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Biomedical subjects

Q Cai

Publications and source records attributed to Q Cai.

At least 55 records · Page 3Linked to original sources
PubMed2000

[A study of apoptosis and related gene bcl-2 and p53 expression in hippocampus of rats exposed to repeated +Gz].

Objective. To investigate the role of apoptosis in mechanisms of brain damage induced by +Gz exposures. Method. Twenty conscious SD rats were randomly divided into 5 groups. Rats in the control group (n=4) were exposed to +1 Gz and rats in the 4 experimental groups (n=16) were exposed to +14 Gz for three times, each for 45 seconds with 30 min interval in between. All the +Gz exposured were on an animal centrifuge. The rat brains were taken 30 min, 6 h, 24 h and 48 h after the last centrifuge run and fixed and embedded. The apoptosis and expression changes of related gene bcl-2 and p53 were detected by terminal deoxynucleotide (correction of deoxynuleotide) transferase-mediated dUTP nick end labeling (TUNEL) technique and immunohistochemical method, respectively. Result. Apoptotic cells and expression changes of bcl-2 and p53 were observed in CA1 subregion of rat hippocampus taken 6 h after repeated +Gz exposures, but returned to normal after 24-48 h. Conclusion. It suggests that apoptosis and expression changes of bcl-2 and p53 in rats hippocampus can be induced by repeated +Gz exposures and the apoptosis is one of the molecular mechanisms of brain damage induced by repeated +Gz exposures.

Animals↗
PubMed2000

[Changes of mRNA expression of IL-1beta and TNF-alpha in rat brains after repeated exposures to +Gz].

Objective. To study changes of mRNA expression of IL-1beta and TNF-alpha in rat brains after repeated exposures to +Gz. Method. Twenty conscious SD rats served as the subjects. They were randomly divided into 5 groups. Using an animal centrifuge, control rats (n = 4) were exposed to +1 Gz and experimental rats (n = 16) were exposed to +14 Gz three times, each for 45 s with 30 min interval in between. The rat brains were taken 30 min, 6 h, 24 h and 48 h after the last centrifuge run and total RNA was isolated. mRNA expression levels of IL-1beta and TNF-alpha in rat brain were measured by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Result. mRNA expression levels of IL-1beta and TNF-alpha in rat brains taken 30 min, 6 h and 24 h after repeated +Gz exposures were significantly higher than those in control rats, but returned to normal after 48 h. Conclusion. It suggested that mRNA expressions of IL-1beta and TNF-alpha in rat brains can be stimulated by repeated +Gz exposures and the increased expression of IL-1beta and TNF-alpha may play a role in the pathologic course of brain damage induced by +Gz exposures, but the damage is reversible.

Acceleration↗
PubMed2000

[Changes of plasma nitric oxide and tumor necrosis factor-alpha in lung elastase injury induced inflammatory response of hamster].

OBJECTIVE: To investigate the role of the NO and TNF-alpha in lung elastase injury induced inflammatory response of hamster. METHODS: Lung elastase injury induced inflammatory hamster model was established. NOS activity in airway epithelial cells and lung monocytes/macrophage, as well as the serum content of NO and TNF-alpha were measured respectively. RESULTS: The results indicated that iNOS activity in epithelium and monocytes/macrophages were significantly enhanced. In the early period of inflammation the NO and TNF-alpha content in serum increased obviously and maintained in a high level (P < 0.001). CONCLUSIONS: This Study suggested that both NO and TNF-alpha are important mediators participating in the lung elastase injury-induced inflammatory response. Our data suggested NO might play a regulatory role in the release of TNF-alpha.

Animals↗
PubMed1999

Antitumor activity and pharmacokinetics of a mixed-backbone antisense oligonucleotide targeted to the RIalpha subunit of protein kinase A after oral administration.

Overexpression of the RIalpha subunit of cAMP-dependent protein kinase (PKA) has been demonstrated in various human cancers. PKA has been suggested as a potential target for cancer therapy. The goal of the present study was to evaluate an anti-PKA antisense oligonucleotide (mixed-backbone oligonucleotide) as a therapeutic approach to human cancer treatment. The identified oligonucleotide inhibited the growth of cell lines of human colon cancer (LS174T, DLD-1), leukemia (HL-60), breast cancer (MCF-7, MDA-MB-468), and lung cancer (A549) in a time-, concentration-, and sequence-dependent manner. In a dose-dependent manner, the oligonucleotide displayed in vivo antitumor activity in severe combined immunodeficient and nude mice bearing xenografts of human cancers of the colon (LS174T), breast (MDA-MB-468), and lung (A549). The routes of drug administration were intraperitoneal and oral. Synergistic effects were found when the antisense oligonucleotide was used in combination with the cancer chemotherapeutic agent cisplatin. The pharmacokinetics of the oligonucleotide after oral administration of (35)S-labeled oligonucleotide into tumor-bearing mice indicated an accumulation and retention of the oligonucleotide in tumor tissue. This study further provides a basis for clinical studies of the antisense oligonucleotide targeted to the RIalpha subunit of PKA (GEM 231) as a cancer therapeutic agent used alone or in combination with conventional chemotherapy.

Administration, Oral↗
PubMed1999

Acute hepatitis due to fluoxetine therapy.

Fluoxetine-induced hepatotoxicity is generally considered of minimal clinical importance and is not well recognized. Asymptomatic increases in liver enzyme values have been observed in 0.5% of patients who take long-term fluoxetine therapy. This report details 2 cases of acute hepatitis believed to be caused by fluoxetine. Three cases of acute hepatitis caused by fluoxetine have been reported previously. The mechanism of fluoxetine-induced hepatotoxicity is unknown. Although routine monitoring of liver function may not be cost-effective, physicians should be alert to the possibility of fluoxetine-associated hepatitis and consider early discontinuation of the drug if this condition is suspected.

Acute Disease↗
PubMed1999

[Effects of EB virus LMP on the differentiation and growth of human nasopharyngeal carcinoma cell line CNE1].

OBJECTIVE: To study the effects of EBV-LMP gene on differentiation and growth of human nasopharyngeal carcinoma (NPC) cell. METHODS: With NPC cell line (CNE1) as target, electroporation was used to transfect EBV-LMP gene and the vector into CNE1 cells. The proliferation changes of transfectants were measured in vitro by proliferation experiment. FCM method and transplantation in nude mice were used. RESULTS: LMP promoted the growth ability of NPC CNE1 cells in vitro. The average A ratio (3.98 +/- 0.11) in the treatment group was higher than in the control group (2.36 +/- 0.05) and also in the negative control group (2.75 +/- 0.07, P < 0.01). Clone forming test (25.2%, 378/1 500) in the treatment group was higher than in the control groups (11.2%, 168/1 500) and negative control groups (13.4%, 201/1 500). When FCM method was used, the keratin positive rate (82.7%) in the treatment group was markedly decreased as compared with the control (92.5%) and negative control groups (95.7%, P < 0. 05). Latent period (26.6 +/- 7.7) days and internal double time (2.51 +/- 0.18) days of transplant tumor of the treatment group were markedly shortened, tumor take rate (5/6) was increased, cells of the transplant tumor in the treatment group showed an image of small size, great allotype, and a trend of low differentiation. CONCLUSION: The EBV-LMP can promote the growth and inhibit the differentiation of NPC CNE1 cells. EBV-LMP may play an important role in the development of NPC and in studying its mechanism.

Animals↗
PubMed1999

Expression of HSP70 gene in rat brain after exposures to repeated +Gz.

OBJECTIVE: To study the changes of mRNA expression of heat shock protein 70 (HSP70) in the rat brain exposed to repeated +Gz. METHOD: The mRNA expression levels of HSP70 in rat brain were measured by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULT: The HSP70 mRNA expression levels in rat brains taken 30 min and 6 h after repeated +Gz exposures were significantly higher than those in control group, while the difference between the levels of control group and those of experimental rat brains taken 24 h after +Gz exposure was not significant. CONCLUSION: It is suggested that HSP70 mRNA expression in rat brain can be induced by repeated +Gz exposures and the increased HSP70 mRNA expression may play an important role in self-protection against brain damage induced by +Gz exposures.

Animals↗
PubMed1999

[Determination of columbianetin, columbianetin acetate and osthol in Angelica pubescens Maxim. f. biserrata Shan et Yuan by HPLC].

OBJECTIVE: To develop a method for the determination of columbianetin, columbianetin acetate and osthol in Angelica pubescens f. biserrata METHOD: HPLC method, ODS column (6.0 mm x 150 mm) with a mobile phase of methanol-acetonitrile-0.025 mol.L-1 phosphoric acid (32:20:48), and wave length detection at 320 nm. RESULT AND CONCLUSION: The method can be used for the quality control of raw medicinal materials.

Angelica↗
PubMed1998

IFN-gamma-inducing factor/IL-18 administration mediates IFN-gamma- and IL-12-independent antitumor effects.

We evaluated the mechanism of the antitumor effects of mouse rIFN-gamma-inducing factor/IL-18 protein on the growth of mouse tumor cell lines in vivo. Mice received IL-18 before or after challenge with CL8-1, a mouse melanoma cell line. Both regimens significantly suppressed tumor growth and reduced the number of mice with growth of tumor from 60% (3/5) to 20% (1/5). Furthermore, IL-18 administered before and after tumor inoculation completely abrogated the establishment of CL8-1 in all animals. IL-18 administration also significantly suppressed the growth of MCA205, a sarcoma cell line, even when treatment was delayed to 7 days following tumor inoculation. Although IL-18/IL-12 combination therapy had the most significant and immediate antitumor effects, many mice so treated succumbed with markedly elevated serum IFN-gamma levels. The antitumor effects of IL-18 were abrogated almost completely when NK cells were eliminated using anti-asialo GM1 Ab administration, but only marginally impaired in IFN-gamma or IL-12 gene-disrupted mice. Immunohistochemical staining revealed that the number of the CD8+ T cells, but not CD4+ T cells, found at the tumor site was reduced in animals treated with IL-18. These results indicate that IL-18 has potent antitumor effects mediated by CD4+ T cells and NK cells, but in IFN-gamma- and IL-12-independent pathways.

Adjuvants, Immunologic↗
PubMed1998

Preclinical pharmacology of the natural product anticancer agent 10-hydroxycamptothecin, an inhibitor of topoisomerase I.

PURPOSE: 10-Hydroxycamptothecin (HCPT) is an indole alkaloid isolated from a Chinese tree, Camptotheca acuminata, and has a wide spectrum of anticancer activity in vitro and in vivo mainly through inhibitory effects on topoisomerase I. HCPT has been shown to be more potent and less toxic than camptothecin and has recently undergone clinical trials. To determine how HCPT might be best used as an anticancer agent, preclinical studies of the pharmacokinetics, tissue distribution, metabolism and elimination of HCPT in rats were undertaken. METHODS: HCPT was administered to rats by i.v. bolus injection at doses of 1, 3, and 10 mg/kg body weight. HCPT (lactone and carboxylate) and its metabolites in plasma, urine, feces, and various tissues were quantitated by reversed-phase HPLC. Pharmacokinetic parameters were then estimated. RESULTS: Following i.v. administration at doses of 3 or 10 mg/kg, the plasma concentration-time profile for lactone HCPT could be best described by a three-compartment model, with terminal elimination half-lives of 140.4 and 428.6 min, respectively. A two-compartment model was used to fit the plasma concentration-time curve at 1 mg/kg, with a terminal elimination half-life of 30.5 min. Carboxylate HCPT had a longer half-life than the lactone form of HCPT. During the initial 6 h after dosing, urinary excretion was the major route of elimination, and fecal excretion became the major route of elimination thereafter. HCPT was widely distributed to various tissues including the enterohepatic system, kidney, and bone marrow. The lactone form of HCPT was detectable in various tissues examined up to 72 h after dosing at all the three test doses. HCPT glucuronides were present in plasma, urine, feces and various tissues. No significant toxicity was observed at doses of 1 or 3 mg/kg. Polyuria and hematuria were observed only during the initial 3 h after dosing at 10 mg/kg. CONCLUSIONS: Prolonged elimination of HCPT in vivo may have a significant impact on its therapeutic effects. HCPT is metabolized to its carboxylate form and glucuronides. Dose-dependent toxicity was observed with i.v. administration of HCPT. The results of this study should be useful in the design of future human trials with this anticancer drug.

Animals↗
PubMed1998

Alterations of antioxidant enzymes and oxidative damage to macromolecules in different organs of rats during aging.

Oxygen free radicals have been hypothesized to play an important role in the aging process. To investigate the correlation between the oxidative stress and aging, we have determined the levels of oxidative protein damage and lipid peroxidation in the brain and liver, and activities of antioxidant enzymes in the brain, liver, heart, kidney, and serum from the Fisher 344 rats at ages of 1, 6, 12, 18, and 24 months. The results showed that the level of oxidative protein damage (measured as carbonyl content) in the brain and liver was significantly higher in older animals than in young animals. No statistical difference was observed in the lipid peroxidation of the liver and brain between young and old animals. The activities of antioxidant enzymes in most tissues displayed an age-dependent decline. Superoxide dismutases in the heart, kidney, and serum, glutathione peroxidase activities in the serum and kidney, and catalase activities in the brain, liver, and kidney, significantly decreased during aging. Cytochrome c oxidase, an enzyme involved in electron transport in mitochondria, initially increased, but subsequently decreased in the aged brain, whereas no significant alteration was observed in the liver mitochondrial antioxidant enzymes. The present studies suggest that the accumulation of oxidized proteins during aging is most likely to be linked with an age-related decline of antioxidant enzyme activities, whereas lipid peroxidation is less sensitive to predict the aging process.

Aging↗
PubMed1998

Tamoxifen reduces endogenous and UV light-induced oxidative damage to DNA, lipid and protein in vitro and in vivo.

We have investigated the effect of tamoxifen (TAM) on endogenous or ultraviolet radiation (UVR)-induced oxidative damage to macromolecules in vitro and in vivo. In a system containing calf thymus DNA exposed to a germicidal UV lamp, both TAM and 4-hydroxytamoxifen (4-OH-TAM) inhibited UVR-induced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA in a dose-dependent manner. At low concentrations, 4-OH-TAM quenched 8-OHdG more potently than TAM. However, the reduction of 8-OHdG by TAM and 4-OH-TAM became similar at a concentration of 10 microM. In contrast, ascorbic acid had the similar effect to TAM, whereas glutathione exhibited little effect on UVR-induced 8-OHdG. The order of quenching efficacy was: 4-OH-TAM > TAM approximately = ascorbic acid > glutathione. We have further determined the effect of TAM on endogenous 8-OHdG formation, lipid peroxidation, and protein oxidation in the skin of SENCAR mice. Topical application of 5 micromol TAM significantly reduced the level of 8-OHdG in mouse epidermis by approximately 27% (P < 0.05). Endogenous lipid peroxidation and protein oxidation, measured as malondialdehyde (MDA) and carbonyl groups, were also substantially reduced by topical TAM. Further study was conducted to evaluate the effect of TAM on UVR-induced 8-OHdG and MDA in skin of hairless mice. In mice subacutely exposed to low dose (3.4 kJ/m2 x six doses) and high dose (16.8 kJ/m2 x three doses) of UVB irradiation, TAM significantly blocked the formation of 8-OHdG in mouse epidermis by 57-81% and MDA by 37-65%, respectively. Our studies suggest that reduction of oxidative damages to biological macromolecules in vitro and in vivo may at least in part explain the anti-carcinogenic and chemopreventive actions of tamoxifen.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

Effect of aspirin on protein binding and tissue disposition of oligonucleotide phosphorothioate in rats.

Pharmacokinetic studies of phosphorothioate oligodeoxynucleotides (PS-oligonucleotides) in animals show that following intravenous administration, PS-oligonucleotide clears out rapidly from the plasma and is distributed to majority of the organs. PS-oligonucleotides are bound to plasma proteins extensively. This study was aimed to determine the effect of aspirin, a commonly used drug, on pharmacokinetics of PS-oligonucleotides. In the present study, PS-oligonucleotide was administered to rats that had received aspirin by gavage. Pharmacokinetic study shows that if PS-oligonucleotide was administered following aspirin administration in rats, a) plasma pharmacokinetic parameters (t1/2alpha?, t1/2beta, AUC, etc.) had lower values, b) tissue disposition was different, and c) rate and route of elimination was affected in animals compared to rats receiving PS-oligonucleotide alone. This finding suggests that pharmacokinetics of PS-oligonucleotides can be affected with certain class of drugs, which may have direct impact on biological activity and safety.

Animals↗
PubMed1998

[Study on the physiological activities of the metabolites from Paecilomyces arovirens].

The metabolites of Paecilomyces arovirens exhibited insecticidal activities to many inscct pcsts, including cotton aphid, Aphis gossypii, hawthorn Ispidcr mitc, Tetranychus viennensis and larvae of imported cabbage worm, Pietis rapae. A comparison was made between the metabolites of P. arovirens and naphthyl acetic acid (NAA) in wheat (Triticum aestivum) and water melon (Cucumis sativus) bioassays on their physiological effects. Results demonstrated that some of the metabolites physiological activities of P. arovirens are same to that of NAA, some are different between them. It indicate that there is a new kind or many kinds of plant growth regulator in the metabolites and need further analysized. The results can offer reference for exploiting a new insecticid which not only can control insect pests, but also increase plant growth.

Cucumis sativus↗
PubMed1998

Sporadic cases of hemorrhagic colitis associated with Escherichia coli O157:H7 in rural Wisconsin.

The epidemiology and clinical aspects of Escherichia coli O157:H7 (E. coli O157:H7) infections in rural Wisconsin have rarely been reported. In the last six years, 66 cases of E. coli O157:H7 infection were encountered at our institution. Bloody diarrhea was the universal presentation and all cases represented apparent sporadic infection as institutional or community-wide outbreaks were not found in our study. The mean age was 31 (range 7 months to 86 years), 25% less than 10 years old and 60% were female. Most cases were seen in summer and early autumn (88%). Two patients (3%) developed hemolytic-uremic syndrome. Case-fatality rate in this study was 1.5%. Antibiotic treatment and hospitalization did not change the course and outcome of the infection. Routine screening of E. coli O157:H7 during winter time (December and January) may not be necessary in our rural area. The understanding gained from our study might foster better infection control.

Adolescent↗
PubMed1997

Upregulation of a novel gene by freezing exposure in the freeze-tolerant wood frog (Rana sylvatica).

A novel gene responsive to freezing exposure was identified among five cDNA clones obtained through differential screening of a cDNA library constructed from liver of frozen wood frogs. The cDNA sequence of this gene, cloned in the recombinant plasmid, pBfFR14, showed no homology to any genes available in the Genbank database. The clone, designated as Fr10, carried a 457 bp cDNA sequence and contained a single open reading frame that could potentially encode a small protein of 90 amino acids with a molecular weight of about 10 kDa, named FR10. The putative protein contained a highly hydrophobic N-terminal region (21 residues) that carries a potential nuclear exporting signal (NES) sequence, LALVVLVIAISGL, similar to the NES found in PKI, an inhibitor of protein kinase A (PKA). A single mRNA transcript with a size of 550 nt was detected when the insert of the pBfFR14 was used as a probe against the Northern blot containing total RNA isolated from wood frog organs. RNA blotting analysis for gene expression in eight organs showed that transcription of the gene was highly induced by 24 h of freezing exposure at -2.5 degrees C in liver and gut, moderately elevated in heart, lung, brain and bladder but showed no change in skeletal muscle and decreased in kidney. A time-course analysis for freezing regulation of gene expression in liver showed that transcript levels were increased by 2-fold in 1 h of freezing exposure and the levels continued to increase up to 3.5-fold over the control after 24 h of freezing exposure, but had returned to control levels after 24 h thawing at 5 degrees C. Gene expression in liver was also up-regulated by whole animal dehydration at 5 degrees C but strongly down-regulated by anoxia exposure, indicating that the gene may respond to cell volume regulatory signals in vivo during natural freezing.

Adaptation, Physiological↗
PubMed1997

Differential regulation of the mitochondrial ADP/ATP translocase gene in wood frogs under freezing stress.

The gene Aat coding for ADP/ATP translocase (AAT) was cloned from liver of the freeze-tolerant wood frog, Rana sylvatica, via differential screening of a cDNA library from liver of frozen frogs and using probes from control versus frozen frogs. Sequence analysis showed that clone pBfFR07 bearing the AAT cDNA contained a 1318-bp insert with one full-length open reading frame. The deduced amino acid sequence included 317 residues, with 81-86% identities to mammalian AAT. A 1750-nt transcript from the Aat gene was detected using pBfFR07 probe and a putative frog AAT of over 30 kDa was visualized by immunoblotting using a polyclonal antibody raised against chicken AAT. Analysis of liver samples from a time course of freezing showed a maximal 4.5-fold increase in mRNA after 8 h with AAT protein peaking in 24-h frozen frogs. Freezing also induced Aat expression in bladder and lung. In liver, mRNA expression also responded positively to anoxia stress but not to experimental dehydration of the animals. These results suggest that AAT induction during freezing may be stimulated by the ischemia that develops when plasma freezes; changes in AAT may contribute to stabilizing energetics in mitochondrial versus cytosolic pools over freeze/thaw cycles.

Amino Acid Sequence↗