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Biomedical subjects

R S Yang

Publications and source records attributed to R S Yang.

At least 127 records · Page 7Linked to original sources

Experimental allograft in spinal fusion in dogs.

Fifty-six dogs were used for the comparison of the allogenous and autogenous bone graft in anterior interbody and posterior spinal fusion. Excluding 7 cases with wound infections, the end results of the allograft and autograft in anterior interbody and posterior spinal fusion were nearly the same, provided that the rules of technique for the spinal fusion were strictly followed, especially in the allograft group. Grossly, there was a reduction tendency in the fusion mass of the allograft group that was proven by roentgenographic examination of the harvested spinal block. Histologically, there was no evidence of regeneration of the allograft that can be readily detected in the autograft. In the allograft group, osteogenesis can only be seen in the recipient sites, the allograft transplants become sequestrated and resorbed.

Animals↗

Arthrodesis of the nonrheumatoid wrist.

From March 1977 to September 1986, wrist arthrodesis was performed on 20 patients with various nonrheumatoid wrist disorders. Among them, 16 patients were men and 4 were women. Their ages ranged from 13 to 48 years, with a mean of 28.1 years. The various disorders included giant cell tumor, tuberculosis, flaccid wrist, and traumatic osteoarthritis. The major symptoms included pain, swelling, stiffness and deformity, that persisted for over 12 months before hospitalization. Both clinical and radiological examination were included for evaluation. The follow-up period ranged from 12 to 126 months, with a mean of 55 months. The results showed that the pain subsided, the grip strength increased, and the functional range of motion was preserved. All patients were able to carry normal lives. The major complication was rare. The only one nonunion case achieved a solid union after revision. Although wrist arthrodesis has its own disadvantages, it still effectively solves many wrist problems in carefully selected cases.

Adolescent↗

Toxicology and pathology of methyl bromide in F344 rats and B6C3F1 mice following repeated inhalation exposure.

The toxicity of methyl bromide was studied in male and female F344 rats and B6C3F1 mice exposed by inhalation to 160 ppm methyl bromide or air 6 hr/day, 5 days/week for up to 6 weeks. The animals were killed after 3, 10, or 30 exposure days, or when 50% mortality was observed in any group. Only female rats survived the entire 30 exposure days at 160 ppm methyl bromide with less than 50% mortality. There were clear species- and sex-related differences in susceptibility of specific organs to methyl bromide. Primary target organs were the brain, kidney, nasal cavity, heart, adrenal gland, liver, and testis. In rats, neuronal necrosis occurred in the cerebral cortex, hippocampus, and thalamus of the brain whereas in mice neuronal necrosis occurred primarily in the internal granular layer of the cerebellum. Nephrosis occurred in all exposed mice, but not rats, and was likely a major cause of moribundity and death. Necrosis of the olfactory epithelium was more severe and extensive in rats than mice. Myocardial degeneration occurred in male and female rats and to a lesser degree in male mice. There was atrophy of the inner zone of the adrenal cortex in female mice and cytoplasmic vacuolation of the adrenal cortex in rats. Testicular degeneration occurred in rats and mice. The target organ specificity of methyl bromide is similar to that of methyl chloride, suggesting that the two monohalomethanes may have a common mechanism of action.

Administration, Inhalation↗

Toxicological studies of chemical mixtures of environmental concern at the National Toxicology Program: health effects of groundwater contaminants.

In cooperation with the Agency for Toxic Substances and Disease Registry, the National Toxicology Program is participating in a Public Health Service activity related to the Comprehensive Environmental Response, Compensation and Liability Act (Superfund Act) by conducting toxicology studies on chemicals found in high-priority hazardous waste sites and for which adequate toxicological data are not available. As part of this effort, a project on the toxicology of chemical mixtures of groundwater contaminants was initiated. The first study, centered on the health effects of groundwater contaminants, is at the contractual stage. Nineteen organic and six inorganic chemicals, selected from more than 1000 known groundwater contaminants, will be given in drinking water to Fischer 344 rats and B6C3F1 mice for 3 or 6 months. Controls and five dose levels, based on average concentrations (i.e., baseline level) of individual component chemicals, or 0.1-, 10-, or 1000-fold of the baseline level, will be used. Toxicological end points include mortality, clinical signs, water and food consumption, body and organ weights, clinical pathology analytes (e.g., hematology, clinical chemistry, and urinalysis), gross and histopathology, neurobehavioral tests, sperm morphology and vaginal cytology evaluations (SMVCE), and cytogenetics. This paper summarizes the rationale behind our experimental design and the factors one must consider when designing studies of complex chemical mixtures.

Animals↗

Evaluation of the teratogenicity of ethylenediamine dihydrochloride in Fischer 344 rats by conventional and pair-feeding studies.

Ethylenediamine dihydrochloride (EDA.2HCl) was fed to groups of 20 (40 controls) timed-pregnant rats on Gestation Days 6 through 15 at 1.0, 0.25, 0.05, or 0 g/kg/day. The day of discovery of a vaginal plug was considered gestation day 0. On Gestation Day 21, the fetuses were delivered by cesarean section, and the standard endpoints for teratogenicity were evaluated. At 1.0 and 0.25 g/kg/day, reductions in maternal diet consumption and weight gain were observed during the exposure period. At 1.0 g/kg/day, fetal weight and crown-rump length were significantly reduced and the percentage of litters with resorptions, with skeletal variants, and with missing or shortened innominate arteries was increased. To circumvent the possible problem of palatability of the diet and/or the effects of reduced food intake, a probe study was performed in which 1.0 or 0 g/kg/day was given to pregnant rats by gavage on Gestation Days 6 through 15. However, food intake was also substantially reduced with gavage dosing of the test substance. To determine whether the arterial defects were the result of reduced food intake, a pair-feeding study was performed in which EDA.2HCl was fed on Gestation Days 6 through 15 at 1.0 g/kg/day. A pair-fed control group received the same amount of diet consumed by the EDA.2HCl-treated rats. An untreated control group was fed ad libitum. All groups contained 20 pregnant females. Maternal weight gain, fetal weight and length, and the length of the innominate artery were all reduced in the EDA.2HCl-treated group compared to both control groups. Two fetuses each in the EDA.2HCl-treated and pair-fed control groups had missing innominate arteries versus none in the untreated controls. The four affected fetuses were from four different litters. Ingestion of EDA.2HCl resulted in reduced maternal weight gain, fetal size, and length of the innominate artery, but the missing innominate artery was not a result of EDA.2HCl treatment. Therefore, there was no evidence of teratogenicity in Fischer 344 rats from EDA.2HCl ingestion during organogenesis.

Animals↗

Biochemical and morphological studies on the percutaneous uptake of [14C] ethylenediamine in the rat.

Male Wistar rats were exposed to aqueous [14C]ethylenediamine (EDA) solutions (10, 25, or 50%) percutaneously over a 7 x 7 cm area on the back with occlusion for 24 h. For each rat dosed, three types of studies were conducted: (1) plasma kinetics, (2) material balance, and (3) histological evaluation, including autoradiography of the skin sample from the dosing area. Adequate kinetic measurements were obtained only from animals treated with 25 and 50% EDA, but not from the 10% treatment group, due to analytical limitations. The uptake of [14C]EDA percutaneously by the rat was relatively slow in comparison with uptake following peroral or endotracheal administration. The absorption of EDA by the animals was estimated to be greater than 61, 55, and 12%, respectively, for the 50, 25, and 10% treatment groups. A large portion (11-32%) of the dose was left on/in the dosing area. Urinary excretion was the predominant route for the disposition of EDA. The recovery of the administered dose was low (70-83%), possibly due to volatilization of EDA from the skin during dosing and holding. Histologic examination of skin sections (dosing areas) revealed a normal, intact epidermis in rats dosed with 10% EDA, but full-thickness epidermal necrosis in rats dosed with 25% or 50% EDA solutions. The damage of the epidermis apparently enhanced the penetration of EDA. Autoradiographic preparations revealed a concentration of the [14C]EDA radiolabel over the keratin layer and hair shafts.

Administration, Topical↗

1,3-Dichloropropene.

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Abnormalities, Drug-Induced↗

Chronic toxicology and carcinogenesis studies of Telone II by gavage in Fischer-344 rats and B6C3F1 mice.

Telone II (technical grade, 1,3-dichloropropene), a soil fumigant, was evaluated in chronic toxicology/carcinogenicity studies using Fischer-344 (F344) rats and B6C3F1 mice of both sexes. Doses administered were 0, 25, or 50 mg/kg to rats and 0, 50, or 100 mg/kg to mice. Telone II was given in corn oil by gavage 3 times per week for 104 wk. Ancillary studies were conducted to determine time-related effects, in which dose groups containing 5 male and 5 females rats were killed after receiving Telone II for 9, 16, 21, 24, or 27 mo. The primary organs affected were the forestomach (rats and mice), urinary bladder (mice), lung (mice), and liver (rats). Compound-related non-neoplastic lesions included basal-cell or epithelial hyperplasia of the forestomach (rats and mice), epithelial hyperplasia of the urinary bladder (mice), and hydronephrosis (mice). Neoplastic lesions associated with administration of Telone II included squamous-cell papillomas of the forestomach (male and female rats, female mice), squamous-cell carcinomas of the forestomach (Male rats, female mice), transitional-cell carcinomas of the urinary bladder (female mice), alveolar/bronchiolar adenomas (female mice), and neoplastic nodules of the liver (male rats). Although cis- and trans-1,3-dichloropropene are the principal components of Telone II, the presence of 1% epichlorohydrin, a direct-acting mutagen and carcinogen added as stabilizer, may have influenced the development of forestomach lesions. The results of the ancillary studies supported the findings of the carcinogenesis studies and demonstrated the time-dependent development of lesions in the forestomach (basal-cell hyperplasia and squamous-cell papilloma). Under the conditions of these gavage studies, Telone II was shown to be carcinogenic in male and female F344 rats and female B6C3F1 mice. Although the study in male B6C3F1 mice was considered inadequate because of the low survival resulting from suppurative inflammation of the heart (myocarditis) in the control group, there was some indication of Telone II-related increases of transitional-cell carcinomas of the urinary bladder, squamous-cell papillomas of the forestomach, and alveolar/bronchiolar adenomas and carcinomas of the lung.

Allyl Compounds↗

Two-generation reproduction study of ethylenediamine in Fischer 344 rats.

Ethylenediamine dihydrochloride (EDA X 2 HCl) was incorporated in the diet of Fischer 344 rats at dosage goals of 0.50, 0.15, 0.05, or 0 g/kg/day in a two-generation reproduction study. The parent generation (F0) and the F1 generation were each bred once. Parameters examined included indices of fertility, gestation of dams, gestation survival, 0- to 4-, 4- to 14- and 4- to 21-day survival of pups, number of pups born alive, and number of pups weaned per litter. Furthermore, observations were made on mortality, diet consumption, and body weight of the adult rats in F0 and F1 generation. Randomly selected F1 weanlings and adults and F2 weanlings were sacrificed and organ weights were obtained; in addition, gross and histologic examinations were conducted on these rats. No reproductive toxicity was observed in this study. Some effects were observed in both sexes for the F0 and F1 parent rats. These effects were mainly associated with the high dosage level and included reduction of body weight gain and changes in liver (decrease) and kidney (increase) weights in the adult rats. The only microscopic lesion observed was hepatocellular pleomorphism in the high level F1 adult males and females; a greater prevalence and severity of this lesion was seen in the female rats.

Animal Feed↗

Age-dependent pharmacokinetic changes of ethylenediamine in Fischer 344 rats parallel to a two-year chronic toxicity study.

As part of a 2-year chronic toxicity study, the pharmacokinetics of ethylenediamine (EDA) was studied in Fischer 344 rats of both sexes at day zero (naive animals), 6 months (controls and high level animals), and 18 months (controls and high level animals). The rats, which were randomized along with the rest of the animals on the toxicity study, were taken for pharmacokinetic experiments at the specified time. A single per os (po) dose of 50 mg [14C]EDA X 2HCl/kg was given to each rat and the plasma kinetics was followed for a 24-hr period. Five pharmacokinetic parameters (absorption rate constant, terminal half-life, area under the curve, volume of distribution, and 14CO2 production rate constant) were compared with respect to age, sex, and chronic dosing. There were no apparent age-, sex-, and/or chronic dosing-related differences in absorption rate constant and terminal half-life. However, age-related changes in area under the curve (AUC) were evident. The older rats had higher values (generally two- to threefold) for AUC than the younger rats. This age-related difference in AUC is closely associated with the volumes of distribution (Vd) of the animals of varying ages. On the basis of liters per kilogram, the Vd's of the older rats are approximately one-fourth to one-half of those for the younger (zero day) rats. The 14CO2 production rate constant was derived from the rate of formation of 14CO2 as a result of [14C]EDA X 2HCl dosing. The comparison of this constant under the various experimental conditions suggests sex-related differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Dermal oncogenicity studies on ethylenediamine in male C3H mice.

The dermal oncogenic potential of ethylenediamine (EDA) was assessed by applying 25 microliter of a 1% solution in deionized water to the skin of 50 male C3H/HeJ mice. This was the highest concentration not producing irritation or weight changes in a preliminary 2-week study. Two EDA samples (Nos. 1 and 2) from different production sources were tested. Applications were made thrice weekly until the death of the animals. A negative control group received deionized water only. This group and the EDA-treated groups were individually housed. A fourth group of 40 mice, housed 5 per cage, received 0.1% 3-methylcholanthrene (MC) in acetone as a positive control substance. A fifth group of 40 mice, housed 5 per cage, also received deionized water to determine the effect of group housing on survival. No skin tumors were observed in the EDA-treated groups. In the positive control group, however, 39 animals (98%) had skin tumors including 37 (92%) with confirmed squamous cell carcinomas. Eleven mice (22%) which received EDA No. 1 had dermal fibrosis indicative of probable skin irritation in this group; there was no such lesion in the controls. The mean survival times were 639, 626, and 598 days for the EDA No. 1, water control, and EDA No. 2 groups, respectively. The survival time of the EDA No. 2 group was significantly reduced compared to the individually housed water controls by one of two statistical tests. Irrespective of this difference, the study is considered to be a valid assessment of the oncogenic potential of EDA No. 2 because the magnitude of the difference in mean survival time was small.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Assessment of genotoxic potential of ethylenediamine: in vitro and in vivo studies.

Ethylenediamine (EDA) was evaluated for potential genotoxic activity using a battery in vitro and in vivo mammalian tests. The tests employed were the Chinese hamster ovary (CHO) gene mutation assay, the sister-chromatid exchange (SCE) test with CHO cells, unscheduled DNA synthesis (UDS) assays with primary rat hepatocytes and a dominant lethal study with Fischer 344 rats. EDA did not produce a positive, dose-related, mutagenic effect in either the CHO mutation assay or in the SCE test when evaluated both with and without the addition of a rat-liver S9 activation system. With hepatocytes, no positive effects of EDA upon UDS values were noted in 2 separate studies using either a scintillation counting procedure or an autoradiographic method to determine UDS activity. In a dominant lethal study, male rats fed for 23 weeks with dietary levels of EDA X 2HCl of 0, 0.05, 0.15 or 0.50 g/kg/day, and mated with 1 virgin female/week for 3 consecutive weeks, showed no dose-related or statistically significant effects upon fertility, total number of implantations/female, or the number of living and dead implants per female; marked effects upon the incidence of dominant lethal mutations were noted in the positive control group injected intraperitoneally with one dose of 0.25 mg/kg triethylenemelamine. We conclude that EDA was not genotoxic in the in vitro and in vivo mammalian test systems employed.

Animals↗

Hypoglycemic effect of guava juice in mice and human subjects.

Guava is a plentiful fruit in Taiwan and it was taken from the plants of Psidium guajava Linn. (Myrtaceae). According to the folklore in Chinese Medicine, gauva was useful in the treatment of diabetes mellitus. In the present study, acute i.p. treatment with 1 g/kg guava juice produced a marked hypoglycemic action in normal and alloxan-treated diabetic mice. Although effective duration of guava is more transient and it is less potent than chlorpropamide and metformin, blood glucose lowering effect of guava also can be obtained by oral administration in maturity-onset diabetic and healthy volunteers. Thus, it is suggested that guava may be employed to improve and/or prevent the disease of diabetes mellitus.

Adolescent↗