With the development of natural products, the research activities on the solubilization methods of water-insoluble natural products have been carried out worldwide. Big molecular weight and poor solubility of most natural active ingredients lead to a very poor oral absorption and low bioavailability, which has extremely limited their development in pharmaceutical fields and clinical application. As a result, it is necessary to find out a suitable technique to improve the solubility and enhance the oral bioavailability of insoluble natural drugs. Based on the related references published in these years, this review introduced some new techniques to improve the solubility and bioavailability of natural drugs, including prodrugs, inclusion complex, solid dispersion, cocrystals, osmotic pump, liquisolid compacts, micronization, self-microemulsifying, nanosuspensions, lipsomes, polymeric micelles and so on, and summarized the theory, characteristics, application range, application examples, problems and development direction of each technique.
Administration, Oral ; Biological Availability ; Biological Products ; administration & dosage ; chemistry ; pharmacokinetics ; Chemistry, Pharmaceutical ; methods ; trends ; Solubility ; Technology, Pharmaceutical ; methods ; trends ; Water

Objective To study the relationship between the genetic polymorphisms of carboxylesterase 1 gene (CESI) and the susceptibility to antituberculosis drug-induced hepatotoxicity (ATBDIH).Methods Genetic polymorphisms of CES1 in 473 tuberculosis patients with or without hepatotoxicity (200∶ 273) after antituberculosis chemotherapy were analyzed by PCR-MassArray.Results In4 tags of CES1 single nucleotide polymorphism (SNP),the frequency of the rs1968753 allele had statistical difference between the hepatotoxicity group and the no-hepatotoxicity group ( P =0.0236 ).The characteristics of anti-hepatotoxicity had been shown relationship with rs8192950 ( P =0.044,OR =0.649,95％ CI =0.426-0.989,AC/AA ) and rs1968753 ( P =0.048,OR =0.556,95％ CI =0.311-0.995,GG/AA).The diplotypes with ‘ CGC' haplotype exhibited significant protection against hepatotoxicity at one copy (P=0.048,OR=0.654,95％CI=0.430-0.996).Conclusions The genetic polymorphisms of CESI might have significant association with ATBDIH.SNP rs8192950 AC genotype and rs1968753 GG genotype might be the candidates for risk prediction of ATBDIH.

To evaluate the automated segmentation algorithm for detection of intra - retinal layers to process images obtained from ultra- high resolution optical coherence tomography ( OCT ) . Graph theory and the shortest path search based on dynamic programming were applied to automatically segment the 8 intra - retinal layers. We experimentally verified the accuracy and reliability of the algorithm. The results showed that the intra-retinal layer boundaries between automated and manual segmentations matched well. The algorithm successfully segmented the intra- retinal layers in glaucoma, high myopia, and retinitis pigmentosa patients. The proposed automatic segmentation for intra-retinal layers provides a promising tool for quantitative analysis in clinical diagnosis and treatment.

BackgroundObstruction of aqueous humor out flow pathway or abnormality of the extracellular matrix( ECM ) of trabecular meshwork cells causes high intraocular pressure. The balance of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases(TIMPs) is critical for the metabolism of ECM. Interleukin1α(IL-1α) can influence outflow of aqueous humor by regulating MMPs level. Objective This study was to investigate the effect of interleukin-1α on the expression of MMP-2,MMP-3 and TIMP-I in cultured swine trabecular meshwork cells.Methods Swine sclera with trabecular meshwork tissue was isolated from 20 swine eyes and cultured with explant cultured method. Cultured cells were passaged and third generation cells were identified by fibronectin ( FN ) and laminin ( LN ) staining. After 24 hours of serum starvation, trabecular meshwork cells treated with IL-1α at the concentration of 10 mg/L were regarded as the IL group,and serum-free culture medium used to treat trabecular meshwork cells was regarded as the control group. The expression of MMP-2, MMP-3 and TIMP-1 proteins in trabecular meshwork cells were detected by immunohistochemistry,and the expression of MMP-2 mRNA, MMP-3 mRNA and TIMP-1 mRNA were detected by RT-PCR. The examination results were compared between the two groups. ResultsThe third generation of cells were positive for FN and LM. Compared with the control group, the expression levels of MMP-3 and TIMP-1 proteins(A value) in trabecular meshwork cells were significantly higher in the IL group than the control group(t=-7. 694,t =-5. 199,P＜0. 05) ,but no obvious difference was found in the expression of MMP-2 between the two groups( t=-2. 365, P＞0.05 ). The higher expression levels in MMP-3 mRNA and TIMP-1 mRNA (A value) in trabecular meshwork cells were seen in comparison with the control group (t =-3. 025,t=-1. 921 ,P＜0. 05). However,similar results were found in the expression of MMP-2 mRNA between the two groups(t =- 1. 173, P＞0.05 ). ConclusionsThe overexpression of MMP-3 and TIMP-1 proteins and their mRNA leads to the imbalance of MMP-3/TIMP-1 and promotes the decomposition of ECM in the trabecular meshwork, and therefore increases aqueous outflow.

BACKGROUND:Percutaneous vertebroplasty and kyphoplasty are both effective in the treatment of osteoporotic vertebral compression fractures, but different in the distribution and dispersion of bone cement. ＜br> OBJECTIVE:To analyze the factors affecting the bone cement dispersion within the vertebral body in treatment of osteoporotic vertebral compression fracture with vertebroplasty or kyphoplasty. ＜br> METHODS:A total of 41 patients with osteoporotic vertebral compression fractures were included, and divided into three groups:group A (22 cases receiving high viscosity bone cement vertebroplasty treatment), group B (5 cases receiving high viscosity bone cement kyphoplasty), group C (14 cases receiving low viscosity bone cement vertebroplasty treatment). The groups A and C were divided into subgroups according to bone cement injection volume, time from fracture to operation, preoperative degree of vertebral compression. The distribution and dispersion of bone cement in the vertebra were reconstructed by the CT three-dimensional imaging and volume rendering analysis. ＜br> RESULTS AND CONCLUSION:In the three groups, after operation, relative dispersion area and relative dispersion volume in the vertebrae had no obvious difference, and the bone cement could al diffuse to upper and lower lamina cross the vertebral midline. There was no significant difference in bone cement diffusion coefficient among the three groups. In a certain range, the bone cement injection volume and bone cement dispersion volume was positively correlated. In groups A and C, bone cement diffusion coefficient decreased with the increasing of bone cement injection volume, time from fracture to operation, and the compression degree of the fractured vertebrae, but showed no significant correlation with bone cement viscosity.

Objective To explore the role of tissue inhibitor of metalloproteinase-1(TIMP-1) during renal senescence by using human TIMP-1 transgenic mice.Methods Renal histological changes of wild type mice and transgenic mice at the age of 3,12,24 months were observed by periodic acid-schiff(PAS)staining of paraffin sections.The numbers of F4/80 positive cells were detected by immunofluoreseence.The protein expressions of TIMP-1,TIMP-2,matrix metalloproteinase(MMP)-9,MMP-2,intercellular adhesion molecule-1(ICAM-1),transforming growth factor?1(TGF-?1),collagenⅢand collagenⅣwere detected by Western blot.The activities of gelatinases and TIMP-1 were examined by gelatin zymography and reverse zymography respectively.Results Focal renal fibrosis was found in two genotypes with aging.At the age of 24 months,compared with wild type,in kidneys of transgenic type,the expressions and activities of gelatinases were dowregulated (MMP-2:2.08?0.20 vs.3.39?0.43;MMP-9:4.02?0.82 vs.6.72?1.40,all P＜0.05);the expressions of collagenⅢ,collagenⅣ,ICAM-1,and TGF-?1 were upragulated(0.72+0.11 vs.0.57?0.09;0.84?0.13 vs.0.6?0.11,0.72?0.12 vs.0.53?0.07; 0.69?0.12 vs.0.45?0.09,all P＜0.05),and the numbers of F4/80 positive cells were increased (18.8?4.4 vs.12.7?3.6,P＜0.05)with the upregulated expression and activity of TIMP-1(1.10?0.18 vs.0.62?0.09;50.75?7.25 vs.20.64?3.50,P＜0.05).Conclusions TIMP-1 could promote age-related renal fibrosis through enhancing inflammation reaction by ICAM-1 upregulation.

OBJECTIVETo explore relationship between HBV DNA level and peripheral blood follicular helper T lymphocyte (Tfh) in patients with chronic hepatitis B (CHB) and its significance.

METHODSHBV DNA levels of 179 cases of CHB patients with positive HBV DNA, positive HBeAg and positive human leukocyte antigen(HLA)-A2 were tested with real time fluorescent quantitative PCR. Tfh and HBV specific CTL were tested with flow cytometry. IL-21 was also tested. 179 cases of CHB patients were divided into group A and group B based on HBV DNA levels, 86 cases in group A, HBV DNA levels were 10(4)-10(5) copies/ml, 93 cases in group B, HBV DNA levels were 10(6)-10(7) copies/ml. Above testing indexes of the two groups were compared.

RESULTSHBV DNA levels of group A were (4.85 +/- 0.37) log10 copies/ml, HBV DNA levels of group B were (6.83 +/- 0.31 ) log10 copies/ml, t = 27.31, P < 0. 001; Tfh of group A was (5.96 +/- 1.59)%, higher than that of group B (3.71 +/- 2.15)%, t = 4.92, P < 0.01; IL-21 of group A was (42.61 +/- 15.11)ng/L, higher than that of group B (14.91 +/- 3.15) ng/L, t = 8.62, P < 0.01; HBV specific CTL of group A was (0.36 +/- 0.08)%, higher than that of group B (0.18 +/- 0.06)%, t = 19.99, P < 0.001.

CONCLUSIONSerum HBV DNA level of CHB patients is related to the level of peripheral blood Tfh level: patients with low HBV DNA level have high Tfh level, high IL-21 level and high HBV specific CTL level. Patients with high HBV DNA level have low Tfh level, low IL-21 level and low HBV specific CTL level. The mechanism of baseline HBV DNA level affecting anti-viral therapy may be related to Tfh level.

Adult ; CD4 Lymphocyte Count ; DNA, Viral ; blood ; genetics ; Female ; HLA-A2 Antigen ; immunology ; Hepatitis B virus ; genetics ; isolation & purification ; Hepatitis B, Chronic ; blood ; immunology ; virology ; Humans ; Interleukins ; immunology ; Male ; T-Lymphocytes, Helper-Inducer ; cytology

BACKGROUNDAcute lung injury/acute respiratory distress syndrome presents with not only local inflammation, but also pulmonary coagulopathy which is characterized by an alveolar procoagulant response, anticoagulant inhibition, fibrinolytic supression and fibrin deposition. We thus had hypothesized that if aerosolized unfractionated heparin was inhaled into alveolar spaces, it could block the procoagulant tendency, lessen depletion of coagulation factors, and even influence the inflammatory response. We also assessed the effects of different administration regimens of heparin.

METHODSMale Wistar rats were given inhaled heparin starting 30 minutes before (prophylactic heparin) or 2 hours after (therapeutic heparin) intravenous lipopolysaccharide (LPS) was administered at 6-hour intervals; control groups received inhaled normal saline with or without being exposed to LPS. Thrombin-antithrombin complexes, activated protein C, tissue type and urokinase type plasminogen activators (t-PA/u-PA), plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-α, interleukin-6 in bronchoalveolar lavage, and lung tissue myeloperoxidase activity, and histology score were measured at three time-points. PAI-1/(t-PA + u-PA) was calculated based on the before-mentioned parameters. Statistical analysis was made using one-way analysis of variance (ANOVA) with post hoc test or Student's t test in the case of heterogeneity of variance.

RESULTSAn alveolar procoagulant reaction, depressed fibrinolysis, and inflammatory response occurred in endotoxemia-induced lung injury. Local prophylactic application of heparin attenuated coagulation and early inflammation, promoted fibrinolysis, and reduced the histology score. Therapeutic application of heparin had similar, but weaker effects.

CONCLUSIONSIntrapulmonary application of unfractionated heparin by inhalation might inhibit alveolar procoagulant reaction and the early inflammatory response, promote fibrinolysis, and alleviate pulmonary pathology in endotoxemia-induced lung injury rats. Administration of heparin before LPS challenge was more efficacious.

Acute Lung Injury ; blood ; drug therapy ; Administration, Inhalation ; Animals ; Blood Coagulation ; drug effects ; Endotoxemia ; complications ; Fibrinolysis ; drug effects ; Heparin ; administration & dosage ; Inflammation ; drug therapy ; Lung ; pathology ; Male ; Rats ; Rats, Wistar

BACKGROUND:Vertebroplasty and kyphoplasty can effectively repair osteoporotic vertebral compression fractures, but postoperative change of stress in the fractured vertebrae and adjacent vertebrae can lead to new fractures. OBJECTIVE:To analyze the stress changes of the fractured and adjacent vertebrae with different bone cement injection volume by three-dimensional finite element method. METHODS:One healthy adult male volunteer was selected for lumbar spine CT scan. The acquired images were imported for three-dimensional reconstruction using Mimics. The three-dimensional model was smoothed, polished and denoised by Geomagic software, and then the solid mode was built under Workbench Ansys. The osteoporotic vertebral compression fracture model in L2-L4 segments was established after assignment. Bone cement of 1, 2, 4, 6 mL was injected into the L3 vertebrae respectively and distributed in the middle of the vertebrae as spherical shape. 500 N pre-load was applied on L2 surface with an additional moment of 50 N·m. The lower surface free degree of L4 was restrainted. The L2-L4 forward flexion, extension, right flexion and axial rotation on the right side were stimulated to compare the stress changes of fractured vertebrae and adjacent vertebrae before and after the bone cement injection with different volume. RESULTS AND CONCLUSION:The stresses of fractured and adjacent vertebrae after the bone cement injection were significantly increased; meanwhile, the stresses of fractured and adjacent vertebrae increased with the increase of bone cement injection volume, which may be one of the factors leading to the compression fractures of adjacent vertebrae.

BACKGROUND:Vertebroplasty and kyphoplasty can effectively repair osteoporotic vertebral compression fractures, but bone cement injection can cause the change of stress in the fractured vertebrae and adjacent vertebrae after surgery, leading to new fractures.
OBJECTIVE: To analyze the stress changes of the fractured vertebrae and adjacent vertebrae after vertebroplasty with different elastic modulus bone cement by a three-dimensional finite element method.
METHODS: One healthy adult male volunteer was selected for lumbar spine CT scan. The acquired images were imported for three-dimensional reconstruction using Mimics. The three-dimensional model was smoothed, polished and denoised by Geomagic software, and then the solid mode was built under Workbench Ansys. An osteoporotic vertebral compression fracture model in L2-4 segments was established after assignment. Bone cement (4 mL) with different elastic moduli (8 000, 4 000, 2 000 and 1 000 MPa) injected into the L3 segment distributed in the middle of the vertebrae as spherical shape. 500 N pre-load was applied on the L2 surface with an additional bending moment of 50 N?m. The lower surface free degree of L4 was restrained. The L2-4 forward flexion, posterior extension, right flexion and axial rotation on the right side were stimulated. The stress changes of the fractured vertebrae and the upper and lower adjacent vertebrae before and after bone cement injection with different elastic moduli were compared.
RESULTS AND CONCLUSION:The stress of the fractured vertebrae and adjacent vertebrae were significantly increased compared with that before operation. With the increase of elastic modulus, the stress of the fractured vertebrae increased, but there were no changes in the stress of adjacent vertebrae. These findings indicate that the elastic modulus of bone cement may be a method to reduce new fractures of the fractured and adjacent vertebrae after bone cement injection.