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Biomedical subjects

S Cao

Publications and source records attributed to S Cao.

At least 73 records · Page 4Linked to original sources

New approaches to supporting the failing liver.

With the continued, growing disparity between the numbers of organ donations and patients waiting for liver transplantation, various efforts have been made to optimize the allocation of organs, as well as to devise means to support the failing liver. Over the years, the development of bioartificial liver-assist devices has aimed at replacing the three main functions of hepatocytes, which are synthetic, metabolic, and excretory. The application of porcine hepatocytes in humans to carry out biotransformation, as well as other metabolic functions and refinement of the membrane separator, have yielded some promising results in supporting patients with acute liver failure. Further advances will need to be made before these bioartificial devices can be considered for routine application in clinical settings.

Animals↗

Health effects of indoor fluoride pollution from coal burning in China.

The combustion of high fluoride-content coal as an energy resource for heating, cooking, and food drying is a major exhaust emission source of suspended particulate matter and fluoride. High concentrations of these pollutants have been observed in indoor air of coal-burning families in some rural areas in China. Because airborne fluoride has serious toxicological properties, fluoride pollution in indoor air and the prevalence of fluorosis have been analyzed in a fluorosis area and a healthy nonfluorosis area in China and in a rural area in Japan. For human health, fluoride in indoor air has not only been directly inhaled by residents but also has been absorbed in stored food such as corn, chilies, and potatoes. In the fluorosis area in China, concentrations of urinary fluoride in the residents have been much higher than in the nonfluorosis area in China and in the rural area in Japan. In the fluorosis area, almost all elementary and junior high school students 10-15 years of age had dental fluorosis. Osteosclerosis in the skeletal fluorosis patients was very serious. Urinary deoxypyridinoline in rural residents in China was much higher than in rural residents in Japan. Data suggest that bone resorption was extremely stimulated in the residents in China and that fluoride may stimulate both bone resorption and bone formation. Because indoor fluoride from combustion of coal is easily absorbed in stored food and because food consumption is a main source of fluoride exposure, it is necessary to reduce airborne fluoride and food contamination to prevent serious fluorosis in China.

Adolescent↗

Current status of living-related liver transplantation.

Living-related liver transplantation has come of age. This manuscript addresses the most important facets of the living-related liver transplant procedure including selection of the donor, the recipient operation, immunosuppression and rejection as well as the most common surgical complications. It also describes the results in terms of patient and graft survival, retransplantation and quality of life. Although living-related liver transplantation has not solved the problem of organ shortage, it has provided many children with an opportunity to live and enjoy life.

ABO Blood-Group System↗

[Assessment of fetal maturation by epithelial growth factor in serum of pregnant women].

OBJECTIVE: To study the concentrations of human epithelial growth factor (EGF), progesterone (P) in serum, and EGF, P, amylase (Ams), creatinine (Cr) and total bilirubin (TB) in amniotic fluid at different trimester normal pregnancy. METHODS: The concentrations of EGF, P in serum of 181 cases of pregnant women (first trimester 35, midtrimester 69, late trimester 77) and the concentrations of EGF, P, Ams, Cr, TB in amniotic fluid of 87 cases (mid-trimester 44, late trimester 43) were determined. At the same time, the concentrations of EGF, P in serum of umbilical veins and arteries from 23 full term neonates were determined as well. The concentrations of EGF and P were measured by radioimmunoassay and Ams, Cr, TB in amniotic fluid by PA110 autobiochemistry analyzer. RESULTS: (1) The concentrations of EGF, P in serum increased as pregnancy advanced. (2) There were significant correlations between EGF level and Ams, Cr levels in amniotic fluid. After 32 gestational weeks, the fetal maturity rate was 70.59% when EGF was > or = 4.5 micrograms/L. There were significant positive correlations between EGF in maternal serum and in amniotic fluid, (3) The maternal serum EGF concentration was significantly higher than that in the umbilical vessels, and there was positive correlations between them. CONCLUSION: The change of maternal serum concentration could be used to determine the fetal maturation.

Amniotic Fluid↗

[Determination of the soluble non-starch polysaccharides in rice and wheat bran by gas chromatography].

Cereal polysaccharides can be broadly classified into two distinct and chemically well-defined types. They are the storage polysaccharides (alpha-glucan) and the structural polysaccharides starch (beta-glucan) which are usually called non-starch polysaccharides (NSP). The determination of soluble non-starch polysaccharides in rice and wheat bran by gas chromatography has been developed. The free sugars in the sample were extracted with 80% ethanol. The residue was hydrolyzed in an acetic acid buffer solution (pH 5.0) in the presence of amylase and amyloglucosidase to remove starch. The soluble NSP obtained was further hydrolyzed in the acidic condition to produce the corresponding monosaccharides which were derivatized to form alditol acetates for GC analysis with allose as the internal standard. The GC conditions were OV-1701 column (25 m x 0.3 mm) with temperature program from 195 degrees C to 225 degrees C and FID.

Chromatography, Gas↗

[The determination of diuron and chlortoluron residues in beef and beef products by high performance liquid chromatography].

Amethod for the determination of diuron and chlortoluron in beef and beef products with high performance liquid chromatography is described. The sample was extracted with a mixture of acetonitrile and methanol (50:50, V/V). After filtration, the filtrate was defatted with petroleum ether, then water was added and further extracted with chloroform. The chloroform collected was evaporated in a rotary evaporator(45 degrees C). The residue was dissolved in acetonitrile-methanol(50:50, V/V) mixture, poured into an Al2O3 column and eluted with the same mixture. The eluate was collected for HPLC analysis. The analytical column was Selectosil C18 (5 microns, 250 mm x 4.6 mm i.d.), mobile phase was methanol-water(60:40, V/V) and detection wavelength was UV-245 nm. The minimum amounts of detection were 0.4 ng for diuron and 0.5 ng for chlortoluron. Recoveries were 87.34%-87.64% for diuron and 88.78%-91.94% for chlortoluron.

Animals↗

[Isolation of a lipase-producing Pseudomonas strain and optimization of its fermentation conditions].

A lipase-producing bacterium strain was isolated from soil and was identified as Pseudomonas sp.. Its lipase yield was improved 2.25-fold by combined treatment of UV irradiation and NTG. The lipase fermentation condition for the mutant strain was optimized with Plackett-Burman design and Response Surface Analysis (RSA), and the formula of the optimum medium suitable for industrial scale fermentation was thereby established. A maximum yield of 87.5 U/ml was obtained.

Culture Media↗

Rational design of irinotecan administration based on preclinical models.

Most clinical drug regimens for irinotecan (CPT-11 [Camptosar]) have been empirically based on classic in vivo pharmacokinetic and pharmacodynamic considerations. We propose an alternative approach that attempts to provide a rationally designed schedule of irinotecan administration based on preclinical data. HL60 cells grown in suspension or as subcutaneously implanted solid xenografts in nude mice served as in vitro and in vivo models to rest the activity of irinotecan or its active metabolite, SN-38. For SN-38, within an effective drug concentration range, scheduling drug administration based on duration of DNA synthesis inhibition significantly potentiated cell kill in vitro, and increasing drug concentrations at suboptimal scheduling did not result in additive cell kill. These data suggested that even though high drug doses may be attainable in vivo, they may not be required to achieve maximum antitumor activity. To test this hypothesis, a sensitive in vivo model to test the toxicity and antitumor activity of CPT-11 is required, which is provided in the human myeloid HL60 xenograft model grown in nude mice. In this model, CPT-11 at a dose 50 mg/kg, daily x5 (MTD) achieved 100% complete tumor regression. This model should be useful to test the hypothesis that for irinotecan, administration of a minimum effective dose (MED) at an optimal schedule can achieve maximum antitumor activity and should therefore prevail over the classic approach of administering the MTD.

Animals↗

Modulation of platinum-induced toxicities and therapeutic index: mechanistic insights and first- and second-generation protecting agents.

Platinum-type drugs have proven to be valuable in the treatment of a variety of solid tumors, beginning with the commercial approval of cisplatin 18 years ago. There are several clinically important toxicities commonly associated with the administration of these drugs. Despite the extensive use of cisplatin and carboplatin, the fundamental chemical transformations and mechanisms that underlie their antitumor and toxic effects have not been fully characterized. Several first-generation protective thiols have been clinically studied in an attempt to reduce the toxicity of platinum-type drugs; while some of these agents appear to protect against certain toxicities, nearly all platinum-protecting drugs have their own intrinsic toxicities, which can be additive to the toxicity of platinum-type drugs. Tumor protection by platinum-protecting drugs is an additional untoward effect that is associated with certain types of agents and must be addressed with care. Recent advances in theoretical and laboratory methods and the use of supercomputers have extended our understanding of the possible major mechanisms underlying platinum drug antitumor activity and toxicity; we present strong evidence that there are two classes of chemical species of platinum drug. One class appears to predominantly account for the antitumor activity, and the other class of chemical species produces many of the toxic effects of platinum drugs. We have discovered a new nontoxic, second-generation platinum-protecting agent, known as BNP7787, which appears to selectively inactivate and eliminate toxic platinum species. BNP7787 has recently entered phase I clinical testing in cancer patients.

Amifostine↗

The study on the relationship between the expression of calponin and gallstone formation.

In order to understand the molecular mechanisms of gallstone formation, the expression of calponin in animal model of gallstone disease was studied. High-cholesterol diet was given to the guinea pigs to induce gallstone formation. RT-PCR and Western-blotting were used to evaluate expression level of calponin gene. Down-regulation of calponin gene expression was observed in animals with gallstone, while myosin expression was relatively stable. Our results indicated that the decrease of calponin could increase the pressure of Oddi's sphincter, aggravate the stasis of bile and promote the gallstone formation.

Animals↗

Emergency transjugular intrahepatic portosystemic shunt (TIPS) in an infant: a case report.

Since the first successful report regarding the feasibility of transjugular intrahepatic portosystemic shunt (TIPS) as an alternative to surgical decompression of portal hypertension, this method has been used extensively as a temporizing measure in controlling refractory variceal bleeding before liver transplantation in adults with cirrhosis. There are few reports of TIPS in pediatric patients because variceal bleeding in most of these patients can often be managed conservatively without invasive intervention. Recently, successful use of TIPS to treat complications of portal hypertension has been described in two children ages 10 and 13. To our knowledge, there are no reports of TIPS used in infants under the age of 1 year. The authors report a case in which TIPS was used to successfully control variceal bleeding in a 10-month-old infant before consideration for hepatic transplantation.

Blood Transfusion↗

Detection of yellowhead virus and Chinese baculovirus in penaeid shrimp by the Western blot technique.

The continuing threat posed by viral diseases in cultured shrimp calls for the development of detection technologies for monitoring the animals, especially broodstock. Two of the most highly pathogenic viruses of penaeid shrimp are the yellow-head virus (YHV) and Chinese baculovirus (CBV, also called white spot baculovirus). A Western blot (WB) protocol capable of detecting YHV and CBV in the hemolymph of infected shrimp was developed. The use of the hemolymph as material for virus detection allowed for sample collection without sacrificing the animals. This protocol was highly specific, rapid, and sensitive enough to detect the presence of the viruses before the appearance of overt symptoms. It was also useful for demonstrating the growth of both viruses in primary shrimp lymphoid cell cultures.

Animals↗

Epstein-Barr virus lymphoproliferative disorders after liver transplantation.

Post-transplant lymphoproliferative disorders (PTLD) represent a spectrum of histological and immunological abnormalities, ranging from benign polyclonal B-cell hyperplasia to monoclonal malignant lymphoma. The important role of Epstein-Barr virus (EBV) in PTLD in liver transplant patients, particularly in pediatric recipients, is reviewed. Understanding the risks of EBV infection, the clinical presentations and diagnosis of PTLD, and its pathophysiology are crucial to the management of these disorders. Current treatment methods have resulted in better outcomes of these disorders, which in the past were uniformly fatal.

Adult↗

Comparative antitumor efficacy of docetaxel and paclitaxel in nude mice bearing human tumor xenografts that overexpress the multidrug resistance protein (MRP)

BACKGROUND: Multidrug resistance has been associated with expression of the multidrug resistance protein (MRP). Recently, MRP-expression has been detected in human tumor samples of patients with breast cancer and non-small-cell lung cancer. Since taxoids are the most active drugs in the treatment of both tumor entities, the antitumor efficacies of paclitaxel and docetaxel were compared in nude mice bearing human tumor xenografts that express MRP. MATERIALS AND METHODS: Athymic nude mice (nu/nu) bearing tumor xenografts of parental human sarcoma HT1080 or MRP-expressing HT1080/DR4 cells (as confirmed by Northern blot analysis) were treated with the maximum tolerated doses (MTD) of doxorubicin ([Dx] 10 mg/kg i.v. push), paclitaxel ([PC] 50 mg/kg three-hour i.v. infusion), or docetaxel ([DC] 40 mg/kg three-hour i.v. infusion). In vitro, the activity of doxorubicin, paclitaxel and docetaxel was evaluated by the sulphorhodamine B (SRB) assay using the pyridine analogue PAK-104P (5 microM), a potent inhibitor of MRP-function. RESULTS: At their MTDs both taxoids showed significant activity against MRP-negative HT1080 xenografts with response rates of 80% (40% CR) for PC and 100% (60% CR) for DC. In contrast, DC was significantly more active than PC in nude mice bearing doxorubicin resistant MRP-expressing HT1080/DR4 tumor xenografts (overall response rates: 100% (60% CR) for DC; 10% (0% CR) for PC; 0% for Dx). Since treatment of mice with the MTD of PC or DC yielded similar overall toxicity (maximum weight loss for HT1080: PC 8.6 +/- 2.2%; DC 7.5 +/- 2.2% and for HT1080/DR4: PC 11.6 +/- 3.0%; DC 7.6 +/- 1.8%, respectively), these results demonstrate the increase in the therapeutic index for docetaxel against MRP-expressing tumors. In vitro, HT1080/DR4 cells were 270-fold, 6.4-fold and 2.8-fold more resistant than parental cells to doxorubicin, PC and DC, respectively. Pyridine analogue PAK-104P completely restored drug sensitivity to PC and DC, while no effect of PAK-104P on parental HT1080 cells was observed. CONCLUSIONS: Both taxoids, when given at their MTDs, showed significant efficacy against parental HT1080 tumor xenografts. However, docetaxel at its MTD was significantly more active against MRP-expressing tumor xenografts than paclitaxel. Furthermore, in vitro resistance of HT1080/DR4 cells was higher for PC (6.4-fold) than for DC (2.8-fold). Since PAK-104P completely restored sensitivity to both taxoids, the observed resistance appears to be related to MRP. These data suggest, that docetaxel is not as readily transported by MRP as paclitaxel leading to an increased therapeutic ratio in MRP-expressing tumors in vivo. Therefore, docetaxel may have therapeutic advantages in the clinical treatment of MRP-expressing tumors.

ATP-Binding Cassette Transporters↗

Potential effect of cyclosporin A in formation of cholesterol gallstones in pediatric liver transplant recipients.

Recent advancements in liver transplantation have resulted in extended survival both for grafts and recipients. Such improvement, together with the shortage of donor organs has prompted expansion of the donor pool to include less than ideal donors, especially in life-threatening situations. The use of older liver donors has been associated with lower long-term survival. However, potential morbidity such as gallstone formation has not been explored. We analyzed bile composition in a child who developed cholesterol gallstones in the proximal bile duct two years after undergoing emergency liver transplantation with a liver from a 78-year-old donor. Oral administration of ursodeoxycholic acid (ursodiol) shifted the cholesterol composition of the bile from a supersaturated, potentially crystallized state to a liquid (micellar) state. Unlike cyclosporin A, FK506 showed an increase in the proportion of chenodeoxycholic acid and a decrease in the proportion of cholic acid, and thus may exhibit minimal or no hepatotoxic effect. Thus, in donor livers with factors known to be associated with cholesterol gallstone formation (such as age, sex, or obesity), one may consider analyzing the bile composition at the time of procurement. Depending on cholesterol and bile acid composition the use of FK506 with or without addition of ursodeoxycholic acid may be warranted.

Adolescent↗

Thymidylate synthase inhibitors in cancer therapy: direct and indirect inhibitors.

PURPOSE AND METHODS: Although fluoropyrimidines, in particular, fluorouracil (5-FU) and fluorodeoxyuridine (FdUrd), are active alone and in combination with other agents in a variety of human malignancies, therapeutic selectivity, resistance, and efficacy have been a major limitation in cancer therapy. Preclinical and clinical results in advanced and adjuvant colorectal cancers confirmed that the therapeutic efficacy of fluoropyrimidines, with thymidylate synthase (TS) as a primary target, can be improved significantly with leucovorin (LV) modulation. With the recognition that TS is an important therapeutic target, direct and specific inhibitors have been developed and are under intensive preclinical and clinical evaluation, primarily in patients with colorectal cancer, with demonstrable activity. The direct TS inhibitors have been shown to be potent, with a high level of specificity under therapeutic conditions for TS. This includes ZD1694, AG337, and LY231514. To date, although the therapeutic activity of both direct and indirect inhibitors of TS is similar, differences in the magnitude and profile of toxicity have been observed. A phase III comparative evaluation of a direct inhibitor of TS (ZD1694) with an indirect inhibitor (5-FU/LV) has been completed and showed similar activity but reduced toxicity in favor of ZD1694. RESULTS: Recognition that greater than 95% of the injected dose of 5-FU is rapidly inactivated by dihydropyrimidine dehydrogenase (DPD) to therapeutically inactive products, but with toxicity to normal tissues, led to the development of inhibitors of this enzyme with the aim to modify the therapeutic index of 5-FU. Several inhibitors in combination with 5-FU are under preclinical and clinical evaluation, including uracil and 5-chloro-2,4-dihydroxy pyridine, as modulators of 5-FU derived from its prodrug tegafur and 5-ethynyluracil as a modulator of 5-FU. CONCLUSION: In this review, an update of the present status of direct and indirect inhibitors of TS is discussed, as well as the future prospect for new drugs alone and in combination.

Antimetabolites, Antineoplastic↗

[Correlation analysis of radiation effects on potential doubling time (Tpot) for human nasopharyngeal carcinoma cells].

OBJECTIVE: To understand radiation-induced cell kinetic changes of human nasopharyngeal carcinoma CNE cells and clarify cell biology basis of repopulation. METHODS: Either exponential growing stage or plateau stage human nasopharyngeal carcinoma CNE cells were measured by BrdUrd/DNA bivariate flow cytometry for phase fraction, BrdUrd labeling index, S phase duration, potential doubling time (Tpot), etc. Correlation analysis of Tpot with other kinetic parameters was made. RESULTS: (1) For exponentially growing CNE cells, shortening of Tpot after irradiation was closely correlated with increased BrdUrd labeled S phase fraction (P < 0.05), whereas no correlation was found between Tpot and other kinetic parameters measured; (2) for plateau stage CNE cells, shortening of Tpot with various radiation doses was closely correlated with decreased G0/G1 phase fraction (P < 0.05) and increased G2M phase fraction (P = 0.002), whereas no correlation was found between Tpot and other parameters measured. CONCLUSION: In a range of 0-8 Gy of irradiation, an increased accelerated repopulation rate was resulted from increasing radiation dose. Recruitment of G0 cells into cell cycle might play a major role in radiation-induced accelerated repopulation for plateau stage CNE cells, while it was contributed by an increased DNA synthesis manifested by an increased BrdUrd labeled S phase fraction for exponential growing CNE cells.

Cell Division↗

[The expression of calponin in Oddi's sphincters and its actions during gallstone formation].

OBJECTIVES: To study on the expression of calponin in an animal model of gallstone disease and investigate the molecular mechanisms of gallstone formation. METHODS: After feeding a high-cholesterol diet to guinea pigs, Oddi's sphincters were disseced on day 30 and day 60 respectively. We used RT-PCR, western-blotting to evaluate expression level of calponin gene. RESULTS: Down-regulation of calponin gene expression was observed in animals with gallstone. The levels of both protein and mRNA expression for calponin on day 30 and day 60 were lower than those of control group with the level from day 60 lower than that from day 60, while myosin expressions were relatively stable. CONCLUSION: Our results indicated that the decrease of calponin could increase the pressure of sphincter of Oddi, aggravate the stasis of bile and promote the gallstone formation.

Animals↗