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Biomedical subjects

T S Chen

Publications and source records attributed to T S Chen.

At least 19 recordsLinked to original sources

Acetaminophen-induced depletion of glutathione and cysteine in the aging mouse kidney.

Glutathione (GSH) plays an essential role in the detoxification of acetaminophen (APAP) and the prevention of APAP-induced toxicity in the kidney. Our previous results demonstrated that a GSH deficiency is a general property of aging tissues, including the kidney, suggesting a hypothesis that senescent organisms are at greater risk to APAP-induced renal damage. To test this, C57BL/6NIA mice of different ages through the life span were injected with various doses of APAP, and the extent of GSH and cysteine (Cys) depletion and recovery were determined. At time intervals up to 24 hr, kidney cortex samples were obtained, processed and analyzed for glutathione status, namely GSH, glutathione disulfide (GSSG), Cys and cystine, using an HPLC method with dual electrochemical detection. In the uninjected controls, GSH and Cys concentrations decreased about 30% in the aging mouse, but the GSSG and cystine levels were unchanged during the life span. APAP administration depleted the kidney GSH and Cys contents in a dose- and time-dependent manner. Four hours after APAP administration, GSH levels of the young, growing (3- to 6-month) and the mature (12-month) mice decreased 34 and 58%, respectively, and recovered to near control values by 24 hr (95 and 98%). In contrast, the extent of depletion in old (31-month) mice was greater (64%) and the 24-hr recovery was less, returning only to 56%. Likewise, Cys levels of the young and mature mice decreased 49 and 65%, respectively, 4 hr following APAP, and increased to 99 and 85% by 24 hr. In contrast, in old mice, there was a 78% depletion after 4 hr followed by a recovery of only 65% by 24 hr. These results demonstrated clearly that in the aging mouse kidney, a GSH and Cys deficiency occurs that is accompanied by an impaired APAP detoxification capacity.

Acetaminophen

Glycocholic acid and glycodeoxycholic acid but not glycoursocholic acid inhibit bile acid synthesis in the rabbit.

Feedback regulation of derepressed hepatic bile acid biosynthesis was studied individually with glycocholic, glycodeoxycholic, and glycoursocholic acids by infusion into bile acid-depleted rabbits. Construction of a bile fistula drained the endogenous bile acid pool (90% glycodeoxycholic acid, 10% glycocholic acid) within 24 hours and elicited maximal bile acid synthesis after about 72 hours, at which time glycocholic acid became the only biliary bile acid (greater than 98%). Replacement of the bile acid pool with glycocholic acid or glycodeoxycholic acid at a rate equivalent to the hepatic endogenous bile acid flux inhibited endogenous biosynthesis by 40%. In contrast, glycoursocholic acid, the 7 beta-hydroxy epimer of glycocholic acid, failed to suppress synthesis. Hepatic bile acid depletion increased hydroxymethyglutary coenzyme A (HMG-CoA) reductase activity fourfold and cholesterol 7 alpha-hydroxylase activity threefold, which were reduced 48% and 51%, respectively, from their maximum levels during replacement with glycocholic acid. Glycodeoxycholic acid infusion depressed cholesterol 7 alpha-hydroxylase activity by 59% without reducing HMG-CoA reductase activity significantly. There was no significant change in the activity of either enzyme during glycoursocholic acid infusion. Biliary cholesterol and cholestanol secretion declined 13% and 53%, respectively, during glycocholic acid infusion, were not affected by glycodeoxycholic acid infusion, but increased 19% and 43%, respectively, during glycoursocholic acid infusion. These results show that in rabbits the feedback regulation of hepatic bile acid synthesis depends on the hepatic flux of the normally present endogenous bile acids glycocholic acid and glycodeoxycholic acid but does not respond to the 7 beta-hydroxy glycoursocholic acid. Glycocholic acid inhibits both HMG-CoA reductase and cholesterol 7 alpha-hydroxylase while glycodeoxycholic acid affects primarily cholesterol 7 alpha-hydroxylase. Thus, the regulation of bile acid synthesis may be mediated by both the availability of cholesterol substrate and the activity of the rate-determining enzyme for bile acid synthesis.

Animals

Gastroenterology in ancient Egypt.

Physicians in ancient Egypt devoted their care to disorders of individual organs. Notable among the specialties was gastroenterology, a subject matter that occupied a major portion of the surviving medical papyri. Although they did not name diseases as we know them, Pharaonic physicians described a host of gastroenterological symptoms for which an extensive array of therapeutics was prescribed. Their clinical accounts indicated an impressive knowledge of gastric and anorectal conditions. In their thinking on disease mechanism, the circulating materia peccans absorbed from feces represented a major cause of medical symptoms and disorders. This served as the rationale for the popular practice of self-purgation with enemas.

Egypt, Ancient

Serologic survey of spotted fever group rickettsiosis on Hainan Island of China.

A serosurvey for antibodies to Rickettsia japonica was conducted on Hainan Island of China. Serum specimens were collected from 1,030 outpatients at hospitals in different parts of the island regardless of their diagnosis. Only two among 538 serum specimens collected in Baoting and Tongshi counties, located in the southern part of the island, were demonstrated to contain antibodies reactive with R. japonica at a high dilution. The specimens also reacted with R. rickettsii at the same titer as with R. japonica. These two specimens reacted with other pathogenic spotted fever group (SFG) rickettsiae to a lesser extent. On the other hand, the specimens were shown to possess antibodies reactive with R. typhi at a significantly lower dilution or were not reactive at all. The findings suggested the occurrence of an SFG rickettsiosis on Hainan Island. More than half of the serum specimens collected from patients with suspected rickettsial infections in the southern area were found to contain IgM and IgG antibodies to R. typhi, indicating a high incidence of murine typhus.

Antibodies, Bacterial

The influence of the interdigestive migrating myoelectric complex on the gastric emptying of liquids.

It is unknown how the interdigestive migrating motor complex influences the gastric emptying of liquids. Therefore, the gastric emptying rate of 50- and 200-mL volumes of phenol red solution were measured while monitoring contractile activity. Motor activity was recorded using a hydraulic manometric system and expressed as either the proximity of dosing time to time of appearance of phase III or as a motility index, defined as (contractile area)/(sampling interval time). After an initial lag period, emptying was log linear. With a 50-mL oral dose, the mean gastric emptying rate of the log-linear phase was successively faster during phase I (0.018 +/- 0.003 min-1), phase II (0.083 +/- 0.031 min-1), and late phase II/III (0.171 +/- 0.066 min-1) (P less than 0.05). Similarly, the mean lag time decreased successively with phases I, II, and late II/III (19.1 +/- 12.4, 7.6 +/- 5.6, and 3.8 +/- 2.8 minutes, respectively). At a 200-mL oral dose, there was no difference in the emptying rate between phase I and phase II (0.104 +/- 0.0014 vs. 0.110 +/- 0.041 min-1), but the emptying rate during late phase II/III was significantly greater (0.236 +/- 0.069 min-1); lag time was not dependent on phase. There was a statistical difference in the overall mean emptying rate between the 50- and 200-mL volumes. Also, during phase I, the emptying rate was faster for the 200-mL volume. This study shows a strong dependence of liquid gastric emptying rate and lag time on interdigestive antral motility, the emptying of small volumes being more dependent on motility phase than that of large volumes. Phase-related fluctuations in contractile activity can account for much of the reported variability in gastric emptying data. Furthermore, this study suggests that dose volume and interdigestive motor activity at the time of drug administration can affect absorption and onset of therapeutic response for some drugs.

Analysis of Variance

Life span differences in digoxin uptake and excretion.

Little is known about the underlying mechanisms for the altered susceptibility to digitalis with age. To this end, we investigated the digoxin uptake and excretion in mice and rats of different ages through the life span, including the periods of growth, maturity, and aging. Digoxin uptake by cardiac slices was linear from 0 to 15 min, with steady state occurring at 45 min. The rate in the mature 12-month mouse was significantly less than that of the senescent 30-month mouse. The kinetic parameters revealed a significant decrease in Km with a concomitant increase in Vmax during senescence. On the other hand, digoxin uptake by renal cortical slices was highest during growth, decreased to a maturation plateau and then declined further during senescence. Renal clearance and the secretory capacity for digoxin increased 30 and 62%, respectively, during growth and progressively decreased from maturity through senescence and were 59 and 77%, respectively, during aging. In summary, there was an increase in digoxin clearance and tubular activity during growth, and an increase in myocardial uptake of digoxin and a decrease in renal excretion during aging. Thus, these results may explain the clinical observations of altered susceptibility to digitalis with age.

Aging

Intestinal transport during the life span of the mouse.

Intestinal malabsorption of nutrients may be a critical factor in aging. For this reason, we investigated the nutrient absorption in mice of different ages of the life span, representing growth (3 mo), young adult (12 mo), mature (24 mo), old (30 mo), and very old (33-36 mo) periods. The everted sac technique was used to study the transepithelial transport of D-glucose, 3-O-methyl-D-glucose (3MG), and L-tyrosine. There was a 32% increase in the rate of D-glucose transepithelial transport during growth followed by a 55% decrease in the old mouse, and the same pattern occurred with 3MG, a nonmetabolized glucose derivative. However, L-tyrosine transepithelial transport was not impaired until the mouse reached the very old, 33-36 mo period. Also, the rate of D-glucose metabolism measured by lactate production in the very old mouse was only 45% of the mature mouse value. In addition, these transepithelial transport changes were accompanied by decreases in the number and the height of villi. The results indicate that intestinal transepithelial transport and the surface area for absorption decrease in aging.

3-O-Methylglucose

Iron status of infancy and early childhood in south Taiwan.

The iron status of 206 infants and young children in South Taiwan were evaluated by measurements of serum iron, total iron binding capacity, serum ferritin, and hematological parameters of peripheral blood including hemoglobin (Hb), hematocrit, mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV). 18 subjects aged 2 months were included in the study and no iron deficiency was found in this group. Four groups of the other subjects aged between 3 and 36 months were studied; A: 3-6 months, 28 subjects, B: 6-12 months, 29 subjects, C: 12-24 months, 91 subjects, D: 24-36 months, 40 subjects. Prevalence of iron deficiency in those between 3 and 36 months was 34%, including iron deficiency without anemia 22.9% (n = 43) and iron deficiency anemia 11.1% (n = 21). Most cases (96.9%) of iron deficiency occurred in the infants and children aged 6-36 months. Iron deficiency without anemia in the A, B, C and D groups was 3.6%, 17.2%, 25.3%, 35.0% respectively and iron deficiency anemia were 3.6%, 17.2%, 12.1%, 10.0% respectively. Hematological parameters are less valuable in diagnosis of iron deficiency, with accuracy of 68.8%, 63.8%, 68.8%, 64.3% respectively for these four groups. These parameters decline significantly in the iron deficiency anemia group, but not in the iron deficiency without anemia group. Low levels (Hb less than 11 g/dl, hematocrit less than 33%, MCH less than 24 pg, MCV less than 72 fl) are indicators of a need to search a cause of anemia, especially iron deficiency anemia in infants and children with ages between 3 and 36 months, but normal values do not exclude iron deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hypochromic

Studies on the biosynthesis of avermectins.

To elucidate the pathway of avermectin biosynthesis, the biosynthetic relationships of avermectins A1a, A2a, B1a, B2a, and their respective monosaccharides and aglycones were studied. 14C-labeled avermectin compounds prepared from [1-14C]acetate were fed to Streptomyces avermitilis strain MA5502 and their metabolites were determined. Two furan ring-free aglycones, 6,8a-seco-6,8a-deoxy-5-keto avermectin B1a and B2a, have been isolated from the fermentation broth of a blocked mutant of S. avermitilis. Addition of the compounds and a semisynthetic compound, 5-keto avermectin B2a aglycone, to the fermentation medium of a second blocked mutant established that the two compounds are intermediates in the avermectin biosynthetic pathway immediately preceding avermectin aglycones.

Acetates

Directed biosynthesis of avermectins.

Avermectin homologs are produced by Streptomyces avermitilis when externally supplied with sodium 2-methylpentanoate and sodium 2-methylhexanoate. The homologs carry 2-pentyl and 2-hexyl groups, respectively, at C-25 of the aglycone moiety as opposed to the 2-butyl group of "a" components and the isopropyl group of "b" components of natural avermectins. The new homologs designated as avermectin "c" and "d" components, respectively, possess potent anthelmintic and insecticidal activity.

Animals

Intestinal autointoxication: a medical leitmotif.

The idea that putrefaction of the stools causes disease, i.e., intestinal autointoxication, originated with physicians in ancient Egypt. They believed that a putrefactive principle associated with feces was absorbed in to the general circulation, where it acted to produce fever and pus. This description of the materia peccans represented the earliest forerunner of our present notion of endotoxin and its effect. The ancient Greeks extended the concept of putrefaction to involve not only the residues of food, but also those of bile, phlegm, and blood, incorporating it into their humoral theory of disease. During the 19th century, the early biochemical and bacteriologic studies lent credence to the idea of ptomaine poisoning--that degradation of protein in the colon by anerobic bacteria generated toxic amines. Among the leading proponents of autointoxication was Metchnikoff, who hypothesized that intestinal toxins shortened lifespan. The toxic process, however, was reversed by the consumption of lactic acid-producing bacteria that changed the colonic microflora and prevented proteolysis. The next logical step in treatment followed in the early 20th century when surgeons, chief among them Sir W. Arbuthnot Lane, performed colectomy to cure intestinal autointoxication. By the 1920s, the medical doctrine fell into disrepute as scientific advanced failed to give support. However, the idea persists in the public mind, probably as an extension of the childhood habit of toilet training.

Egypt

The effect of aging on glutathione and cysteine levels in different regions of the mouse brain.

A general glutathione (GSH) deficiency occurs in many tissues of the aging mouse. However, there is no information on GSH in the aging brain even though it has been involved in a number of neurobiologic reactions. To this end, C57BL/6 mice, 3-31 months old, representing the growth, maturation, and aging periods of the life-span were studied. Brain cortex, hippocampus, and stem samples were dissected, processed, and analyzed specifically for reduced and oxidized glutathione (GSH, GSSG) and cyst(e)ine using high performance liquid chromatography with dual electrochemical detection. The GSH content of each brain region varied in the order brain cortex greater than brain hippocampus greater than brainstem. However, the GSH profiles of all regions were the same through the life-span, namely, high values during growth dropping to a maturation plateau and then decreasing 30% during aging. In contrast to GSH, the order of cysteine levels was brain cortex less than brain hippocampus less than brainstem and no life-span changes occurred in any region. In addition, the brain GSSG and cystine contents of all regions were very low and did not change during the life-span. Thus, the GSH loss was not accountable by oxidation to GSSG or degradation to cyst(e)ine. Altogether these results demonstrated a GSH deficiency in brain tissues of aging mice like that found previously in other tissues. These findings suggest an increased susceptibility of the aging brain to oxidative damage.

Aging

Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

Animals

Incidence of massive rebleeding from nonbleeding visible vessels in benign gastroduodenal lesions and prospective study in assessing the efficacy of endoscopic hemostasis with local ethanol injection for prevention of rebleeding.

Twenty-seven patients presenting with massive upper gastrointestinal bleeding in whom endoscopy revealed nonbleeding visible vessels in benign gastroduodenal lesions were prospectively and nonrandomly allocated to receive endoscopic injection therapy with pure ethanol or conservative treatment. Those who received conservative therapy were used as a control group. The purpose of this study is to evaluate the incidence of massive rebleeding from the nonbleeding visible vessel which was defined by a more rigid criteria and to evaluate the efficacy of endoscopic pure ethanol local injection to prevent rebleeding. Nine out of the 10 (90%) controls had recurrent major bleeding, in contrast to the 2/17 (12%) of those who received hemostatic endoscopy (p less than 0.0002). Pure ethanol local injections also minimized further transfusion requirements (p less than 0.03). The complications of hemostatic endoscopy in this study are negligible. It is concluded that 1) by restrictive definition nonbleeding visible vessels in benign gastroduodenal lesions carry a high potential of recurrent massive bleeding; 2) rebleeding can be safely and effectively prevented by pure ethanol local injection.

Adolescent

[Renal function in chronic cor pulmonale monitored with beta 2-microglobulin].

Serum and urine levels of beta 2-microglobulin (beta 2-MG) were measured with radioimmune assay in 40 chronic cor pulmonale patients (52 episodes) and 26 normal controls. The results showed that the serum and urine levels of beta 2-MG were 2.01 +/- 0.47 mg/L and 0.10 +/- 0.08 mg/L respectively, in the normal controls, while in the cor pulmonale group 3.86 +/- 1.58 mg/L and 0.66 +/- 0.34 mg/L respectively, with statistical significance (P less than 0.001, less than 0.005). It was shown that there was a positive correlation between the levels of serum and urine beta 2-MG and PaCO2 and a negative correlation between the levels of serum and urine beta 2-MG and PaO2. The results indicated that determination of serum and urine beta 2-MG could be used in the early detection of the renal impairment in chronic cor pulmonale. The predisposing factors of renal dysfunction in cor pulmonale were also discussed.

Adult