Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and beta-cyclodextrin (beta-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of beta-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s(-1). Then, the synergetic drug delivery systems were prepared with the ratio of 6.74 : 1 (w/w) for beta-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in beta-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, beta-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems approximately lipid microspheres < beta-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and beta-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by beta-CD through hydrogen bonds.
Acetaminophen ; administration & dosage ; chemistry ; Administration, Oral ; Drug Delivery Systems ; Electrical Equipment and Supplies ; Electrochemical Techniques ; instrumentation ; methods ; Hydrogen Bonding ; Kinetics ; Lipids ; chemistry ; Microspheres ; Solubility ; Taste ; drug effects ; beta-Cyclodextrins ; chemistry

OBJECTIVETo investigate the influence of partial deletions in the AZFc region of the Y chromosome on spermatogenesis.

METHODSWe selected 9 sequence tagged sites (sY1258, sY1291, sY254, sY255, sY1201, sY1206, sY1161, sY1197 and sY1191) in the AZFc region of the Y chromosome, with ZFX/ZFY and SRY (sY14) as the interior control. We amplified by multiplex PCR the DNA of 160 patients with azoospermia or severe oligozoospermia that showed no microdeletion of the Y chromosome (the case group) and another 76 males with normal fertility (the control group). For the individuals suspected of DAZ gene deletion, we detected the single nucleotide polymorphism sites (SNPs) in the four copies of the DAZ gene by single nucleotide variation (SNV) analysis to determine the types of DAZ copy deletion.

RESULTSIn the case group, there were 10 cases of gr/gr (sY1291) deletion (6.3%), 14 b2/b3 (sY1191) deletion (8.8%), 1 sY1291,sY1197 deletion (0.6%), 1 b1/b2 deletion (0.6%) and 1 b1/b3 deletion (0.6%), while in the control group, there were 4 cases of gr/gr deletion (5.3%) and 4 b2/b3 deletion (5.3%). SNV analysis showed DAZ1/DAZ2 deletion in all those with gr/gr and those with b1/b3 deletion, DAZ3/DAZ4 deletion in those with b2/b3 deletion, and DAZ-SNV sY587 deletion in 1 case of sY1291, sY1197 deletion, but no DAZ deletion was found in 1 case of b1/b2 deletion.

CONCLUSIONB2/b3 (sY1191) and gr/gr (sY1291) deletions are genomic polymorphisms and quite common in the normal Chinese population; while b1/b2, b1/b3, and sY1291, sY1197 deletions may be high risk factors of dyszoospermia.

Case-Control Studies ; Chromosomes, Human, Y ; Humans ; Male ; Oligospermia ; genetics ; Sequence Deletion ; Spermatogenesis

OBJECTIVETo determine 1, 2, 3, 4, 6-penta-O-galloyl-D-glucose (PGG) in forty four kinds of Chinese traditional medicines by HPLC.

METHODThe PGG was extracted with a solvent consisting of ethanol and water (50:50) in ultrasonic bath at 50-60 degrees C for 1 hour. A Diamonsil C18 column (4.6 mm x 250 mm, 5 microm) was used for the separation and analysis of PGG with a mobile phase consisting of acetonitrile and 2. 5 % acetic acid solution (18:82). The wavelength of detection was at 280 nm, and flow rate was set at 1.0 mL min(-1).

RESULTThe calibration curve for PGG is linear over the range of 1-150 microg mL(-1) (r =0.9994), and PGG was found in seventeen kinds of Chinese traditional medicines, such as gall tree peony bark, red peony root, white peony root, and so on.

CONCLUSIONThe contents of PGG were determined in forty four kinds of Chinese traditional medicines by a rapid and precision HPLC method.

Calibration ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Hydrolyzable Tannins ; analysis ; Sensitivity and Specificity

AIM To observe the curative effects of Modified Buzhong Yiqi Decoction (Codonopsis Radix,Astragali Radix,Atractylodis macrocephalae Rhizoma,ect.) on perioperative period of intertrochanteric fractures in elderly patients with Qi deficiency and blood stasis type.METHODS One hundred and twenty cases of elderly intertrochanteric fractures were randomly divided into treatment group and control group,60 cases in each group.All patients underwent closed fracture reduction and proximal femoral nail anti-rotation (PFNA) fixation.During the perioperative period,the control group only received conventional treatment,while the treatment group received conventional treatment and Modified Buzhong Yiqi Decoction once a day.The levels of interleukin-6 (IL-6),interleukin-10 (IL-10) and tumor necrosis factor (TNF-α) of both groups in preoperative and in the 1st day,the 7th day,the 14th day of postoperative were observed and compared.The complications and the curative effects according to the Harris score also were observed and compared between the two groups.RESULTS In preoperative,there was no significant difference in levels of IL-6,IL-10 and TNF-α between the two groups (P ＞ 0.05).The levels of IL-6 and TNF-α in the 1 st day of postoperative in the control group were significantly higher than those in the treatment group (P ＜0.05,P ＜0.01).And the levels of IL-10 were similar between the two groups (P ＞0.05).In addition,in the 7th day and the 14th day of postoperative,the levels of IL-6,IL-10 and TNF-α in both groups were all decreased,moreover,the descent degree in treatment group was more significant than those in the control group (P ＜ 0.05,P ＜ 0.01).The treatment group had the lower incidence of complications and the higher curative effects than those in the control group,both differences were statistically significant (P ＜0.05).CONCLUSION Modified Buzhong Yiqi Decoction applying to the perioperative period of femoral intertrochanteric fractures in elderly patients with Qi deficiency and blood stasis,can effectively reduce the perioperative inflammatory response,reduce the incidence of postoperative complications,and improve the curative effects.So it has a positive effect on the rehabilitation for the traumatic patients and is worthy of clinical promotion.

The aim is to observe the expression of human factor VIII gene in mice tranduced in vivo and ex vivo. The vector pLNC-FVIII BD was generated by cloning a B-domain-deleted (760aa-1639aa) FVIII cDNA (FVIIIBD cDNA) into retroviral vector pLNCX. 2 x 10(6) of mouse bone marrow stroma cells transduced by LNC-FVIII BD were infused into 4-week-old BALB/c mice by tail-vein injection. pLNC-FVIII BD was conjugated with PAMAM dendrimer to form complex PAMAM-pLNC-FVIII BD, with which C57BL/6J were injected by tail vein (200 micro l contained 15 micro g/mouse) and sacrificed at days 1, 2, 7, 14, 21 and 28, respectively after injection. Tissue such as liver, spleen, lung and kindney were harvested, with which the transcription were detected by means of RT-PCR. In addition, blood was collected to be measured human FVIII Ag, human FVIIIc and anti-FVIII of human inhibitors. The results showed that the highest level of human FVIII in the recipient BALB/c mice was 8.6 +/- 1.44 ng/ml detected on the first day post-injection; anti-FVIII antibodies were detected from the first week post-injection, and then the level of FVIII Ag decreased and cannot be measured on the fourth week. In the C57BL/6J mice physiological level of human FVIII was expressed in plasma at 48 hours after injection and the average human FVIIIc was 0.62 U/ml and the average human FVIII Ag was 115.5 ng/ml, and gradually reduced later. Anti-FVIII of human inhibitors was not revealed all the time. Syngene image scanning demonstrated that the transcription of the human FVIII BD cDNA occurred mainly in spleen and lung, and secondarily in liver and kidney. No side effects of PAMAM-pLNC-FVIII BD were observed in mice tissue by pathological examination at 4 weeks. In conclusion, retrovirus-transduced bone marrow stroma cells effectively produced human FVIII after ex vivo transduction, but the development of anti-FVIII antibodies in recipient mice influenced the expression level. The human FVIII gene can successfully be transduced in vivo through injecting PAMAM-pLNC-FVIII BD cDNA into mice intravenously. There was physiological level expression of human FVIII in plasma at 48 hours after injection and the average human FVIIIc is 0.62 U/ml and the peak in the six mice was 0.89 U/ml, and gradually reduced later.
Animals ; DNA, Complementary ; analysis ; Factor VIII ; genetics ; Genetic Therapy ; Hemophilia A ; therapy ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Transfection

OBJECTIVETo investigate the effect of melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) on the hepatocellular carcinoma cell lines and normal liver cell line in vitro.

METHODSHepatocellular carcinoma cell lines HepG2, SMMC7721, Hep3B, MHCC97L, M6 and normal liver cell line L02 were infected with Ad.mda-7. The gene expression of mda-7/IL-24 in these cell lines was confirmed by RT-PCR and ELISA assay. MTT assay and flow cytometry were used to study tumor cell proliferation and cell cycle in vitro. Hoechst staining and cytometry assay after Annexin-V and PI staining were studied to indicate the apoptosis effect.

RESULTSIt was confirmed by RT-PCR that the exogenous mda-7/IL-24 gene expressed in all of these cells. The mda-7/IL-24 protein product was confirmed by assaying the supernatant with ELISA. MTT and apoptosis test indicated mda-7/IL-24 can induce the hepatocellular carcinoma cell lines growth suppression, apoptosis in vitro but not in normal liver cell line L02, cell cycle test revealed mda-7/IL-24 can block cancer cell lines in G2/M but not in L02.

CONCLUSIONSmda-7/IL-24 selectively induces growth suppression, apoptosis in hepatocellular carcinoma lines but not in normal liver cell in vitro.

Adenoviridae ; genetics ; Apoptosis ; genetics ; physiology ; Carcinoma, Hepatocellular ; genetics ; pathology ; physiopathology ; Cell Cycle ; genetics ; physiology ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Genetic Vectors ; Hepatocytes ; cytology ; Humans ; Interleukins ; genetics ; physiology ; Liver Neoplasms ; genetics ; pathology ; physiopathology ; Transfection

OBJECTIVETo summarize the Chinese experience in pathologic diagnosis of liver biopsies after orthotopic liver transplantation (OLTx).

METHODS1123 post-transplant liver biopsies from 665 OLTx patients from the Shanghai Eastern Hepatobiliary Surgery Hospital, Tianjin First Central Hospital, Guangzhou Sun Yat-sen University and Chongqing Southwest Hospital were retrospectively analyzed. All liver biopsies were stained with hematoxylin and eosin. Immunohistochemical studies for cytomegalovirus, HBsAg, CK19, CD4 and CD8 were also performed in selected examples.

RESULTSIn the involved hospitals, 4 to 12 types of complications were encountered after OLTx. The number of liver biopsies performed for each patient ranged from 1 to 9 (mean = 2.2). The timing of these biopsies varied from the second to the 2877 th post-transplant day. The 5 most common complications were acute cellular rejection (35.6%), ischemic-reperfusion injury (13.4%), biliary stricture (5.6%), drug complication (5.0%) and chronic rejection (4.7%). The 5 earliest complications after OLTx were primary non-function (occurring at day 4.7 +/- 2.1), ischemic-reperfusion injury (occurring at day 14.0 +/- 4.0), acute cellular rejection (occurring at day 32.1 +/- 62.9), hepatic artery thrombosis / stricture (occurring at day 62.9 +/- 74.2) and cytomegalovirus infection (occurring at day 107.7 +/- 93.0).

CONCLUSIONSThis study has evaluated the types, incidence and timing of major complications occurring after OLTx. The most important issue is the distinction between rejection and non-rejection pathology. Thorough understanding of atypical pathologic features of these complications is necessary. The Banff Schema (rejection activity index) for grading liver allograft rejection is useful for monitoring anti-rejection therapy and should be used routinely.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Child ; Child, Preschool ; Cholestasis, Intrahepatic ; pathology ; Female ; Graft Rejection ; pathology ; Hepatic Artery ; pathology ; Humans ; Infant ; Liver Transplantation ; pathology ; Male ; Middle Aged ; Postoperative Complications ; pathology ; Reperfusion Injury ; pathology ; Retrospective Studies ; Thrombosis ; pathology

OBJECTIVETo investigate the mechanism that mda-7/IL-24 selectively kills hepatocellular carcinoma (HCC) HepG2 cells in vitro.

METHODSHCC cell line HepG2 and normal liver cell line L02 were infected with Ad.mda-7. The expression of mda-7/IL-24 was detected by RT-PCR and ELISA, respectively. The apoptotic effects were confirmed by Hoechst staining and flow cytometry assay, respectively. Furthermore, Bcl-2 family proteins, cytochrome C, Smac/DIABLO and caspase-9 were determined by Western blot.

RESULTSThe exogenous mda-7/IL-24 gene was expressed in HepG2 and L02 cells infected with Ad.mda-7. Ad.mda-7 induced apoptosis in HepG2 but not in L02 cells in vitro. The induction of tumor cell apoptosis is correlated with the increasing expression of Bax and decreasing expression of Bcl-2 and Bcl-xL genes, then facilitated the releasing of cytochrome C and Smac/DIABLO from mitochondria to cytoplasm and increasing the expression of caspase-9, eventually, resulted in apoptosis.

CONCLUSIONAd.mda-7 selectively induces growth inhibition and apoptosis in hepatocellular carcinoma HepG2 cells but not in normal L02 hepatocytes in vitro, and the mechanism might involve the decrease of Bcl-2 and Bcl-xL and increase of Bak expression, facilitating the release of cytochrome C and Smac/DIABLO from mitochondria in HCC cells.

Adenoviridae ; genetics ; Apoptosis ; Caspase 9 ; metabolism ; Cytochromes c ; metabolism ; Hep G2 Cells ; Hepatocytes ; cytology ; Humans ; Interleukins ; genetics ; metabolism ; Intracellular Signaling Peptides and Proteins ; metabolism ; Mitochondria ; metabolism ; Mitochondrial Proteins ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Transfection ; bcl-2-Associated X Protein ; metabolism ; bcl-X Protein ; metabolism

The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10-16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (ρ ranging from 0.39-0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (ρ=0.24; P=0.12) or delayed (T3) PHE volume (ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.

AIM: To study the chemical constituents of the whole plant of Lysionotus pauciflorus METHODS: Chromatographic separations on silica gel, Toyopearl HW-40F gel, and MCI gel were used to isolate the compounds. The structures were elucidated on the basis of spectral data. RESULTS: Three compounds were obtained and their structures were identified as 3, 10-dihydroxyacoronene (1), bis(2-butylhexyl)phthalate (2) and 3, 5-dimethoxy-4-hydroxy-trans-stilbene (3). CONCLUSION Compound 1 is a new acorane sesquiterpene, this is the first report of acorane sesquiterpenes from the Lysionotus genus.
Magnoliopsida ; chemistry ; Molecular Structure ; Plant Extracts ; chemistry ; isolation & purification ; Sesquiterpenes ; chemistry ; isolation & purification