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Biomedical subjects

B Wang

Publications and source records attributed to B Wang.

At least 415 records · Page 23Linked to original sources

Effects of various kinds of dietary amino acids on the hepatotoxic action of D-galactosamine in rats.

The protective effects of various kinds of dietary amino acids against the hepatotoxic action of D-galactosamine (GalN) were examined. Male Wistar rats fed with 20% casein diets containing 10% or 5% amino acid for one week were injected with GalN (800 mg/kg body weight), and the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, the hepatic glycogen concentration, and the serum glucose-level were examined 20 hours after the injection. In the groups with the 10% amino acid diets, activities of AST, ALT, and LDH in serum of 10% L-glutamine (Gln), 10% L-asparagine (Asn), and 10% L-serine (Ser) groups were significantly lower than those of the control group, and in the groups with the 5% amino acid diets, those activities of 5% L-histidine (His), 5% L-tyrosine (Tyr), 5% L-lysine (Lys), and 5% L-glycine (Gly) groups were also lower than those of the control group. The concentration of liver glycogen of 10% Gln-, 10% Asn-, and 10% Ser- groups and those levels of 5% His-, 5% Tyr-, 5% Lys-, and 5% Gly-groups were also significantly higher than that of the control group. As a result, it was found that some kinds of dietary amino acid such as L-Ser, L-Asn, L-His, L-Lys, L-Tyr, and L-Gly, in addition to L-Gln were effective to protect the rats from GalN-induced injury.

Alanine Transaminase↗

The role of the renin-angiotensin and cardiac sympathetic nervous systems in the development of hypertension and left ventricular hypertrophy in spontaneously hypertensive rats.

To elucidate the relationship between the development of left ventricular hypertrophy (LVH) in hypertension and the development of both the cardiac sympathetic nervous and renin-angiotensin systems, as measured by norepinephrine and angiotensin II levels, respectively. In this longitudinal study, we compared blood pressure (BP), left ventricular weight, and norepinephrine (NE) and angiotensin II (Ang II) concentrations, in Spontaneously Hypertensive Rats (SHR) and age-matched Wistar-Kyoto (WKY) rats at 5, 10, 15, 20, and 28 wk of age. Blood pressure, plasma and ventricular Ang II and tissue NE were measured by the tail-cuff method, radioimmunoassay, and high-performance liquid chromatography (HPLC), respectively. At 5 wk, systolic blood pressure was the same in both strains. But the left ventricular plus septum weight to body weight (LVSW/BW) ratio was higher in SHR than in WKY rats (p < 0.01), which finding may have been related to the increased cardiac tissue NE concentration, and this increase tended to parallel the rise in blood pressure. Both left ventricle and forelimb muscle NE concentrations were significantly higher in SHR than in WKY rats at 5, 10, and 15 wk of age (p < 0.01, respectively), and were similar at 20 and 28 wk of age. The heart and plasma Ang II levels decreased with age, which results were in keeping with the known developmental tendencies of the biological aging progress. There was no significant difference in plasma Ang II levels between the two strains from 5 to 20 wk, whereas these levels were remarkably higher in WKY than in SHR rats at 28 wk (p< 0.01). Otherwise, the left ventricular tissue Ang II concentrations were significantly higher in SHR than in WKY rats at the late stage (from 15 to 28 wk), which may have contributed to the late-stage cardiac hypertrophy. These results suggested that the sympathetic nervous system (SNS) and the renin-angiotensin-system (RAS) in SHR may contribute to the pathogenesis of hypertension and LVH at the early and late stages, respectively.

Animals↗

Prodrug approaches to the improved delivery of peptide drugs.

Undesirable pharmaceutical and biopharmaceutical properties, which include low water solubility, poor stability, and low permeability through biological membrane barriers, often hinder the clinical development of biologically active peptides. Finding solutions to these problems is a contemporary issue in developing clinically the vast number of biologically active peptides as drugs. In recent years, significant progress has been made in developing prodrug approaches for the improvement of the water solubility, stability, and membrane permeability of peptides. For improving water solubility, the focus has been on the bioreversible introduction of ionizable functional groups to peptides, which helps to increase the polarity and thus water solubility of the peptide drugs. For improving stability, efforts have focused on stabilizing peptides against exopeptidase-mediated hydrolysis by bioreversibly masking the terminal carboxyl and/or amino groups. For improving permeability through biological barriers, recent efforts have focused on both improving the lipophilicity of a peptide in order to facilitate its passive permeation through biological membranes and conjugation of a peptide to a carrier which allows for the active transport of the peptide-carrier conjugate. Many of the prodrug systems developed recently have the potential to be used clinically for the delivery of peptide drugs to the desired site of action.

Animals↗

Adaptive response in embryogenesis: II. Retardation of postnatal development of prenatally irradiated mice.

We previously reported that a priming dose of 0.3 Gy on gestation day 11 significantly increased the rate of living fetuses and reduced the incidence of congenital malformations caused by exposure to 5 Gy X rays on gestation day 12 in ICR mice. In the present study, postnatal development of the live offspring was investigated using a set of developmental and behavioral parameters. The offspring of the mice irradiated with 0.3 Gy generally showed a delay in the appearance of most of the physiological markers, impaired acquisition of neonatal reflexes, and alteration of adult behavior. However, an increase in body weight in the females was observed 4 weeks postnatally. In the offspring primed with 0.3 Gy followed by a challenging dose of 5 Gy prenatally, a high postnatal mortality was found, and all the survivors had various radiation-induced detrimental effects. The results indicated that the priming dose was advantageous to survival itself, but was disadvantageous to the health of survivor. The results also suggested that studying the whole animal can show the extent of the effects of radiation, i.e. quality of life, in a way that cellular or molecular studies cannot.

Abnormalities, Radiation-Induced↗

Effects of prenatal low-dose beta radiation from tritiated water on learning and memory in rats and their possible mechanisms.

Pregnant adult Wistar rats were randomly divided into four groups. Three of these groups were irradiated with beta rays by a single intraperitoneal injection of tritiated water ((3)H(2)O) administered on the 13th day of gestation. The doses absorbed by their offspring were estimated to be 4.6, 9.2 and 27.3 cGy. The influence of radiation on the postnatal learning ability and memory behavior and on brain development of the offspring was investigated. The number of pyramidal cells (in areas CA1, CA2, CA3 and CA4) and neurons in the hippocampus of the offspring was also measured. In addition, the Ca(++) conductance of hippocampal pyramidal cells cultured in vitro was observed. The results showed that an exposure to 4.6 cGy could prolong avoidance response time significantly and decrease the number of hippocampal pyramidal cells in the CA1 area compared to controls. An exposure to 9.2 cGy significantly decreased the establishment of conditioned reflexes and the number of hippocampal pyramidal cells in the CA3 area. This exposure also induced the degeneration and malformation of hippocampal neurons cultured in vitro, in addition to decreasing the number of hippocampal neurons observed on each culture day. A dose of 27.3 cGy significantly decreased brain and body weights and the maximum electric conductance of Ca(++) in hippocampal pyramidal neurons. In general, dose-dependent effects were observed for most of the parameters assessed in the present study. Possible mechanisms are discussed.

Animals↗

[Long-term effect of lamivudine treatment in chronic hepatitis B virus infection].

OBJECTIVE: To evaluate the long-term effect of lamivudine on the loss of serum HBV DNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis B patients and its safety profile and tolerance with multi-center, randomized, double blind and placebo controlled trial. METHOD: 429 patients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine and placebo groups. 322 patients received lamivudine 100 mg daily and 107 patients received placebo treatment for 12 weeks. Then, all patients were offered a further 40 weeks of open label lamivudine treatment. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters. RESULTS: After 12 weeks treatment, HBV DNA response (serum HBV DNA < 1.6 ng/L) rate in lamivudine group was higher than in placebo group (92.2% VS 14.1%, P < 0.01); but at week 52, there was no difference between lamivudine and placebo/lamivudine groups (71.0% VS 77.7%, P > 0.05). Rate of HBV DNA breakthrough in lamivudine group was higher than in placebo/lamivudine group (24.4% VS 8.5%, P < 0.01). Proportion of HBeAg/anti-HBe seroconversion had no difference in two groups (7.5% VS 5.2%, P > 0.05). By week 12, ALT normalization rate in lamivudine group was higher than in placebo group (60.3% VS 27.5%, P < 0.01); but after 52 weeks treatment, there was no difference between two groups (70.9% VS 74.5%, P > 0.05). At week 48, HBV YMDD mutation rate in lamivudine group was higher than in placebo/lamivudine group (14.6% VS 5.0%, P < 0.05). The incidence of adverse events was similar for both lamivudine and placebo/lamivudine group up to week 12 and 52. There was few severe drug-related adverse event. CONCLUSION: Sustained HBV replication suppression could be obtained from long-term treatment with lamivudine 100 mg daily accompanied with good tolerance and safety.

Adolescent↗

E-cadherin regulates the function of the EphA2 receptor tyrosine kinase.

EphA2 is a member of the Eph family of receptor tyrosine kinases, which are increasingly understood to play critical roles in disease and development. We report here the regulation of EphA2 by E-cadherin. In nonneoplastic epithelia, EphA2 was tyrosine-phosphorylated and localized to sites of cell-cell contact. These properties required the proper expression and functioning of E-cadherin. In breast cancer cells that lack E-cadherin, the phosphotyrosine content of EphA2 was decreased, and EphA2 was redistributed into membrane ruffles. Expression of E-cadherin in metastatic cells restored a more normal pattern of EphA2 phosphorylation and localization. Activation of EphA2, either by E-cadherin expression or antibody-mediated aggregation, decreased cell-extracellular matrix adhesion and cell growth. Altogether, this demonstrates that EphA2 function is dependent on E-cadherin and suggests that loss of E-cadherin function may alter neoplastic cell growth and adhesion via effects on EphA2.

Breast Neoplasms↗

[Mutation analysis of p16 gene in non-small cell lung carcinomas].

OBJECTIVE: To investigate the role of p16 gene in the tumorigenesis of non-small cell lung carcinomas (NSCLC). METHODS: Homozygous deletion and mutation of exon 2 of p16 genes in 40 NSCLC tissues were analyzed using PCR and dsDNA direct sequencing technique. RESULTS: In 2 NSCLC tissues, homozygous deletions of p16 gene were detected; in 14 NSCLC tissues, 19 point mutations and a frameshift were detected. CONCLUSION: Point mutations of p16 gene were frequent and might play a role in the initiation and progression of NSCLC. Nt380 in this gene was a hot spot of mutation.

Carcinoma, Non-Small-Cell Lung↗

[Comparative genomic hybridization analysis of primary gastric carcinomas].

OBJECTIVE: To investigate whether unknown genes are involved in the tumorigenesis of gastric cancer. METHODS: Fourty-three primary gastric carcinomas were analyzed by comparative genomic hybridization(CGH). RESULTS: A gain in chromosome 3p(8/43), 8q(8/43), 20[20(9/43), 20p(7/43), 20q(4/43)], 12q (16/43), and 13q(12/43) was observed while a loss of 19[19(15/43), 19p (13/43)], 17[17(8/43), 17p(10/43)], 16(10/43) and 1p(11/43) was discovered. CONCLUSION: There were characteristic changes in 3p, 8q, 20, 12q, 13q, 19, 17, 16, and 1p in gastric carcinoma, and some unknown genes located in the above regions might be of importance to gastric carcinoma pathogenesis.

Chromosome Aberrations↗

Inhibitory effect of recombinant TGF alpha-PE40 on vascular smooth muscle cell proliferation.

AIM: To study inhibitory effect of recombinant transforming growth factor alpha-Pseudomonas exotoxin fusion protein (TP40) on proliferation of the cultured vascular smooth muscle cells (SMC). METHODS: Expression of epidermal growth factor receptor (EGFR) mRNA and EGFR in cultured proliferating and quiescent SMC was analyzed with Northern blot and immunohistochemistry. Inhibitory effects of TP40 on SMC proliferation and protein synthesis were analyzed with crystal violet staining and [3H]leucine incorporation. Competition assays were performed by the addition of 100-fold excess of EGF. RESULTS: Expression of EGFR mRNA and EGFR in rapidly proliferating SMC increased than that in quiescent SMC. When the concentration of TP40 was 10 or 100 micrograms.L-1, inhibitory effects of TP40 on rapidly proliferating SMC proliferation and protein synthesis were much higher than that on quiescent SMC (P < 0.01), and the IC50 of [3H]leucine incorporation against rapidly proliferating and quiescent SMC were 8.01 (5.05-12.69) and 121.95 (90.98-163.47) micrograms.L-1. Excess EGF completely blocked inhibitory effects of TP40. CONCLUSION: The rapidly proliferating SMC express EGFR at a high level. TP40 selectively inhibited the proliferation of rapidly proliferating SMC. The cytotoxic effects of TP40 were specifically mediated by EGFR.

Animals↗

[The origin of calcitonin gene-related peptide (CGRP) in burned skin of rats].

OBJECTIVE: To investigate the origin of calcitonin gene related-peptide (CGRP) in skin burn wound. METHODS: Immunohistochemistry technique was used to determine change in distributive density in CGRP-containing nerve fibers in the wound, wound margin, remote intact skin of rats during the first 96 hours postburn. RESULTS: It was shown that the distributive density of CGRP-containing nerve fibers in all areas decreased at 15 min postburn, but the density recovered earlier in wound margins compared to other sites. In addition, CGRP immunoreactive positive cells, which emigrated from blood vessel in dermis underneath the wound and wound margin, were related to CGRP-containing nerve fibers at 12 hours. Stronger staining intensity to CGRP was observed in those cells and they disintegrated and released CGRP immunoreactive materials into the dermis at 24 hours. Thereafter, those cells disappeared. CONCLUSION: CGRP not only is released from cutaneous nerve, but also is synthesized and released by immune cells in response to burns.

Animals↗

Inhibitory effects of 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate (TMB-8) on intracellular Ca2+ elevated by neurotransmitters in brain cells.

AIM: To study the effects of TMB-8 on [Ca2+]i elevation induced by neurotransmitters in dissociated brain cells. METHODS: The brain cell suspension was made using a gentle trituration for 1 min with a polished pipette. The changes of [Ca2+]i were detected by the fluorescent indicator, Fura 2-AM. RESULTS: In the presence of extracellular Ca2+ 1.3 mmol.L-1, sodium glutamate (Glu), histamine (His), and serotonin (5-HT) markedly increased the [Ca2+]i which were reduced by TMB-8 30 mumol.L-1. TMB-8 3 mumol.L-1 produced inhibitory effects on the increase of [Ca2+]i by His and 5-HT in a Ca(2+)-free Hanks' solution. The increase of [Ca2+]i by His and 5-HT was reduced to control level by TMB-8 10 mumol.L-1. CONCLUSION: TMB-8 inhibited the [Ca2+]i elevation induced by Glu, 5-HT, and His in brain cells.

Animals↗

[The effect of chlamydia trachomatis infection in pregnant women on pregnant outcome and neonates].

OBJECTIVE: To determine the prevalence of chlamydia trachomatis (CT) in pregnant women and its effect on pregnant outcome and neonate. METHODS: Specimen of cervical swab were collected and detected for CT by polymerase chain reaction (PCR) method meanwhile relevant factors were investigated. Pregnant outcome and neonatal situation were also followed up. RESULTS: The infection rates of CT in pregnant women were 35.90%. The Incidence of abnormal pregnant outcome (premature delivery and abortion) was significantly higher in CT positive groups (24.72%) than that in negative groups (12.20%) (P < 0.05). Incidence of neonatal conjunctivitis and pneumonia were significantly higher in CT positive groups (17.98%) than that of negative groups (0.61%) (P < 0.01). There was statistically significant difference in the prevalence of low birth weight (< 2,500 g) between the two groups (13.48% versus 4.88%) (P < 0.05), and mode of delivery also had influence on neonatal morbidity. CONCLUSION: Prevalence of CT infection in pregnant women is rather common, and it may cause adverse pregnancy outcome.

Abortion, Spontaneous↗

[Cloning of rat beta-defensin rBD-1 cDNA].

This is a study aimed at the molecular mechanisms of beta-defensins gene expression and it's gene transfer experiments for preventing mucosal infection. A rat rBD-1 cDNA was cloned. The total RNA was isolated from rat kidney. The cDNA fragment was amplified by RT-PCR with specific primers. The purified RT-PCR product was cloned in pGEM-T Easy vector. The results of restriction endonuclease pattern analysis of the recombinant plasmid, DNA sequencing, and aligning of the putative amino acid sequence with hBD-1 and mBD-1 demonstrated that rat beta-defensin rBD-1 gene was cloned successfully.

Amino Acid Sequence↗

[The establishment of a modified lateral fluid percussion model of brain injury in rat and the pertinent pathologic changes].

For the purpose of studying the molecular mechanism of the traumatic brain injury, we have established a reproducible graded lateral fluid percussion model of experimental brain injury in the rat with a modified fluid percussion device. The device consists of a stainless steel cylindrical reservoir instead of the plexiglass reservoir, a steel reservoir filled with compressed gas instead of the pendulum for making more accurate percussion pressure, an apparatus for releasing the pressure immediately after the percussion, and a computer for recording and storing the percussion data. Pathologic examination demonstrated subdural hemorrhage, subarachnoid hemorrhage, and hemorrhage in the lateral ventricle and corpus callosum on the percussion side. The severity of pathologic changes increased with the magnitude of percussion. The results indicate that the new device could inflict reproducible graded lateral fluid percussion brain injury on rats and the model can be used for the studies of neuropathologic and molecular mechanism of brain injury.

Animals↗

[The changes of calcitonin gene-related peptide (CGRP)-containing nerve fibers in adrenal gland of burned rats].

OBJECTIVE: To investigate the changes in calcitonin gene-related peptide(CGRP) within the adrenal glands medulla and cortex of the rat during early post burn period and the effect of CGRP on function of adrenal gland of burned rats. METHODS: The rats were randomly divided into two groups: control and burned. The distribution density of CGRP containing nerve fibers and cells in medulla of adrenal gland were determined at different timepoints post burn. RESULTS: 1. The CGRP-containing nerve fibers were distributed in capsule, cortex and medulla. CGRP-containing nerve fibers were associated with CGRP immunoreactive cell in medulla of adrenal glands. 2. Distribution density of CGRP-containing nerve fiber was decreased, but distribution density of CGRP-containing cells in medulla increased. CONCLUSION: CGRP may affect function of the adrenal gland of burned rats.

Adrenal Cortex↗

A randomized double-blind placebo-controlled study of lamivudine in the treatment of patients with chronic hepatitis B virus infection.

OBJECTIVE: To evaluate the effect of lamivudine on the loss of serum hepatitis B virus (HBV) DNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis B patients and its safety profile and tolerance compared with placebo. METHODS: Four hundred and twenty-nine patients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine and placebo groups. Three hundred and twenty-two patients received lamivudine 100 mg daily and 107 patients received placebo treatment for 12 weeks. Then, all patients were offered a further 9-month open label lamivudine treatment. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters. RESULTS: During the 12-week treatment period, 92.2% of lamivudine treated patients became HBV DNA negative (below 1.6 pg/ml) compared with only 14.1% of those receiving placebo (P < 0.01). At the end of 12 week, the sustained negative rate for HBV DNA in the lamivudine treated group was 78.5% compared with the placebo group (11.1%; P < 0.01). There was a trend to a high proportion of patients treated with lamivudine to lose HBeAg (8.1%) and develop antiHBe (10.2%) than treated with placebo (5.3% and 6.4% respectively), but this difference was not statistically significant. Patients with elevated ALT levels at baseline became normal in 60. 3% of the lamivudine treated group compared with the placebo group where only 27.5% were normal (P < 0.01). Lamivudine was well tolerated in a dose of (100 mg daily) and the overall incidence of adverse events was similar to that of the placebo. CONCLUSIONS: Lamivudine (100 mg daily) is very effective in the inhibition of HBV replication, indicated by the rapid loss of serum HBV DNA, and often accompanied by a decrease of serum ALT levels. Lamivudine is well tolerated without severe adverse events during treatment.

Adolescent↗