OBJECTIVETo investigate the dosage-efficacy/toxicity relationship of prepared rhubarb, in order to explore the bidirectional effects in hepatoprotection and hepatotoxicity of prepared rhubarb and the objective authenticity for attenuating toxicity by processing.

METHODNormal and pathological animals were adopted simultaneous to investigate the effect of total extracts from prepared rhubarb within a high dose range (2.0, 5.4, 14.7, 40.0 g x kg(-1) x d(-1)) on normal state, biochemical index and histopathology of experimental animals. The factor analytic approach was used to analyze the dosage-efficacy/toxicity relationship of prepared rhubarb.

RESULTThe factor analytic approach was used to extract two common factors from the nine biochemical indexes. The firs common factor was mainly dominated by HA, LN and TGF-β1, and could be explained as fibrotic factors. The second common factor was mainly dominated by ALT, AST and ALP, and could be explained as cellular factor. The results of the factor analysis suggested that prepared rhubarb showed significant bidirectional effects in hepatoprotection and hepatotoxicity, which could protect liver in CC14 injured chronic hepatic injury, but had a certain hepatotoxic effect to normal animals. The pathological examination showed consistent results with the factor analysis. Under comparable dosages, prepared rhubarb showed a stronger liver protecting effect than crude rhubarb, with a lower toxicity.

CONCLUSIONAlthough prepared rhubarb has a certain hepatotoxic effect to normal animals, it has also a significant therapeutic effect to animals with liver injury. The results proved the symptom-based prescription theory and the scientificity of the symptom-based medication. The symptom-based prescription theory is important to correctly realize the dosage-efficacy/toxicity relationship of traditional Chinese medicines and guide the symptom-based medication.

Animals ; Dose-Response Relationship, Drug ; Drug Prescriptions ; Drugs, Chinese Herbal ; pharmacology ; toxicity ; Female ; Fibrosis ; Liver ; drug effects ; metabolism ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry ; Toxicity Tests

Diabetic ulcer is recognized as a chronic nonhealing wound, often associated with bacterial infection and tissue necrosis, which seriously affect patients' health and quality of life. The traditional treatment methods exist some problems, such as bacterial resistance and secondary trauma, so it is urgent to find new methods to meet the requirements of diabetic ulcer treatment. In this study, we prepared a drug delivery system (DFO@CuS nanoparticles) based on hollow copper sulfide (CuS) nanoparticles loaded with deferoxamine (DFO), which realized the synergistic therapy of promoting angiogenesis and photothermal antibacterial. The morphological structure and particle size distribution of DFO@CuS nanoparticles were characterized by transmission electron microscopy and particle size analyzer, respectively. The antibacterial effect of DFO@CuS nanoparticles was evaluated by the plate coating method. The effects of DFO@CuS nanoparticles on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8 (cell counting kit-8) assay, cell scratch assay, and tube formation assay. The results showed that DFO@CuS nanoparticles were hollow and spherical in shape with an average particle size of (200.9 ± 8.6) nm. DFO@CuS nanoparticles could effectively inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) under near-infrared (NIR) light irradiation. DFO@CuS nanoparticles showed negligible cytotoxicity and effective acceleration of cell migration and tube formation in a certain concentration range. In conclusion, the prepared DFO@CuS nanoparticles exhibit good photothermal antibacterial properties and pro-angiogenic effects, providing a basis for their application in the treatment of diabetic ulcer.

AIM: To analyze the effect of pigment epithelium derived factor (PEDF) on nitrogen monoxide (NO) and expression of cysteine-containing, aspartate-specific proteases-3 (caspase-3) in retinal tissues of model rats with optic nerve crush injury.METHODS: A total of 60 SD rats were randomly divided into the blank control group, model group and PEDF group, with 20 rats in each group.Except the blank control group, the optic nerve crush injury rat models were established in the other groups, and left eyeballs were taken as samples.After successfully modeling, the model group were treated with intravitreal injection of 5μL of balanced salt solution while PEDF group were treated with intravitreal injection of 5μL of PEDF (0.2μg/μL).Two weeks later, the retinal tissues were collected, and changes of shape were observed under microscope after HE staining.The changes of NO level were measured by colorimetry assay, the expression of caspase-3 mRNA and caspase-3 protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western-blot.RESULTS: HE staining showed that retinal tissues of the blank control group arranged neatly and clearly.Retinal ganglion cells (RGCs) arranged in a monolayer, and cells were oval, uniform in size and distribution, the cell nuclei were clear, closely arranged, with clear boundaries.The retinal tissues of the model group were sparse in shape, RGCs showed vacuolar changes, the overall number of cells was reduced, and cell nuclei of residual RGCs showed pyknosis and uneven staining.RGCs in PEDF group were with slightly edema and arranged closely, and the degree of injury was significantly milder than that in the model group.Levels of Caspase-3 mRNA and protein and NO levels in the three groups showed the model group > PEDF group > blank control group (all P < 0.05).CONCLUSION: The application of PEDF can down regulate the expression of Caspase-3 and NO in rates with optic nerve injury and reduce RGCs injury.

Humans ; Membrane Glycoproteins ; immunology ; SARS Virus ; immunology ; Severe Acute Respiratory Syndrome ; prevention & control ; Spike Glycoprotein, Coronavirus ; Vaccines, DNA ; immunology ; Vaccines, Inactivated ; immunology ; Vaccines, Synthetic ; immunology ; Viral Envelope Proteins ; immunology ; Viral Vaccines ; immunology ; Virion ; immunology

Objective To understand non-typhoid Salmonella in diarrhea patients from Guangdong province in order to timely discover the outbreaks caused by them as well as to grasp the serotypes, antibiotic resistance and pulse-field gel electrophoresis (PFGE) types of those strains isolated from this surveillance program. Methods Salmonella strains from diarrhea patients were detected and all the positive strains were tested by serum agglutination, antibiotic susceptibility and PFGE. Results 71 nontyphoid Salmonella strains were isolated from 1128 stoop samples, with a positive rate of 6.29 %. All the strains were divided into 29 serotypes, with Salmonella serotype enteritidis and typhimurium showing the most common serotypes. Most of the strains were sensitive to cephalosporins and quinolones. The antibiotic resistance rates of S. typhimurium were higher than S. enteritidis and S. stanley. Other than S. enteritidis, all the serotype strains did not have the same type of PFGE. 17 S. enteritidis strains digested by Xba Ⅰ were divided to 8 PFGE types while the PFGE 4 type appeared the most common one. 12 S. enteritidis strains were typed again by Sfi Ⅰ and Not Ⅰ , and there were still 3 groups of strains showing the same PFGE pattern. Conclusion Most of the infection caused by non-typhoidal Salmonella was sporadic in Guangdong province in 2007. Cephalosporins and quinolones seemed the best in curing the infection of non-typhoidal Salmonella at the clinics.

Objective The aim of our study was to investigate the influence of hexavalent chromium exposure on mRNA expression of cell cycle related genes in electroplating workers, and to provide population data for investigating the toxic mechanisms of hexavalent chromium. Methods A total of 155 cases of workers occupationally exposed to hexavalent chromium were selected, including 89 males and 66 females, and the average age of workers was 39.65±8.856 years old. Questionnaire was used to collect essential information of workers. Peripheral blood was collected from electroplating workers. The inductively couple plasma mass spectrometry (ICP-MAS) was used to measure total blood chromium content. The workers were divided into four groups according to the blood chromium content. After extracting total RNA from whole blood and reverse transcription, the mRNA expression levels of p16 and CDK6 genes were detected by real-time quantitative PCR. Meanwhile, the levels of blood chromium (BCr) and the mRNA expression of p16 and CDK6 genes were compared among four groups. The impact of BCr, smoking habits, drinking habits, gender on the mRNA expression of CDK6 gene was analyzed. Results The levels of BCr in group 1 to 4 were 0.04ppb, 0.47±0.29 ppb, 2.76±1.16 ppb, 9.36 ±4.38 ppb, respectively, and the difference between every two groups was significant (P<0.05) . The median of p16 gene expression in four groups was 4.22, 7.19, 7.47, and 14.60, respectively, and the difference between every two groups was not significant (P>0.05) . The mRNA expression levels of CDK6 gene in groups 2 to 4 were 15.05, 8.03 and 24.81, respectively, which were significantly higher than that in group 1 (P<0.05) . The results of logistic regression showed that the level of Bcr was the main influence factor, while smoking habits, drinking habits and gender had no obvious impact on the mRNA expression of CDK6 gene. Conclusions Long-term exposure of hexavalent chromium led to higher mRNA expression of CDK6 gene, and it may serve as a biomarker for workers occupationally exposed to hexavalent chromium.

Objective To discuss the relationship between the level of ghrelin and leptin of patients with gastric carcinoma and the hypoalbu-minemia of advanced gastric carcinoma , and its significance of clinical pathology as well.Methods Radioimmunoassay ( RIA ) and enzyme linked immunosorbent assay (ELISA) were used to determine the changes of the ghrelin and leptin level in 20 cases of normal healthy people and 120 patients with gastric cancer ( including 37 cases of hypoalbuminemia ( albumin<35 g· L-1 ) and 88 cases of normal protein people ( albumin≥35 g· L-1 ) , their expressions and the relevance of clinical pathology parameters were also detected.Results The ghrelin and leptin levels of patients with gastric carcinoma were significantly higher than those of nor-mal group (P<0.01), and the ghrelin and leptin levels of patients with the hypoalbuminemia were obviously higher than those of health subjects with normal protein.In addition, in patients with high content of ghrelin and leptin , the rate of patients with poorly differentiated carcinoma and lymph node metastasis was obviously increased.Conclusion The detec-tion of the changes of ghrelin and leptin levels will be of great significance in the diagnosis and prognosis of gastric carcinoma , which provides theoretical basis for the diagnosis and treatment of cancerous hypoalbuminemia .

OBJECTIVETo investigate the steroid 21-hydroxylase gene (CYP21) mutations in families with 21-hydroxylase deficiency (21-OHD).

METHODSThe CYP21 gene mutations were detected in four patients with 21-hydroxylase deficiency and their relatives. The genomic DNA of the patients was isolated from whole blood.Two pairs of primers were used to amplify the CYP21 gene. The amplified PCR products were purified by agarose gel and then directly sequenced.

RESULTSSix kinds of mutations were found. In the first family, the patient was a compound heterozygote carrying four different mutations (cluster E6, Q318X, A391T, P459H) onCYP21 gene, three mutations (cluster E6, Q318X, A391T) were on her maternal allele, a novel mutation was found:P459H. It located at codon 459 in exon 10 and changing a proline (CCC) to a histidine (CAC), and A391T was a rare mutation. In the second family, two kinds of mutations were found:cluster E6 and R483W. R483W was also a rare mutation. In the third family, the sequencing of the CYP21 gene of two patients revealed a homozygous T to A transition in codon 172 leading to substitution of isoleucine by asparagine (I172N).

CONCLUSIONSix kinds of mutations were found in three families with 21-hydroxylase deficiency. Using DNA sequencing we have identified a novel mutation (P459H) and two rare mutations (A391T, R483W) of the CYP21 gene. Although microconversion events are the main cause of mutations in the CYP21 gene, random mutations can also be the cause of 21-hydroxylase deficiency.

Adrenal Hyperplasia, Congenital ; genetics ; Amino Acid Substitution ; Exons ; genetics ; Female ; Humans ; Multigene Family ; Mutation ; Polymerase Chain Reaction ; Steroid 21-Hydroxylase ; genetics

OBJECTIVETo investigate the chemical constituents of the rhizome of Ervatamia hainanensis.

METHODThe solvent extraction and silica column chromatography were used to separate the chemical constituents, and their structures were identified by physico chemical properties and spectra analysis.

RESULTTwelve compounds were isolated and their structures were identified as voacangine (1), ibogaine (2), ibogamine (3), coronaridine (4), 19-heyneanine (5), 19-epi-heyneanine (6), 3-hydroxyl coronaridine (7), coronaridine hydroxyindolenine (8), 3-(2-oxopropyl) coronaridine (9), vobasine (10), alpha-amyrin (11), alpha-amyrin acetate (12).

CONCLUSIONCompounds 1, 2, 6, 11 and 12 were first found from this plant.

Apocynaceae ; chemistry ; Chromatography, Gel ; Ibogaine ; analogs & derivatives ; chemistry ; isolation & purification ; Oleanolic Acid ; analogs & derivatives ; chemistry ; isolation & purification ; Plants, Medicinal ; chemistry ; Rhizome ; chemistry

BACKGROUNDBecause of the pivotal role of the human leukocyte antigen (HLA) class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin.

METHODSRadioallergosorbent test was used to examine 8 kinds of specific IgE antibodies (4 major and 4 minor antigenic determinants) in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some (113 patients and 87 healthy control subjects) were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction.

RESULTSCompared with control subjects, a significantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria (P = 0.011; P = 0.019; P = 0.005 respectively). Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group (P = 0.024; P = 0.038; P = 0.038). A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not (chi(2) = 5.134, P = 0.023), and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl (PVA, chi(2) = 4.057, P = 0.044).

CONCLUSIONHLA-DRB gene may be involved in allergy to penicillins through modulating specific serum IgE to penicillins.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Child ; Child, Preschool ; Drug Hypersensitivity ; genetics ; immunology ; Female ; Genotype ; HLA-DR Antigens ; genetics ; Humans ; Immunoglobulin E ; blood ; Male ; Middle Aged ; Penicillins ; adverse effects ; immunology