Biomedical subjects

W C Huang

Publications and source records attributed to W C Huang.

At least 37 records · Page 2Linked to original sources

PubMed1999

Changes of superoxide dismutase gene expression and activity in the brain of streptozotocin-induced diabetic rats.

In an attempt to discover the changes of superoxide dismutase (SOD) in the brain of diabetic state, we investigated the level of SOD in streptozotocin-induced diabetic rats (STZ-diabetic rats) using enzyme activity assay, Northern blotting analysis of mRNA levels and Western blotting of enzyme amount. Five discrete brain regions, cerebrocortex, hypothalamus, hippocampus, the remaining non-cortex cerebrum (NCC area) and cerebellum, were examined in STZ-diabetic rats to compare with age-matched normal rats. Higher levels of Mn-SOD including the activity, mRNA expression and immunoblot of enzyme were found in all areas of the brain from STZ-diabetic rats as compared with that in Wistar rats. Except in the cerebellum, similar changes of Cu,Zn-SOD were found in the brain of STZ-diabetic rats. These results indicate an increase of SOD both gene expression and activity in the brain of STZ-diabetic rats. This alteration of SOD may be one of the important factors for the vulnerability of the brain to oxygen free radicals or may be related to the pathophysiology of diabetes.

Animals↗

PubMed1999

Repaglinide pharmacokinetics in healthy young adult and elderly subjects.

In this open-label, single-center, pharmacokinetic study of repaglinide, 12 healthy volunteers (6 men, 6 women) were enrolled in each of 2 groups (total, 24 volunteers). One group consisted of young adult subjects (18 to 40 years), and the other group consisted of elderly subjects (> or = 65 years). On day 1, after a 10-hour fast, all 24 subjects received a single 2-mg dose of repaglinide. Starting on day 2 and continuing for 7 days, subjects received a 2-mg dose of repaglinide 15 minutes before each of 3 meals. On day 9, subjects received a single 2-mg dose of repaglinide. Pharmacokinetic profiles, including area under the curve, maximum concentration (Cmax), time to Cmax, and half-life, were determined at completion of the single-dose and multiple-dose regimens (days 1 and 9, respectively). Trough repaglinide values were collected on days 2 through 7 to assess steady state. The single-dose and multiple-dose pharmacokinetic variables of serum repaglinide were not significantly different between young adult and elderly subjects. Repaglinide was well tolerated in both groups. Hypoglycemic events occurred in 5 young adult and 5 elderly subjects. This study demonstrates that the pharmacokinetics of repaglinide are similar in healthy young adult and elderly subjects.

Adult↗

PubMed1999

Repaglinide versus glyburide: a one-year comparison trial.

This prospective, 1-year, multicenter, double-blind, randomized, parallel-group study was designed to show that repaglinide was at least equivalent to glyburide in patients with type 2 diabetes. Five hundred and seventy-six patients with type 2 diabetes of at least 6 months' duration were randomized to receive monotherapy with repaglinide (n = 383) or glyburide (n = 193). During weeks 1-8, doses were gradually increased to achieve a target fasting plasma glucose (FPG) range of 80-140 mg/dl. The final adjusted dose was maintained for 12 months. Repaglinide patients received a starting dose of 0.5 mg three times/day preprandially, adjusted as necessary to 1, 2 or 4 mg before breakfast, lunch and dinner. Glyburide patients received a starting dose of 2.5 mg before breakfast and placebo before lunch and dinner. Glyburide was increased as necessary to 5 or 10 mg before breakfast (placebo before lunch and dinner) or to 15 mg (10 mg before breakfast, placebo before lunch, and 5 mg before dinner). After study drug was stopped, patients were transferred to an appropriate therapy, as recommended by the investigator. Efficacy was assessed by changes from baseline in glycemic control parameters and in C-peptide, insulin, and lipid profiles. Repaglinide provided glycemic control that was at least as effective and potentially safer than that provided by glyburide. The glucose-lowering effect of repaglinide was most pronounced in pharmacotherapy-naive patients, who showed rapid and marked decreases in mean glycosylated hemoglobin levels from baseline (9.4%) to month 3 (7.6%) and month 12 (7.9%). Mean FPG levels also decreased overall in this group, from 222 mg/dl at baseline, to 175 mg/dl at month 3, to 188 mg/dl at month 12. At endpoint, morning C-peptide levels had increased significantly in glyburide-treated patients compared with those treated with repaglinide, but morning fasting insulin levels did not differ significantly between the two groups. Repaglinide efficacy was sustained over 1 year and was not influenced by age or sex. Overall safety and changes in lipid profile and body weight were similar with both agents, with no significant change after extended pharmacotherapy. Weight gain data for the subset of pharmacotherapy-naïve patients suggest that patients given repaglinide may gain less weight than those given glyburide. Repaglinide, at doses of 0.5-4.0 mg administered three times preprandially, was well tolerated and provided safe and consistently effectiveglycemic control during this 1-year study. Patients using repaglinide received the same therapeutic benefits as those using glyburide, and may have received additional benefits.

Adult↗

PubMed1999

Antioxidant status following acute ischemic limb injury: a rabbit model.

Although ischemic injury to skeletal muscle is a matter of great clinical importance, relatively little is known about the mechanisms which determine systemic responses. One purpose of this study is to elucidate the systemic antioxidant status following an episode of acute ischemic limb injury and subsequent reperfusion. Twelve New Zealand white rabbits were used in this study. After the animals were anesthetized, an ischemic insult was created in the right hind limb for twelve hours, followed by four hours of reperfusion. Several series of blood samples were obtained. At the end of the experiment, the animals were killed and necropsies undertaken in order to evaluate the antioxidant status of various visceral organs. The results link ischemia and reperfusion injury to a significant decline in antioxidative activity in various tissues. The weakening in antioxidant status after ischemic limb injury was most pronounced in the heart tissue, followed in descending order by the spleen, skeletal muscle, lung, liver, and kidney tissue. The levels of specific antioxidants and reactive oxygen species in various organs changed significantly, and the changes were tissue specific. Endogenous radical scavenging systems were not entirely overwhelmed in most of the tissues studied. But higher levels of malondialdehyde (MDA) found in cardiac tissue suggest that the production of oxygen free radicals is accelerated by an ischemic injury. Based on the study, we believe that the cardiac tissue is particularly susceptible to the effects of ischemia and reperfusion injury. Damage to cardiac tissue is probably the major cause of mortality following acute ischemic injury in a limb.

Animals↗

PubMed1999

Pharmacokinetics, pharmacodynamics, and dose-response relationship of repaglinide in type 2 diabetes.

BACKGROUND: The pharmacodynamics and dose-response relationship of repaglinide, a novel oral hypoglycemic agent, were evaluated in steady-state treatment of patients with type 2 diabetes. METHODS: Efficacy of repaglinide (0.25 mg, 0.5 mg, 1 mg, 2 mg, and 4 mg) was compared to that of placebo in a double-blind, randomized, parallel-group, 4-week dose-response clinical trial in 143 patients. Repaglinide was administered 15 minutes before meals (breakfast, lunch, and dinner). Efficacy of repaglinide therapy was assessed by measuring changes from baseline in mean levels of blood glucose (BGmean), fasting serum glucose (FSG), and mean levels of serum insulin (INSmean). RESULTS: Blood concentrations of repaglinide were proportional to the dose administered. INSmean values increased in all repaglinide treatment groups (by 6.7 to 12.9 microU/mL). All doses of repaglinide significantly decreased values of BGmean and FSG as compared with the placebo group. BGmean values stabilized between the second and third week of repaglinide treatment. A well-defined dose-response relationship was observed for BGmean and FSG values. All doses of repaglinide were well tolerated, and there were no serious adverse events. CONCLUSIONS: These findings show that the therapeutic reduction of serum glucose levels produced by repaglinide is dose-dependent for the 0.25- to 4-mg dose range. All doses of repaglinide tested were effective and well tolerated in patients with type 2 diabetes.

Adult↗

PubMed1999

Identification of the RNA-binding sites of the triple gene block protein 1 of bamboo mosaic potexvirus.

The triple gene block protein 1 (TGBp1) encoded by open reading frame 2 of bamboo mosaic potexvirus (BaMV) was overexpressed in Escherichia coli and purified in order to test its RNA-binding activity. UV crosslinking assays revealed that the RNA-binding activity was present mainly in the soluble fraction of the refolded TGBp1. The binding activity was nonspecific and salt concentration-dependent: activity was present at 0-50 mM NaCl but was almost abolished at 200 mM. The RNA-binding domain was located by deletion mutagenesis to the N-terminal 3-24 amino acids of TGBp1. Sequence alignment analysis of the N-terminal 25 amino acids of the TGBp1 homologues of potexviruses identified three arginine residues. Arg-to-Ala substitution at any one of the three arginines eliminated most of the RNA-binding activity, indicating that they were all critical to the RNA-binding activity of the TGBp1 of BaMV.

Amino Acid Sequence↗

PubMed1999

Pharmacokinetic profiles of repaglinide in elderly subjects with type 2 diabetes.

Pharmacokinetic profiles of single- and multiple-dose regimens of repaglinide were evaluated in 12 elderly subjects with type 2 diabetes. On day 1, following a 10-hour fast, subjects received a single 2-mg dose of repaglinide. Starting on day 2 and continuing for 7 days, each subject received a 2-mg dose of repaglinide 15 minutes before each of the three main meals. On day 9, subjects received a single 2-mg dose of repaglinide. Pharmacokinetic profiles, including area under the curve (AUC), log(AUC), maximal concentration (Cmax), log(Cmax), time to maximal concentration (Tmax), and half-life (T(1/2)), were determined at completion of the single- and multiple-dose regimens (days 1 and 9, respectively). Trough repaglinide values were collected on days 2 through 7. The mean log(AUC) values after multiple dosing were significantly higher than the values obtained after a single dose. The mean values for log(Cmax), and Tmax were comparable after each dosing regimen. The T(1/2) of repaglinide after multiple dosing was 1.7 hours. The trough values for repaglinide were low. No hypoglycemic events were reported. The pharmacokinetic profiles of repaglinide after single- and multiple-dose regimens were similar, and repaglinide was well tolerated by elderly subjects with type 2 diabetes.

Aged↗

PubMed1999

The efficacy of potassium citrate based medical prophylaxis for preventing upper urinary tract calculi: a midterm followup study.

PURPOSE: We examined the efficacy of potassium citrate based medical prophylaxis for preventing upper urinary calculous recurrence, and compared it with the stone recurrence rate in patients who only received intermittent or no medical prophylaxis. MATERIALS AND METHODS: We retrospectively reviewed the records of 493 patients with upper urinary calculi, of whom 237 men and 76 women with a mean age of 56.1 and 51.4 years, respectively, were enrolled in the study. Of the 313 participants 64 (group 1, 20.4%) received regular medical prophylaxis for 24 to 42 months (mean 27.8), 80 (group 2, 25.6%) received intermittent medical prophylaxis for 1.5 to 19 months (mean 7.9) and 169 (group 3, 54%) did not receive any medical prophylaxis. RESULTS: At midterm followup of 24 to 60 months 107 patients (34.2%) had stone recurrence. In group 1 the stone recurrence rate was 7.8%, which was significantly less (p <0.001) than in groups 2 (30%) and 3 (46.2%). Similarly new calculous events in patients with a history of multiple stone recurrence were less frequent in group 1 than in groups 2 and 3 (9.7, 47.4 and 52.2%, respectively, p <0.001). Multiple stone recurrence history, hypercalciuria, hyperuricosuria and calcium oxalate dihydrate calculi were independent risk factors for stone recurrence. CONCLUSIONS: Regular medical prophylaxis may effectively prevent stone recurrence regardless of previous treatment modalities, stone composition, metabolic abnormalities and stone-free status. Cost effectiveness, patient compliance and gastrointestinal upset may limit patient acceptability and clinical use of medical prophylaxis. However, patients with a history of multiple stone recurrence, calcium oxalate dihydrate stones, hypercalciuria and hyperuricosuria benefit from regular medical prophylaxis.

Adult↗

PubMed1999

Recurrent inverted papilloma: diagnosis with pharmacokinetic dynamic gadolinium-enhanced MR imaging.

BACKGROUND AND PURPOSE: Dynamic gadolinium-enhanced MR imaging has been used successfully to identify post-treatment recurrence or postoperative changes in rectal and cervical carcinoma. Our purpose was to evaluate the usefulness of dynamic gadolinium-enhanced MR imaging for distinguishing recurrent inverted papilloma (IP) from postoperative changes. METHODS: Fifteen patients with 20 pathologically proved lesions (recurrent IP, 12; fibrosis or granulation tissue, eight) were enrolled in the study. Three observers, blinded to pathologic results, independently evaluated conventional MR images, including T1-weighted (unenhanced and postcontrast), proton-density-weighted, and T2-weighted spin-echo images. Results then were determined by consensus. Dynamic images were obtained using fast spin-echo sequences at 5, 30, 60, 90, 120, 150, 180, and 300 seconds after the injection of gadolinium-diethylene-triamine penta-acetic acid. Time-signal intensity curves of suspected lesions were analyzed by a pharmacokinetic model. The calculated amplitude and tissue distribution time were used to characterize tissue, and their values were displayed as a color-coded overlay. RESULTS: T2-weighted images yielded a sensitivity of 67%, a specificity of 75%, and an accuracy of 70% in the diagnosis of recurrent IP. Contrast-enhanced T1-weighted images yielded a sensitivity of 75%, a specificity of 50%, and an accuracy of 65%. Pharmacokinetic analysis showed that recurrent IP had faster (distribution time, 41 versus 88 seconds) and higher (amplitude, 2.4 versus 1.2 arbitrary units) enhancement than did fibrosis or granulation tissue. A cut-off of 65 seconds for distribution time and 1.6 units for amplitude yielded a sensitivity of 100% and a specificity of 100% for diagnosing recurrent IP. CONCLUSION: Dynamic MR imaging can differentiate accurately recurrent IP from postoperative changes and seems to be a valuable diagnostic tool.

Adult↗

PubMed1998

An ultra-weak chemiluminescence study on oxidative stress in rabbits following acute thermal injury.

It is not easy to detect oxygen free radicals directly because of their very short half-life. In the present study, a sensitive ultra-weak chemiluminescence detector was used to detect the generation of oxygen free radicals following thermal injury. Twelve New Zealand white rabbits were used in this study. After anesthesia, the bilateral hind-limbs were exposed to 100 degrees C water for 30 s. Six control animals were exposed to 22 degrees C water to act as a control. The chemiluminescence of whole blood and visceral organs were measured with both luminol-amplified t-butyl hydroperoxide-initiated and lucigenin-initiated methods. The results showed that chemiluminescence of blood was affected significantly by acute thermal injury. The chemiluminescence of blood increased significantly at 1 h following acute thermal injury, reached a peak at 2 h, then decreased but still remained above the control level at 4 h following thermal injury. The results for TBHP-initiated chemiluminescence from visceral organs following acute thermal injury were much higher than that of the control rabbits. The effects of lucigenin-initiated tissue chemiluminescence following acute thermal injury were not statistically significant. It is suggested that the decreased vascular antioxidant activity following local thermal injury is partially contributed by the superoxide pathway; while, the remote pathophysiologic events are mediated by the defective scavenging defenses.

Acridines↗

PubMed1998

Role of angiotensin II in hyperinsulinemia-induced hypertension in rats.

OBJECTIVE: To investigate the role of angiotensin II in the pathogenesis of hyperinsulinemia-induced hypertension in rats. MATERIALS AND METHODS: Chronic hyperinsulinemia was achieved by infusing insulin (3 mU/kg per min) subcutaneously by an osmotic minipump for 6 weeks. An angiotensin converting enzyme inhibitor (fosinopril, 10 mg/kg per day) was added in drinking water and the angiotensin II subtype 1 receptor antagonist losartan (3.5 microg/kg per min) was co-infused via the minipump. Control rats were administered the vehicle only. The rats were housed in individual metabolic cages and fed a sodium-controlled diet. Food and water intake and urine output were measured daily. Systolic blood pressure and heart rate were measured by the tail-cuff method twice a week. RESULTS: By the end of weeks 4 and 6 of the sustained insulin infusion, systolic blood pressure had increased significantly (P < 0.05), from 134+/-1 to 157+/-2 and 158+/-2 mmHg, respectively, and the heart rate had increased significantly (P< 0.05), from 380+/-9 to 423+/-7 and 426+/-6 beats/min, respectively. The plasma insulin concentration increased by 2-2.5 times but no significant changes in plasma glucose and triglyceride levels were noted. Concomitant treatment with fosinopril prevented the rises in systolic blood pressure and heart rate in the insulin-infused rats. When the insulin-induced hypertension had become established (systolic blood pressure increased from 132+/-3 to 155+/-2 mmHg 4 weeks after the infusion, P< 0.05 ), subsequent fosinopril or losartan treatment for 2 weeks reversed the elevated systolic blood pressure and heart rate to the control levels. There were no significant differences in water intake, urine flow, sodium gain and body weight gain between the control and the insulin-infused rats. CONCLUSIONS: Angiotensin converting enzyme inhibition or angiotensin II type 1 receptor antagonism can prevent and reverse insulin-induced hypertension in rats, suggesting that angiotensin II itself or an angiotensin II-dependent mechanism has an etiological influence in the pathogenesis of this hypertension model.

Angiotensin II↗

PubMed1998

Angiotensin receptor blockade blunts hyperinsulinemia-induced hypertension in rats.

The study was conducted to examine the effects of the angiotensin subtype 1 and 2 receptor antagonists (losartan and PD123319, respectively) on blood pressure (BP) and renal excretory function in chronic hyperinsulinemia-induced hypertension in rats. Hyperinsulinemia was achieved by insulin infusion (21.5 pmol/kg per minute) via osmotic minipump for 6 weeks. Losartan or PD 123319 was coinfused either at the beginning or after 4 weeks of insulin infusion. The results showed that insulin infusion significantly increased the plasma insulin concentration from 259.0+/-22.2 to 646.5+/-33.0 and 713.9+/-26.5 pmol/L (P<0.05) by the end of the fourth and sixth weeks, respectively, after insulin infusion. There were no significant changes in plasma glucose and triglyceride concentrations. Systolic BP increased from 139+/-3 to 156+/-1 and 157+/-2 mm Hg (P<0.05) at the corresponding time points. Combined losartan (3.5 microg/kg per minute) and insulin infusion prevented the rise in BP and improved insulin resistance. When hypertension had been established after 4 weeks of insulin infusion, superimposed infusion of losartan on insulin reversed the elevated BP to control levels within 1 week. In contrast, administration of PD123319 (0.5 and 10 microg/kg per minute) failed to alter insulin-induced hypertension. Combined PD123319 with losartan did not alter the losartan-induced hypotensive effect in insulin-infused rats. There were no significant differences in water intake, urine flow, body weight gain, and sodium gain before and after antagonist administration among groups. These results indicate that angiotensin type 1 receptors play a determinant role in the pathogenesis of insulin-induced hypertension in rats.

Angiotensin Receptor Antagonists↗

PubMed1998

Renal denervation prevents and reverses hyperinsulinemia-induced hypertension in rats.

Experiments were performed to evaluate the role of the renal nerves in hyperinsulinemia-induced hypertension. Male Sprague-Dawley rats were made hyperinsulinemic by insulin infusion via osmotic minipumps implanted subcutaneously (3.0 mU/kg per minute for 6 weeks). Rats with vehicle infusion served as controls. Bilateral renal denervation was performed either at the beginning of or 4 weeks after insulin infusion. The systolic blood pressure was measured by the tail-cuff method twice a week. Food and water intake and urine flow were measured daily. The results showed that sustained insulin infusion significantly increased plasma insulin concentrations from 277.7+/-25.8 pmol/L to 609.9+/-22.2 and 696.7+/-23.0 pmol/L by the end of weeks 4 and 6, respectively (P<0.05). Systolic blood pressure was significantly increased from 135+/-3 to 157+/-3 and 159+/-2 mm Hg (P<0.05) at the corresponding time points. There was a significant increase in the plasma norepinephrine concentration after insulin infusion, whereas no significant changes in plasma triglyceride and glucose concentrations, water intake, urine flow, sodium excretion, sodium gain, and body weight gain were observed. Bilateral renal denervation depleted renal norepinephrine stores and prevented the development of hyperinsulinemia-induced hypertension. After hyperinsulinemia-induced hypertension had been fully established (from 134+/-2 to 157+/-2 mm Hg), bilateral renal denervation reversed the elevated systolic blood pressure to normotensive levels within 2 weeks. Transient denervated diuresis and natriuresis were observed. These results indicate that chronic hyperinsulinemia-induced hypertension requires the presence of intact renal nerves in rats.

Animals↗

PubMed1998

Nitric oxide synthesis inhibition retards surgical reversal of one-kidney Goldblatt hypertension in rats.

Surgical correction of renal artery stenosis in Goldblatt hypertension rapidly normalizes blood pressure and increases renal function. This study was conducted in 1-kidney, 1 clip (1K1C) Goldblatt hypertensive rats to examine whether the unclipping-induced reversal of blood pressure and renal function is mediated by nitric oxide (NO). The 1K1C rats were prepared and given tap water with or without supplementation of NG-nitro-L-arginine methyl ester (L-NAME). Systolic blood pressure (SBP) before and after renal artery clipping was measured with the tail-cuff method. Four weeks later, surgical unclipping was performed while blood pressure and renal function responses were determined. The results show that clipping the renal artery for 4 weeks increased SBP from 140+/-5 to 183+/-6 mm Hg (P<0.05). Concurrent L-NAME treatment accelerated and aggravated the clipping-induced increases in SBP from 138+/-6 to 219+/-8 mm Hg (P<0.05). Surgical unclipping reduced blood pressure to normotensive levels within 2 hours in all hypertensive rats with and without chronic or acute L-NAME treatment. However, the magnitude of reductions in blood pressure in the initial 1 hour after unclipping was significantly less in L-NAME-treated rats than in nontreated rats (9+/-2% versus 16+/-1%, P<0.05). Despite reducing blood pressure, unclipping significantly increased glomerular filtration rate, urine flow, and sodium and potassium excretions, but the extent of the increases in these renal functions was significantly attenuated in L-NAME-treated rats. These data suggest that NO production partly contributes to the hypotensive and renal responses to unclipping but does not mediate the reversal of renovascular hypertension of this model.

Animals↗

PubMed1998

A randomized placebo-controlled trial of repaglinide in the treatment of type 2 diabetes.

OBJECTIVE: The objective of the study was to assess the efficacy and safety of repaglinide compared with placebo in the treatment of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a phase II multicenter, double-blind, placebo-controlled, randomized, dose-adjustment and maintenance trial. After screening and a 2-week washout period, 99 patients were randomized to receive either repaglinide (n = 66) or placebo (n = 33). Patients underwent 6 weeks of dose adjustment followed by 12 weeks of dose maintenance. Fasting and stimulated glycosylated hemoglobin (HbA1c), plasma glucose, insulin, and C-peptide were measured at predetermined intervals. Adverse events and hypoglycemic episodes were recorded. RESULTS: From baseline to last visit, mean HbA1c decreased from 8.5 to 7.8% in patients treated with repaglinide and increased from 8.1 to 9.3% in patients receiving placebo, with a statistically significant difference of - 1.7% (P < 0.0001) between treatment groups at the last visit. Mean fasting plasma glucose and postprandial glucose increased in patients receiving placebo and decreased in patients treated with repaglinide, with statistically significant (P < 0.01) differences between groups at the last visit. Concentrations of fasting and postprandial insulin and C-peptide were lower at the last visit compared with baseline for patients treated with placebo and higher for patients treated with repaglinide, and the differences between groups were statistically significant (P < 0.05). Overall, repaglinide was well tolerated. CONCLUSIONS: This study demonstrated that repaglinide was safe and efficacious in lowering blood glucose concentrations. In addition to overall improvement in glycemic control noted with repaglinide in both sulfonylurea-treated patients and oral hypoglycemic agent-naive patients, repaglinide had a potent glucose-lowering effect in the postprandial period.

Adult↗

PubMed1998

Vascular expression of heat shock protein 72 in fructose-induced hypertensive rats.

Heat shock proteins (HSPs) have been implicated in protecting the cardiovascular system and in the pathogenesis of hypertension in stressed animals. In the present study, we used a fructose-induced hypertension model to explore the vascular expression of HSP72, the major inducible heat shock protein, in response to stress. Normal Sprague-Dawley rats gradually developed hypertension about 2 weeks after feeding with fructose-enriched diet and the elevated blood pressure became stable 5 weeks following diet treatment. The in vivo expression of HSP72 was absent in control rats but was transiently induced in the aorta of fructose-fed rats during the development of hypertension. Aortic HSP72 was undetectable at the established phase of hypertension. The expression of HSP72 in responses to heat shock, or vasoactive agents were examined in cultured aortic smooth muscle cells. Heat shock induced the expression of HSP72 in cells from fructose-fed rats and age-matched control rats, and the expression levels were generally not significantly varied at different sampling time points in either cell source. Also, there was no apparent difference in the magnitude of HSP72 expression between two cell sources at each selected time point. Norepinephrine or angiotensin II induced a similar level of HSP72 expression in either cell source regardless of sampling time point. These data suggest that HSP72 is associated with the development of hypertension in this model and may exert protective effect on the vasculature in response to hemodynamic stress during the early stage of hypertension.

Angiotensin II↗

PubMed1997

Menadione-induced cytotoxicity to rat osteoblasts.

Oxygen-derived free radical injury has been associated with several cytopathic conditions. Oxygen radicals produced by chondrocytes is an important mechanism by which chondrocytes induce matrix degradation. In the present study, we extend these observations by studying oxidative processes against osteoblasts. Osteoblasts were mixed in in vitro culture with 200 microM menadione. The cytotoxic effect of menadione-induced oxidative stress was monitored by lucigenin- or luminol-amplified chemiluminescence, tetrazolium assay and immunocytochemical study. Results showed that adding menadione induces an oxidative stress on osteoblasts, via superoxide and hydrogen peroxide production, that can be eradicated by superoxide dismutase (SOD) and catalase in a dose-dependent manner. Catalase and the appropriate concentration of dimethyl sulfoxide have a protective effect on cytotoxicity induced by menadione, whereas SOD does not. Menadione-treated osteoblasts have a strong affinity for annexin V, and the nuclei are strongly stained by TUNEL (TdT-mediated dUTP nick-end labelling). The results suggest that menadione-triggered production of reactive oxygen species leads to apoptosis of osteoblasts.

Acridines↗

PubMed1997

Blunted renal responses to atrial natriuretic peptide and its reversal by unclipping in one-kidney, one clip Goldblatt hypertensive rats.

OBJECTIVE: To evaluate the hypotensive and renal effects of atrial natriuretic peptide (ANP) in one-kidney, one clip Goldblatt hypertensive rats with and without renal arterial stenosis. METHODS: The one-kidney, one clip hypertensive rats were divided into four groups: untreated time control, ANP-infused, unclipped and unclipped plus ANP-infused. The changes in blood pressure, glomerular filtration rate and renal excretory function were determined during intravenous vehicle and ANP infusions while the renal arterial clip was in place or removed acutely. One-kidney normotensive rats infused with ANP were used for comparison. RESULTS: In one-kidney control rats, ANP infusion at doses of 0.15, 0.30 and 0.45 microg/kg per min decreased the mean blood pressure from 121 +/- 4 to 108 +/- 5 (9%, P < 0.05), 104 +/- 5 (17%, P < 0.05) and 89 +/- 4 mmHg (25%, P < 0.05), respectively. There was no significant change in glomerular filtration rate. However, the absolute sodium excretion rate increased significantly, by 343 +/- 66, 770 +/- 91 and 786 +/- 78%, respectively. A comparable magnitude of increase in the fractional sodium excretion was noted. In one-kidney, one clip hypertensive rats, the similar three doses of ANP infusion reduced blood pressure from 179 +/- 7 to 162 +/- 8 (8%, P < 0.05), 146 +/- 9 (17%, P < 0.05) and 138 +/- 8 mmHg (22%, P < 0.05), respectively. A slight but insignificant increase in renal function was observed during ANP infusion. Removal of the renal arterial clip reduced blood pressure rapidly and caused a transient increase in renal function. Subsequent infusion of ANF further reduced blood pressure but increased sodium and water excretion markedly. CONCLUSION: There is a blunted natriuresis and diuresis in response to ANP infusion in one-kidney, one clip hypertensive rats. Surgical removal of the clip from the renal artery restores the natriuretic and diuretic effects of ANP.

Animals↗