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Biomedical subjects

Hong Shen

Publications and source records attributed to Hong Shen.

At least 73 records · Page 4Linked to original sources
PubMed2004

Combination therapy with lamivudine and famciclovir for chronic hepatitis B infection.

BACKGROUND & AIMS: Lamivudine suppresses hepatitis B replication, but drug-resistant mutants emerge with long-term therapy. In vitro data suggest that lamivudine and famciclovir might synergistically inhibit hepadnaviral replication. We reviewed our experience with lamivudine and famciclovir in 24 patients with chronic hepatitis B infection. METHODS: Patients with chronic hepatitis B infection and detectable HBV DNA received lamivudine and famciclovir combination therapy. The primary end point was HBV DNA suppression at week 48. Follow-up was reviewed for those who remained on combination therapy beyond the first 48 weeks. RESULTS: Thirteen treatment-naïve HBeAg-positive subjects received 48 weeks of therapy; all had undetectable HBV DNA levels (less than 2.5 pg/mL) at week 48. Three patients underwent HBeAg seroconversion at week 48 and discontinued therapy. Ten patients remained on combination therapy; 3 developed YMDD (tyrosine-methionine-aspartate-aspartate) mutations at year 2, although HBV DNA levels remained below 2.5 pg/mL at a mean of 39 months. A second heterogeneous group of 5 subjects including interferon therapy failures and those with HBeAg-negative infection also received 48 weeks of combination therapy, with 1 subject developing redetection of HBV DNA by week 48. YMDD mutations were noted in the other 4 subjects at year 2, although just 1 subject had HBV DNA greater than 2.5 pg/mL at 39 months of therapy. CONCLUSIONS: In this small pilot study, 48 weeks of therapy with lamivudine and famciclovir was effective in suppressing HBV replication. A randomized controlled trial is required to define the role of combination therapy with lamivudine and famciclovir in delaying the clinical emergence of resistant strains.

2-Aminopurine↗
PubMed2004

Role of PEPT2 in the choroid plexus uptake of glycylsarcosine and 5-aminolevulinic acid: studies in wild-type and null mice.

PURPOSE: To determine the importance of PEPT2 in the uptake of glycylsarcosine (GlySar) and 5-aminolevulinic acid (5-ALA) in mouse choroid plexus whole tissue. METHODS: Uptake studies were performed in bicarbonate artificial cerebrospinal fluid buffer using choroid plexuses isolated from PEPT2+/+ and PEPT2-/- mice. [14C]GlySar and [14C]5-ALA were studied as a function of temperature, concentration, potential inhibitors, and low sodium conditions. RESULTS: PEPT2-/- mice exhibited a 90% reduction in GlySar uptake (p < 0.001) and a 92% reduction in 5-ALA uptake (p < 0.001) as compared to wild type animals. At 4 degrees C (vs. 37 degrees C), GlySar uptake was reduced by 95% in PEPT2+/+ mice; no difference was observed in null animals. Unlabeled GlySar inhibited the uptake of [14C]GlySar in PEPT2+/+ mice (p < 0.01); self-inhibition did not occur in PEPT2-/- mice. GlySar demonstrated saturable uptake in PEPT2+/+ mice (Vmax = 16.4 pmol mg(-1) min(-1), Km = 70 microM, Kd = 0.014 microl mg(-1) min(-1)), however, uptake was linear in PEPT2-/- mice (Kd = 0.023 microl mg(-1) min(-1)). Low sodium buffer (1 mM) resulted in 75% and 59% reductions, respectively, in GlySar (p < 0.001) and 5-ALA (p < 0.01) uptake in PEPT2+/+ mice; no differences were observed in PEPT2-/- mice. Overall, about 90-95% of the choroid plexus uptake of GlySar and 5-ALA was mediated by PEPT2, with about 5-10% of the residual uptake occurring by nonspecific mechanisms. CONCLUSIONS: The results demonstrate that PEPT2 is the only transporter responsible for the choroid plexus uptake of GlySar and 5-ALA. They also suggest a role for PEPT2 in the clearance of dipeptides and endogenous peptidomimetics from cerebrospinal fluid.

Aminolevulinic Acid↗
PubMed2004

The role of phosphorus in aluminium-induced citrate and malate exudation from rape (Brassica napus).

Exudation of organic anions is believed to be a common tolerance mechanism for both aluminium toxicity and phosphorus deficiency. Nevertheless, which of these stresses that actually elicit the exudation of organic anions from rape (Brassica napus L) remains unknown, and the combined effects of Al toxicity and P deficiency on rape have not been reported before. Therefore, in the current study, Brassica napus var. Natane nourin plants grown with or without 0.25 mM P were exposed to 0 or 50 micro M AlCl(3) and several parameters related to the exudation of organic anions from the roots were investigated. Eight days of P deficiency resulted in a significant growth reduction, but P deficiency alone did not induce exudation of organic anions. In contrast, Al strongly induced organic acid exudation, while simultaneously inhibiting root growth. Increased in-vitro activity of citrate synthase (CS, EC 4.1.3.7), malate dehydrogenase (MDH, EC 1.1.1.37) and phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31), together with reduced root respiration, indicated that the Al-induced accumulation and subsequent exudation of citrate and malate were associated with both increased biosynthesis and reduced metabolism of citric and malic acid. Phosphorus-sufficient plants showed more pronounced aluminium-induced accumulation and exudation of organic anions than P-deficient plants. A divided root chamber experiment showed the necessity of direct contact between Al and roots to elicit exudation of organic anions. Prolonged exposure (10 days) to Al resulted in a decrease in the net exudation of citrate and malate, and the rate of decrease was much more rapid in P-deficient plants than in P-sufficient plants. It is concluded that P nutrition affects the level of Al-induced synthesis and exudation of organic anions. However, the mechanism needs further investigation.

Journal Article↗
PubMed2004

Carnosine uptake in rat choroid plexus primary cell cultures and choroid plexus whole tissue from PEPT2 null mice.

PEPT2 is functionally active and localized to the apical membrane of rat choroid plexus epithelial cells. However, little is known about the transport mechanisms of endogenous neuropeptides in choroid plexus, and the role of PEPT2 in this process. In the present study, we examined the uptake kinetics of carnosine in rat choroid plexus primary cell cultures and choroid plexus whole tissue from wild-type (PEPT2(+/+)) and null (PEPT2(-/-)) mice. Our results indicate that carnosine is preferentially taken up from the apical as opposed to basolateral membrane of cell monolayers, and that basolateral efflux in limited. Transepithelial flux of carnosine was not distinguishable from that of paracellular diffusion. The apical uptake of carnosine was characterized by a high affinity (K(m) = 34 microM), low capacity (V(max) = 73 pmol/mg protein/min) process, consistent with that of PEPT2. The non-saturable component was small (K(d) = 0.063 microL/mg protein/min) and, under linear conditions, was only 3% of the total uptake. Studies in transgenic mice clearly demonstrated that PEPT2 was responsible for over 90% of carnosine's uptake in choroid plexus whole tissue. These findings elucidate the unique role of PEPT2 in regulating neuropeptide homeostasis at the blood-cerebrospinal fluid interface.

Amino Acids↗
PubMed2004

[Study on apoptosis of lung tissue cells in patients with severe brain injury complicated with aspiration-induced lung injury].

OBJECTIVE: To investigate the role of apoptosis of pulmonary cells in aspiration induced lung injury in patients with severe brain injury with or without aspiration-induced lung injury. METHODS: The Glasgow scale (GCS) of 11 dead patients with severe closed brain injury was 3-8. There 11 cases were divided into aspiration-induced lung injury (AILI) and non-aspiration-induced lung injury (NAILI) groups. The plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) were measured, and the ratio of apoptosis in lung tissue cells was also determined. RESULTS: The plasma levels of TNF-alpha and IL-8 in NAILI and AILI groups were (2.17+/-0.41)nug/L vs. (3.14+/-0.28)nug/L and (0.42+/-0.05)nug/L vs. (0.91+/-0.08) nug/L (P<0.05) respectively. Lung tissue cell apoptosis ratio was significantly higher in AILI group than NAILI group (P<0.01). CONCLUSION: TNF-alpha and IL-8 may induce apoptosis in lung tissues through different signaling pathway. During the early phase of aspiration-induced lung injury complicating severe closed brain injury, apoptosis in cells of lung tissue may play a role in the pathogenes.

Adult↗
PubMed2004

[Early-stage hemodynamic changes in dogs with gunshot wound in seawater].

OBJECTIVE: To investigate the hemodynamic changes in the early stages of gunshot wound of dogs in seawater for exploring early treatment protocol. METHOD: Fourteen conventional Beagles models undergoing gunshot wound in seawater were used along with another 2 dogs receiving the wound on land to serve as control. After the dogs were rescued from the seawater, the respiration (R), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), central venous pressure (CVP), pulmonary arterial wedge pressure (PAWP), and cardiac output (CO) were measured continuously in the early stages of the wound (53.62+/-12.19 min following injury), followed by statistical analysis of the results. RESULTS: Compared with the control group, the hemodynamic disturbance of the dogs receiving the wound in seawater was relatively severe during the first 15 min of the wound. The mortality tended to descend relevant to the position of the wounds, in the order of the head, chest, abdomen and limbs. CONCLUSIONS: Gunshot wound in seawater may cause severe hemodynamic changes, resulting in progressive dysfunction of circulation and high mortality rate. Early treatment should be targeted at hemodynamic stabilization in accordance to the characteristic changes during the early stages of the wound.

Animals↗
PubMed2004

Management of posttraumatic brain swelling based on clinical typing.

OBJECTIVE: To investigate the clinical typing and prophylactico-therapeutic measures for acute posttraumatic brain swelling (BS). METHODS: A retrospective study was performed in 66 cases of acute posttraumatic BS. There were 3 groups based on computered tomography (CT) scanning: 23 cases of hemisphere brain swelling (HBS) with middle line shift for less than 5 mm within 24 hours (Group A), 20 with middle line shift for more than 5 mm (Group B), and 23 with bilateral diffuse brain swelling (Group C). RESULTS: (1) The mortality rates of the operative and nonoperative management in Group A, Group B, and Group C were 20.0%, 31.6%, and 75.0% versus 44.4%, 0, and 85.7%, respectively (P>0.05); while the rates in subgroups with different middle line shift (more than 5 mm and less or equal 5 mm) were 29.2% and 75.0% versus 75.0% and 44.4%, respectively (0.05>P>0.01). (2) The good recovery rate and mortality in Group A were 47.8% and 39.1%, respectively and in Group C, 8.7% and 78.3%, respectively. There was a very significant difference between Group A and Group C (P<0.01). (3) The total survival rate of the selective comprehensive therapy was 53.1%. CONCLUSIONS: (1) Acute posttraumatic BS needs to be diagnosed correctly and promptly with CT scanning within 4 hours. (2) For patients with midline shift for more than 5 mm, especially with thin-layered subdural hematoma, surgical intervention is essential to reduce the fatality of acute posttraumatic BS.

Adult↗
PubMed2004

[Intel random number generator-based true random number generator].

OBJECTIVE: To establish a true random number generator on the basis of certain Intel chips. METHODS: The random numbers were acquired by programming using Microsoft Visual C++ 6.0 via register reading from the random number generator (RNG) unit of an Intel 815 chipset-based computer with Intel Security Driver (ISD). RESULT: We tested the generator with 500 random numbers in NIST FIPS 140-1 and X(2) R-Squared test, and the result showed that the random number it generated satisfied the demand of independence and uniform distribution. We also compared the random numbers generated by Intel RNG-based true random number generator and those from the random number table statistically, by using the same amount of 7500 random numbers in the same value domain, which showed that the SD, SE and CV of Intel RNG-based random number generator were less than those of the random number table. The result of u test of two CVs revealed no significant difference between the two methods. CONCLUSION: Intel RNG-based random number generator can produce high-quality random numbers with good independence and uniform distribution, and solves some problems with random number table in acquisition of the random numbers.

Algorithms↗
PubMed2004

[Comparison of serum biochemical features between SARS and other viral pneumonias].

OBJECTIVE: To identify blood chemistry changes in coronavirus of severe acute respiratory syndrome (SARS). METHODS: Biochemical changes in SARS patients were summarized and compared with other viral pneumonias. Serum total protein (TP), albumin (Alb), total cholesterol (TC), triglyceride (TG), calcium (Ca), ferrum (Fe), lactate dehydrogenase (LDH), creatine kinase (CK), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between SARS and other viral pneumonias were examined by Roche Diagnostics assay, HITACHI7600 automatic analyzer. Clinically confirmed SARS patients, patients with other viral pneumonias, and healthy controls were included in the study. RESULTS: Compared with healthy person, the levels of serum TC, Fe, Ca, Alb were significantly lowered (P<0.05 or P<0.01), while the activity of LDH, CK, ALT, AST were elevated, the increase of CK and the decrease of Fe were the most significant (P<0.05 or P<0.01), the changes of TP and TG were not obvious. In the other viral pneumonias patients, ALT, AST, LDH were elevated slightly than those of healthy person, while Fe, Ca, Alb, TC, CK were a little reduced, but there was no significant difference between the two groups. In convalescent stage, all the tests were returned to normal ranges except ALT, AST were still elevated in SARS patients. CONCLUSION: The changes in serum biochemistry are more marked in SARS patients compared with patients suffering from other viral pneumonias, the decrease of Fe as well as the inhibition of TC may be caused by the treatment of anti-virus.

Adult↗
PubMed2004

[A preliminary report of SARS coronavirus specific RNA in SARS convalescents and medical person].

OBJECTIVE: To observe the method of fluorescent-polymerase chain reaction (F-PCR) and gene-hip technique in detecting coronavirus in severe acute respiratory syndrome (SARS) and its value for clinical application. METHODS: Serum of 60 SARS patients, 20 samples of serum and 20 samples of gargling fluid of medical staff of the "Fever Clinic", and one cDNA specimen obtained from one SARS suspect patient were examined with F-PCR diagnosis kit and gene-chip technique for SARS coronavirus. RESULTS: Three methods, including DR Chip and two F-PCR kit from Zhongshan College Da'an gene stock company and Shanghai Fortune industrial joint-stock Co, Ltd, were used, and the results were all negative for all specimens, except one cDNA specimen, which was obtained from one SARS suspect patient, virus could be amplified by F-PCR. CONCLUSION: Special RNA fragment of SARS virus has not been detected in gargling fluid and serum of SARS convalescents and medical staff.

Adolescent↗
PubMed2004

[Effects of iptakalim on the proliferation of cultured rabbit pulmonary arterial smooth muscle cells induced by endothelin-1].

OBJECTIVE: To explore the effects of iptakalim on the proliferation of rabbit pulmonary arterial smooth muscle cell(PASMC) induced by endothelin-1(ET-1) in vitro. METHODS: The experimental models of proliferation of rabbit PASMC induced by ET-1 in vitro were established and [(3)H]-thymidine ([(3)H]-TdR) incorporation and flow cytometric analysis(FCA) were used. RESULTS: The value of [(3)H]-TdR incorporation in ET-1 group was increased 1.468 times higher than that in control group. Iptakalim at the concentrations of 10(-7) mol/L, 10(-6) mol/L, 10(-5) mol/L lowered [(3)H]-TdR incorporation by (19.8 +/- 4.6)%,(41.2 +/- 9.5)%, (54.7 +/- 10.1)%, declined the total of the DNA synthesis (S) and the mitotic phase (G(2)/M) ratios by (36.6 +/- 5.7)%, (42.6 +/- 4.9)%, (66.3 +/- 4.7)%, and increased the static phase (G(0)/G(1)) ratio by (14.4 +/- 3.0)%, (17.9 +/- 2.6)%, (27.9 +/- 3.2)%, respectively, compared with the value of the cells treated with ET-1 only (P < 0.01). Glibenclimide abolished the effect of iptakalim on [(3)H]-TdR incorporation. CONCLUSION: Iptakalim has an inhibitory effect on PASMC proliferation induced by ET-1 through activating ATP sensitive potassium (K(ATP)) channels.

ATP-Binding Cassette Transporters↗
PubMed2004

Cross-reaction of SARS-CoV antigen with autoantibodies in autoimmune diseases.

To investigate the significance of the SARS-associated coronavirus (SARS-CoV) antibody, detected by ELISA and indirect immunofluorescence assays (IFA) for the SARS-CoV Vero E6 cell lysates, in non-SARS subjects, 114 serum samples from healthy controls and 104 serum specimens from autoimmune disease patients were collected. The results of ELISA showed that among 114 sera from healthy controls, 4 (3.5%) were positive of SARS-CoV-IgG antibody and 114 (100%) were all negative of SARS-CoV-IgM antibody; the specificity of SARS-CoV-IgG antibody for SARS patients was 96.5%, but the specificity of both SARS-CoV-IgG and -IgM antibodies for SARS patients was 100%. In 58 cases with SLE, positive rates of SARS-CoV-IgG and -IgM antibodies were 32.8% (19/58) and 8.6% (5/58), respectively, in which 11 cases (19%) were positive of both SARS-CoV-IgG and -IgM antibodies; in 10 cases with SS, positive rate of both SARS-CoV-IgG and -IgM antibodies was 10% (1/10); in 16 cases with MCTD, positive rate of SARS-CoV-IgG was 37.5% (6/16), positive rate of both SARS-CoV-IgG and -IgM antibodies was 6.3% (1/16); in 20 cases with RA, one case was positive (5%) of SARS-CoV-IgG. However, of all samples with positive SARS-CoV-IgG and -IgM antibodies for autoimmune diseases and healthy controls, SARS-CoV RNA and antibodies were all negative by RT-PCR and IFA. All sera for negative or positive ELISA results were also negative or positive results using ELISA with Vero E6 cells lysates. These studies showed that SARS-CoV Vero E6 cell lysates for the ELISA to detect SARS-CoV antibodies could lead to the false-positive reactions or cross-reactions of SARS-CoV antibodies in non-SARS diseases and healthy controls, and the false-positive reactions or cross-reactions were related to Vero E6 cell lysates and autoantibodies in non-SARS population.

Animals↗
PubMed2003

Mechanisms of cefadroxil uptake in the choroid plexus: studies in wild-type and PEPT2 knockout mice.

The choroid plexus uptake of [(3)H]cefadroxil was studied in peptide transporter 2 (PEPT2) wild-type and null mice as a function of temperature, transport inhibitors, pH, and saturability. At normal pH (7.4) and temperature (37 degrees C), the uptake of 1 microM cefadroxil was reduced by 83% in PEPT2(-/-) mice as compared with PEPT2(+/+) mice (p < 0.001). A further reduction was achieved in null animals by reducing the temperature to 4 degrees C, or by adding saturating concentrations of unlabeled cefadroxil or p-aminohippurate (p < 0.05). Glycylsarcosine coadministration could inhibit the uptake of cefadroxil in PEPT2(+/+) mice (p < 0.01) but not PEPT2(-/-) mice. Although a proton-stimulated uptake of cefadroxil was demonstrated in PEPT2(+/+) mice (pH 6.5 versus pH 7.4; p < 0.01), no pH dependence was observed in PEPT2(-/-) mice. Kinetic parameters for cefadroxil (without p-aminohippurate) in wild-type mice were: V(max) = 5.4 pmol/mg/min, K(m) = 34 microM, and K(d) = 0.0069 microl/mg/min; in the presence of p-aminohippurate, the parameters were: V(max) = 4.1 pmol/mg/min, K(m) = 27 microM, and K(d) = 0.0064 microl/mg/min. In null animals, the kinetic parameters of cefadroxil (without p-aminohippurate) were: V(max) = 2.7 pmol/mg/min, K(m) = 110 microM, and K(d) = 0.0084 microl/mg/min; in the presence of p-aminohippurate, only a K(d) = 0.010 microl/mg/min was observed. Based on kinetic and inhibitor analyses, it was determined that (under linear conditions), 80 to 85% of cefadroxil's uptake in choroid plexus is mediated by PEPT2, 10 to 15% by organic anion transporter(s), and 5% by nonspecific mechanisms. These findings demonstrate that PEPT2 is the primary transporter responsible for cefadroxil uptake in the choroid plexus. Moreover, the data suggest a role for PEPT2 in the clearance of peptidomimetics from cerebrospinal fluid.

Animals↗
PubMed2003

Change in lipid profile and impairment of endothelium-dependent relaxation of blood vessels in rats after bile duct ligation.

Hyperlipidemia, a condition normally observed in cholestatic liver disease, is also a risk factor for the development of atherosclerosis. The relationship between the elevation of lipoproteins in cholestatic liver diseases and atherosclerosis formation has not been elucidated. In this study, we propose that the impairment of endothelium-dependent relaxation (EDR) of blood vessels in cholestatic liver diseases may lead to the development of atherosclerosis. Using bile duct ligation (BDL) in rats as a model, we examined the liver function, serum lipid profile, EDR and morphologic change of the aorta from both sham operated and BDL rats. Significant increases in liver and spleen weights, serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and the bilirubin level were observed in BDL rats. Upon bile duct ligation, the total and low-density lipoprotein cholesterol levels were increased but the high-density lipoprotein cholesterol and triglyceride levels were reduced. Less contractility and lowered response to acetylcholine-induced relaxation were found in aorta segments. In addition, the acetylcholine-induced relaxation was blocked by both L-NAME and 15 mM KCl. Our results suggest that both nitric oxide and endothelium-derived hyperpolarizing factor are important elements for the impairment of the EDR in BDL rats. In addition, a mild atrophy of the media of the aorta was detected in BDL rats. We conclude that the alterations of lipid profile and the mild atrophy of the media may lead to the impairment of EDR in the aorta in BDL rats, and these factors may potentiate the development of atherosclerosis.

Acetylcholine↗
PubMed2003

Transforming growth factor-beta1 downregulation of Smad1 gene expression in rat hepatic stellate cells.

Smads are intracellular signaling molecules of the transforming growth factor-beta (TGF-beta) superfamily that play an important role in the activation of hepatic stellate cells (HSCs) and hepatic fibrosis. Excepting the regulation of Smad7, receptor-regulated Smad gene expression is still unclear. We employed rat HSCs to investigate the expression and regulation of the Smad1 gene, which is a bone morphogenetic protein (BMP) receptor-regulated Smad. We found that the expression and phosphorylation of Smad1 are increased during the activation of HSCs. Moreover, TGF-beta significantly inhibits Smad1 gene expression in HSCs in a time- and dose-dependent manner. Furthermore, although both TGF-beta1 and BMP2 stimulate the activation of HSCs, they have different effects on HSC proliferation. In conclusion, Smad1 expression and phosphorylation are increased during the activation of HSCs and TGF-beta1 significantly inhibits the expression of the Smad1 gene.

Animals↗
PubMed2003

Gene expression and mucosal immune responses after vaginal DNA immunization in mice using a controlled delivery matrix.

IgA antibodies in the vaginal tract are essential as a first defense line against microorganisms that enter the body via mucosal surfaces. Several studies have shown that direct application of DNA to the vaginal mucosal surface can induce secretion of IgA molecules specific to the expressed protein. The major challenge of formulating effective vaccines is to overcome the barriers to DNA administration caused by the estrus cycle and physical environment of the vaginal tract. In this study, we investigated whether controlled delivery of DNA to the vaginal surface would induce long-term IgA antibody production by applying controlled delivery matrices to the vaginal tract. The controlled DNA delivery matrices were composed of poly(ethylene-co-vinyl acetate) (EVAc) and loaded with a model plasmid encoding sperm-specific lactate dehydrogenase C(4) (LDH-C(4)). These EVAc matrices provided a controlled and sustained DNA release to the vaginal mucosal surface. The DNA released from the EVAc disks was functionally active and capable of transfecting vaginal tissues. When inserted into the vaginal tract of mice, the DNA-loaded EVAc matrices triggered the immune system and induced specific IgA to LDH-C(4) in the vaginal secretions. These results demonstrate that the EVAc disks are efficient and convenient vehicles for delivering DNA to the vaginal tract and providing long-term local immunity.

Administration, Intravaginal↗