Hua xi yi ke da xue xue bao = Journal of West China University of Medical Sciences = Huaxi yike daxue xuebao最新文献

Objective: To probe the biological character of liposome-mediated 99m-technetium-labeled antisense oligonucleotide of c-myc mRNA, and lay the foundations for clinical research on antisense image or treatment.

Methods: Antisense, sense and scrambled oligonucleoyide, each containing 15 bases, were synthesized elsewhere. The rates of liposome-entrapped 99mTc-DNA and 99mTc-DNA combination with plasma protein were tested through trichloroacetic acid precipitation. BALB/c mice were used to test the biodistribution in vivo, and rabbits were used to investigate the pharmacokinetics characters.

Results: Their rates of combination with plasma protein ranged from 34.81% to 70.53%. Reticuloendothelial system played an important role in the biodistribution; stomach, blood and intestines were less important; other tissues accumulated the least of the liposome-mediated 99mTc-labeled c-myc oligonucleotides. The pharmacokinetics of liposome-entrapped 99mTc-DNA fitted the open dithecal model. Their distribution (t1/2 alpha) half time was about 2 to 5 minutes, and clearance (t1/2 beta) half time about 100 to 150 minutes. Plasma clearance was smaller than 2 ml/min.

Conclusion: The rate of 99mTc-DNA combination with plasma protein was high. The biological half time of liposome-mediated 99mTc-DNA was proper. Plasma clearance was high. So liposome-mediated 99mTc-DNA is a potential kind of radioactive agent.

Objective: To observe whether Tutin microinjection into the pontine NPBM respiratory area of rabbit will cause morphological damage to that area two hours later.

Methods: At two hours after the microinjection of Tutin into NPBM, the experimental effects on respiration came to be remarkable and the physiological condition was well, the rabbit was subjected to morphological sampling then. The sample was cut into slices for LM (Nissl dyeing) and transmission EM observation and photography.

Results: Under the LM and EM examination, no remarkable morphological damage done by Tutin microinjection into the pontine NPBM was observed. By comparing the Tutin-injected side with the other side of NPBM where equal normal saline microinjection was given, no apparent morphological difference could be found.

Conclusion: In our experiment condition, there was no morphological damage caused by Tutin microinjection into pontine NPBM respiratory area of the rabbit.

Objective: To investigate the serum lipid and apolipoprotein levels in pregnancy-induced hypertension (PIH or pre-eclampsia), normotensive pregnant women and non-pregnant women.

Methods: Twenty-eight women with PIH, 31 normatensive and 24 non-pregnant ones were studied, from whom maternal blood samples were collected. Serum lipid levels were measured by enzymatic method and apolipoproteins AI, B100, C II, CIII and E levels by radial immunodiffusion kits developed by our Lab.

Results: 1. Serum TG, apoC II and apoC III were highly increased in normotensive pregnant women by 3.5, 2.4 and 2.8 times respectively, when compared with those in non-pregnant ones (P < 0.001); serum TC, nHDL-C and apoAI, B100 and E were also increased in normotensive pregnant women by 21%, 33%, 55%, 79% and 77% respectively, when compared with those in non-pregnant ones (P < 0.001). TG/HDL-C in normotensive pregnant women was also significantly, higher than that in non-pregnant ones(P < 0.01). Serum HDL-C levels remained unchanged in both groups. 2. Serum TG, apoC II and apoC III were highly increased in PIH patients by 2.3, 4.0 and 2.8 times respectively, when compared with those in non-pregnant ones (P < 0.001); serum TC, nHDL-C and apoAI, B100 and E were also increased in PIH patients by 27%, 26%, 52%, 90% and 67% respectively, when compared with those in non-pregnant ones (P < 0.001) TG/HDL-C in PIH patients was also significantly higher than that in non-pregnant ones (P < 0.01). Serum HDL-C levels were increased in PIH patients by 29%, when compared with non-pregnant women. Only serum HDL-C level in PIH patients was higher than that in normotensive pregnant women. No significant differences were seen in other lipid and apolipoprotein levels between PIH patients and normotensive pregnant ones. 3. There was no significant difference in the levels of serum lipid and apolipoprotein between the subgroups of PIH patients according to the severity of the disease.

Conclusion: The increase of serum lipid and apolipoprotein levels in PIH is probably not the predictor for pre-eclampsia.

Objective: To investigate the effects of CCK8 on protein kinase C activity in rat cerebral cortex.

Methods: The cerebral cortex neurocytes were isolated and used as a model. The effects of CCK8, L-364, 718 and L-365, 260 on PKC activities were detected by using a non-radioactive method.

Results: CCK8 caused a detectable increase in PKC activity at 10(-11) mol/L, and a peak increase of PKC activity was observed at 10(-5) mol/L (about 4.5 U/mg protein). PKC activity was increased in dose-dependent manner by CCK8(10(-11)-10(-6) mol/L). The CCKB-selective receptor antagonist L-365, 260 with a higher efficiency, and the CCKA-selective receptor antagonist L-364, 718 with a lower efficiency were able to block a maximal effect of CCK8-induced PKC activation.

Conclusions: CCK8 may regulate PKC activities in rat cerebral cortex through CCKB receptor.

Objective: To investigate the effects of human wild-type p53 gene transfection on the growth and chemosensitivity of human cervical carcinoma.

Methods: Recombinant eukaryotic expression vector pCB6.p53 containing human wild-type p53 cDNA was introduced by lipofectamine transfection regent into HeLa cell line. The expression of p53 was detected by immunohistochemistry. Cell proliferation was measured by methyl thiazolyl tetrazolium after the treatment of cisplatin.

Results: Expression of p53 was detected by immunohistochemistry. The growth rate of p53-transfected HeLa decreased. Wild-type p53-positive HeLa was more sensitive to cisplatin, compared with the control cell lines.

Conclusion: The exogenous wild-type p53 expression not only induced great suppression of cell growth but also increased chemosensitivity of human cervical carcinoma.

Objective: To investigate the therapeutic effect of high-density lipoprotein (HDL) of human plasma on rat endotoxemia.

Methods: Rats were divided into 2 groups randomly, the treated group received bolus intravenous endotoxin (500 EU/kg), then followed by a bolus HDL (75 mg/kg) intravenously as their blood pressure decreased obviously. The control group just received bolus intravenously endotoxin (500 EU/kg) without HDL. Blood pressure, survival time, the concentration of TNF and the levels of endotoxin in plasma were determined using radioimmunoassay and limulus lysate test.

Results: The decrease of blood pressure was obviously attenuated (P < 0.01), the survival time was significantly increased (P < 0.01) and the concentration of plasma TNF was decreased (P < 0.05) in the treated group, compared with those in the control group. The levels of endotoxin were of no significant difference between the two groups (P > 0.05).

Conclusion: HDL of human plasma has obvious therapeutic effect on rat endotoxemia it could enhance the resistance of rats to endotoxemia, and the mechanism therein may be related to the inhibition of the release of TNF.

Objective: To detect the effect of mechanical stretch on shape, alignment, proliferation, and metabolism of tendon cells maintained in three-dimensional culture.

Methods: A cyclic mechanical strain apparatus for three-dimensional cell cultures was developed. Based on the apparatus, a specific stretch pattern (10% elongation, 12 stretches/min for 15 min of each hour) was applied to tenocytes-scaffolding composites.

Results: Initial studies demonstrated that the stretch-mediated effects on cell division, DNA synthesis, and metabolism in such cultures were influenced by the amplitude, frequency, periodicity, and duration of the applied stretch. After 48 hours' exposure to the stretch, the cell number and [3H] thymidine incorporation into DNA were increased, compared with those of the nonstretched controls(P < 0.05). Under the stretch pattern, the shape of cells changed to oblate and spread to the direction of the stretch. The cyclic stretch also caused an increase in collagen synthesis by tendon cells (P < 0.05), which was predominant in type I.

Conclusion: Cyclic mechanical stretches act directly to stimulate tendon cell growth and these results are compatible with a significant role for stretch in tissue-engineered tendon construction.

Objective: To study the preparation method and in vitro killing effect of adriamycin (ADR)-loaded human serum albumin (HSA) immunonanosphere (HAb18 F(ab')2-ADR-HSA-NP) against hepatoma led by F(ab')2 fragment of human hepatoma specific monoclonal antibody HAb18.

Methods: After ADR loaded HSA nanosphere (ADR-HSA-NP) was prepared in the emulsifying high temperature solidifying way, HAb18 F(ab')2-ADR-HSA-NP was prepared using the modified N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) method. In vitro binding characters of HAb18 F(ab')2-ADR-HSA-NP and ADR-HSA-NP and hepatoma cell SMMC-7721 were observed under optical microscopy and electronic microscopy. In vitro effects of killing hepatoma cell SMMC-7721 of two microspheres were determined using the method of 3H-TdR.

Results: The surfaces of HAb18 F(ab')2-ADR-HSA-NP gave out bright yellow-green fluorescence after it was dyed with fluorescent agent, whereas ADR-HSA-NP did not give out fluorescence. HAb18 F(ab')2-ADR-HSA-NP could integrate with hepatoma cell SMMC-7721 and effectively killed hepatoma cell SMMC-7721 with dose dependence, but ADR-HSA-NP could not obviously integrate and kill SMMC-7721. Neither of the two microspheres could bind and kill human large intestine cancer cell SW1116.

Conclusion: HAb18 F(ab')2-ADR-HSA-NP has a good character for in vitro specific targeting to bind and kill human hepatoma cell.

Objective: This study was conducted to assess the growth inhibition of colorectal adenoma cells by sulindac and identify the possible mechanisms.

Methods: The colorectal adenoma cells from human sporadic adenomatous polyps were cultured, and then treated with sulindac. The cell viability was examined by MTT colorimetric assay; the S-phase fraction and the percentage of apoptosis were measured by flow cytometry.

Results: Following sulindac treatment at different concentrations for 24, 48 and 72 hours, reduction of the cell viability was time- and dose-dependent. After 48-hour-treatment, S-phase fraction was decreased and the percentage of apoptosis was increased; both indexes of all groups except 0.3 mmol/L group were different from those of controls (P < 0.05).

Conclusion: These data suggested that sulindac could inhibit the growth of the colorectal adenoma cells, and its mechanisms might be related to suppressing proliferation and inducing apoptosis.

Objective: To determine the influence of placenta on fetal hypoxia in intrahepatic cholestasis of pregnancy (ICP).

Methods: The transfer of oxygen across the placental membranes in ICP group (n = 7) was compared with that of controls (n = 8) by dual perfusion of the human placental lobule in vitro.

Results: The oxygen consumption and the volume loss of perfusate from the fetal circuit (< 5 ml/h) of placental lobule from women with ICP are similar to controls. The rate of oxygen transfer across the placental membranes in ICP was similar to controls, too (P < 0.05, Power > 0.08). These findings suggest that the transfer of oxygen across the placental membrane in ICP is normal value.

Conclusion: The placenta in ICP has not direct impact on the fetal oxygenation just leads to insufficiency of placental oxygen reserve resulting from a reduction in the size of the intervilous space.