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Biomedical subjects

C Cho

Publications and source records attributed to C Cho.

71 records · Page 4Linked to original sources
PubMed1983

Hepatotoxicity and metabolism of acetaminophen in male and female rats.

This present study was designed to assess the role of metabolic and pharmacokinetic factors in the lower susceptibility of female rats compared to male rats to xenobiotics metabolized by the cytochrome P-450-dependent mixed-function oxidase (MFO) system. Adult intact male and female Sprague-Dawley rats were administered labeled acetaminophen (1 g/kg body weight + 5 microCi [3H]acetaminophen) after an overnight fast. They were bled and killed at 0.5, 1, 2, 3, 6, 12, 24, and 36 h after drug administration. The percentage of [3H]acetaminophen radioactivity remaining in blood, liver, GI tract, and excreted in the urine was determined at all time intervals. Plasma prothrombin time and serum transaminases were determined as indices of hepatotoxicity. Hepatic GSH and glycogen were assayed. Total urinary acetaminophen and its metabolites and the molar percent of various metabolites excreted during the first 6 h were determined. Castrated male and ovariectomized female rats and their respective controls were also given acetaminophen (APAP) and were killed 24 h later to determine hepatotoxicity. The extent of hepatic damage in the intact male rats was greater and appeared sooner than in the female rats. Hepatic GSH and glycogen were depleted earlier in female rats. The percent of the administered dose excreted in the urine during the first 6 h was 17.5 for the male rat versus 24.5 for the female rat. While the APAP glucuronide conjugate concentration was significantly higher, the APAP sulfate conjugate concentration was lower in the female than it was in the male rat. Although peak radioactivity in serum was reached by 30 min in both male and female rats, suggesting quick intestinal absorption, it was significantly higher in female rats and was associated with decreased intestinal and hepatic levels and increased urinary excretion when compared to male rats. While castration of male rats decreased susceptibility to hepatotoxicity, ovariectomy of female rats tended to increase susceptibility to hepatotoxicity in comparison to their respective controls. Our data suggest that aside from the reported sex differences in the cytochrome P-450-dependent MFO enzymes, there are significant differences in GSH utilization. There are also significant changes in glucuronidation and sulfation pathways, as well as in the pharmacokinetics of acetaminophen, which tend to protect female rats against acetaminophen hepatotoxicity.

Acetaminophen↗
PubMed1983

Effects of propylthiouracil on urinary metabolites of cyclophosphamide in rats.

Our previous studies have shown a protective effect of propylthiouracil (PTU) pretreatment against the toxicity of cyclophosphamide (CP). The present study was undertaken to investigate the mechanism of the PTU protection. CP is metabolized by the cytochrome P-450 drug-metabolizing enzyme system in the liver to alkylating metabolites, to active antineoplastic agents, and to acrolein, the most toxic and least antineoplastic metabolite. Measurements of CP metabolites in blood and urine during a 4-hr i.v. infusion of CP (50 mg/kg body weight/hr) showed urinary acrolein excretion to be 2.5 times higher in control rats as compared to PTU-treated rats. Since it has been reported that urinary acrolein levels are directly related to the frequency and severity of hemorrhagic cystitis, it is concluded from our observations that prevention of hemorrhagic cystitis is probably mediated by the PTU effect on lowering urinary acrolein concentration and excretion. Serum alkylating activity was significantly higher in the PTU-pretreated rats, which may enhance the antineoplastic potential of CP.

Animals↗
PubMed1983

Effect of riboflavin status on acetaminophen toxicity in the rat.

The effect of riboflavin status on acetaminophen hepatotoxicity was determined in the rat. Groups of rats were fed one of the following diets: "riboflavin-free" (RFF), low riboflavin (LRF), high riboflavin (HRF), or high riboflavin pair-fed (HRF pair-fed) with RFF group. After riboflavin deficiency was established by determining erythrocyte glutathione reductase activity coefficient, rats in all groups were administered a toxic dose of acetaminophen (1 g/kg body weight) orally. Their controls were given the vehicle alone. All animals were killed 24 h later and hepatotoxicity was assessed by the elevation of serum transaminases and by a necrotic score based on histological examination. The RFF diet induced biochemical riboflavin deficiency, decreased food intake and body weight gain, and was associated with almost complete protection against acetaminophen toxicity. Rats on the LRF diet, with less severe riboflavin deficiency and no significant change in weight gain, showed some necrosis, but it was much less than in the HRF ad libitum-fed rats. The HRF pair-fed rats with no biochemical riboflavin deficiency but with considerable growth retardation also showed very little hepatic necrosis. Our results suggest that riboflavin deficiency protects rats against acetaminophen toxicity but it is confounded by decreased food consumption and body weight.

Acetaminophen↗
PubMed1982

Colonic lymphoma producing alpha-chain disease protein.

Alpha-chain disease with involvement of small intestine-resulting in characteristic villus atrophy and malabsorption has not been reported in this country. We studied a 57-yr-old male who presented with a polypoid tumor of the hepatic flexure of the colon. There was no evidence of malabsorption as manifested by a normal fat balance, serum carotene, and D-xylose absorption studies and the small bowel biopsy did not show villus atrophy. The tumor in the colon was surgically removed and diagnosed as a malignant lymphoma of lymphocytic type. Tumor tissue infiltrated in the mesentery could not be excised. Alpha-chain disease protein was demonstrated in serum and urine, and also in tumor tissue by immunoperoxidase techniques. The alpha-chain disease protein was further purified and classified as subclass 1. The patient had a good clinical response to cyclophosphamide and prednisone, but still has intraabdominal lymphoma with gastric involvement, and his serum alpha-chain protein persists. This case report may represent a distinct variant of alpha-chain disease.

Colonic Neoplasms↗
PubMed1980

Heat stroke. Report of three fatal cases with emphasis on findings in skeletal muscle.

Three fatal cases of heat stroke were encountered in the central New York area over a two-month period. Although in each instance one or more predisposing factors were identified, exertion clearly played a role in its development in only one case. In addition to laboratory and postmortem findings indicative of dysfunction of many organ systems, there was morphological evidence of widespread damage to skeletal muscle.

Adult↗
PubMed1978

Bile duct adenomas as liver nodules.

Bile duct adenomas can be difficult to differentiate at laparotomy from small metastatic tumor nodules in the liver. This can present a problem to the pathologist and surgeon relative to the advisability of attempted curative vs pallative surgery. We report two such cases. Review of our autopsy materials shows the incidence of bile duct adenoma to be higher than usually reported. Even though they all present as grayish-white, firm nodules, usually frozen section will reveal the true nature of the lesion. Occasionally, however, the lesions with active bile duct proliferation can cause problems in diagnosis, even after such examination. Accurate diagnosis by recognition of the entity and its histological characteristics may be very important in the surgical treatment of patients.

Adenocarcinoma↗
PubMed1978

Effects of chronic beta-glycerophosphate administration on growth rate and on serum, liver and bile lipid composition in the squirrel monkey--a toxicity study.

Oral administration of beta-glycerophosphate lowers the lithogenic index in patients with cholesterol gallstones and is considered to have potential for dissolving them. A high dose of beta-glycerphosphate was fed to primates (Squirrel monkeys) for a period of 15 months. There were no adverse effects on body weight, hematological or liver function tests. Serum, liver and bile lipids concentrations were not significantly changed, although serum and hepatic bile phospholipids were increased. Organ weights expressed as percent of body weight were not changed except for a slight increase in kidney weight. Histological examination of liver and kidneys did not reveal any pathological findings. Slight renal hypertrophy was attributed to the sodium content of beta-glycerophosphate.

Animals↗
PubMedDate not supplied

3D reconstruction of gastric surface using endoscopic 3 source photometry.

Extraction and recognition of three-dimensional (3D) shape information of gastric surface become increasingly important in the field of gastric diagnosis. But there is no practical method that can extract the 3D shape information of gastric surface. For obtaining this 3D information, we developed a new photometric method that can be used in TV endoscope, and evaluated the proposed method theoretically and experimentally. As the results of simulation and experiment, it could be concluded that the proposed method is effective for 3D reconstruction of gastric surface.

Computer Graphics↗
PubMedDate not supplied

Increased glycodelin levels in gynecological malignancies.

Glycodelin, an immunosuppressive protein with contraceptive properties, is synthesized by a variety of tissues and cell types. The ability of reproductive tissues to synthesize glycodelin is of major interest in pregnancy and disease conditions. We studied glycodelin levels in subjects with malignant gynecological tumors and in control subjects. Using a polyclonal glycodelin antibody against the synthetic glycodelin peptide sequence, an enzyme-linked immunosorbent assay (ELISA) was devised to measure plasma glycodelin levels. The assay detected as much as 5 ng/ml of glycodelin. There was a significant increase in plasma glycodelin levels in endometrial > ovarian > cervical cancer subjects when compared to those of controls. Strong expression of mRNA and protein were found in the ovarian and endometrial tumor tissues. Given glycodelin's immunosuppressive abilities, increased level of glycodelin may facilitate tumor growth in gynecological malignancies.

Adolescent↗
PubMedDate not supplied

Swelling of multicellular spheroids induced by hyperthermia.

EMT6 multicellular spheroids invariably swell by 10 to 50 per cent after incubation at 43 to 45 degrees C for 1 h. Both scanning electron and optical microscopy reveal morphological alterations particularly in the outer region of the spheroids. While the control cells are contiguous to one another and tightly held to the spheroid body, the heated spheroids exhibit partially disrupted contacts among cells. Measurements of intercellular volume and water volume of spheroids with labelled water and inulin show that changes in the spheroid volume are not due to an increase in cell volume, but that they can be explained by a 60-100 per cent increase in the intercellular space within a spheroid. Continuous observation of individual spheroids heated to 43-45 degrees C shows loss of adhesion of cells in the outer region and even detachment of a few surface cells. This 'melting' of the spheroid surface appears to result from a disorder in the extracellular material. Treatment with cell swelling agents such as hypotonic solution, ouabain, excess extracellular potassium ions, or ionophore nigericin, K+/H+ exchanger, each separately causes the spheroids to swell at the control temperature. On the other hand, A23187, Ca2+ ionophore, causes shrinkage of the spheroids. Thus, under hyperthermia, the volume of spheroids increases due to the disruption in the cell organization in their outer region.

Calcimycin↗