OBJECTIVETo construct multifunctonal nano-delivery system crossing the blood brain barrier (BBB).

METHODSThe magnetic nanoparticles were preprared with O-carboxylmethylated chitosan (O-CMC) and conjugated with a peptide sequence from the human immunodeficiency virus 1-tat protein and transferrin (Tf), and anti-tumor drug methotrexate (MTX), and thus constructed a O-CMC magnetic nanoparticles carrier system conjugating with Tat and Tf (O-MNPs-Tat-Tf) that combines multiple functions including crossing BBB, magnetism, receptor-mediated dual targets and anti-tumor capabilities. The appearance, diameter, and magnetism of MTX-O-MNPs-Tat-Tf carrier system were characterized with transmission electronic microscopy, atomic force microscopy and vibrating samples magnetometer. The cytotoxicity of MTX-loaded O-MNPs-Tat-Tf was investigated with C6 glioma cells. The ability of O-MNPs-Tat-Tf crossing BBB was investigated in rats by single photon emission computed tomography.

RESULTSThe mean particle diameter was 75 nm, along with good anti-tumor property. The multi-functioned carrier system successfully crossed the BBB in rat.

CONCLUSIONThe establishment of MTX-O-MNPs-Tat-Tf carrier model implies a promising future for its application in therapy of cerebral diseases.

Blood-Brain Barrier ; drug effects ; metabolism ; Chitosan ; analogs & derivatives ; chemistry ; Drug Carriers ; Drug Delivery Systems ; Humans ; Magnetics ; Nanoparticles ; Transferrin

This study was performed to evaluate the usefulness of carbohydrate-deficient transferrin (CDT) as a marker of heavy drinking in Korean males. The subjects (143 Korean males) were classified into 2 groups according to the amount of drinking, moderate drinkers (72 individuals) who drank 14 drinks or less per week and heavy drinkers (71 individuals) who drank more than 14 drinks per week. Using %CDT, gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) as clinical markers for heavy drinking, sensitivity, specificity, positive and negative predictive values were investigated. Sensitivities of %CDT, GGT, AST, and ALT were 83.1%, 67.6%, 52.1% and 46.5%, respectively. Specificities were 63.9%, 45.8%, 72.2%, and 54.2%, respectively. Positive predictive values were 69.4%, 55.2%, 64.9%, and 50.0% respectively. Negative predictive values were 79.3%, 58.9%, 60.5%, and 50.6% respectively. The areas under the receiver operating characteristic curve (95% confidence interval) for %CDT, GGT, AST, and ALT were 0.823 (0.755-0.891), 0.578 (0.484-0.673), 0.622 (0.528-0.717), and 0.516 (0.420-0.613), respectively. CDT is considered as the most reliable marker for detecting heavy drinking in Korean males.
Adult ; Alanine Transaminase/blood ; Alcoholism/blood/*diagnosis/ethnology ; *Asian Continental Ancestry Group ; Aspartate Aminotransferases/blood ; Biological Markers/*blood ; Humans ; Korea ; Male ; Middle Aged ; Sensitivity and Specificity ; Transferrin/*analogs & derivatives/analysis ; gamma-Glutamyltransferase/blood

BACKGROUND: Carbohydrate-deficient transferrin (CDT) levels have rarely been determined in an Asian population. We evaluated the analytical performance of a test for measuring CDT levels by using capillary electrophoresis (EP). METHODS: We determined the precision of CDT measurement by using capillary EP and nephelometry and compared the CDT values obtained using both the methods. We included healthy control subjects, abstinent patients with liver disease, and individuals consuming varying amounts of alcohol. RESULTS: The CDT measurement by using capillary EP were correlated well with those CDT measurement by using nephelometry, N Latex CDT assay, Y=0.5706X+1.581, R=0.930. The results obtained from both methods showed good qualitative agreement with each other (kappa coefficient=0.61). Genetic variants of transferrin isoforms were detected in 4.1% of the tested population. Both the CDT and gamma-glutamyl transpeptidase (GGT) levels in the abstinent patients with liver disease were significantly higher than those in healthy abstinent individuals (0.9% vs. 0.5%, 109.5 mg/dL vs. 28.5 mg/dL, respectively), but the difference in CDT values in the 2 groups was less pronounced for the CDT values. Individuals who had a mean daily alcohol intake of more than 60 g/day showed significantly higher CDT levels than those who had a mean daily alcohol intake of less than 60 g/day (1.9% vs. 0.7%, P=0.03). CONCLUSIONS: The CDT test using capillary EP showed good performance, and this method has several advantages such as automation and detection of variant forms. Thus, CDT can be a more useful marker than GGT for monitoring alcohol abstinence, especially in patients with liver disease.
Adolescent ; Adult ; Aged ; Automation ; Electrophoresis, Capillary/*methods ; Female ; Gene Frequency ; Humans ; Liver Diseases, Alcoholic/diagnosis ; Male ; Middle Aged ; Nephelometry and Turbidimetry/methods ; Protein Isoforms/analysis ; ROC Curve ; Republic of Korea ; Transferrin/*analogs & derivatives/analysis ; gamma-Glutamyltransferase/analysis

OBJECTIVETo investigate the relationship between alcohol consumption and risk factors for cardiovascular disease.

METHODSTwo hundreds and twenty six subjects were enrolled in the study and grouped to non-drinkers, mild drinkers, moderate drinkers and heavy drinkers. Serum GGT, hs-CRP, %CDT, HCY, lipoprotein were measured in all groups.

RESULTThere were significantly higher GGT levels with heavy drinkers than those with other groups (P <0.05), and GGT levels were increased with increasing alcohol intake; and there were significantly higher %CDT levels with heavy drinkers compared with those with no-drinkers; there was significant higher hs-CRP levels with heavy drinkers compared with those with mild and moderate drinkers (P<0.05); but in moderate drinkers there was significantly lower hs-CRP levels than non drinkers (P<0.05). Compared with non-drinkers, there were significantly lower LDL-C and TG levels with mild and moderate drinkers. There were no significant differences in CHOL, HDL-C, HCY, WBC, MCV levels among all groups. Heavy drinkers had higher smoking rate and higher prevalence of hypertension (P <0.05).

CONCLUSIONHeavy alcohol consumption results in increasing GGT,%CDT and hs-CRP and may increase cardiovascular disease risk along with other risk factors.Mild to moderate alcohol consumption is associated with lower hs-CRP concentration,which may protect the cardiovascular system through anti-inflammatory mechanism.

Adolescent ; Adult ; Aged ; Alcohol Drinking ; adverse effects ; blood ; Alcoholism ; blood ; C-Reactive Protein ; metabolism ; Cardiovascular Diseases ; epidemiology ; China ; epidemiology ; Humans ; Male ; Middle Aged ; Risk Factors ; Surveys and Questionnaires ; Transferrin ; analogs & derivatives ; metabolism ; Young Adult ; gamma-Glutamyltransferase ; blood

OBJECTIVETo explore the transgenic efficiency of non-viral vector Tf-PEG-PEI and the cell specific silencing effect of plasmid pPSMAe/p-shNS-ploy(A) on prostate cancer cells.

METHODSPolyethyleneimine (PEI) was modified by using polyethylene glycol and transferrin to synthesize the non-viral vector Tf-PEG-PEI. NS-specific plasmids pPSMAe/p-shNS-ploy(A) and Tf-PEG-PEI were used to transfect prostate cancer LNCap and PC-3 cells. The changes of cell morphology, proliferation ability and cell cycle were studied after down-regulating the NS gene level.

RESULTSTf-PEG-PEI was successfully modified. After transfection, the PSMA-expressing LNCaP cells became larger and showed more pseudopodia, having a tendency to differentiate. Their cell proliferation ability was reduced, and the detection of cell cycle showed a decrease of S phase and an increase of G(1) phase after knocking down NS gene. These targets were not changed in non-PSMA-expresing PC-3 cells.

CONCLUSIONSThe non-viral vector Tf-PEG-PEI has a high ability to transfer targeted gene into target cells. The cellular specificity of short-hairpin RNA transcription driven by PSMAe/p is confirmed by silencing NS gene. The use of cell specific promoter may be an effective strategy of gene therapy for prostate cancer.

Antigens, Surface ; genetics ; metabolism ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; GTP-Binding Proteins ; genetics ; metabolism ; Genetic Vectors ; Glutamate Carboxypeptidase II ; genetics ; metabolism ; Humans ; Male ; Nuclear Proteins ; genetics ; metabolism ; Plasmids ; Polyethylene Glycols ; Polyethyleneimine ; analogs & derivatives ; Promoter Regions, Genetic ; Prostatic Neoplasms ; pathology ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Transfection ; Transferrin ; genetics