茶碱和双丁酰-cAMP对巨噬细胞水解酶影响的细胞化学观察

本文通过细胞体外培养,细胞化学定量分析等方法,观察了茶碱和双丁酰-cAMP对C_(57)BL/6J小鼠腹腔巨噬细胞酸性磷酸酶、α-醋酸萘酚酯酶的作用和影响.卡介苗活化的巨噬细胞与固有巨噬细胞相比,其酸性磷酸酶、α-醋酸萘酚酯酶活性明显升高.卡介苗活化的巨噬细胞在茶碱或双丁酰-cAMP作用下。酸性磷酸酶、α-醋酸萘酚酯酶活性明显受到抑制.茶碱或双丁酰-cAMP对固有巨噬细胞的酸性磷酸酶、α-醋酸萘酚酯酶无抑制作用.     

Ascorbic acid (vitamin C) modulates the mutagenic effects produced by an alkylating agent in vivo

Recent reports suggest that ascorbic acid (vitamin C) inhibits tumorigenesis as well as exerts a protective effect against mutagenesis in vitro; however, there is no information on its ability to affect gene mutations induced in vivo. In this study, we have investigated the antimutagenic effects of ascorbic acid on the frequency of 6-thioguanine-resistant (6-TGr) T-lymphocytes produced in Fischer 344 rats dosed with the direct-acting alkylating agent, N-ethyl-N-nitrosourea (ENU). The freqeuncy of 6-TG^r T-lymphocytes from the spleen measured five weeks after ENU treatment indicated that ENU produced a substantial mutagenic response. Pretreatment and/or post-treatment of rats with ascorbic acid administered in the drinking water appeared to inhibit the response, but the inhibition was statistically significant only when data from the various dosing schedules were pooled. In addition, there was no clear dose-dependency to the inhibitory effect of ascorbic acid. To further evaluate the time effects of the vitamin supplement on ENU mutagenicity, rats were exposed to the mutagen together with ascorbic acid, which was given continuously for the entire duration of the experiment. At specific times after ENU treatment, the frequency of 6-TG^r T-cells was determined in lymphocytes isolated from the spleen and the thymus. Time-dependent increases in the frequency of 6-TG^r T-cells were observed with ENU treatment; ascorbic acid significantly reduced the ENU-mediated mutagenic responses, most dramatically in the spleen at weeks 6 and 8 (P < 0.0001), and to a lesser extent in the thymus (P < 0.01 at week 6 and P < 0.006 at week 8). Our data suggest that ascorbic acid intake affects the in vivo mutagenicity of ENU, a direct-acting mutagen/carcinogen, and that the reported inhibitory effects of the antioxidant on carcinogenesis may be partially mediated by its effects on mutagenesis. Although it is difficult to extrapolate from rodent studies to humans, the results presented suggest an explanation for epidemiological data that link vitamin C ingestion with decreased cancer risk. © 1994 Wiley-Liss, Inc.     

Synaptic potentials and effects of amino acid antagonists in the auditory cortex

Neurons of in vitro guinea pig and rat auditory cortex receive a complex synaptic pattern of afferent information. As many as four synaptic responses to a single-stimulus pulse to the gray or white matter can occur; an early-EPSP followed, sequentially, by an early-IPSP, late-EPSP, and late-IPSP. Paired pulse stimulation and pharmacological studies show that the early-IPSP can modify information transmission that occurs by way of the early-EPSP. Each of these four synaptic responses differed in estimated reversal potential, and each was differentially sensitive to antagonism by pharmacological agents. DNQX (6,7-dinitroquinoxaline-2,3-dione), a quisqualate/kainate receptor antagonist, blocked the early-EPSP, and the late-EPSP was blocked by the NMDA receptor antagonist APV (D-2-amino-5-phosphonovalerate). The early-IPSP was blocked by the GABA-a receptor antagonist bicuculline, and the late-IPSP by the GABA-b receptor antagonists 2-OH saclofen or phaclofen. Presentation of stimulus trains, even at relatively low intensities, could produce a long-lasting APV-sensitive membrane depolarization. Also discussed is the possible role of these synaptic potentials in auditory cortical function and plasticity.     

Fusidic acid viscous eyedrops – an evaluation of pharmacodynamics, pharmacokinetics and clinical use for UK optometrists

Recent changes in UK law have allowed UK-based optometrists to sell and supply fusidic acid viscous eyedrops, providing it is in the course of their professional activity and in an emergency. Alternatively, the optometrist may access fusidic acid viscous eyedrops, for a named patient, using a written order supplied to a pharmacy. This review provides details of the legal background to these changes, examines the common causes of a bacterial conjunctivitis, examines the mechanism of action of this narrow spectrum antibiotic as a bacteriostatic agent, reviews the susceptibility of common ocular isolates of bacteria to the drug and presents details of the expected pharmacokinetics of the viscous eyedrops. From this perspective, a systematic review is provided of the clinical studies which have investigated the use of fusidic acid viscous eyedrops and their outcome. The indicated use is generally for the treatment of bacterial conjunctivitis and/or blepharoconjunctivitis, especially that caused by Staphylococcus, but not Streptococcus or Haemophilus sp. (more likely associated with concurrent nasopharyngeal infections). The usual regimen for use is twice daily for 5-10 days, depending on severity, and can initially be used more intensively (four times per day). It may also be used for the management of corneal and conjunctival abrasions and foreign body injuries, or some cases of chronic blepharitis.     

NGF对小脑皮质细胞凋亡影响的实验研究

目的　探讨神经生长因子 (NGF)对小脑皮质神经细胞凋亡的影响 ,为临床治疗小脑变性疾病提供新的措施。方法　以原代培养的新生SD乳鼠小脑皮质细胞建立谷氨酸诱导的神经细胞凋亡模型。为观察NGF对受损细胞的保护作用 ,应用MTT法测定细胞的存活率和细胞代谢情况 ;利用光学显微镜技术观察细胞凋亡的形态学改变。结果　Glu (5 0 0 μmol/L)作用 5min可诱导小脑神经细胞凋亡。MTT法计数结果显示 ,NGF高剂量治疗组细胞存活率显著高于模型组 (P <0 0 1) ,光学显微镜观察发现受损细胞的形态学变化也得到明显改善。结论　外源性NGF能够减轻大鼠小脑皮质神经细胞凋亡。     

Plasma Concentrations of Mycophenolic Acid Acyl Glucuronide Are Not Associated with Diarrhea in Renal Transplant Recipients

The aim of this study was to determine whether plasma concentrations of the acyl (AcMPAG) and phenolic (MPAG) glucuronide metabolites of mycophenolic acid (MPA) were related to diarrhoea in renal transplant patients on mycophenolate mofetil (MMF) with cyclosporine (CsA) or tacrolimus (TCL). Blood samples (0, 30, 120 min) were taken at days 3, 10, week 4, months 3, 6 and 12 for determination of MPA, MPAG and AcMPAG. MPA-AUC was estimated using validated algorithms. Two hour AUCs were calculated for MPAG and AcMPAG. Immunosuppressive therapy consisted of CsA/MMF (n= 110) and of TCL/MMF (n= 180). In 70/290 (24%) patients 86 episodes of diarrhoea were recorded during 12 months. Significantly more patients on TCL (31.1%) suffered from diarrhea compared to CsA (12.7%). MMF dose, MPA-AUC and the 2 h AUCs of MPAG and AcMPAG did not differ between patients with and without diarrhoea. Plasma AcMPAG and MPAG concentrations were substantially higher in patients on CsA compared with TCL, while MPA-AUC was lower in the former group. These data support the concept that CsA inhibits the biliary excretion of MPAG and AcMPAG, thereby potentially reducing the risk of intestinal injury through enterohepatic recycling of MPA and its metabolites.     

Engineering angiogenesis following spinal cord injury: a coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood–spinal cord barrier

Angiogenesis precedes recovery following spinal cord injury and its extent correlates with neural regeneration, suggesting that angiogenesis may play a role in repair. An important precondition for studying the role of angiogenesis is the ability to induce it in a controlled manner. Previously, we showed that a coculture of endothelial cells (ECs) and neural progenitor cells (NPCs) promoted the formation of stable tubes in vitro and stable, functional vascular networks in vivo in a subcutaneous model. We sought to test whether a similar coculture would lead to the formation of stable functional vessels in the spinal cord following injury. We created microvascular networks in a biodegradable two-component implant system and tested the ability of the coculture or controls (lesion control, implant alone, implant + ECs or implant + NPCs) to promote angiogenesis in a rat hemisection model of spinal cord injury. The coculture implant led to a fourfold increase in functional vessels compared with the lesion control, implant alone or implant + NPCs groups and a twofold increase in functional vessels over the implant + ECs group. Furthermore, half of the vessels in the coculture implant exhibited positive staining for the endothelial barrier antigen, a marker for the formation of the blood–spinal cord barrier. No other groups have shown positive staining for the blood–spinal cord barrier in the injury epicenter. This work provides a novel method to induce angiogenesis following spinal cord injury and a foundation for studying its role in repair.     

Mefenamic acid-induced bilateral transient myopia, secondary angle closure glaucoma and choroidal detachment

Drug-induced secondary angle closure is quite common and in the majority of cases simply stopping the medication leads to rapid reversal of the condition and resolution of glaucoma. We describe here a patient who presented with secondary angle closure glaucoma and myopia following mefenamic acid ingestion which was managed successfully by stopping the medication, symptomatic treatment and reassurance.     

Review of long-term adverse effects associated with the use of chemically-modified animal and nonanimal source hyaluronic acid dermal fillers

Although only recently introduced, chemically-modified hyaluronic acid dermal fillers have gained widespread acceptance as “redefining” dermal fillers in the fields of dermatology and cosmetic facial surgery. Although hyaluronic acid-based dermal fillers have a low overall incidence of long term side effects, occasional adverse outcomes, ranging from chronic lymphoplasmacytic inflammatory reactions to classic foreign body-type granulomatous reactions have been documented. These long-term adverse events are reviewed.