Biomedical subjects

L W Chang

Publications and source records attributed to L W Chang.

156 records · Page 9Linked to original sources

PubMedDate not supplied

Protective effect of vitamin E on genotoxicity of methylmercury.

The cytogenetic effects of methylmercury (MeHg) producing chromosomal breakages, C-mitosis, and sister chromatid exchange are well documented. The present investigation was to determine whether vitamin E, which has been shown to exert a certain protective measure on the nervous system of animals exposed to methylmercury, also will diminish the genotoxicity of MeHg. Adult hamsters were given a daily injection (ip) of methylmercury chloride at a dosage of 2.0 mg/kg body weight (kg b.w.) and/or with 2.0 mg/kg b.w. vitamin E for 3 wk. All animals were sacrificed 5 d after the last day of MeHg exposure. Fibroblast cultures were established with cells obtained from skins of these animals. Chromosome preparations were made from these cultures and evaluated, using a double-blind system, for incidences of chromosomal breakage. It was found that all the fibroblast cultures grew well except from those animals treated with MeHg. Furthermore, while the saline control and vitamin E alone cultures showed no significant number of chromosomal breakages, cells from animals treated with only MeHg showed a high incidence of chromosomal damage (50% with 1 break and 15% with 2 or more breaks). Such chromosomal damage, however, was totally eliminated by vitamin E treatment (no chromosomal breakage was observed in cultures from MeHg/vitamin E animals). Our present study represents the first report on in vitro chromosomal damages as a result of in vivo MeHg exposure. Furthermore, our investigation also demonstrated the protective potential of vitamin E against genotoxicity of methylmercury.

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PubMedDate not supplied

Clinical utility of monitoring serum cryptococcal antigen (sCRAG) titers in patients with AIDS-related cryptococcal disease.

PURPOSE: The purpose of our study was to define the time course and clinical role of monitoring serum cryptococcal antigen titers (sCRAG) in patients with AIDS-related cryptococcal disease. METHOD: A retrospective chart review was conducted. The medical records for all HIV-infected patients with positive cryptococcal antigen (CRAG) tests from January 1993 to May 1998 at San Francisco General Hospital (SFGH) were reviewed for sCRAG titer levels and clinical outcomes. RESULTS: Out of the 314 patients found to have positive antigen tests, 136 met the inclusion criteria. Twelve (8.8%) had no change in titer from baseline, 6 (4.4%) had an increase, and 118 (86.8%) had a decrease. Examining the association of sCRAG with time to relapse using a variety of Cox models produced largely null results. Rate of change in sCRAG over time (slope) was not significantly predictive of time to relapse nor of time to definite relapse/probable relapse/persistent disease. CONCLUSION: Although in the majority of patients, the sCRAG titers appeared to decrease over time, we could not detect a significant correlation between sCRAG titer results of patients who had a clinical response to treatment and sCRAG titers in patients who experienced persistent disease, probable relapse, or definitive relapse of cryptococcal disease. We conclude that follow-up monitoring of the sCRAG titer is not useful in the management of patients with AIDS-related cryptococcal disease on treatment.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Effects of trimethyltin and triethyltin on lever pressing, water drinking and running in an activity wheel: associated neuropathology.

Rats were given single injections of saline solution, or doses of triethyltin, or trimethyltin, and their drinking behavior, lever pressing for food pellets and running in an activity wheel were measured continuously for 16 consecutive days. At doses of 3.0 and 4.5 mg/kg, triethyltin decreased lever pressing, drinking and running, usually for more than a week. Subsequently, drinking and running showed increases. Only the highest dose (4.5 mg/kg) produced decreases in body weight. Doses of 6.0 and 9.0 mg/kg trimethyltin generally decreased lever pressing, drinking and running for several days, but large increases were observed subsequently for all of these measures. Rats receiving 9.0 mg/kg died 6 to 8 days after trimethyltin administration, but rats receiving 6.0 mg/kg continued to show increases in behavior for 12 to 16 days after trimethyltin administration. Examination of the brains by light microscopy of the same animals used in the behavioral studies showed high correlations between behavioral changes and neuropathology in individual animals.

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PubMedDate not supplied

Effects of triethyltin on responding of mice under a multiple schedule of reinforcement.

The lethality and behavioral effects of triethyltin (TET) were determined in adult, male BALB/c mice. Following a single IP dose of TET (10, 12.5 or 15 mg/kg), the lethality was determined at 24-hr intervals. By 144 hr after TET administration, lethality had risen to greater than 90% in the groups receiving the 12.5 and 15 mg/kg and 20% (6/30) in the group which received 10 mg/kg. No additional deaths were observed over the remainder of the two week observation period. The behavioral effects of 5, 7.5 or 10 mg/kg were determined in mice trained to respond under a multiple fixed-ratio 30, fixed-interval 600-sec schedule of milk presentation. At 3 hr after TET administration, the rate of responding was decreased at all three doses. However, by 27 hr after 5 or 7.5 mg/kg TET the rate of responding had returned to pre-injection control values while the responding of the mice in the 10 mg/kg group did not return to pre-injection control values until 51 hr after administration. In a separate group of mice, 7.5 mg/kg was administered at 2 week intervals for a total of 5 separate administrations. No evidence for a cumulative or diminished behavioral effect was observed. Neuropathological examination revealed a direct dose and time related pathology in the white matter of the CNS. Maximal edematous vacuolar change was observed 72 hr after TET administration. Such morphological changes, however, were totally absent 12 days after a single 10 mg/kg exposure. Multiple exposure to TET (7.5 mg/kg) at 2 week intervals for 10 weeks showed only minimal morphological alterations in the brain.

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PubMedDate not supplied

Septotemporal gradients of trimethyltin-induced hippocampal lesions.

Rats were administered 6 mg/kg trimethyltin (TMT) PO, and sacrificed at various time points (up to 60 days) for pathological evaluation. Studies along the full extent of the septotemporal axis revealed region-specific and cell field-specific damage. Dentate granule cells were most affected at the temporal pole and were only minimally affected at the septal pole. CA3c pyramidal neurons were affected along the full extent of the septotemporal axis. CA3a and CA3b pyramidal cells were most affected in the septal pole, and virtually unaffected in the temporal pole. It is suggested that CA3a and CA3b pyramidal cell damage may be dependent upon functionally intact granule cells.

Animals↗

PubMedDate not supplied

Effects of triethyltin and its interaction with d-amphetamine and chlorpromazine on responding under a multiple schedule of food presentation in rats.

Effects of triethyltin (TET) were studied in rats performing under a multiple fixed-ratio 30 fixed-interval 5-min schedule of food presentation. A dose of 1.0 mg/kg TET produced only marginal effects on responding. A dose of 3.0 mg/kg suppressed responding 3 hours after administration, but responding returned to control levels by the next day. During a period 2 to 6 weeks after the 3.0 mg/kg dose, small rate increases were observed for fixed-interval responding. The 5.6 mg/kg dose eliminated responding under both schedule components and all the animals died on the fourth day. Rats were also given d-amphetamine and chlorpromazine before and beginning six weeks after 1.0 and 3.0 mg/kg TET treatment. Both doses of TET attenuated the rate-increasing effect of d-amphetamine on fixed-interval responding, but d-amphetamine dose-effect curves determined before and after TET administration differed significantly only for 3.0 mg/kg dose of TET. Chlorpromazine dose-effect curves did not differ significantly before and after TET treatment.

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PubMedDate not supplied

A time-course study of trimethyltin induced neuropathology in rats.

The extent and time course of trimethyltin (TMT) induced lesions in the rat nervous system was studied. Adult Long-Evans rats were treated with a single dose of 6.0 mg TMT/kg b.w. and were sacrificed at 8 hours, 3, 15, 30 or 60 days following exposure. Histopathological examination of the brains revealed that neurons in the pyriform/entorhinal cortices and in the olfactory tubercle were extremely sensitive to TMT toxicity showing significant necrotic changes 3 days after exposure. Extensive neuronal loss and astrogliosis were observed 15 days after intoxication. In the hippocampal formation, the granule cells of fascia dentata showed early changes; however, evidence of toxic destruction in this area was not extensive and subsided considerably by the 3rd week of intoxication. On the other hand, destruction of the pyramidal neurons in Ammon's horn became more pronounced throughout the experimental period, resulting in extensive cell loss in this structure. It is interesting to note that the CA3 neurons in the anteromedial (septal) portion of the Ammon's horn appeared to be more vulnerable than those located more laterally (temporally), while the reverse pattern was observed for the CA1,2 neurons. Large mesencephalic trigeminal neurons in the brain stem also showed early chromatolytic changes. Since total normal morphology of these neurons was observed at later posttreatment time without apparent neuronal loss in these areas, total recovery of these nerve cells could be postulated.

Animals↗

PubMedDate not supplied

Trimethyltin induced pathology in sensory neurons.

Pathologic changes in the retina, inner ear, pyriform cortex, olfactory tubercle, and dorsal root ganglia as a result of trimethyltin (TMT) intoxication were investigated. Long-Evans rats were orally intubated with TMT chloride at a dose of 6.0 mg TMT/kg b.w. Swelling of the optic fiber layer and necrotic changes in the ganglion and inner nuclear layers were observed in the retina as early as 72 hours after intoxication. Large segments of the retina were devoid of ganglion cells at later posttreatment times. The inner ear was also found to be extremely vulnerable to the toxicity of TMT. Edematous swelling of the hair cells and vacuolar changes of the spiral ganglion cells in the Organ of Corti were observed 24 hours after TMT exposure. Extensive destruction of these structures was evident 15-30 days after intoxication. Small neurons in the olfactory cortex (pyriform cortex and olfactory tubercle) also degenerated rapidly after TMT exposure. Electron microscopy demonstrated lysosomal accumulation and vacuolar changes in these nerve cells. Extensive destruction of both the pyriform cortex and olfactory cortex was observed 15 days after exposure. Although no necrotic change was observed in the neurons of the dorsal root ganglia, electron microscopy revealed extensive accumulation of lysosomes and formation of myeloid bodies both in the neuronal bodies and dorsal root fibers. Vacuolar breakdown and dissolution of the Nissl substance were found in some neurons. Thirty days after treatment, hypertrophy and hyperplasia of the neuronal mitochondria were observed. Such a change was believed to represent a compensatory response by these organelles. These findings provide the first morphological evidence of neuronal damage in the sensory neurons of both the central and peripheral nervous system following acute TMT administration.

Animals↗

PubMedDate not supplied

Species and strain comparison of acute neurotoxic effects of trimethyltin in mice and rats.

Pathological changes in the central nervous system in two strains of mice (BALB/c and C57BL/6) and two strains of rats (Long Evans and Sprague Dawley) as a result of trimethyltin (TMT) intoxication were compared. Both strains of mice were administered with trimethyltin chloride at a dosage of 3.0 mg TMT-Cl/kg b.w. while both strains of rats were exposed to 7.5 mg TMT-Cl/kg b.w. Animals were sacrificed at the time of development of observable neurological signs (tremor, aggression): 2 days for both strains of mice, 3 days for Long Evans (LE) rats, and 5 days for Sprague Dawley (SD) rats. It was found that there were both species and strain differences in TMT toxicity. Despite being exposed to a lower dose of TMT and for a shorter duration of time, mice showed more prominent neurological signs and hippocampal lesions than rats. Among the two strains of rats studied, LE rats were more sensitive than SD rats to TMT toxicity. The regional sensitivity of the CNS between mice and rats was also different, with mice showing most lesions in the hippocampal fascia dentata and rats showing more prominent neuronal damages in the olfactory cortices and hippocampal Ammon's horn. Our present investigation provides the first species/strain comparison on lesion development as a result of TMT intoxication.

Animals↗

PubMedDate not supplied

Neuropathology of mouse hippocampus in acute trimethyltin intoxication.

BALB/c mice were injected IP with a single dose of trimethyltin chloride (3.0 mg TMT/kg body weight). Severe body tremor was observed within 12 hours post-injection. All animals were sacrificed 48 hours post-injection by means of intracardial perfusion with 2.5% buffered glutaraldehyde. Light microscopic examination revealed extensive neuronal necrosis in the granule cells of the fascia dentata of the hippocampus. Scattered neuronal loss was also observed in the pyriform cortex, the neocortex, amygdaloid nucleus, and the brainstem. Electron microscopic examination of the hippocampus revealed lysosomal accumulation in both the granule cells and pyramidal neurons. While extensive cellular necrosis was observed in the granule cells, the pyramidal neurons only displayed some dilatation and vacuolation of their endoplasmic reticulum. This report represents the first in depth pathological study in the mouse hippocampus following an acute exposure to TMT.

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PubMedDate not supplied

Behavioral toxicology of acute trimethyltin exposure in the mouse.

Adult BALB/c mice were injected IP with trimethyltin . HCl (TMT), and the effects of TMT were studied on gross behavior, lethality, spontaneous motor activity (SMA), and responding under a multiple fixed-ratio 30, fixed-interval 600 sec (mult FR30 FI600) schedule of reinforcement. Following doses of 4, 5, and 6 mg/kg, the cumulative 48-hr lethality was 10% at 4 mg/kg, IP, and 100% at 5 and 6 mg/kg, IP. No deaths were observed during the first 48 hrs following 3 mg/kg TMT. This non-lethal dose produced whole body tremors. The SMA of mice receiving 3 mg/kg was reduced to 70% during the first 24-hr period following TMT and some recovery of total activity was observed during the second 24-hr period. The reduction in SMA was accompanied by a change in the normal circadian cycle of activity. Responding under the mult FR30 FI600 schedule was severely disrupted. Three hours after TMT administration and rate of responding in both components was decreased and the decrease became progressively larger over the next 48 hrs. In addition to the rate of FI600 responding being reduced, the normal pattern of FI responding was altered with an increase in responding observed in the early portions of the FI. These results suggest that the mouse is much more sensitive to the effects of TMT than the rat and may have potential as an animal model in the study of the neurotoxicity of TMT.

Animals↗

PubMedDate not supplied

Methylmercury induced biochemical and microsomal changes in the rat liver.

The change in the levels of DNA, RNA, protein, glucose-6-phosphatase, and microsomal enzymes in the rat liver following exposure to methylmercury was studied. The turnover rate of the membranes was also investigated by means of radioactive glycerol. A marked increase in microsomal enzyme levels, with no increase in smooth endoplasmic reticulum, was found one to four hours following administration. A delay in incorporation of radioactive glycerol and more rapid degradation of microsomal membranes were also detected as a result of mercury intoxication. These observations suggest an instability of the microsomal membranes which would be responsible for the early increase in microsomal enzymes upon homogenization. A general inhibition of the microsomal enzymes and proteins was found 1-2 days after mercury administration. The inhibition of glucose-6-phosphatase activity, however, was not noted until day 5. Most of the enzymatic activities returned to normal between days 5 and 8. A reduction of DNA and protein was found in the liver homogenate after 2 hours of intoxication. However, no change in the RNA level was detected.

Animals↗