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Biomedical subjects

H S Huang

Publications and source records attributed to H S Huang.

At least 19 recordsLinked to original sources

Enalapril hepatotoxicity in the rat. Effects of modulators of cytochrome P450 and glutathione.

The effects of modulators of cytochrome P450 and reduced glutathione (GSH) on the hepatotoxicity of enalapril maleate (EN) were investigated in Fischer 344 rats. Twenty-four hours following the administration of EN (1.5 to 1.8 g/kg), increased serum transaminases (ALT and AST) and hepatic necrosis were observed. Pretreatment of the animals with pregnenolone-16 alpha-carbonitrile, a selective inducer of the cytochrome P450IIIA gene subfamily, enhanced EN-induced hepatotoxicity, whereas pretreatment with the cytochrome P450 inhibitor, cobalt protoporphyrin, reduced the liver injury. Depletion of hepatic non-protein sulfhydryls (NPSHs), an indicator of GSH, by combined treatment with buthionine sulfoximine (BSO) and diethyl maleate (DEM) produced marked elevations in serum transaminases by 6 hr after EN treatment. Administered on its own, EN decreased hepatic NPSH content and when combined with the BSO/DEM pretreatment, the liver was nearly completely devoid of NPSHs. Protection from EN-induced hepatotoxicity was observed in animals administered L-2-oxothiazolidine-4-carboxylic acid, a cysteine precursor. Together, these observations suggest the involvement of cytochrome P450 in EN bioactivation and GSH in detoxification. The results corroborate previous in vitro observations pertaining to the mechanism of EN-induced cytotoxicity towards primary cultures of rat hepatocytes. Although the doses of EN used in this study were far in excess of therapeutic doses, under certain circumstances, this metabolism-mediated toxicologic mechanism could form the basis for idiosyncratic liver injury in patients receiving EN therapy.

Alanine Transaminase

IL-1 synergizes with ARA-C in aborting the development of chloroleukemia while protecting from ARA-C-induced alopecia in the rat model.

Recently, interleukin 1 (IL-1) was shown to protect rats from ARA-C-induced alopecia. The present study was designed to investigate the effect of combination rHu-IL-1 and ARA-C on transplantable chloroleukemia (C51) and at the same time evaluate the protective effect of IL-1 on the ARA-C-induced alopecia in the rat model. In vitro, IL-1 had no direct effect on growth, viability or differentiation of C51 cells, neither did IL-1 protect the C51 cells from ARA-C cytotoxicity. In vivo, the combination treatment of ARA-C + IL-1 aborted the development of transplanted chloroleukemia in 100% of rats, vs 60%, 10% and 0% survival for rats treated with IL-1, ARA-C and buffer respectively. All rates treated with ARA-C alone developed complete body alopecia. In contrast, none of the rats treated with combination IL-1 and ARA-C combination developed alopecia. Thus, IL-1 demonstrated a double beneficial effect, synergism with ARA-C against the leukemic cells on the one hand, and protection from ARA-C-induced alopecia, on the other.

Alopecia

Protection from chemotherapy-induced neutropenia by ImuVert.

Neutropenia is a major cause of chemotherapy-induced morbidity. This study examines the effect of ImuVert on the course of neutropenia from Cytoxan and Adriamycin. In adult rats treated with either Cytoxan or Adriamycin and ImuVert, the absolute neutrophil count remained above 7,000 and 2,000, respectively, for the duration of ImuVert therapy. In contrast, in the control Cytoxan group the absolute neutrophil count reached 300/mm3 on day 5 and remained below 1,000 from day 4 through day 7. In the Adriamycin control group, the nadir absolute neutrophil count reached 600/mm3 on day 7 and remained below 100 from day 6 through day 8. C3H/EJ mice (endotoxin-hyporesponsive) treated with Cytoxan developed an absolute neutrophil count below 1,000 from day 4 through day 7. In contrast, in the group concomitantly treated with ImuVert, the nadir absolute neutrophil count remained below 1,000 only on days 4 and 5. The authors conclude that stimulation of endogenous cytokine production by ImuVert may provide a potentially useful approach to bone marrow rescue from chemotherapy.

Animals

Treatment with ImuVert/N-acetylcysteine protects rats from cyclophosphamide/cytarabine-induced alopecia.

Chemotherapy-induced alopecia is a distressing problem to the cancer patient for which currently there is no effective preventive measure. Recently ImuVert, a biologic response modifier, has been shown to protect from cytarabine-induced alopecia in the young rat model, but not from alopecia induced by cyclophosphamide. In the present study, the rat model was used to examine the effect of N-acetylcysteine on the course of alopecia from cyclophosphamide and of ImuVert plus N-acetylcysteine on alopecia induced by cytarabine-cyclophosphamide combination. The following observations were made: (1) Cyclophosphamide-induced alopecia could be effectively prevented by N-acetylcysteine, administered parenterally or applied topically in liposomes. (2) Alopecia caused by the combination of cyclophosphamide and cytarabine could be prevented by the parenteral or topical administration of ImuVert plus N-acetylcysteine. The potential applicability of these observations to the clinical settings remains to be determined.

Acetylcysteine

[Low dose radioiodine treatment of papillary thyroid carcinoma in a child--a case report].

The thyroid carcinoma is rare in children and the optimal management is rather controversial. We report a case of a 7-year-old boy who had right neck masses and proved to be papillary thyroid carcinoma after near-total thyroidectomy. Post-operative 20 mCi radioiodine-131 (I-131) ablation scan, lung metastasis was suspected but the chest X ray was normal. After being lost to follow up for 4 years, the patient returned with the complaints of cough; the chest X ray was still normal. He then received 5 treatment with low dose (30 mCi) I-131 therapy and continued thyroxine replacement. Progressive decrease both of the thyroglobulin level and the intensity of radioactivity of lung were noted. After a total doses of 193 mCi I-131 therapy, neither pulmonary fibrosis nor bone marrow suppression was seen. Although the low dose (< or = 30 mCi) I-131 therapy was recommended, it was limited for the ablation therapy of the remnant thyroid tissue. Upon consideration of economics and the convenience of not being admitted to the isolation room, the low dose I-131 therapy seems feasible for children with thyroid carcinoma with systemic disease. However, the long term efficacy needs further evaluation.

Carcinoma, Papillary

[Cushing's syndrome with pregnancy. Report of three cases].

Cushing's syndrome with pregnancy is rare, and only about 60 cases have been reported. In the recent 4 years, 3 cases were diagnosed in Chang Gang Memorial Hospital. They presented with serious maternal complications early in the second month of pregnancy, including hypertension, proteinuria and lower leg edema. Unfortunately it was not diagnosed until the 20th week of pregnancy. They had the same hormone profile as other Cushing's syndrome patients who were not pregnant. Under the supportive treatment they had outcomes of two premature deliveries and one still birth. Just after delivery all patients received left adrenalectomy and pathology showed adenoma. All of them had good recovery courses. According to the literature, early treatment (surgical operation, medical treatment, or irradiation) could decrease maternal morbidity and fetal loss rate.

Adult

[Pituitary apoplexy: a study of eighteen cases].

Pituitary Apoplexy is a rare but sometimes life threatening condition which requires prompt recognition and timely medical intervention to avoid catastrophic consequences. From January 1979 to June 1989 and total of one hundred and ninety eight pituitary tumor patients were operated on our hospital. Eighteen cases (9.1%) were diagnosed "pituitary apoplexy" according to histopathological findings. The group consisted of twelve men and six women ranging in age from twenty two to sixty one years with a mean of forty. There were three cases of prolactin-secreting adenomas (16.7%), four growth-hormone secreting adenomas (22.2%), and eleven nonfunctional adenomas (61.1%) with an incidence of 6.1%, 8.3%, and 11.4% respectively (P > 0.05). Clinical manifestation occurred acutely in 66.7% and nonacutely in 33.3%. The patients presented with headaches (100%), visual impairment (83.3%), visual field defects (66%), disturbed consciousness (22%), fever and meningismus (11%). Radiological examinations able to demonstrate abnormalities included plain skull films (84%), computed tomography (84.6%), and angiography (93.8%). Various investigations of endocrine function pre and post operatively showed a deficient gonad axis (53%, 62.5%), adrenal axis (26.7%, 56.2%), and thyroid axis (20%, 43.8%). Sixteen cases received a transsphenoid operation and three cases underwent a transfrontal craniotomy. No case of mortality was reported. Postoperative radiotherapy was given to nine cases and nine cases were followed up on a regular basis. Therefore, our retrospective study suggests that pituitary apoplexy is not uncommon and has an acute clinical presentation. No particular tumor type was prone to occur. Various radiological examinations could define perisellar abnormalities. With a decreasing order of hormone deficiency, gonad, adrenal and thyroid axis were observed during the course of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

C-peptide response to glucagon in patients with non-insulin-dependent diabetes mellitus.

To understand pancreatic beta cell function in patients with non-insulin-dependent diabetes, we analyzed C-peptide response to glucagon in 101 nonketotic patients with onset of diabetes at over 25 years of age and duration of diabetes of more than one year. The fasting serum C-peptide values (FCP), maximal incremental (delta CP) and 6-minute (6'CP) serum C-peptide values after 1 mg of intravenous glucagon administration were not related to age at diagnosis (r = 0.12, 0.06 and 0.10, respectively), duration of diabetes (r = 0.15, 0.05 and 0.10, respectively), fasting plasma glucose concentrations (r = 0.01, 0.18 and 0.12, respectively) or glycohemoglobin (HbA1c, r = 0.13, 0.22 and 0.16, respectively). In contrast, they showed a clear positive correlation with body mass index (BMI, r = 0.36, 0.52 and 0.41, p < 0.001). In order to evaluate the beta cell function in patients with different responses to treatment modalities, a subgroup of 45 patients was divided into three groups: diet successes (DS, n = 14), oral hypoglycemic agent (OHA) successes (OS, n = 19) and OHA failure (OF, n = 12). Among the three groups, patients in the OF group had the longest duration of diabetes (9.4 +/- 1.9 years) and the lowest BMI (19.3 +/- 1.0 kg/m2). Serum C-peptide responses to glucagon were different in the three study groups. Patients in the DS group had the highest response and patients in the OF group had the lowest response. However, the differences in mean FCP, delta CP and 6'CP among the three groups were not statistically significant, and there was a wide overlap of individual C-peptide values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Apolipoprotein levels in normolipidemic non-insulin-dependent diabetes mellitus.

The purpose of this study was to examine the change in apolipoprotein and lipoprotein levels in patients with normolipidemic untreated non-insulin-dependent diabetes mellitus (NIDDM). Fifteen untreated, non-obese male NIDDM patients without hyperlipidemia were chosen, and 15 healthy subjects, matched for age, sex, body weight, alcohol consumption and cigarette smoking served as the control group. We observed that the concentrations of plasma total cholesterol (TC), triacylglycerol (TG) and very low density lipoprotein cholesterol (VLDL-C) were identical in both NIDDM and control groups. The levels of low-density lipoprotein cholesterol (LDL-C) were slightly increased in the diabetic group, but the difference did not reach statistical significance in our study. High-density lipoprotein cholesterol (HDL-C) was lower in the NIDDM group than in the controls. Significantly increased TC/HDL-C and LDL-C/HDL-C ratios were found in NIDDM patients compared with controls. The apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) levels were decreased in NIDDM patients, while the apolipoprotein B (apo B) level remained similar to that of the control subjects. The ratio of apo A-I/apo B was decreased significantly in the NIDDM group. Our results suggest that NIDDM patients are at higher risk of coronary heart disease, even if they remain normolipidemic.

Adult

Assessment of the association of HLA-DR 3/4 heterozygotes with diabetes mellitus and non-diabetic diseases.

To evaluate the disease association with HLA-DR 3/4 heterozygotes, 1,074 subjects, who had been analyzed consecutively for HLA-DR antigens for organ transplantation or to study the disease association with HLA from June 1984 to June 1986, were enrolled in this study. Of these subjects, 278 had diabetes, 168 were healthy controls or donors, and 628 had other diseases. Of the 1,074 subjects, 35 subjects (3.2%) were DR 3/4 heterozygotes and 1,039 subjects (96.7%) were non-DR 3/4 heterozygotes. Among the 35 DR 3/4 positive subjects, 23 were diabetic (65.7%), two were healthy donors (5.7%), 10 had other diseases (28.5%) such as recurrent abortion (n = 3), hepatoma (n = 2), Graves' disease (n = 1), idiopathic hypoparathyroidism (n = 1), IgA nephropathy (n = 1), uveitis (n = 1) and gout (n = 1). Among the 23 DR 3/4 positive diabetics, 19 (82.6%) had insulin-dependent diabetes mellitus (IDDM), three (13.0%) had non-insulin-dependent diabetes mellitus (NIDDM), and one (4.3%) had maturity onset diabetes of the young (MODY). When these DR 3/4 positive diabetics were compared with the other disease and control/donor groups, significant increases in the relative risk were seen for IDDM patients (RR = 32.61, 43.80, respectively, p < 0.001). No significant association could be seen for NIDDM and MODY patients. In those non-diabetic patients positive for DR 3/4, there was no significant association with DR 3/4 heterozygotes. These findings suggest that: 1) DR 3/4 positive subjects are highly associated with IDDM; and 2) there is no significant association of DR 3/4 with NIDDM, MODY and other non-diabetic diseases.

Adult

Vasodilator and oxidant scavenger in the neurogenic pulmonary edema induced by cerebral compression.

In vagotomized rats, cerebral compression (CC) produced marked increase in arterial pressure and pulmonary hemorrhagic edema (PHE). We studied the effects of a vasodilator and an oxidant scavenger to delineate the role of hemodynamic and permeability factors in this type of neurogenic PHE. Infusion of sodium nitroprusside at a dose of 5 micrograms/kg/min significantly reduced the CC-induced pressor response by 14% and the lung edema by 41%. A dose of 10 micrograms/kg/min blocked the pressor response by 51%, and completely prevented the lung injury. Dimethylthiourea (DMTU), a potent scavenger for oxidants such as hydroxyl radical and hydrogen peroxide, in doses of 300 and 600 mg/kg was pretreated 15 min before CC. Although DMTU was shown to block the permeability lung damage caused by phorbol myristate acetate (a neutrophil activator), this agent did not exert any effect on the CC-induced pressor response and lung injury. The data indicate that granulocyte-mediated oxidants such as hydroxyl radical and hydrogen peroxide do not appear to be involved in this type of neurogenic lung pathology. The results support the concept that PHE induced by intracranial hypertension is initiated by hemodynamic changes in the systemic and pulmonary circulation. Hydrostatic effect plays a major role in this type of neurogenic lung pathology.

Animals

Reversed-phase high-performance liquid chromatography of amphoteric beta-lactam antibiotics: effects of columns, ion-pairing reagents and mobile phase pH on their retention times.

The separation of five amino beta-lactam antibiotics by reversed-phase high-performance liquid chromatography was studied as an insight into their retention behaviour. These five amphoteric compounds are cephradine, cephalexine, cefaclor, ampicillin and amoxicillin. Both octadecylsilane-bonded silica (C18) columns and phenyl-bonded silica (phenyl) columns were used, with mobile phase pH values between 2.5 and 7.4. In the absence of ion-pairing reagents the retention times for all the five compounds were the shortest at pH 4-6. The phenyl column was found to improve the separation between cephradine and ampicillin at pH values lower than 3, when these two compounds appeared as fused peaks on the C18 on C18 columns, with mobile phases both with and without ion-pairing reagents, were compared. The addition of 0.005 or 0.02 M tetraethylammonium acetate to the mobile phase did not result in significant ion-pair formation, except at pH values higher than 5.5. A strong ion-pairing effect was obtained at pH values higher than 6 with 0.005 or 0.02 M tetrabutylammonium phosphate, and the retention was decreased at pH values lower than 4. On the other hand, 0.005 M heptanesulphonic acid exhibited an ion-pair retention effect at pH values lower than 5. The molecular structures and pK(a) values were used to account for the retention behaviour of these antibiotics in the various mobile phases.

Amoxicillin

Intrapericardial pheochromocytoma.

In a 34-year-old man with hypertension and increased urinary catecholamine excretion for 12 years, an m-[131I]iodobenzylguanidine scan and chest computed tomography located an intrapericardial pheochromocytoma in the left atrium. The tumor was excised through a left thoracotomy with cardiopulmonary bypass and circulatory arrest. At 34-month follow-up, blood pressure and urine catecholamine levels were normal. In the 15 cases of intrapericardial pheochromocytoma treated by resection reported in the literature, all 11 survivors were symptom-free except 1 who had residual left atrial tumor and multiple skeletal metastatic lesions. Computed tomography directed by the m-[131I]iodobenzylguanidine scan can be used for detailed location of the tumor. Appropriate surgical approach and use of cardiopulmonary bypass are critical in the resection of these highly vascular tumors.

Adult

Estrogens influence cholecystokinin stimulated pancreatic amylase release and acinar cell membrane cholecystokinin receptors in rat.

This study examines the influence of ovariectomy and administration of a pharmacologic dose of estradiol on amylase release from isolated-dispersed rat pancreatic acini and cholecystokinin receptors on rat acinar cell membranes. Rats were sham ovariectomized (intact) or ovariectomized (Ovx) and 21 day timed release pellets containing either estradiol (2.5 mg) or vehicle, were implanted subcutaneously. Eighteen days later, pancreatic acini were isolated from rats by collagenase digestion and differential centrifugation. Total cellular amylase, basal and cholecystokinin octapeptide (CCK8) stimulated amylase release and CCK membrane receptors were measured. Acini isolated from estradiol treated Ovx rats had significantly greater total cellular amylase, compared to acini isolated from either intact or Ovx rats. The amplitude of both total stimulated amylase release and percent total stimulated amylase release were significantly greater for acini isolated from vehicle treated Ovx rats, than acini isolated from either intact or estradiol treated Ovx rats. The magnitude of percent total amylase release of acini isolated from estradiol treated Ovx rats was significantly lower than that of acini isolated from intact rats. Cholecystokinin receptor concentration was significantly greater on membranes prepared from vehicle treated Ovx rats, compared to membranes prepared from either intact or estradiol treated Ovx rats. These data indicate that ovariectomy is associated with increased responsiveness of pancreatic acini to CCK stimulation, while chronic estradiol treatment of ovariectomized rats is associated with increased total cellular amylase and decreased acinar cell responsiveness to CCK8. Estrogen mediated alterations in acinar cell amylase content and amylase release may play a role in estrogen related pancreatitis.

Amylases

Enalapril cytotoxicity in primary cultures of rat hepatocytes. I. Effects of cytochrome P450 inducers and inhibitors.

Enalapril maleate (EN) incubated with primary cultures of rat hepatocytes was cytotoxic in concentrations of 0.5 mM or greater. Toxicity was measured by release of lactate dehydrogenase (LDH) into the culture medium at 24 h. SKF525A, alpha-naphthoflavone (alpha NF) and metyrapone (MTP) reduced the toxicity of EN. In vivo pretreatment with phenobarbital (PB) and beta-naphthoflavone (beta NF) had minor protective effects on the responses of hepatocytes to EN exposure. However, in vivo pretreatment with pregnenolone-16 alpha-carbonitrile (PCN) substantially potentiated EN cytotoxicity. These results suggest that the cytocidal hepatotoxicity of EN in primary culture depends to some degree on metabolic activation by a cytochrome P450 species.

Animals

Enalapril cytotoxicity in primary cultures of rat hepatocytes. II. Role of glutathione.

The cytotoxicity of enalapril maleate (EN) in primary cultures of rat hepatocytes, at concentrations of 0.5 mM or greater, was measured by the release of lactate dehydrogenase (LDH) into the culture medium. Pretreatment of the hepatocytes with L-buthionine-(S,R)-sulfoximine (BSO) and diethyl maleate (DEM) potentiated the toxicity whereas N-acetyl-L-cysteine (NAC) provided protection. EN produced a dose-dependent reduction in intracellular glutathione (GSH) concentration. This was an early effect, apparent after only 1 h of exposure to the drug, whereas loss of cell viability occurred after 6-18 h. These results suggest that the mechanism of EN cytotoxicity involves a GSH-dependent detoxification pathway.

Acetylcysteine

Immune responses of the ovine lymph node to Chlamydia psittaci. A cellular study of popliteal efferent lymph.

The popliteal efferent lymphatics were cannulated in sheep of two categories, seronegative or immune to Chlamydia psittaci. Following subcutaneous injection of live C. psittaci or control material into the draining area of the popliteal node, sequential samples of efferent lymph were collected and analysed. Both categories of sheep responded to C. psittaci with increased outputs of lymphocytes and blast cells. Numbers of blast cells rose both absolutely and as a proportion of the total. Plasmablasts increased in number only in seronegative sheep. Outputs of total T cells (CD5+), helper T cells (CD4+), cytotoxic/suppressor T cells (CD8+) and non-helper, non-suppressor T cells (T19) were maximal 4 and 7 days after challenge in immune and seronegative sheep, respectively. Proportionally, CD4+ T cells declined, CD8+ T cells increased and T19 cells were unaltered with time after infection. Chlamydial antigens could not be demonstrated in the cells of efferent lymph by an immunoperoxidase method. The results of this preliminary study show that both T and B cell responses are involved in immunity to C. psittaci.

Abortion, Veterinary

Agranulocytosis associated with anti-thyroid drug in patients with Graves' thyrotoxicosis--report of 11 cases.

Retrospective analysis of 11 Chinese patients with Graves' thyrotoxicosis developing agranulocytosis during anti-thyroid treatment was done. Seven of them received methimazole and 4 received carbimazole. None of the 11 patients had taken propylthiouracil. The major chief complaints were high fever (100%), chillness (91%), and sore throat (73%). The duration of drug treatment prior to the detection of agranulocytosis ranged from 13 to 63 days (mean +/- 1SE: 33.1 +/- 16.1). At the time of agranulocytosis detected, the peripheral leukocyte counts were 0.5 to 2.1 X 1000/mm3 (mean +/- 1SE: 1.05 +/- 0.47 X 1000/mm3), absolute neutrophil counts 0 to 450/mm3 (mean +/- 1SE: 54.27 +/- 132.12/mm3), and hemoglobin 8.2 to 15.9 g/dl (mean +/- 1SE: 11.85 +/- 2.24 gm/dl). Three of the 11 patients had positive bacterial blood cultures. The recovery time of absolute neutrophil counts above 500/mm3 ranged from 3 to 25 days (mean +/- 1SE: 10.5 +/- 6.6) after discontinuation of antithyroid drugs. Mortality was found in 2 of them (18%).

Adolescent