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Biomedical subjects

J Shen

Publications and source records attributed to J Shen.

At least 487 records · Page 27Linked to original sources

[Effects of indomethacin on 45Ca uptake and membrane fluidity of mitochondria and microsomes from rat liver].

We have reported previously that indomethacin-pretreatment could induce marked hepatic protection in rats. The present work reported effects of indomethacin on calcium regulation and membrane fluidity of mitochondria and microsomes of hepatocytes. The results showed that calcium uptake and membrane fluidity increased significantly in mitochondria and microsomes of hepatocytes isolated from the rats pretreated with indomethacin in vivo as compared with that from the control; adding indomethacin directly to isolated mitochondria and microsomes from normal rats in vitro, on the contrary, decreased membrane fluidity. These changes may be related to the protective effect of indomethacin.

Animals↗

[Observing cytoprotection of indomethacin on primary cultured hepatocytes of rats].

We observed previously that indomethacin induced hepatic protection against CCl4 and galactosamine in rats. In this work we further investigated this phenomenon on primary cultured rat hepatocytes. The results showed that cultured hepatocytes of rats pretreated with indomethacin in vivo still retained the ability resisting CCl4-induced cytotoxicity, as indicated by lower leakage of enzymes. However, cultured hepatocytes of normal rats treated with indomethacin in vitro had no obvious resistance to CCl4-induced cytotoxicity. The results suggest that indomethacin pretreatment in vivo enables hepatocytes to resist injury, which probably also needs participation of other factors.

Animals↗

Superoxide dismutase: fluctuations in the structure and solvation of the active site channel studied by molecular dynamics simulation.

The molecular dynamics (MD) simulation of superoxide dismutase (SOD) in water is carried out for a total of 23 ps. The simulation system is a 26 A sphere centered at the active site of SOD, including 1602 atoms from SOD and 1761 water molecules. There is no gross deviation from the x-ray structure for the average MD structure. The structure and potential fluctuations around the active site are examined. The results provide new insight to the interactions between SOD and its substrate superoxide.

Binding Sites↗

Mesencephalic dopamine neurons become less sensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity during development in vitro.

The in vitro development of monoamine oxidase (MAO) activity and [3H]dopamine (DA) uptake capacity of dissociated cell cultures from rat embryo mesencephalon were correlated with the potency of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+) neurotoxicity. Specific activities of both MAO-A and MAO-B increased during in vitro development of the cultures, with MAO-B activity increasing 20-fold between the first and fourth week. Similarly, [3H]DA accumulation increased 2.6-fold between the first and third week in vitro, when it reached a plateau. Unexpectedly, the toxicities of MPTP and MPP+ were substantially decreased in the older cultures. Exposure to MPTP reduced [3H]DA accumulation per culture by 77% in 1-week-old cultures and by 36% in 4-week-old cultures. Similarly, damage caused by MPPT was reduced from 84% of control in the first week to 34% of control in the fourth week. The attenuation of neurotoxicity was not due to an increase in storage of MPP+ in the synaptic vesicles of DA neurons, nor to a change in the distribution of MPP+ between dopaminergic and other cellular components of the cultures. The damage to DA neurons caused by the mitochondrial toxin, rotenone, also showed a similar reduction in the older cultures. These observations coupled with an increase in lactate formation and glucose consumption during the in vitro development of the cultures suggest a shift toward increased glycolysis and decreased dependence on aerobic metabolism. This would render the cells more resistant to the inhibition of mitochondrial function by MPP+.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

[Value of colonoscopy in postoperative care of colorectal carcinoma].

From 1981 to 1986, fiberoptic colonoscopy was performed in 2225 patients, of whom 356 cases (16%) were operated on for colorectal carcinoma and followed up for three months to twenty years. 27 cases were detected to have a second primary cancer and 1 case third primary cancer. In addition, 1 case of carcinoid, 6 cases of in-situ cancers, and 77 cases of adenomas were found. Among the 138 asymptomatic cases, 8 were proved to have a second cancer and 6 to be in early stage. Among the remaining 218 symptomatic cases, 26 with second cancers and 10 in the early stage were detected. The study shows that periodic colonoscopic examinations are mandatory for asymptomatic postoperative patients.

Adenoma↗

[Hemodynamic effects of naloxone in early acute pancreatitis in the dog and its efficacy in treating acute pancreatitis].

Naloxone, an opiate receptor blocker, has been shown in earlier studies to have positive effect on cardiovascular function in a variety of diseases in which the secretion of endogenous opioid peptides was suspected. In this communication, a dog model of acute pancreatitis (AP) was made by intraductal injection of fresh trypsin-bile mixture, in which the hemodynamic changes were measured, the therapeutic efficacy of naloxone was evaluated. Pancreatitis was characterized by a fall in SAP, CO, dp/dt, an increase in PVR, SVR and the early reduction of pancreatic blood flow (QP). Administration of naloxone produced a significant increase in QP and led to normalization in SAP, CO, dp/dt, PVR and, SVR. In addition, Naloxone significantly reduced the severity and mortality of AP. These results suggest that naloxone appears to limit the progression from edematous to hemorrhagic pancreatitis through preserving QP at the early phase of AP. We propose the hypothesis that endogenous opiates may play a role in the pathophysiology of AP.

Acute Disease↗

Factors associated with the decline of the Cooperative Medical System and barefoot doctors in rural China.

The Cooperative Medical System (CMS) and its barefoot doctors have been in decline in rural China for nearly a decade. In order to explore the reasons for this, in 1987 we carried out a survey of villagers, barefoot doctors, and local administrators in Fengxian, Shanggoa, and Loaan counties, where incomes are good, fair, and low, respectively. The state of the CMS in these counties was contrasted and the situations which prevailed in 1978, 1982, and 1985, when the system was, respectively, at its peak, had begun to decline, and had declined markedly, were compared. A random sample of villages was selected and all the barefoot doctors and administrators as well as a random sample of households were surveyed. The results indicate that health status (as measured by infant mortality, immunization coverage, and rate of infectious diseases) has decreased in areas where the CMS has declined, while per capita incomes increased. Concomitantly, villager's expenditures on health care have increased. Barefoot doctors and their patients were, however, reasonably happy with the system, and in its absence the doctors are no longer able to obtain ongoing training. The CMS was fiscally sound, and did not decline to the same extent in all areas--it continues to thrive in Fengxian, which is relatively affluent. It is concluded that the system probably declined because many local administrators perceived that it no longer enjoyed the backing of the central government.

China↗

Treatment of stage I endometrial carcinoma.

Cases of stage I endometrial carcinoma treated at Columbia-Presbyterian Medical Center, New York, between 1966 and 1980 were evaluated with regard to clinical parameters, surgicopathologic findings, treatment modalities and survival. Four factors significantly influenced survival: tumor grade, patient's age, uterine size and addition of postoperative external radiotherapy in cases of significant myometrial invasion or a poorly differentiated lesion. No deaths or significant morbidity resulted from the use of adjuvant whole pelvic radiation.

Adenocarcinoma↗

Coinduction of glucose-regulated proteins and doxorubicin resistance in Chinese hamster cells.

The glucose-regulated protein (GRP) system in mammalian cells is induced by glucose deprivation, anoxia, the calcium ionophore A23187, and 2-deoxyglucose. In Chinese hamster ovary cells the major GRPs are approximately equal to 76, 97, and 170 kDa. Removal of each of these four GRP-inducing stresses leads to the coordinate repression of GRPs and induction of the major heat shock proteins at 70 and 89 kDa. The application of each of these four GRP-inducing conditions leads to a significant induction of resistance to the drug doxorubicin. Removal of each GRP-inducing condition results in the rapid disappearance of this resistance in a manner that correlates with the repression of the GRPs. The retention of doxorubicin by GRP-induced cells does not explain the induced drug resistance. When the RIF in vitro/in vivo tumor system is probed with an antibody against the 76-kDa GRP, a significant increase in this GRP is observed in cells obtained from the central regions of tumors. Since hypoxia and/or nutrient deprivation can occur during tumor development, a GRP-induced state in the tumor may confer resistance to doxorubicin treatment.

Animals↗

The effect of nitroimidazoles on glucose utilization and lactate accumulation in mouse brain.

The radiation sensitizers misonidazole (MISO) and desmethylmisonidazole (DMM) can produce central and peripheral neuropathy in patients and laboratory animals. Behavioral and pathological investigations have indicated that in the central nervous system this primarily involves the cochlear and vestibular systems. Nitroimidazoles can also interfere with glycolysis in vitro under aerobic and anaerobic conditions. In the present work we have studied the effect of MISO or DMM on lactate production and glucose utilization in mouse brain. It is observed that these compounds result in a 25% inhibition of lactate production in brain slices relative to the control at a 10 mM level. Additionally, MISO (1.0 mg/g/day) or DMM (1.4 mg/g/day) were administered daily (oral) for 1, 4, 7, or 14 days to examine the effect of these two drugs on the regional glucose utilization in C3Hf mouse brain. Five microcuries of 2-deoxy[14C]glucose was given following the last drug dose and autoradiographs of serial brain sections were made and analyzed by a densitometer. Following a single dose of either MISO or DMM, no significant differences in glucose uptake were observed when compared with controls. However, following 4, 7, and 14 doses the rate of glucose utilization was significantly reduced in the intoxicated animals. Larger reductions were measured in specific regions including the posterior colliculus, cochlear nuclei, vestibular nuclei, and pons with increasing effects observed at later stages. These results share a degree of correspondence with the regional brain pathology produced by these nitroimidazoles.

Animals↗