Radix Scutellaria is widely applied to the treatment of diabetes mellitus in China. Its main bioactive constituents contain baicalin, wogonoside, oroxyloside, and their aglycones. To investigate the effect of type 2 diabetes mellitus on both pharmacokinetics and tissue distribution of these flavonoid compounds, the six flavonoids in plasma and tissues from the normal and type 2 diabetic rats after oral administration of Radix Scutellaria extract were simultaneously measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The results showed that baicalin, wogonoside, and oroxyloside had higher C and AUC values (P < 0.05) in type 2 diabetic rats than that in normal rats and the tissue-distribution behaviors of the six flavonoid compounds in hearts, livers, spleens, lungs, kidneys, brains, pancreas, fat and muscle of the type 2 diabetic rats showed obviously differences from the normal rats (P < 0.05). In conclusion, the differences in the pharmacokinetics of oroxyloside and tissue distribution of the six flavanoids in Radix Scutellaria extract between diabetic and normal rats were found for the first time. The results from the present study provided a crucial basis for a better understanding of in vivo anti-diabetic mechanism of action of the six flavonoids from Radix Scutellaria.
Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; physiopathology ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Flavonoids ; analysis ; chemistry ; pharmacokinetics ; Male ; Molecular Structure ; Plant Roots ; chemistry ; Rats ; Rats, Wistar ; Reproducibility of Results ; Scutellaria baicalensis ; chemistry ; Tandem Mass Spectrometry ; Tissue Distribution ; physiology

We developed a method that allows us to label nociceptive neurons innervating tooth-pulp in rat trigeminal ganglion neurons using a retrograde fluorescence-tracing method, to record ATP-activated current in freshly isolated fluorescence-labeled neurons and to conduct single cell immunohistochemical staining for P2X1 and P2X3 subunits in the same neuron. Three types of ATP-activated current in these neurons (F, I and S) were recorded. The cells exhibiting the type F current mainly showed positive staining for P2X3, but negative staining for P2X1. The results provide direct and convincing evidence at the level of single native nociceptive neurons for correlation of the characteristics of ATP-activated currents with their composition of P2X1 and P2X3 subunits and cell size. The results also suggest that the P2X3, but not P2X1, is the main subunit that mediates the fast ATP-activated current in nociceptive neurons.
Action Potentials ; physiology ; Adenosine Triphosphate ; metabolism ; Animals ; Dental Pulp ; innervation ; physiology ; Nociceptors ; cytology ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Purinergic P2X1 ; metabolism ; Receptors, Purinergic P2X3 ; metabolism ; Tissue Distribution ; Trigeminal Nerve ; cytology ; metabolism

Smac is a mitochondrial protein that interacts with inhibitor of apoptosis proteins (IAPs). Upon apoptotic stimuli, the Smac is released into the cytoplasm to inhibit the capase-binding activity of IAPs. The low expression of Smac in tissues has been reported existing in various cancers. Smac plays key roles in prognosis and chemoradiotherapy resistance of malignant tumor besides neoplasm genesis and growth. Furthermore, Smac may be a molecular therapeutic target in cancer patients. Overexpression of Smac by transfecting extrinsic Smac gene or Smac mimetic into tumor cell can improve their sensitivity to radiotherapy and chemotherapy, which has great significance to the treatment of tumor. Our review will focus on the roles of Smac in structure, pro-apoptotic mechanism, tissue distribution and cancer treatment.
Humans ; Intracellular Signaling Peptides and Proteins ; chemistry ; metabolism ; physiology ; Mitochondrial Proteins ; chemistry ; metabolism ; physiology ; Neoplasms ; therapy ; Tissue Distribution

Multidrug resistance proteins (MRPs) are members of the C family of a group of proteins named ATP-binding cassette (ABC) transporters. These ABC transporters together form the largest branch of proteins within the human body. The MRP family comprises of 13 members, of which MRP1 to MRP9 are the major transporters indicated to cause multidrug resistance in tumor cells by extruding anticancer drugs out of the cell. They are mainly lipophilic anionic transporters and are reported to transport free or conjugates of glutathione (GSH), glucuronate, or sulphate. In addition, MRP1 to MRP3 can transport neutral organic drugs in free form in the presence of free GSH. Collectively, MRPs can transport drugs that differ structurally and mechanistically, including natural anticancer drugs, nucleoside analogs, antimetabolites, and tyrosine kinase inhibitors. Many of these MRPs transport physiologically important anions such as leukotriene C4, bilirubin glucuronide, and cyclic nucleotides. This review focuses mainly on the physiological functions, cellular resistance characteristics, and probable in vivo role of MRP1 to MRP9.
Antineoplastic Agents ; metabolism ; pharmacology ; Biological Transport ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Glutathione ; metabolism ; Humans ; Leukotriene C4 ; metabolism ; Multidrug Resistance-Associated Proteins ; metabolism ; physiology ; Neoplasms ; drug therapy ; metabolism ; Tissue Distribution

Amyotrophic Lateral Sclerosis ; genetics ; Animals ; Biological Transport, Active ; Bipolar Disorder ; genetics ; Glucose Transporter Type 4 ; metabolism ; Hepacivirus ; physiology ; Humans ; Neoplasm Metastasis ; Neoplasms ; metabolism ; Point Mutation ; Polymorphism, Single Nucleotide ; R-SNARE Proteins ; metabolism ; Tissue Distribution ; Transport Vesicles ; physiology ; Vesicular Transport Proteins ; chemistry ; genetics ; metabolism ; physiology ; Virus Replication

OBJECTIVETo examine the effect of body fat mass and fat distribution on pulmonary ventilatory function among the adult females.

METHODSBased on the multistage cluster sampling principal, we selected 935 healthy adult females with ages of 19-81 years old in Heilongjiang province to conduct the study. Every 10-years old as a age group. Firstly obtain the basic situation through the questionnaire survey, and then measure the height, body weight, waistline, hip circumference, body composition and lung function. FVC, FEV1, PEF, FEF25%, FEF 50%, FEF 75% and MMEF were determined. This study also examined the relationships between percentage body fat (PBF), waist-hip ratio (WHR) and FVC, FEV1, PEF, FEF25%, FEF 50%, FEF 75%, MMEF.

RESULTSPBF of subjects with ages of 19 - 29 years old and over 60 years old were (16.89 ± 5.34)% and (24.39 ± 6.83)%, WHR were 0.77 ± 0.05 and 0.88 ± 0.06, respectively. PBF and WHR tended to increase with age (F = 50.11, P value < 0.01). PBF obesity rates of subjects with ages of 19 - 29 years old and over 60 years old were 3.23% (7/217) and 43.75% (28/64), WHR obesity rates were 19.35% (42/217) and 85.94% (55/64) respectively. PBF obesity rate and WHR obesity rate tended to increase with age (χ(2) = 161.66, P value < 0.01; χ(2) = 159.61, P value < 0.01). PBF obesity groups compared with the normal groups, the former pulmonary ventilation function reduced significantly, of which FEF 50%, FEF 75% and MMEF decreased 2.61%, 19.44%, 10.28%, respectively. WHR obesity groups compared with the normal groups, the former pulmonary ventilation function reduced significantly, of which FEF 50%, FEF 75% and MMEF decreased 7.61%, 23.15%, 12.04%. After adjustment of age, height and body mass index (BMI), PBF was negatively correlated with FVC, FEV1, PEF and FEF25% (r values were -0.14, -0.14, -0.07, -0.07, respectively, all P value s < 0.05); WHR was negatively correlated with FEV1 (r value was -0.07, P value < 0.05) after adjustment of age, height and BMI.

CONCLUSIONPBF augmentation and abdominal obesity among adult females may be the risk factors of pulmonary function impairment.

Adipose Tissue ; Adult ; Aged ; Aged, 80 and over ; Body Fat Distribution ; China ; Female ; Humans ; Lung ; physiology ; Middle Aged ; Pulmonary Ventilation ; Risk Factors ; Sampling Studies ; Surveys and Questionnaires ; Waist-Hip Ratio ; Young Adult

Hydroxycamptothecin (HCPT) loaded PEG modified nanostructured lipid carriers (HCPT-PEG-NLC) and nanostructured lipid carriers (HCPT-NLC) were prepared by melt emulsification and homogenization method. The morphology, particle size and encapsulation efficiency of them were investigated. HCPT concentrations in plasma, heart, liver, spleen, lung, kidney and ovary were determined after iv of HCPT injection, HCPT-PEG-NLC and HCPT-NLC in mice. The targeting indexes of HCPT-PEG-NLC and HCPT-NLC were calculated. The transmission electron microscope imaging showed that HCPT-PEG-NLC and HCPT-NLC exhibited a spherical shape. The particle sizes of them were (88.6 +/- 22.5) and (127.2 +/- 43.4) nm. The encapsulation efficiency were (90.51 +/- 3.29)% and (84.37 +/- 2.81)%, respectively. After iv injection into the tail vein of mice, HCPT plasma concentrations of HCPT-PEG-NLC and HCPT-NLC were higher than that of HCPT injection at each sampling time. They also showed longer elimination time in every tissue. HCPT-NLC accumulated in endothelial system (RES), Re and Ce of it in liver and spleen were significantly higher than HCPT-PEG-NLC. HPCT-PEG-NLC prolonged circulation time and increased bioavailability of HCPT. MRT and AUC0-24 h of it were 19.80 and 17.02 times higher than those of HCPT injection. It also significantly reduced phagocytosis of RES, and showed lung targeting effect (Re and Ce were 14.51 and 41.35). To summarize, HCPT-PEG-NLC could prolong the circulation time of HCPT in vivo, and had the lung targeting effect. It was a promising carrier to increase therapeutic effect of HCPT in treating lung cancer.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; blood ; chemistry ; pharmacokinetics ; Biological Availability ; Camptothecin ; administration & dosage ; analogs & derivatives ; blood ; chemistry ; pharmacokinetics ; Delayed-Action Preparations ; Drug Delivery Systems ; Drug Stability ; Female ; Lipids ; chemistry ; Lung ; metabolism ; Mice ; Mononuclear Phagocyte System ; physiology ; Nanoparticles ; Particle Size ; Phagocytosis ; drug effects ; Polyethylene Glycols ; chemistry ; Tissue Distribution

Xenotransplantation, the transplantation of cells, tissues or organs between individuals of different species, would resolve the current shortage of organs, but rejection remains the major hurdle to successful xenotransplantation. In the present study, we analyzed mixed lymphocyte reactions (MLRs) and used 51Cr release assays in order to identify the proliferation and expansion of mouse CD8+ cytotoxic T lymphocyte cells against PK15, PK15/pIL-18 or PK15/mIL-18 cells. In addition, we identified T cell populations in mouse splenocytes and lymph node cells using two-color flow cytometry. It was found that the CD8+T cells of xenograft recipients proliferated extensively and that the survival rates of populations of PK15/mIL-18 or PK15/pIL-18 cells were higher than untransfected controls. Moreover, CD3+T cells were increased in mice injected with PK15 cells or PK15/pIL-18 cells but PK15/pIL-18 cell numbers were lower in lymph nodes than untransfected controls. CD8+T cells numbers were reduced in the lymph nodes of PK15/pIL-18 injected mice. These results suggest that porcine IL-18 regulates anti-pig cellular rejection in C57BL/6 mice.
Transplantation, Heterologous ; Transplantation ; Transgenes/immunology/physiology ; Transfection ; Tissue Distribution ; T-Lymphocytes/metabolism ; Swine ; RNA, Messenger/metabolism ; Phenotype ; Mice, Inbred C57BL ; Mice ; Lymphocyte Culture Test, Mixed ; Lymphocyte Activation ; Kidney/cytology/*immunology ; Interleukin-18/*genetics/metabolism/physiology ; Immunosuppression/*methods ; Graft Rejection/immunology/*prevention & control ; Genetic Vectors/chemical synthesis ; Female ; Epithelial Cells/*drug effects/*transplantation ; Cytokines/metabolism ; Cells, Cultured ; Animals

AIMTo study the release and cell uptake characteristics of 9-nitrocamptothecin (9-NC) nanostructured lipid carrier system (NLC) in vitro and its tissue distribution characteristics in vivo.

METHODSMouse peritoneal macrophages were used to investigate the uptake of nanoparticles by cells in vitro. The tissue distribution of 9-nitrocamptothecin solution and stealth nanostructured lipid carrier system (S-NLC) was determined after intravenous administration to mice at a single dose of 1.5 mg kg(-1). The release and crystalloid characteristics were also investigated.

RESULTSX-ray diffraction spectrum showed that 9-NC probably was amorphous in S-NLC. The liquid lipid did not change the characteristics of the solid matrix in nanoparticles. The in vitro release and cell uptake characteristics of stealth and non-stealth 9-NC-NLC were investigated, separately. The results showed that the stealth 9-NC-NLC had sustained-release characteristics and could resist the absorption effect of the additional plasmas to a certain extent. In addition, the cell uptake percentage of stealth 9-NC-NLC was much lower than that of the non-stealth ones. The tissues distribution results showed that 9-NC in the S-NLC was mainly found in the lung, liver, pancreas and ovary/uterus, while the quantity of 9-NC was much lower in heart and kidney. The AUQ(0-t), of S-NLC in blood, ovary/uterus, pancreas, liver and lung were higher than that of 9-nitrocamptothecin solution. The weight-average drug targeting efficiency (Te*) of S-NLC in liver and lung were significantly higher than that of 9-nitrocamptothecin solution. The mean residence times (MRT) of S-NLC was 44 h, while that of 9-nitrocamptothecin solution was 8 h. Therefore, S-NLC showed obvious targeting effects on liver and lung.

CONCLUSIONS-NLC with PEG flexible chains has sustained-release characteristics and can prolong its circulation in blood and have good targeting efficiency on liver and lung.

Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; pharmacokinetics ; Camptothecin ; administration & dosage ; analogs & derivatives ; chemistry ; pharmacokinetics ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Female ; Hexoses ; chemistry ; Liver ; metabolism ; Lung ; metabolism ; Macrophages, Peritoneal ; physiology ; Mice ; Nanoparticles ; Particle Size ; Phagocytosis ; Phosphatidylcholines ; chemistry ; Polyethylene Glycols ; chemistry ; Tissue Distribution

Animals ; Atherosclerosis ; etiology ; metabolism ; Gene Expression Regulation ; Humans ; Lipase ; analysis ; genetics ; physiology ; Lipoproteins ; metabolism ; Lipoproteins, HDL ; metabolism ; Lipoproteins, LDL ; metabolism ; Polymorphism, Genetic ; Tissue Distribution