Objectives To assess the effects of alpha-glucosidase inhibitors in patients with type 2 diabetes mellitus. Method We searched The Cochrane Library, MEDLINE, EMBASE, Current Contents, LILACS, databases of ongoing trials, reference lists of reviews on the topic of alpha-glucosidase inhibitors and we contacted experts and manufacturers for additional trials. Date of most recent search: December 2003 (Current Contents) and April 2003 (other databases). Randomised controlled trials of at least 12 weeks duration comparing alpha-glucosidase inhibitor monotherapy in patients with type 2 diabetes with any other intervention and that included at least one of the following outcomes: mortality, morbidity, quality of life, glycemic control, lipids, insulin levels, body weight, adverse events. Two reviewers read all abstracts, assessed quality and extracted data independently. Discrepancies were resolved by consensus or by the judgement of a third reviewer. A statistician checked all extracted data entrance in the database. We attempted to contact all authors for data clarification. Results We included 41 trials (8130 participants), 30 investigated acarbose, seven miglitol, one trial voglibose and three trials compared different alpha-glucosidase inhibitors. Study duration was 24 weeks in most cases and only two studies lasted amply longer than one year. We found only few data on mortality, morbidity and quality of life. Acarbose had a clear effect on glycemic control compared to placebo: glycated haemoglobin –0.77% (95% confidence interval –0.90 to –0.64), fasting blood glucose –1.1 mmol/L (95% confidence interval –1.4 to –0.9), post-load blood glucose –2.32 mmol/L (95% confidence interval –2.73 to –1.92). The effect on glycated haemoglobin by acarbose was not dose-dependent. We found a decreasing effect on post-load insulin and no clinically relevant effects on lipids or body weight. Adverse effects were mostly of gastro-intestinal origin and dose dependent. Compared to sulphonylurea, acarbose decreased fasting and post-load insulin levels by –24.8 pmol/L (95% confidence interval –43.3 to –6.3) and –133.2 pmol/L (95% confidence interval –184.5 to –81.8) respectively and acarbose caused more adverse effects. Conclusions It remains unclear whether alpha-glucosidase inhibitors influence mortality or morbidity in patients with type 2 diabetes. Conversely, they have a significant effect on glycemic control and insulin levels, but no statistically significant effect on lipids and body weight. These effects are less sure when alpha-glucosidase inhibitors are used for a longer duration. Acarbose dosages higher than 50 mg TID offer no additional effect on glycated haemoglobin but more adverse effects instead. Compared to sulphonylurea, alpha-glucosidase inhibitors lower fasting and post-load insulin levels and have an inferior profile regarding glycemic control and adverse effects.
Ras homolog family (Rho)/ Rho-associated coiled-coil kinase (ROCK) signaling pathway widely exists in human and mammal cells, which is closely related to inhibition of repair after optic nerve damage. The expression level of Rho/ROCK signaling pathway-related proteins is up-regulated in glaucoma, and related with the death of retinal ganglionic cell (RGC) and the axon activity. ROCK inhibitors can protect the surviving RGC and promote axon extension with a dose-dependent manner. ROCK inhibitors also can inhibit glial scar formation, lower intraocular pressure and inhibit inflammatory response to some degrees. Rho/ROCK signaling pathway correlates with the optic nerve disease progression, and ROCK inhibitors hope to become a new therapeutic drug.
Objective To investigate the effects of celecoxib-poly lactide-co-glycolide microparticles (CEL-PLGA-MS) on rat retina after intravitreal injection. Methods A total of 32 male Brown Norway rats were randomly divided into CEL-PLGA-MS group and celecoxib group, 16 rats in each group. The rats in CEL-PLGA-MS group were divided into four dosage group, four rats in each group, which received intravitreal injection of PLGA with celecoxib at the concentration of 40, 80, 160, 320 mu;mol/L, respectively. The rats in celecoxib group were divided into four dosage group, four rats in each group, which received intravitreal injection of celecoxib at the concentration of 40, 80, 160, 320 mu;mol/L, respectively. Phosphate buffer solution (PBS) was injected in two rats as PBS control group. Two rats as normal control group received no treatment. The difference of retinal thickness among groups was measured by optical coherence tomography (OCT). The morphological and histological change of retina was evaluated under light microscope and transmission electron microscope. Results There was no difference of retinal thickness between normal control group and PBS control group (F=0.12,P＞0.05). At the first week after injection, the retinal thickness of CEL-PLGA-MS group and celecoxib group were thicker than that in normal control group and PBS control group (F=9.62, 46.13;P＜0.01). The retinal thickness of celecoxib group was thicker than that in CEL-PLGA-MS group (F=165.15,P＜0.01). The retinal thickness was estimated equal among 40, 80, 320 mu;mol/L dosage groups in CEL-PLGA-MS group (F=4.79,P＜0.01). The retinal thickness of 160, 320 mu;mol/L dosage group were thicker than that in 40, 80 mu;mol/L dosage group in celecoxib group (F=28.10,P＜0.01). At the second week after injection, there was no difference of retinal thickness between CEL-PLGA-MS and celecoxib group (F=3.79,P＞0.05); the retinal thickness of CEL-PLGA-MS and celecoxib group became thinner gradually compare to the first week after injection (F=7.28, 103.99; P＜0.01). At the fourth week after injection, the retinal thickness of celecoxib group was thicker than that in CEL-PLGA-MS group (F=19.11,P＜0.01). The retinal thickness of CEL-PLGA-MS group was approximately the same to normal control group and PBS control group (F=2.02,P＞0.05). The retinal thickness of celecoxib group was thicker than that in normal control group and PBS control group. No considerable abnormality of the retina was seen by light microscope and the retinal thickness corresponded with the values measured by OCT at the first week after injection. The abnormal structures of the retina were seen in 160, 320 mu;mol/L dosage group of celecoxib group and inner changed evidently by the transmission electron microscope. Disordered arrangement of microfilaments, dilated microtubule and some mitochondria vacuolation were observed in 320mu;mol/L dosage group of celecoxib group. Others changed slightly. Conclusions CEL-PLGA-MS has less toxicity on the retina than free-celecoxib after intravitreal injection. The safety of intravitreal injection with CEL-PLGA-MS is better than celecoxib.
Objective To evaluate the expressive varieties of Nogo-A mRNA in injured optic nerves of rats. Methods Reverse transcription polymerase chain reaction (RT-PCR) method was used to hemi-quantitatively analyze the levels of Nogo-A mRNA in the optic nerves 3, 7, 9, 15, 21, and 25 days respectively after injury.Results The level of the expression of Nogo-A mRNA was low in the normal optic nerves, while it was significantly high in the optic nerves 3 days after in jury, and kept the high level still after 25 days.Conclusion The expression of Nogo-A mRNA in injured optic nerves is increased. (Chin J Ocul Fundus Dis，2003，19：201-268)
ObjectiveTo observe the effect of complement receptor 1 (CR1) on barrier of cultured human retinal epithelial cells (hRPE) under complement-activated oxidative stress. MethodsThe third to fifth passage of hRPE cultured on Transwell insert were used to establish a stable hRPE monolayer barrier. The hRPE monolayer barrier was exposed to 500 μmol/L ten-butyl hydroperoxide and 10% normal human serum to establish the hRPE monolayer barrier model of complement-activated oxidative stress in vitro. hRPE monolayer barriers under complement-activated oxidative stress were divided into two groups including model group and CR1 treatment (1 μg/ml) group. Model group and CR1 treatment group were treated with 1 μl phosphate buffer solution (PBS) or CR1 for 4 hours. Normal hRPE monolayer barrier were used as control in transepithelial resistance (TER) measurement experiment. TER was measured to evaluate the barrier function of hRPE. The hRPE-secreted vascular endothelial growth factor (VEGF) and chemokine (C-C Motif) Ligand 2 (CCL2), together with complement bioactive fragments (C3a, C5a) and membrane-attack complex (MAC) in the supernatant were detected by enzyme-linked immune sorbent assay. ResultsStable hRPE monolayer barrier was established 3 weeks after hRPE seeded on Transwell insert. Complement-activated oxidative stress resulted in a sharp decrease of TER to 54.51% compared with normal hRPE barrier. CR1 treatment could significantly improve TER of barrier under complement-activated oxidative stress to 63.48% compared with normal hRPE barrier(t=21.60, P < 0.05). Compared with model group, CR1 treatment could significantly decrease the concentration of VEGF and CCL2 by 11.48% and 23.47% secreted by hRPE under complement-activated oxidative stress (t=3.26, 2.43; P < 0.05). Compared with model group, CR1 treatment could also decreased the concentration of C3a, C5a and MAC by 24.00%, 27.87%, 22.44%.The difference were statistically significant (t=9.86, 2.63, 6.94; P < 0.05). ConclusionsCR1 could protect the barrier function of hRPE cells against complement-activated oxidative stress. The underlying mechanism may involve inhibiting complement activation and down-regulating the expression of VEGF and CCL2.
ObjectiveTo compare the efficacy of photodynamic therapy (PDT) alone or in combined with ranibizumab versus ranibizumab monotherapy (intravitreal injection, IVR) in patients with polypoidal choroidal vasculopathy (PCV). Methods80 eyes of 72 patients with PCV were enrolled into this retrospective and comparative study according to their therapeutic plan. 30 eyes of 28 patients, 28 eyes of 30 patients and 22 eyes of 21 patients were divided into PDT group, ranibizumab 0.5 mg group (IVR group) or the combination group, respectively. The patients with PCV were diagnosed according to clinical symptoms, optical coherence tomography (OCT) and fluorescent indocyanine green angiography (ICGA). The baseline best-corrected visual acuity (BCVA) before treatment was more than 0.05, and there was no retinal fibrosis and scar for all patients. There was no statistical difference of age (F=0.187), gender (χ2=0.423), average BCVA (F=1.120) and central retinal thickness (CRT) (F=0.431) among three groups (P > 0.05). They had not received any treatment before. Patients received verteporfin PDT in PDT group, 3 consecutive monthly IVRs starting day 1 in IVR group, and 3 IVRs after 3 days, 1 month, 2 months of PDT starting day 1 in combination group. Re-treatment was considered 3 months later if the follow up shown no changes in fundus photography, OCT and ICGA. The average follow-up time was 19 months. BCVA at baseline and follow-up visit at 1, 3, 6, 12 months was measured, and the proportion of patients with ICGA-assessed complete regression of polyps at month 6 was recorded as primary outcome. The CRT was measured at baseline and 6 months as secondary outcome. ResultsThere were significant difference of BCVA at 1, 3, 6 and 12 months among three groups(F=5.480, 5.249, 3.222, 4.711; P < 0.05). The average BCVA was significantly better at 1, 3, 6, 12 month than that at baseline(t=-6.632, -4.127, -3.904, -4.494; P < 0.05) in combination group, and was significantly better at 3, 6, 12 months than that at baseline (t=-5.636, -3.039, -3.833; P < 0.05) in IVR group. However there was no significant difference of the average BCVA in PDT group between follow-up at 1, 3, 6, l 2 months and baseline (t=1.973, 0.102, -0.100, -0.761; P > 0.05). The proportion of patients with complete regression of polyps at 6 months was higher in PDT (76.7%) or combination group (68.2%) than IVR group (35.7%) (χ2=0.003, 0.025; P < 0.05). There was no significant difference of CRT among 3 groups at baseline (P=0.651). The mean CRT decreased in all 3 treatment groups over 6 months (t=5.120, 3.635, 5.253; P < 0.05), but there was no significant difference of CRT among 3 groups (F=1.293, P > 0.05). ConclusionsThree therapies could effectively decrease CRT. IVR or IVR combined with PDT are both more effective than PDT therapy to improve vision of PCV patients. PDT or PDT combined with IVR was superior to IVR pnly in achieving complete regression of polyps in 6 months in PCV patients.
ObjectiveTo assess the efficacy and safety of intravitreal aflibercept injection (IAI) compared with photodynamic therapy (PDT) in the treatment of Chinese patients with predominantly classic subfoveal choroidal neovascularization (CNV) lesions secondary to neovascular age-related macular degeneration (nAMD).MethodsA randomized, double-blind, multi-center phase-3 clinical trial lasting for 52 weeks (from December 2011 to August 2014). Subjects were randomized in a 3:1 ratio to either IAI group or PDT-to-IAI group. Subjects in the IAI group received 2 mg IAI at baseline and at week 4, 8, 16, 24, 32, 40, 48, with sham injection at week 28, 36. Subjects in the PDT-to-IAI group were forced to receive PDT once at baseline and more time at week 12, 24 if PDT retreatment conditions were met. Sham injections were given in PDT-to-IAI group at baseline and at week 4, 8, 16 and 24, followed by 2 mg IAI at week 28, 32, 36, 40, 48. The primary outcome of efficacy were the change in mean Best Corrected Visual Acuity (BCVA) from baseline to week 28, and that of week 52. Safety evaluation included the percentage of subjects who suffered treatment emergent adverse events (TEAEs).ResultsAmong the 304 subjects enrolled, there were 228 and 76 cases in IAI group and PDT-to-IAI group respectively. At week 28, the changes of mean BCVA in IAI group, PDT-to-IAI group compared to baseline were +14.0, +3.9 letters, respectively. At week 52, the changes of mean BCVA in two groups were +15.2, +8.9 letters respectively with the difference of +6.2 letters (95%CI 2.6−9.9, P=0.000 9). At week 52, the mean foveal retinal thickness in the two groups decreased by −189.6, −170.0 μm, respectively. Subjects with the most BCVA increase in IAI group were those aged ＜65, and those with active CNV lesion area ＜50% of total lesion area. The most common TEAEs in IAI group and PDT-to-IAI group are macular fibrosis [11.8% (27/228), 6.6% (5/76)] and BCVA decline [6.6% (15/228), 21.1% (16/76)]. There were 3 cases of arterial thromboembolic events defined in the antiplatelet experimental collaboration group, but all were considered unrelated to interventions.ConclusionsThe efficacy of aflibercept is superior to that of PDT in nAMD patients in China. The therapeutic effect of aflibercept persisted to week 52 in all subjects. The rate of adverse events was consistent with the safety data of aflibercept known before.
【Abstract】Objective To investigate the expression of extracellular matrix metalloproteinase inducer(EMMPRIN)，matrix metalloproteinase-1(MMP1)，MMP9，tissue inhibitors of metalloproteinase-1(TIMP1) and the mast cell count (MCC) and to detect their clinicopathologic significance and relationship in pancreatic cancer tissues. Methods Immunohistochemical method of avidin-biotin complex was used for those 5 targets on the routinely paraffinembedded sections of surgical resected specimen of 51 cases with pancreatic carcinoma. Results The positive rates of EMMPRIN，MMP1，MMP9 and TIMP1 were 56.9%，54.9%，60.8% and 49.0% and its scoring were 2.5±1.5，2.3±1.9，2.4±1.6 and 1.9±1.6 respectively. The mean of MCC was (16.1±6.8)/HP in total cases. The positive rates or scorings of EMMPRIN，MMP1，MMP9 and MCC were significantly lower in high differentiated or without-metastatic cases than in low differentiated or with-metastatic ones(P＜0.05 or P＜0.01), and those targets (except MCC and scoring of MMP9) of middle differentiated ones were lower than those of low differentiated while that of TIMP1 was opposite(P＜0.01). The MCC showed significantly higher in the positive cases of EMMPRIN, MMP1 and MMP9 or negative cases of TIMP1 than in the negative ones of EMMPRIN, MMP1 and MMP9 or positive ones of TIMP1. The closely positive correlations were found among the MCC and the scoring of EMMPRIN, MMP1 and MMP9. The closely negative correlations existed among the scoring of TIMP1 and the other four targets.Conclusion The MCC and the expressions of EMMPRIN, MMP1, MMP9 and TIMP1 might be important biological markers for reflecting the progression and the prognosis of pancreatic carcinoma. They might have co-regulated effects on the potentials of invasion and metastasis of pancreatic carcinoma or other malignant lesions.
According to the best corrected visual acuity and the morphological changes of the macular fovea, responses to the neovascular age-related macular degeneration (nAMD) who receive anti-vascular endothelial growth factor (VEGF) therapy show large variability, including poor and non-responders. Various factors will be reviewed to account for poor and non-response to anti-VEGF therapy, such as the related susceptibility genes, factors related with the development of choroidal neovascularization and morphologic parameters, pharmacokinetics and tachyphylaxis. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy to improve the therapeutic outcome of nAMD.
ObjectiveTo systematically review the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) in the treatment of Parkinson's disease patients with depression. MethodsThe Cochrane Library (Issue 5, 2014), PubMed, EMbase, CNKI, VIP and WanFang Data databases were searched from inception to May 2014 for randomized controlled trials (RCTs) investigating the efficacy and safety of SSRIs for Parkinson's disease patients with depression. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of included studies. Then meta-analysis was performed using RevMan 5.2 software. ResultsA total of 12 RCTs were included. The results of meta-analysis showed that the efficacy of SSRIs was better than placebo (RR=2.18, 95%CI 1.60 to 2.97, P<0.000 01) and the dropouts rates of SSRIs were higher than placebo (OR=3.02, 95%CI 1.04 to 8.79, P=0.04). However, the incidence rate of adverse events between the SSRIs group and the placebo group was not statistically different. ConclusionCurrent evidence indicates that SSRIs are effective for the Parkinson's disease patients with depression. Because of the limitation of quantity and quality of included studies, large-scale multi-center RCTs are required to confirm these findings.