The expression of cyclooxygenase-1 and -2 in proliferative endometrium and endometrial adenocarcinoma

BACKGROUND. The activity of cyclooxygenase-2 (COX-2) is increased in inflammation and in several cancer types. We investigated the expression of COX-2, cyclooxygenase-1 (COX-1), nitric oxide synthase-2 (NOS-2) and nitric oxide synthase-3 (NOS-3) in normal proliferative and secretory human endometrium, and in endometrial adenocarcinoma. METHODS. Human endometrium was collected at hysterectomy. Seven samples were in proliferative and 11 samples in secretory stage. Twelve specimens from endometrial carcinoma were collected, as well. Immunohistochemistry was used to investigate the expression of COX-1, COX-2, NOS-2 and NOS-3. RESULTS. COX-2 immunostaining was detected in most specimens of normal proliferative glandular epithelium (86%) and of endometrial carcinomas (92%). COX-2 staining was often detected in cancer cells on the border areas of the tumour and on the areas of invasive growth. Staining for COX-2 was seen in proliferative glands usually only in the basal layer of the endometrium. NOS-2 was usually absent or negligible in proliferative endometrial glands and also in the cancer cells of endometrial adenocarcinomas. No staining for either COX-2 or NOS-2 was seen in specimens of secretory glandular epithelium. The expression of the constitutive COX-1 and NOS-3 was negligible or weak in the glandular epithelium of proliferative and secretory endometrium and in endometrial cancer cells. CONCLUSIONS. The expression of the inducible COX-2 but not of COX-1 is stimulated in the glandular epithelium of proliferative endometrium and in the cancer cells of human endometrial adenocarcinoma, in particular in those in the borders of carcinoma and spreading into lymphatic vessels.     

Effect of different fixative solutions on eyes with experimental proliferative vitreoretinopathy

The aim of this study was to evaluate the use of different fixatives on the reliability of histopathological changes in a rabbit model of proliferative vitreoretinopathy (PVR). Twenty eyes from 10 rabbits were divided into four groups. The right eyes were used in two experimental groups (each n = 5), and the left, in two control groups (each n = 5). Using a newly developed scleral incision marker, an oblique scleral incision was standardized in the experimental groups, followed by intravitreal injection of 0.4 ml autologous blood and the left for wound repair for four weeks. Eyes were enucleated at four weeks. The groups differed in the type of used fixative solution (formaldehyde 4% vs. 1% buffered formaldehyde and 1.25% glutaraldehyde). The eyes were evaluated for the development of fibrosis, retinal detachment (RD), and processed for histopathology. Fibrous ingrowth of a variable degree was present in the experimental groups originating from the trauma site. Experimental eyes fixed with formaldehyde 4% had RD extension that was greater than that fixed in formaldehyde/glutaraldehyde mixture; however, the difference did not reach statistical significance (P = 0.15). This difference was not fully explained by the fibrosis which developed. In addition, in control groups, formaldehyde 4% induced a fixative-dependent retinal separation that was absent in eyes fixed with formaldehyde/glutaraldehyde mixture (P = 0.03). In conclusion, a mixture of buffered formaldehyde 1% and glutaraldehyde 1.25% combined with standardized scleral incision resulted in consistent pathological changes. A reliable PVR model is a condition sine qua non to evaluate antifibrotic treatment strategies.     

血浆促红细胞生成素可作为预测增殖性糖尿病性视网膜病的危险因素

目的 探讨可作为预测增殖性糖尿病性视网膜病的危险因素.方法 选取2011年5月至2013年11月间在我院眼科怀疑为糖尿病视网膜病变患者168例作为研究对象,空腹抽取静脉血,送检验科实验室检测EPO、糖化血红蛋白、FBS、CRP水平、血脂、载脂蛋白A和B.采用t检验和x2检验、多因素logistic回归分析确定增殖性糖尿病性视网膜病发生的独立危险因素.结果 在怀疑为糖尿病视网膜病变患者168例中,测得患增殖性糖尿病性视网膜病患者28例,通过计算得出患者中增殖性糖尿病性视网膜病的患病率为16.67％.为了探讨PDR的危险因素,我们将全部PDR患者的可能危险因素纳入多因素logistic回归分析.结果表明,EPO(OR =0.31,95％CI:0.04～0.95,P=0.042)是预测增殖性糖尿病性视网膜病的独立危险因素.结论 血浆促红细胞生成素可作为预测增殖性糖尿病性视网膜病的危险因素.     

家族性渗出性玻璃体视网膜病变的临床研究

目的：了解家族性渗出性玻璃体视网膜病变(familial exudative vitreoretinopathy,FEVR)的发病状况,探讨足月产儿眼病筛查的必要性。

方法：回顾分析2014-01/2015-08我院772例1544眼足月产儿眼底检查的资料。

结果：足月产儿772例1 544眼中,发现各期FEVR共8例15眼,检出率0.97%; 包括1期2例2眼,2期3例5眼(含1期1例另1眼),3期2例4眼,4期1例2眼,5期1例2眼。

结论：家族性渗出性玻璃体视网膜病变在新生儿眼病筛查中并不少见,甚至病情严重者在婴儿期就丧失视功能。新生儿期和婴儿期是FEVR筛查的关键时间点,早期发现、早期干预是FEVR患者获得较好视功能的关键。     

Diabetic retinopathy is associated with a switch in splicing from anti- to pro-angiogenic isoforms of vascular endothelial growth factor

Aims/hypothesis Proliferative diabetic retinopathy results from excess blood vessel growth into the vitreous fluid of the eye. Retinal angiogenesis is regulated by expression of vascular endothelial growth factor (VEGF), and many studies have shown that VEGF is critically involved in proliferative diabetic retinopathy. VEGF is alternatively spliced to form the angiogenic (VEGF_xxx) and potentially anti-angiogenic (VEGF_xxxb) family of isoforms. The VEGF_xxxb family is found in normal tissues, but down-regulated in renal and prostate cancer. Previous studies on endogenous expression of VEGF in the eye have not distinguished between the two families of isoforms.Methods We measured VEGF_xxxb isoform expression in normal human eye tissue (lens, sclera, retina and iris) and vitreous fluid using enzyme-linked immunosorbent assay and Western blotting with a VEGF_xxxb-specific antibody.Results VEGF_xxxb protein was expressed in lens, sclera, retina, iris and vitreous fluid. Multiple isoforms were seen, including VEGF₁₆₅b, VEGF₁₂₁b, VEGF₁₄₅b, VEGF₁₈₃b and VEGF₁₈₉b. In non-diabetic patients, 64±7% of the VEGF in the vitreous was VEGF_xxxb (n=18), whereas in diabetic patients only 12.5±3.6% of total VEGF was VEGF_xxxb.Conclusions/interpretation Since VEGF_xxxb inhibits VEGF_xxx-induced angiogenesis in a one-to-one stoichiometric manner, these results show that in the eye of diabetic patients VEGF splicing was switched from an anti-angiogenic to a pro-angiogenic environment. This occurred through changes to the ratio of VEGF_xxx : VEGF_xxxb. Alterations to splicing, and through that to the balance of VEGF isoforms, could therefore be a potential therapeutic strategy for diabetic retinopathy.Konopatskaya and Perrin are joint first authors.     

Low oxygen delays fibroblast senescence despite shorter telomeres

It has been widely accepted that telomere shortening acts as a cell division counting mechanism that beyond a set critical length signals cells to enter replicative senescence. In this study, we demonstrate that by simply lowering the oxygen content of the cell culture environment 10-fold (20–2%) extends the replicative lifespan of fetal bovine fibroblasts at least five-times (30–150 days). Although, low oxygen fibroblasts display a slightly slower rate (P > 0.05) of telomere attrition than their high oxygen counterparts (171 bp versus 182 bp/PD), late passage fibroblasts (>50 PD) that have extended their replicative capacity under low oxygen conditions exhibited significantly (P < 0.05) shorter telomere lengths (11,135 ± 467 bp) compared to senescent cells (25–34 PD) cultured under high oxygen conditions (14,827 ± 1173 bp). There was a significant increase (P < 0.05) in chromosomal abnormalities with continual cell division under both high and low oxygen environments, however, fibroblasts displayed a significant reduction (P < 0.001) in chromosomal abnormalities at low oxygen tensions compared to those under 20% oxygen. These apparent protective effects on telomere shortening, delayed senescence and reduced chromosomal aberrations may be attributed to the up-regulation of telomerase activity observed for fibroblasts cultured under low oxygen. These results are consistent with the idea that a critically short telomere length may not be the sole trigger of replicative senescence, but may be regulated by the integrity of telomere structure itself and/or the amount of oxidative DNA damage in the cell.