Advances in drug delivery systems using fibrin glue / 中国药学杂志

Fibrin glue or fibrin sealant has been used surgically as sealant for hemostasis for decades. At the same time, due to the biocompatibility of fibrin glue, it has been studied as a hydrogel drug delivery system, applied in clinical practice and biomedical engineering, especially suitable for local drug delivery for anti-tumor, antibiosis, wound healing, nerve regeneration, and bone healing after fracture. In recent years, novel functional vehicles such as liposomes, microspheres, and nanoparticles have been researched for the feasibility of combined use with fibrin glue. Drugs can be directly sent to the positions that need treatment by using fibrin glue as carriers. Additionally it can extend the residence time of drugs at the administration site and reduce administration frequency. The fibrin glue drug delivery system can also decrease blood drug concentration to avoid systemic adverse effects. This review will highlight recent research of fibrin glue as a drug delivery system.

Stent effects on hemodynamics of cerebral aneurysm by non-uniform lattice Boltzmann method / 医用生物力学

Objective To investigate the effects of triangle stents with different rotation angles on hemodynamics of cerebral aneurysms. Methods A non-uniform lattice Boltzmann method (LBM) was adopted to make local refinement on grids near the stent, and a scheme for the curved boundary conditions was used to numerically simulate the stented cerebral aneurysms. The stream plots of flows in the aneurysms, the velocity profiles at the aneurysm orifice and the velocity reduction were obtained and analyzed to evaluate the effects of stents with different rotation angles on treating cerebral aneurysms. Results With respect to velocity reduction, the best treatment effect was achieved in the triangle stent with rotation angle of 180°, while the triangle stent without any rotation caused the smallest velocity reduction. In addition，the dynamic differences were not obvious in triangle stents with different rotation angles at small porosities. Conclusions The non-uniform LBM combined with curved boundary conditions can be used to study hemodynamic characteristics of the cerebral aneurysm accurately, which provides reference for the design of such stent and also offers some guidance for intervention therapy in clinic.

Suppressing SNAP-25 and reversing glial glutamate transporters relieves neuropathic pain in rats by ameliorating imbalanced neurotransmission / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters (inhibitory GABA transporters GAT and excitatory glutamate transporters GT). Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP-25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter (GLT) is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP-25 and GLT as well as GAT is not clearly understood.</p><p><b>METHODS</b>We used the rat chronic constriction injury (CCI) model for research, and degraded SNAP-25 by a single intrathecal administration of BoNT/A. The mechanical (MWT) and thermal withdrawal latency (TWL) were tested. The level of SNAP-25, GLT, and GAT-1 were assayed using RT-PCR and Western blotting.</p><p><b>RESULTS</b>SNAP-25 was suppressed by a single intrathecal administration of 0.01U BoNT/A and the reduction of SNAP- 25 was correlated with the relief of nociceptive responses in CCI rats. MWT and TWL returned to normal from the 5th to 14th day (P < 0.05) after the administration. On the 14th day after surgery, compared to the sham group, the upregulation of SNAP-25 in CCI rats was reversed after BoNT/A treatment (P < 0.05). The decreased GLT was reversed after BoNT/A treatment but increased GAT-1 was not influenced by BoNT/A treatment.</p><p><b>CONCLUSIONS</b>SNAP-25 and GLT play important roles in the development of neuropathic pain, and the mechanism may involve the imbalance of neurotransmission after peripheral nerve injury. Intrathecal administration of BoNT/A reversed the upregulation of SNAP-25 and downregulation of GLT after CCI, but had no significant effect on the expression of GAT-1.</p>

Association of MMP14 gene polymorphisms and osteoporosis in Zhuang men from Baise region of Guangxi / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between membrane type 1 matrix metalloproteinase gene (MT1-MMP, MMP14) polymorphisms and osteoporosis in Zhuang men from Baise region of Guangxi.</p><p><b>METHODS</b>Genotypes of 5 loci (rs1003349, rs3751488, rs2269213, rs2236303 and rs743257) of MMP14 gene in 301 Zhuang men were determined with single base extension methods, and bone mineral density (BMD) at left calcaneus was evaluated with quantitative ultrasound with measured values of broadband ultrasonic attenuation (BUA). The subjects were divided according to BMD into osteoporosis group, osteopenia group and normal bone density group.</p><p><b>RESULTS</b>All selected loci were in Hardy-Weinberg equilibrium (P> 0.05). By multiple linear stepwise regression analysis, polymorphisms of the five loci were not associated with BUA. But a significant higher risk of osteoporosis was found in individuals with MMP14 rs1003349 GT genotype (vs. GG genotype; P<0.05) and rs2236303 CC and CT genotypes (vs. TT genotype; P<0.05). Genetic linkage between rs1003349 and rs2236303 was also discovered (D'= 0.839, r(2) = 0.458, P<0.01). Compared with the normal bone density group, the frequency of a G-T haplotype of rs1003349 and rs2236303 was significantly lower in the osteoporosis group (P<0.05). And the risk of osteoporosis for individuals with G-C and T-C haplotypes was 2.556 (95% CI: 1.029-6.349, P = 0.038) and 5.111 (95% CI: 1.341-19.485, P = 0.011) compared with G-T haplotype.</p><p><b>CONCLUSION</b>Polymorphisms of rs1003349 and rs2236303 loci of MMP14 gene are associated with the susceptibility of osteoporosis in Zhuang men in Guangxi. G-C and T-C haplotypes for loci rs1003349 and rs2236303 may increase the disease risk.</p>

Intrathecal injection of ketamine and clonidine for chronic neuropathic pain model in rats / 中南大学学报(医学版)

OBJECTIVE@#To observe the effect of intrathecal injection of ketamine and clonidine for chronic constriction injury (CCI) in rats.@*METHODS@#Thirty-two SD male rats weighing 220-280 g were anesthetized with intraperitoneal chloral hydrate 300 mg/kg. A catheter was implanted in the subarachnoid space at the lumbal region and CCI rat models were made successfully. On the 4th day after the surgery, the rats were randomly divided into 4 group: a control group,injecting 0.9%NS 20 microL intrathecally; a ketamine group, injecting ketamine 1 mg/kg(20 microL) intrathecally; a clonidine group (CL), injecting clonidine 20 microg/kg (20 microL) intrathecally; a combined ketamine and clonidine group, injecting ketamine 0.5mg/kg and clonidine 10 g/kg (20 microL) intrathecally, once a day for 1 week. BME-410A Plantar Analgesia Tester was used to measured pain threshold before the administration and 30 min after the administration. The rats were killed after the test was finished. And then we detected the nitric oxide synthase (NOS) activity and the NO production in the spinal cord.@*RESULTS@#The combined injection of ketamine (0.5mg/kg)and clonidine(10 g/kg) produced significantly more potent analgesia than the injection of ketamine (1 mg/ kg) or clonidine (20 microg/ kg)alone. The NOS activity and the production of NO in the combined injection group were significantly lower than those of the single injection group (P<0.05). The weight of rats post-administration increased obviously in the 4 groups (P<0.05).@*CONCLUSION@#The combined injection of ketamine and clonidine can produce synergistic ab-irritation without obvious side effects.