表面睫状体透热治疗绝对期青光眼

本文报告了22例各种类型的绝对期青光眼经表面睫状体透热治疗,平均随访3.5年,不用任何药物,13例获得满意眼压控制,2例眼压降低50％、症状消退,有效率68％。并介绍了手术方法及并发症。本术式简便易行、并发症少,为治疗各种类型的绝对期青光眼之可取的手术方式     

Structure,function, and regulation of renal organic anion transporters

Renal elimination of anionic drugs, xenobiotics, and toxins is necessary for the survival of mammalian species. This process is mediated by vectorial transport from blood to urine through the cooperative functions of specific transporters in the basolateral and apical membranes of the proximal tubule epithelium. The first step of this process is the extraction of organic anions from the peritubular blood plasma into proximal tubule cells largely through the organic anion transporter (OAT) pathway. Therefore, the OAT pathway is one of the major sites for body drug clearance/detoxification. As a result, it is also the site for drug-drug interaction and drug-induced nephrotoxicity. To maximize therapeutic efficacy and minimize toxicity, the structure-function relationships of OATs and their regulation must be defined. The recent cloning and identification of OATs have paved the way for such investigations. This review summarizes the available data on the general properties of OATs, focusing in particular on the recent progress made from the author's laboratory as well as from other's, on the molecular characterization of the structure-function relationships of OATs and their regulatory mechanisms.     

A sulfonamide based glucose-responsive hydrogel with covalently immobilized glucose oxidase and catalase.

A new glucose-sensitive hydrogel, based on sulfonamide chemistry with covalently conjugated glucose oxidase and catalase, was synthesized and tested. The pH-induced full swelling transition of the gel occurred in the range of pH 6.5 approximately 7.5. In a glucose concentration range of 0-300 mg/dl in an isotonic phosphate buffered saline solution (pH 7.4), the pH inside the gel varied from pH 7.4 to 7.2. At the same glucose concentration range, the gel showed reversible glucose dependent swelling without hysteresis from 12 to 8, expressed in water (g)/polymer (g).     

Adriamycin loaded pullulan acetate/sulfonamide conjugate nanoparticles responding to tumor pH: pH-dependent cell interaction, internalization and cytotoxicity in vitro.

The cytotoxicity of adriamycin (ADR)-loaded and pH-sensitive nanoparticles made of pullulan acetate (PA) and sulfonamide (sulfadimethoxine; SDM) (PA/SDM) conjugate to a breast tumor cell line (MCF-7) was investigated to test the feasibility of the nanoparticles in targeting acidic tumor extracellular pH (pH(e)). At pH 6.8, ADR loaded PA/SDM nanoparticles showed cytotoxicity in the cell culture experiment, comparable to that of free ADR at the same ADR concentrations, while the relative cytotoxicity at pH 7.4 was low at the tested concentration range. This pronounced cytotoxicity of the nanoparticles at low pH was attributed to the accelerated release of ADR triggered by pH, enhanced interaction with cells, and internalization. At pH 6.8 and 6.4, the PA/SDM nanoparticles aggressively bounded to MCF-7 cells, probably due to interactions of the cells with hydrophobized nanoparticle surfaces caused by SDM deionization. A confocal laser microscopic study revealed intracellular localization of the drug-loaded nanoparticles. Based on these findings, the pH-sensitive nanoparticles deserve further investigation with an in vivo animal model as a targeted carrier of pH(e).     

Poly( -histidine)–PEG block copolymer micelles and pH-induced destabilization

Poly(L-histidine)-poly(ethylene glycol) diblock copolymers (polyHis-b-PEG) were prepared and used for the construction of polymeric micelles responding to local pH changes in the body. PolyHis was synthesized by ring opening polymerization of L-histidine N-carboxyanhydride, the imidazole amine group of which was protected by the dinitrophenyl group. The resulting polymer (M(n): 5,000 g/mole) was coupled to poly(ethylene glycol) (M(n): 2,000 g/mole) via an amide linkage using the dicyclohexyl carbodiimide and N-hydroxysuccinimide-mediated reaction. The block copolymer in dimethyl sulfoxide formed polymeric micelles on diafiltration against a borate buffer at pH 8. Dynamic light scattering and atomic force microscopy showed the micelles were spherical, diameter approximately 114 nm, with a unimodal distribution. The critical micelle concentration (CMC) at pH 8.0 was 2.3 mg/l. The CMC increased markedly on decreasing the pH of the diafiltration medium below 7.2. Micelles prepared at pH 8.0 were gradually destabilized below pH 7.4, as evidenced by a slight increase in light transmittance, an alteration in size distribution, and a decrease in the pyrene fluorescence intensity. It was concluded that the ionization of the polyHis block forming the micelle core determined the pH-dependent CMC and stability. After further optimization of the pH-sensitivity, pH-sensitive micelles are expected to have application for solid tumor treatment, exploiting the fact that most solid tumors have an acidic extracellular pH.     

Polymeric gene carrier for insulin secreting cells: poly(L-lysine)-g-sulfonylurea for receptor mediated transfection.

Ex vivo transfer of therapeutic genes to cells is one of the potential strategies to prolong the life span of cell transplants. However, relatively safe non-viral carriers have not been extensively investigated due to their lower transfection efficiency. In this study, poly(L-lysine)-g-sulfonylurea varying SU content (PLL-SU) was synthesized to promote gene delivery efficacy to an insulin secreting cell line, RINm5F, which is known to express sulfonylurea receptor (SUR). The polymer formed complexes with a model reporter gene of pCMV-Luc (DNA) and the size of resulting particles was around 100 nm. The transfection efficiency of a polymer synthesized with 5 mol% of SU in the reaction feed (PLL-SU5%) to RINm5F cell was at least 5 times higher than that of PLL. The cytotoxicity of PLL-SU5%/DNA complex was equivalent to that of PLL/DNA complex. PLL-SU5% showed less transfection efficiency than PLL to NIH3T3 and HepG2 cells which are SUR negative. In RINm5F cells, the addition of free SU decreased the transfection efficiency of PLL-SU5%/DNA complex, suggesting that the complex shares the same receptors for SU. The PLL-SU5%/DNA complex seems to be internalized via SUR-mediated endocytosis pathway as suggested by vacuolar ATPases inhibition by Bafilomycin A1. It is noted that RINm5F cells treated with PLL-SU5%/DNA complex secreted more insulin than control, untreated cells, suggesting the insulinotropic effect of SU in PLL-SU5%. In conclusion, PLL-SU may be useful for transfer of therapeutic genes into insulin secreting cells.     

Characteristics of regional bone quality in cervical vertebrae considering BMD: Determining a safe trajectory for cervical pedicle screw fixation

This study aimed to report the mechanical strength and characteristics of the lateral mass and pedicle considering BMD for the safe insertion of pedicle screws in the subaxial cervical level. We evaluated BMD and Hounsfield unit (HU) values of cortical bones at the lateral mass and pedicle of C3‐7 from CT images in 99 patients. Patients were divided into three groups (Group A, T‐score ≥ ?1; Group B, ?2.5 < T‐score < ?1.0; Group C, T‐score ≤ ?2.5). The HU numbers of cortical bone in the vertebral canal (medial wall of the lateral mass; cHU), posterior wall of the transverse foramen (fHU), and medial wall, lateral wall, and trabecular area of the pedicle (mHU, lHU, and pHU, respectively) were measured on the CT images in the middle of the pedicle. A mechanical study was also performed to measure cortical bone strength using 10 fresh cadavers. The cHU and mHU values in Group C were higher than lHU and fHU in Groups A and B, and there was a wide gap between the pHU value and other areas. The penetrating force also had a close correlation with HU number. The mean penetrating force of the medial wall of the lateral mass and the posterior wall of the transverse foramen were 210.08 ± 110.46 and 50.51 ± 46.09 N, respectively. The cortical bones in the vertebral canal and medial wall of the pedicle were stronger than the lateral wall and the trabecular area. The cHU and mHU in the osteoporotic group were higher than fHU and pHU in the normal group. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:217–223, 2018.

     

Increased Complications for Schizophrenia and Bipolar Disorder Patients Undergoing Total Joint Arthroplasty

Background

Although it has been shown that anxiety and depression are associated with increased complications after total joint arthroplasty (TJA), the outcomes of TJA in patients with a history of psychosis are unknown. This study evaluated the influence of bipolar and schizophrenic disorders on complications after TJA, particularly aseptic and septic revisions.

Modulation of the nuclear factor kappa B pathway by Shp-2 tyrosine phosphatase in mediating the induction of interleukin (IL)-6 by IL-1 or tumor necrosis factor

Shp-2, a src homology (SH)2-containing phosphotyrosine phosphatase, appears to be involved in cytoplasmic signaling downstream of a variety of cell surface receptors, although the mechanism is unclear. Here, we have determined a role of Shp-2 in the cytokine circuit for inflammatory and immune responses. Production of interleukin (IL)-6 in response to IL-1 alpha or tumor necrosis factor (TNF)-alpha was nearly abolished in homozygous mutant (Shp-2(-/)-) fibroblast cells. The targeted Shp-2 mutation has no significant effect on the activation of the three types of mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase (Erk), c-Jun NH(2)-terminal kinase (Jnk), and p38, by IL-1/TNF, indicating that Shp-2 does not work through MAP kinase pathways in mediating IL-1/TNF-induced IL-6 synthesis. In contrast, IL-1/TNF-stimulated nuclear factor (NF)-kappa B DNA binding activity and inhibitor of kappa B (I kappa B) phosphorylation was dramatically decreased in Shp-2(-/)- cells, while the expression and activity of NF-kappa B-inducing kinase (NIK), Akt, and I kappa B kinase (IKK) were not changed. Reintroduction of a wild-type Shp-2 protein into Shp-2(-/)- cells rescued NF-kappa B activation and IL-6 production in response to IL-1/TNF stimulation. Furthermore, Shp-2 tyrosine phosphatase was detected in complexes with IKK as well as with IL-1 receptor. Thus, this SH2-containing enzyme is an important cytoplasmic factor required for efficient NF-kappa B activation. These results elucidate a novel mechanism of Shp-2 in cytokine signaling by specifically modulating the NF-kappa B pathway in a MAP kinase-independent fashion.