8-Br-cAMP, forskolin, and DOC-stimulated corticosterone secretion in rat ZFR cells. Likewise, PTU > 2 mg/mL inhibited the ACTH and 8-Br-cAMP-stimulated levels of intracellular cAMP in rat ZFR cells. CONCLUSIONS: These results suggest that PTU counteracts both basal and ACTH-induced adrenal steroidogenesis through their attenuation of the activity of 11 beta-hydroxylase and cAMP production in rat ZFR cells.

Adrenal Cortex↗

PubMed1997

Neurotoxicity of soluble macrophage products in vitro--influence of dexamethasone.

When macrophage conditioned medium is added to neurons in vitro, there is a loss of cell membrane integrity, a loss of cell processes, and a large increase in apoptotic neurons. We tested the influence of a potent anti-inflammatory steroid on the interaction between macrophages and neurons. Dexamethasone was applied to macrophages in culture for 24 h while the culture was stimulated with lipopolysaccharide and hypoxia. Conditioned medium was collected after dexamethasone was removed. The dexamethasone pretreated medium was not toxic to hippocampal neurons in contrast to medium from stimulated macrophages not treated with steroid. The dexamethasone effect was concentration dependent. Pretreatment of macrophages with indomethacin and transforming growth factor beta had similar but less impressive effects when compared to dexamethasone. The effect of dexamethasone may have been mediated by inhibiting the synthesis or release of neurotoxic macrophage protein(s), as a combination of medium from steroid pretreated macrophages with medium from nontreated macrophages was not neuroprotective. The toxin(s) did not appear to be tumor necrosis factor alpha or arginase. A role for most neutral proteases was also excluded. We also assessed the consequence of stressing neurons with a mild hypoxic exposure immediately prior to conditioned medium application. Medium from dexamethasone-treated macrophages did not exaggerate hypoxic neuronal injury, unlike medium from non-dexamethasone-treated macrophages. It did not, however, block the exaggerating effect when coapplied in equal volume with medium from nontreated macrophages. Dexamethasone at 100 nM had no impact when applied directly to neurons while they were being exposed to conditioned medium. This in vitro protection by dexamethasone may be relevant to the demonstrated benefit of glucocorticoids in selected brain and spinal cord conditions. Suspicion of a potential link between this in vitro finding and in vivo CNS injury justifies an assessment of more specific agents acting on macrophage protein synthesis or secretion.

Animals↗

PubMed1997

Incidence of NIDDM and the effects of gender, obesity and hyperinsulinaemia in Taiwan.

Our aim is to determine non-insulin-dependent diabetes mellitus (NIDDM) incidence in Taiwan and examine its relation to obesity and hyperinsulinaemia in Chinese men and women. A total of 995 men and 1195 women aged 35-74 years free from diabetes in two townships in Taiwan were followed up with a second examination. At baseline general and metabolic data were recorded, and detailed anthropometric parameters and plasma glucose and insulin were assessed. World Health Organisation (WHO) criteria of fasting glucose 7.8 mmol/l or greater was utilized for defining diabetes. The age-standardized incidence rate based on the United States population in 1970 was 9.3/1000 (CI 5.8-12.8) in men and 9.3/1000 (CI 6.2-12.4) in women and the based on the WHO population in 1976 was 8.9/1000 (CI .5-12.3) in men and 8.9/1000 (CI 5.9-11.9) in women for the Chinese who had a mean BMI slightly greater than 24 (kg/m2). The predictability of the plasma glucose level was greater than that of the insulin level and the obesity indices. NIDDM incidence increased approximately threefold with each 0.67 mmol/l increase in plasma glucose level in men and women. The present study demonstrated the essential relationship of not only BMI but also central obesity indices (such as subscapular and waist circumference) to the incidence of NIDDM among men and women and a stronger relationship between NIDDM incidence and obesity in women than in men. The predictive effects of obesity indices and fasting plasma insulin values on NIDDM risk were independent of each other in men. Obesity and hyperinsulinaemia each without the presence of the other can lead to an increased risk of NIDDM. In women the NIDDM incidence increased more than additively in those with both obesity and hyperinsulinaemia compared to those with single obesity or hyperinsulinaemia. A slightly higher incidence of NIDDM in Taiwan than in western countries was found. The importance of obesity is indicated for predicting NIDDM in the community. Hyperinsulinaemia was found to play a significant role in predicting NIDDM incidence independent of obesity in men and synergistically with obesity in women.

Adult↗