A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.
Biological Transport ; Blood-Brain Barrier ; Bornanes ; chemistry ; Cell Line, Tumor ; Dendrimers ; Doxorubicin ; pharmacology ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Folic Acid ; chemistry ; Glioma ; Humans

OBJECTIVETo observe the effects of taurine on hemorheology and oxidative stress of diabetic rats.

METHODS40 rats were divided into control group, diabetes group and treatment group at random. Diabetic model was reproduced by intraperitoneal injection of streptozotocin. After having been treated with taurine for 8 weeks, glycosylated hemoglobin (HbA1c) and the serum contents of glucose, superoxide dismutase(SOD), malondialdehyde (MDA) were measured. The changes of hemorheology in different groups were detected respectively.

RESULTSCompared with control group, the content of glucose, MDA and HbA1c in diabetic rats was increased, the activity of SOD was decreased, the levels of whole blood viscosity and the aggregation index of red blood cells and hematocrit were increased and RBC deformability index was decreased in diabetic rats. Moreover, taurine was able to apparently reduce high blood glucose and HbA1c (P < 0.05), markedly elevated the activity of SOD, lowered the content of MDA (P < 0.01); and taurine also could significantly reduce the levels of whole blood viscosity and the aggregation index of red blood cells and hematocrit in the meanwhile, and increase RBC deformability index (P < 0.05 or P < 0.01).

CONCLUSIONTaurine could enhance the ability of oxidation resistance, improve blood rheology property in diabetic rats, at the same time it could be beneficial to prevent and cure the development of diabetic blood vessel complication.

Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; blood ; Diabetes Mellitus, Type 2 ; blood ; Erythrocyte Deformability ; Glycated Hemoglobin A ; metabolism ; Hemorheology ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism ; Taurine ; pharmacology

The recombinant adenoviruses containing pGH cDNA and pGH cDNA with the first intron under the control of CMV promoter were constructed respectively by homogenous recombination method. The results showed that the recombinant adenoviruses could mediate pGH cDNA expression in CHO cells infected with the recombinant adenoviruses. The expression level of pGH cDNA with the first intron increased by 117% compared with pGH cDNA without intron. This indicate that the first intron of pGH gene have the function of improving the expression of the pGH gene.
Adenoviridae ; genetics ; Animals ; CHO Cells ; Cricetinae ; Cytomegalovirus ; genetics ; Gene Expression ; Genetic Engineering ; Genetic Vectors ; genetics ; Growth Hormone ; genetics ; Introns ; Promoter Regions, Genetic ; Recombinant Fusion Proteins ; genetics ; Swine

The purpose of this study was to investigate the clinical signs and therapy of primary non-Hodgkin's lymphoma of bone (PLB). The clinical symptoms, signs, X-ray features, pathological morphology, immuno-phenotype and treatment of 23 patients with PLB were analyzed retrospectively. The results indicated that the main complains of 23 cases of PLB were local pain and tenderness; the radiographic and CT findings showed invasive in 15 cases, osteolytic in 5 cases, sclerotic in 2 cases and cystiform expansion in 1 cases. Most of histological types were diffuse large B cell lymphoma; there were single bone involvement in 21 cases and multiple involvement in 2 cases; 3 cases had pathologic fracture. In conclusion, PLB usually involved single bone, roentgenography and CT showed erosive and osteolytic bone destruction. The roentgenography and CT are difficult to diagnose PLB, the final diagnosis should be confirmed according to clinical features, pathological findings and immunohistochemistry assay. The immunohistochemistry is helpful to diagnosis and identification of histological type for PLB. The therapeutic procedure for PLB mainly includes local radiotherapy combined with chemotherapy.
Adult ; Aged ; Bone Neoplasms ; diagnosis ; therapy ; Combined Modality Therapy ; Female ; Humans ; Lymphoma, B-Cell ; diagnosis ; therapy ; Lymphoma, Non-Hodgkin ; diagnosis ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

In order to evaluate the efficacy of FLAG protocol (fludarabine, cytosine arabinoside and granulocyte colony-stimulating factor) in treatment of the first time induced non-remission acute myeloid leukemia (AML), 19 patients with first time induced non-remission acute myeloid leukemia were treated with FLAG protocol. The results showed that out of the 19 patients 13 patients obtained complete remission (CR) and the CR rate was 68.4%, 2 patients obtained partial remission (PR) and the PR rate was 10.5%, the overall remission rate was 78.9%. Among the patients in CR 5 patients had been received allogeneic stem cell transplantation, 3 patients from them survived without disease, including 1 patient has survived 26 months and still remains in CR. Main toxicities of this protocol were gastrointestinal side effects, myelosuppression and neutropenia, slight abnormality of liver function and so on. It is concluded that the FLAG protocol should be employed for the the first time induced non-remission patients as early as possible, and provides conditions for the hematopoietic stem cell transplantation.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cytarabine ; adverse effects ; therapeutic use ; Female ; Granulocyte Colony-Stimulating Factor ; adverse effects ; therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Remission Induction ; Vidarabine ; adverse effects ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVEImpulsivity is one of the core symptoms of children with attention deficit hyperactivity disorder (ADHD). In order to understand the neuromechanism of the impulsive behaviors in ADHD children, this study investigated the specific functional areas of the brain by functional MRI.

METHODSThe subjects consisted of 10 ADHD children with impulsivity, 7 ADHD children without impulsivity and 9 normal children. A functional MRI examination was performed when the subjects were instructed to finish GO and STOP tasks with the GO-STOP impulsivity paradigm. The MRI data during the two tasks of GO and STOP were averaged and the corresponding activation regions between groups were compared.

RESULTSThe data from the GO task revealed that the main activation regions of the normal children included frontal pole (superior frontal gyrus, middle frontal gyrus and medial frontal gyrus); the main activation regions of ADHD children without impulsivity were cerebellum (posterior lobe and anterior lobe bouton) and cingulated gyrus; those of ADHD children with impulsivity were medial globus pallidus and insula. The data from the STOP task showed that the main activation regions of normal children included superior frontal gyrus and middle frontal gyrus; those of ADHD children without impulsivity were middle frontal gyrus and cingulate gyrus; those of ADHD children with impulsivity were uncus and putamen. The activation regions of ADHD children with impulsivity were much fewer than the other two groups.

CONCLUSIONSThe behavior of impulsivity-control involves a number of specific functional areas in the cerebral cortex. Compared with normal children, ADHD children without impulsivity have weaker brain function and brain activation, and ADHD children with impulsivity demonstrate much fewer brain activation regions, worse brain function and little awareness of the cerebral cortex.

Adolescent ; Attention Deficit Disorder with Hyperactivity ; physiopathology ; Brain ; physiopathology ; Child ; Humans ; Impulsive Behavior ; physiopathology ; Magnetic Resonance Imaging ; Male

OBJECTIVETo explore the feasibility of IGF2 imprinting system in target gene therapy for tumors.

METHODSThe mouse H19 enhancer, DMD and promoter H19 were amplified by PCR from mouse genomic DNA and then cloned into the plasmid pDC312. The EGFP and DT-A fragments were amplified by PCR and cloned into the recombinant plasmid, and then the shuttle plasmid were transfected into HEK293 cells together with the adenoviral vector Ad5, namely, Ad-EGFP and Ad-DT-A. Adenovirus hexon gene expression was applied to confirm the presence of adenovirus infections. The effect of the IGF2 imprinting system was tested by fluorescence microscopy. RT-PCR and Western blotting after transfection of the recombinant adenoviral vectors into cancer cells were used to show loss of IGF2 imprinting (LOI) and maintenance of IGF2 imprinting (MOI), respectively. The anti-tumor effect was assessed by MTT and flow cytometry after the HCT-8 (LOI). Human breast cancer cell line MCF-7 (MOI) and human normal gastric epithelial GES-1 (MOI) cell line were transfected with Ad-DT-A in vitro. The anti-tumor effect was detected by injecting the Ad-DT-A in nude mice carrying HCT-8 tumors.

RESULTSThe expression of EGFP protein, DT-A mRNA and DT-A protein were seen to be positive only in the HCT-8 tumor cell line. Infection with Ad-DT-A resulted in obviously growth inhibition in HCT-8 cells (75.4 ± 6.4)% compared with that in the control group, and increased the percentage of apoptosis in the HCT-8 cells (20.8 ± 5.9)%. The anti-tumor effect was further confirmed by injecting the recombinant adenoviruses in HCT-8 tumor-bearing nude mice, and the results showed that the Ad-DT-A inhibited the tumor growth, with on inhibition rate of 36.4%.

CONCLUSIONSThe recombinant adenoviruses carrying IGF2 imprinting system and DT-A gene have been successfully constructed, while Ad-DT-A can effectively kill the tumor cells showing loss of IGF2 imprinting. It might play an important role in future target gene therapy against malignant tumors based on loss of IGF2 imprinting.

Adenoviridae ; genetics ; Animals ; Apoptosis ; Breast Neoplasms ; genetics ; pathology ; Colonic Neoplasms ; genetics ; pathology ; therapy ; Diphtheria Toxin ; biosynthesis ; genetics ; Female ; Genetic Therapy ; methods ; Genetic Vectors ; Genomic Imprinting ; Green Fluorescent Proteins ; biosynthesis ; genetics ; Humans ; Insulin-Like Growth Factor II ; genetics ; metabolism ; MCF-7 Cells ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Peptide Fragments ; biosynthesis ; genetics ; Plasmids ; RNA, Messenger ; metabolism ; Random Allocation ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Transfection

The growth inhibitory effects of D-glucosamine hydrochloride (GlcNH(2).HCl), D-glucosamine (GlcNH(2)) and N-acetyl glucosamine (NAG) on human hepatoma SMMC-7721 cells in vitro were investigated. The results showed that GlcNH(2).HCl and GlcNH(2) resulted in a concentration-dependent reduction in hepatoma cell growth as measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. This effect was accompanied by a marked increase in the proportion of S cells as analyzed by flow cytometry. In addition, human hepatoma SMMC-7721 cells treated with GlcNH(2).HCl resulted in the induction of apoptosis as assayed qualitatively by agarose gel electrophoresis. NAG could not inhibit the proliferation of SMMC-7721 cells. GlcNH(2).HCl exhibited antitumor activity against Sarcoma 180 in Kunming mice at dosage of 125-500 mg/kg, dose of 250 mg/kg being the best. GlcNH(2).HCl at dose of 250 mg/kg could enhance significantly the thymus index, and spleen index and could promote T lymphocyte proliferation induced by ConA. The antitumor effect of GlcNH(2).HCl is probably host-mediated and cytocidal.
Animals ; Antineoplastic Agents ; therapeutic use ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA ; metabolism ; DNA Fragmentation ; drug effects ; Glucosamine ; analogs & derivatives ; therapeutic use ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; Male ; Mice ; Sarcoma 180 ; drug therapy

OBJECTIVETo explore the mechanism of occupational medicamentosa-like dermatitis (OMDT) induced by trichloroethylene (TCE) and some immunity indexes in workers occupationally exposed to TCE.

METHODSThe blood samples from 8 cases with medicamentosa-like dermatitis in 1st, 2nd, 3rd, 4th and 5th weeks after admitting to hospital were examined for liver function, immunoglobulin and some complement indexes. Thirty nine workers occupationally exposed to TCE were investigated for urinary TCE and some immuno-complement indexes. The TCE concentrations of air in workplaces were monitored.

RESULTSC3d-CIC and C3 of patients before admission were (92.86 ± 44.80) mg/L and 0.91 ± 0.19 mg/L, respectively. C3d-CIC and C3 of patients before discharge were (52.41 ± 17.75) mg/L and (1.14 ± 0.22) mg/L, respectively. There were significant differences between admission and discharge (P < 0.05). The average TCE concentration in 4 workplaces was (351.96 ± 36.72) mg/m(3), which was higher than the occupational exposure limits (OELs). The number of workers exposed to the TCE concentration-time weighted and TCA in urine over OELs were 28.21% and 56.41% of total subjects, respectively. The serum IgG and CIC levels of patients before discharge were (10.03 ± 1.21) mg/L and 103.50 ± 29.17 mU/L, which were significantly lower than those (17.21 ± 1.85) mg/L and (227.46 ± 111.67) mU/L of patients before admission (P < 0.01).

CONCLUSIONThe type II and III hypersensitivity may be associated with OMDT and the organ injure induced by TCE.

Adolescent ; Adult ; Complement System Proteins ; immunology ; Dermatitis, Occupational ; immunology ; Female ; Humans ; Male ; Occupational Exposure ; Trichloroethylene ; toxicity ; Young Adult

AIMTo investigate the antagonistic effects of the novel compounds on vasoconstriction induced by ET-1 and the effect on the blood pressure of stroke-prone spontaneously hypertensive rats.

METHODSOrgan bath experiment and whole cardiac function experiment were used.

RESULTSThe analogues of o-CPhe-D-Trp-D-Phe(-X)-OH showed good ability against endothelin biological effects. When X was displaced by 3-F, 3-Cl or 4-Cl, the novel compounds inhibit the vascular constriction induced by ET-1 in a concentration-dependent manner, the IC50 +/- L95 were (0.09 +/- 0.05), (0.15 +/- 0.06) or (0.11 +/- 0.03) mumol.L-1 respectively. The blood pressure of stroke-prone spontaneously hypertensive rats was decreased. No significant effect on cardiac function of rats was discovered.

CONCLUSIONThe results demonstrate that among the six kinds of compounds, those with o-CPhe-D-Trp-D-Phe (-X)-OH configuration showed good biological effects.

Animals ; Aorta ; drug effects ; Blood Pressure ; drug effects ; Endothelin Receptor Antagonists ; Endothelins ; pharmacology ; Hypertension ; drug therapy ; physiopathology ; Male ; Molecular Structure ; Peptides ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Rats ; Rats, Inbred SHR ; Rats, Wistar ; Structure-Activity Relationship ; Vasoconstriction ; drug effects