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Biomedical subjects

R Zhong

Publications and source records attributed to R Zhong.

At least 109 records · Page 6Linked to original sources
PubMed1995

Liver transplantation induces cytochrome P450 1A1 dependent monooxygenase activity in rat lung and kidney.

Although liver transplantation has been the subject of intensive investigation, comparatively little is known regarding the effects of this procedure on the metabolism of xenobiotics. The objective of the present study was to examine the effect of orthotopic liver transplantation on rat hepatic, pulmonary, and renal microsomal cytochrome P450 (P450) monooxygenase activity through the use of isozyme-selective substrates. Pulmonary microsomal P450 1A1 dependent 7-ethoxyresorufin O-deethylation (ERFD) activity increased over time in recipient rats, with maximal induction (750% of donor) observed after 21 days. Similarly, ERFD activity in renal microsomes was increased (200% of donor) after 21 days. Both pulmonary and renal microsomal P450 2B dependent 7-pentoxyresorufin O-depentylation (PRFD) activity was decreased (50 and 75% of donor) 1 day after transplantation but was essentially unchanged 3, 7, and 21 days after transplantation. Pulmonary and renal microsomal heme oxygenase activities were not significantly affected by liver transplantation. In contrast, total hepatic microsomal P450 concentrations were decreased maximally (to 45% of donor concentration) 7 days after transplantation and remained low (55% of donor) up to 21 days. Similarly, hepatic P450 1A dependent ERFD and P450 2B dependent PRFD activities were maximally depressed (20 and 25% of donor activities) after 7 days and remained low (75 and 30% of donor) up to 21 days after transplantation. The decreases in rates of hepatic P450 monooxygenation were accompanied by significant increases in microsomal heme oxygenase activity. The data presented in this study suggest the existence of generalized stress responses to inflammation that result in tissue- and isozyme-selective modulation of P450 monooxygenase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[The effect of moxibustion on gastric mucosa in rats and its relation to copper, zinc contents in serum].

18 rats were randomly deivided into 3 groups: control grup, the group merely with experimental gastric ulcer and the group with experimental gastric ulcer after 3-week moxibustion. The results showed: (1) moxibustion could significantly reduce the ulcer area of the rats (P < 0.05); (2) compared with control group, the experimental gastric ulcer model rats had an increase in copper content and Cu/Zu ratio, the differences were statistically significant (P < 0.05, P < 0.01); (3) in contrast to the rats merely with experimental gastric ulcer, moxibustion-pretreated rats had a significant increase in Zinc content in serum (P < 0.01), but its copper content and Cu/Zn ratio in serum were significantly decreased (P < 0.05, P < 0.01). The results confirmed that moxibustion pretreatment at "Shen-Jue" could protect the gastric mucosa from strass-induced ulcer, having protective effect on gastric mucosa. The results also suggested that there was a disbalance in trace elements metabolism, but moxibustion could improve it. This was most likely to be one of the mechanisms of moxibustion protection on gastric mucosa.

Animals↗
PubMed1994

Endotoxin in the peripheral blood during acute intestinal allograft rejection.

Intestinal rejection is associated with increased gut permeability and bacterial translocation. The present study examined endotoxin and proinflammatory cytokines in the peripheral circulation during acute intestinal rejection. Heterotopic intestinal transplants were performed using Lewis rats (RT1(1)) as donors and DA rats (RT1a) as recipients. DA rats with intestinal isografts were used as controls. Serum samples were obtained at sacrifice on postoperative days (POD) 7 and 14. Lipopolysaccharide (LPS) was measured using the limulus amoebocyte lysate assay. Interleukin-1 (IL-1) and 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured using bioassays. Large amounts of LPS were detected in the serum of intestinal allograft recipients concurrent with the development of graft rejection. Serum IL-6 and TNF-alpha levels were significantly elevated in the allograft recipients on both POD 7 and 14 when compared to DA isografts (P < 0.05). Serum IL-1 activity was not detected in the allograft or isograft recipients at either of the two time points. Further studies are warranted to determine the role of intraluminal bacteria and their products in the pathophysiology of intestinal allograft rejection.

Acute Disease↗
PubMed1994

Host immune suppression after small bowel/liver transplantation in rats.

Simultaneous liver grafting in the Lewis (RT1)-to-DA (RT1) rat strain combination protects small intestinal grafts from rejection. The present study examined host immune responses after combined small bowel/liver transplantation (SBL) in this model. Orthotopic liver transplantation and heterotopic small intestinal transplantation were performed simultaneously and compared with isolated small bowel allografts (SBA) and isolated small bowel isografts (SBI). All rats were sacrificed on postoperative day (POD) 7 or 14 for immunological and histological studies. The mean time to rejection of the SBA was 6.6 +/- 0.3 days. In contrast, there was no clinical or histological evidence of intestinal rejection in SBL recipients during the 14 days of follow-up. The SBL recipients showed clinical and histological evidence of graft-versus-host disease (GVHD). Lymphocyte proliferation and IL-2 production in response to donor antigens were suppressed after SBL transplantation compared with the SBA or the SBI controls (P < 0.05). Cell-mediated cytotoxicity and lymphocytotoxic antibody production against donor cells were also significantly inhibited in the SBL recipients compared with the SBA control group (P < 0.05). We conclude that SBL transplantation in the Lewis-to DA rat strain combination: (1) suppresses host alloimmune responses, (2) prevents early intestinal rejection, and (3) favors the development of GVHD.

Animals↗
PubMed1994

Small bowel transplantation.

After struggling for three decades, SBT is finally emerging as a clinical reality. To become the standard therapy for the treatment of end-stage intestinal failure, SBT must offer a better quality of life, fewer risks, and lower costs than home TPN. To achieve this standard, protocols must be refined to obtain lower rates of rejection and infection as well as more consistent graft function.

Clinical Protocols↗
PubMed1993

Development of a mouse intestinal transplantation model.

We have recently developed a mouse intestinal transplantation model. The proximal segment of donor jejunum is transplanted into the recipient in a heterotopic position. End-to-side anastomoses are performed between donor aorta and recipient aorta and between donor portal vein and recipient inferior vena cava. Mortality rates were initially high due to shock, arterial thrombosis, and postoperative sepsis. Refinements in surgical techniques reduced these complications, resulting in a high rate of success. Important technical factors included (1) minimizing ischemic injuries to the graft in both the donor and the recipient, (2) using an aortic patch and elliptical aortotomy for anastomosis, (3) administering large volumes of crystalloid to maintain normal blood pressure during the donor and recipient surgeries, and (4) using broad-spectrum antibiotics as postoperative prophylaxis. The mice with isografts had normal intestinal function and histology when they were sacrificed 1 month after surgery. This new model of small bowel transplantation will be a useful tool to study the immunology of intestinal grafting at the molecular level.

Anastomosis, Surgical↗
PubMed1993

Nephrotoxicity in rats following liver transplantation from cadmium-exposed rats.

Although kidney is considered as the critical organ for cadmium (Cd) toxicity, little is known about the transport of Cd to kidney after chronic exposure. In order to study this transfer, male Lewis rats (150-200 g) were given eight injections (sc) of CdCl2 (3 mg Cd/kg) over 2 weeks which resulted in increases of tissue Cd and metallothionein (MT) concentrations (223 and 1850 micrograms/g, respectively, in the liver and 118 and 873 micrograms/g, respectively, in the kidney). Livers from Cd-injected rats were transplanted to age-matched control healthy Lewis rats and the recipient rats were killed at 2 to 47 days after transplantation. The levels of Cd and MT in the liver of recipient rats were decreased (106 and 1503 micrograms/g, respectively) with time after surgery. On the other hand, renal Cd and MT levels were markedly increased (195 and 1468 micrograms/g, respectively) and most of the Cd in the kidney was bound to MT. About 100 ng/ml of Cd and MT were detected in the plasma of recipient rats by ELISA. There was some periportal fibrosis in the liver due to transplant procedure which did not anastomose hepatic arteries. There was an increase in blood urea nitrogen levels in rats transplanted with Cd-containing liver. In addition, both necrosis and inflammation were observed in the epithelial cells in the proximal tubules in the kidney which typically occurs in chronic Cd toxicity. These results suggest that the major source of renal Cd in chronic Cd exposure may be derived from hepatic Cd which is transported in the form of Cd-MT in blood plasma.

Animals↗
PubMed1993

Regulation of endothelin-1 expression in normal and transfected endothelial cells.

Calcium phosphate precipitation and retrovirus-mediated infection methods were used to stably infect bovine pulmonary artery endothelial cells (BPAECs) with mammalian expression vectors bearing human prepro-ET-1 cDNA. The calcium phosphate precipitation method afforded a stably transfected cell line that expressed approximately four times higher ET-1 than untransfected BPAEC by radioimmunoassay and at the mRNA level. The retrovirus-mediated transfection method yielded stably infected clones that secreted eightfold to 10-fold higher ET-1 than the nontransfected BPAECs; one clone continued to produce 10-fold higher levels after continuous assay for 1 year. Both transfected and nontransfected cells showed an increase (approximately twofold) in ET-1 production in response to thrombin (10 U/ml). Downregulation of ET-1 production was exhibited by both transfected and nontransfected cells in response to nitric oxide (NO) donors: sodium nitroprusside (NOPr), S-nitroso-N-acetoxy penicillamine (SNAP), and acetoxime. The potentiation of NO by superoxide dismutase (SOD) also downregulated ET-1 production. These studies show that an exogenous gene introduced into a cell type that normally expresses that gene product can be regulated by agonists and antagonists in a manner similar to the normal gene regulatory mechanisms for that cell type. This is of potential importance in gene therapy experiments, where mechanisms for regulation of expression remain elusive.

Animals↗
PubMed1993

Controlling unwanted sources of threshold change in disability glare studies: a prototype apparatus and procedure.

One of the main purposes of cataract surgery is to reduce the debilitating effects of light scatter by the lens. An important effect of this intraocular forward scatter is to produce a veiling retinal illuminance from a glare source. The retinal contrast of the stimulus is thus reduced, and a quantifiable "disability glare" effect may be measured. A complication is introduced by the fact that intraocular scatter arises from other sources in addition to the lens. All present tests of glare disability fail to eliminate or control for these factors, nor do they control for the light adaptation effect of the glare source. The effects of lens removal may not be predicted accurately by such tests, and patients may report little improvement in visual function after surgery. The goal of this research is to provide the background for developing a method of measuring disability glare due only to light scatter in the lens. Thirty-seven patients with mild to moderate cortical cataracts served as subjects. A disability glare effect (DG) was measured with a Maxwellian-view system that eliminates or controls scatter from the iris, sclera, and retina, and which controls for light-adaptation effects from the glare source. DG with this method showed a significant correlation with objective measures of lens light back scatter. Suggestions were made for improvements in the apparatus and procedures for future clinical studies.

Aged↗
PubMed1993

Tolerance by old livers of prolonged periods of preservation in the rat.

To determine the tolerance of old livers to prolonged preservation, livers from aged rats (corresponding to humans in the sixth to seventh decades of life) were transplanted after specific periods of cold preservation. Male BN/BiRij rats received orthotopic, arterialized liver grafts from either young (5 months) or old (25 to 28 month) donor rats after liver storage for 12 (n = 6), 24 (n = 6) or 30 (n = 10) hours in University of Wisconsin solution. Outcome was assessed by survival, liver enzymes after transplantation, and histology of the grafts. There were no significant differences in survival rates between recipients of old and young grafts. All rats survived after 12-hr and 24-hr preservation except one recipient of an old graft preserved for 24 hr. After 30-hr preservation recipients of old and young livers had identical survival rates (60%). There was a strong correlation between the highest postoperative AST and ALT and the duration of preservation in all groups (P < 0.0001), but only in the 24-hr preservation experiments was the ALT significantly higher in recipients of old grafts than in recipients of young livers (P = 0.025). Age of the donor did not significantly affect the peak AST, but there was a correlation between donor age and the highest postoperative ALT (P = 0.007). Although intracellular vacuolization was a prominent histological finding in more than half of the old livers at the end of preservation, it was not associated with an increase in mortality. It is concluded that under the ideal conditions provided in the experiments, old rat livers tolerate long preservation periods with satisfactory graft survival compared with young livers.

Age Factors↗
PubMed1993

The effect of donor-recipient strain combination on rejection and graft-versus-host disease after small bowel/liver transplantation in the rat.

The initial clinical experience with simultaneous small bowel/liver transplantation (SBL) suggests that liver grafting may protect the small bowel from rejection. A pilot study of SBL in DA (RT1a) rats with Lewis (RT1l) allografts in our laboratory provided experimental support for this concept. However, the clinical applicability of the data was questioned because the transplants were performed in a low-immune-responder rat strain combination. This study examined the outcome of SBL in several rat strain combinations. Isolated small bowel transplants (SB) and SBL were performed in three groups: DA-->PVG (low immune responder), BN-->LEW (intermediate immune responder) and ACI-->LEW (high immune responder). Lewis-->Lewis isografts were used as controls. All of the rats with SB rejected their allografts, whereas all of the rats with simultaneous liver grafts had minimal or no signs of intestinal rejection. The outcome of SBL was profoundly affected by the donor-recipient strain combination. The low immune responders developed severe graft-versus-host disease. The intermediate immune responders developed mild-to-moderate GVHD and moderate liver rejection. The high immune responders developed severe liver rejection. In this study, the outcome of small bowel transplantation depended upon the strain combination used and whether or not a simultaneous liver graft was transplanted. The immune interactions that occur after multi-visceral transplantation are complex and cannot be easily predicted.

Animals↗