Vitreous levels of vascular cell adhesion molecule and vascular endothelial growth factor in patients with proliferative diabetic retinopathy: a case-control study

OBJECTIVE: To evaluate the intravitreous concentration of vascular cell adhesion molecule (VCAM)-1 in diabetic patients with proliferative diabetic retinopathy (PDR) and the relationship of VCAM-1 with vascular endothelial growth factor (VEGF). RESEARCH DESIGN AND METHODS: Serum and vitreous fluid samples were obtained simultaneously at the onset of vitrectomy from 20 diabetic patients with PDR and 20 nondiabetic control subjects with nonproliferative ocular disease. Both groups were matched by serum levels of VCGM-1 and VEGF. VCAM-1 and VEGF were determined by enzyme-linked immunosorbent assay. Statistics were determined using the Mann-Whitney U test and Spearman's rank correlation test. RESULTS: The intravitreous concentration of VCAM-1 was signifcantly elevated in diabetic patients with PDR compared with control subjects (26 ng/ml [19-118] vs. 22 ng/ml [20-47], P < 0.05). A direct correlation between VCAM-1 and total vitreous proteins was detected in diabetic patients (r = 0.64, P = 0.003), but not in control subjects. After adjusting for total intravitreous proteins, VCAM-1 was significantly lower in diabetic patients with PDR than in control subjects (8.2 ng/ml [4-31.4] vs. 43.1 ng/ml [9.7-100], P < 0.001). Intravitreous VEGF concentrations were higher in patients with PDR than in control subjects in absolute terms (1.34 ng/ml [0.16-6.22] vs. 0.009 ng/ml [0.009-0.044], P < 0.0001) and after correcting for total vitreal proteins (0.33 ng/ml [0.01-2.3] vs. 0.013 ng/ml [0.003-0.035], P = 0.0001). Finally, the vitreous ratio of VCAM-1 to proteins correlated with the vitreous ratio of VEGF to proteins in both diabetic patients (r = 0.74, P = 0.001) and control subjects (r = 0.84, P = 0.005). CONCLUSIONS: The low proportion of VCAM-1 in relation to total vitreal proteins observed in diabetic patients with PDR suggests that VCAM-1 is quenched by diabetic retina. In addition, the direct correlation detected between VCAM-1 and VEGF suggests that cellular adhesion and neovascularization may be linked processes.     

Deficit of somatostatin-like immunoreactivity in the vitreous fluid of diabetic patients: possible role in the development of proliferative diabetic retinopathy

OBJECTIVE: To evaluate the vitreous levels of somatostatin-like immunoreactivity (SLI) in patients with proliferative diabetic retinopathy (PDR). RESEARCH DESIGN AND METHODS: A total of 14 diabetic patients with PDR, in whom a vitrectomy was performed, were included in the study. Sixteen nondiabetic patients, with other conditions requiring vitrectomy, served as a control group. Both venous blood and vitreous samples were collected at the time of vitreoretinal surgery. Patients in whom intravitreous hemoglobin was detectable were excluded. In addition, a correction for plasma levels of SLI and intravitreal proteins was performed. SLI was measured by radioimmunoassay and vitreous hemoglobin by spectrophotometry. RESULTS: SLI in the vitreous fluid was significantly lower in diabetic patients than in the control group (68 +/- 18.7 vs. 193.6 +/- 30.8 pg/ml, P < 0.01). The vitreous SLI-to-plasma SLI ratio was strikingly higher in nondiabetic subjects than in diabetic patients with PDR (5.3 [1.2-71.1] vs. 0.6 [0.03-4.1], P < 0.01). After correcting for total vitreous protein concentration, SLI (pg/mg of proteins) remained significantly higher in nondiabetic control subjects than in diabetic patients with PDR (186 [51-463] vs. 7.5 [0.8-82], P < 0.0001). Remarkably, intravitreous levels of SLI were higher than those obtained in plasma in nondiabetic control subjects (193.6 +/- 30.8 vs. 43.5 +/- 10.7 pg/ml, P < 0.0001). Finally, a lack of relationship between plasma and vitreous levels of SLI was observed in both diabetic patients with PDR and nondiabetic control subjects. CONCLUSIONS: The significantly higher SLI in the vitreous fluid than in plasma detected in nondiabetic control subjects supports the concept that somatostatin plays a relevant role in retinal homeostasis. In addition, the intravitreous deficit of SLI observed in diabetic patients with PDR suggests that it might contribute to the process of retinal neovascularization.     

Accumulation of NH2-terminal fragment of connective tissue growth factor in the vitreous of patients with proliferative diabetic retinopathy

OBJECTIVE: To evaluate the expression of connective tissue growth factor (CTGF) and its fragments in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to localize CTGF expression in associated preretinal membranes. RESEARCH DESIGN AND METHODS: Vitreous was obtained from 24 patients with active PDR, 4 patients with quiescent PDR, and 23 patients with other retinal diseases and no diabetes, including 5 patients with vitreous hemorrhage. Enzyme-linked immunosorbent assay was used to determine levels of whole CTGF and its NH2- and COOH-terminal fragments. Preretinal membranes from three patients with active PDR were stained immunohistochemically for the presence of CTGF and cell type-specific markers. RESULTS: A significant increase in NH2-terminal CTGF fragment content was found in vitreous samples from patients with active PDR when compared with samples from nondiabetic patients (P<0.0001) or patients with quiescent PDR (P=0.02). Levels of NH2-terminal CTGF were also greater in vitreous samples from diabetic patients with vitreous hemorrhage compared with samples from nondiabetic patients with vitreous hemorrhage (P=0.02). Vitreous levels of whole CTGF were similar in all groups. COOH-terminal fragments of CTGF were not detected. CTGF immunoreactivity was predominantly localized to smooth muscle actin-positive myofibroblasts within active PDR membranes. CONCLUSIONS:-NH2-terminal CTGF fragment content is increased in the vitreous of patients with active PDR, suggesting that it plays a pathogenic role or represents a surrogate marker of CTGF activity in the disorder. The localization of CTGF in myofibroblasts suggests a local paracrine mechanism for induction of fibrosis and neovascularization.     

Somatostatin molecular variants in the vitreous fluid: a comparative study between diabetic patients with proliferative diabetic retinopathy and nondiabetic control subjects

OBJECTIVE: There is growing evidence to indicate that somatostatin could be added to the list of natural antiangiogenic factors that exist in the vitreous fluid. In addition, a deficit of intravitreous somatostatin-like immunoreactivity (SLI) has been found in diabetic patients with proliferative diabetic retinopathy (PDR). In the present study, we have determined the main molecular variants of somatostatin (somatostatin-14 and somatostatin-28) in the vitreous fluid and plasma of nondiabetic control subjects and diabetic patients with PDR. In addition, the contribution of cortistatin, a neuropeptide with strong structural similarities to somatostatin, to SLI and its levels in vitreous and plasma in both nondiabetic and diabetic patients has also been measured. RESERCH DESIGN AND METHODS: Plasma and vitreous fluid from 22 diabetic patients with PDR and 22 nondiabetic control subjects were analyzed. Somatostatin-14, somatostatin-28 and cortistatin were measured by radioimmunoassay but separation by high-performance liquid chromatography was required to measure somatostatin-14. RESULTS: The predominant molecular form of somatostatin within the vitreous fluid was somatostatin-28 (fivefold higher than somatostatin-14 in control subjects and threefold higher in patients with PDR). Cortistatin significantly contributed to SLI and its intravitreous levels were higher than those detected in plasma (nondiabetic control subjects: 147 [102-837] vs. 78 [24-32] pg/ml; patients with PDR: 187 [87-998] vs. 62 [24-472] pg/ml; P = 0.01 for both). Intravitreous somatostatin-14 was similar in both subjects with PDR and the control group (P = 0.87). By contrast, somatostatin-28 concentration was lower in patients with PDR than in nondiabetic control subjects (350 +/- 32 vs. 595 +/- 66 pg/ml; P = 0.004). CONCLUSIONS: Somatostatin-28 is the main molecular variant in the vitreous fluid. The intravitreous SLI deficit detected in patients with PDR is mainly due to somatostatin-28. Cortistatin is abundant in the vitreous fluid and significantly contributes to SLI. These findings could open up new strategies for PDR treatment.     

Vitrectomy in diabetics. A new procedure for prevention of blindness in diabetic retinopathy

A report is presented of 46 diabetics submitted to pars plana vitrectomy on account of severe intravitreal haemorrhage. The follow-up period lasted up to 15 months. The visual acuity alone is not an adequate parameter for the evaluation of postoperative success in view of the central retinal lesions resulting from severe diabetic retinopathy. The vitreous cavity was found to be clear in 33 cases and in 27 cases visual acuity reached at least 6/60. In 11 cases new haemorrhages occurred postoperatively, 6 of which cleared spontaneously within 2 weeks. In the remaining cases irrigation of the vitreous chamber by means of the vitrectomy instrument was necessary. Retinal injury due to the tip of the instrument was avoided in every case. The patients were out of bed on the first postoperative day and discharged between the 8th and 10th postoperative day provided that no relapse haemorrhage occurred.     

Vitreous levels of IGF-I, IGF binding protein 1, and IGF binding protein 3 in proliferative diabetic retinopathy: a case-control study

OBJECTIVE: To evaluate vitreous levels of IGF-I and its binding proteins IGFBP-1 and IGFBP-3 in patients with proliferative diabetic retinopathy (PDR). Because intravitreal proteins are elevated in patients with PDR due to the disruption of the blood-retinal barrier, we have corrected vitreal IGF-I and IGFBPs by total vitreal proteins to avoid this confounding factor. RESEARCH DESIGN AND METHODS: We compared 21 diabetic patients with proliferative retinopathy (group A) and 13 nondiabetic patients (group B) in whom a vitrectomy was performed. Both groups were matched by age, serum IGF-I, IGFBP-1, and IGFBP-3 levels. Serum and vitreous levels of IGF-I, IGFBP-1, and IGFBP-3 were measured by immunological methods. Vitreal proteins were assessed by turbidimetric method. RESULTS: Vitreal levels of IGF-I were elevated in group A (median 1.35 ng/ml [range 0.3-8.7]) in comparison with group B (median 0.25 ng/ml [range 0-1.38]), P<0.001. After adjusting by vitreal proteins [ratio IGF-I (ng/ml)/protein (mg/ml)], the differences remain significant (P<0.005). Vitreal levels of IGFBP-1 and IGFBP-3 were also elevated in diabetic patients (IGFBP-1: group A, median 1.6 ng/ml [range 0.6-20.7]; group B, median 0.4 ng/ml [range 0.3-1.9], P<0.001. IGFBP-3: group A, median 102.6 ng/ml [range 53.9-350.8]; group B, median 29.0 ng/ml [range 3.2-87.8], P<0.001). However, when the ratio IGFBP/protein was considered, the differences were not significant. CONCLUSIONS: Intraocular synthesis contributes to elevated vitreous concentrations of IGF-I found in PDR. By contrast, unspecific increase of intravitreal proteins is the main factor explaining the elevated vitreous levels of IGFBP-1 and IGFBP-3 found in diabetic patients.     

Erythropoietin is expressed in the human retina and it is highly elevated in the vitreous fluid of patients with diabetic macular edema

OBJECTIVE: Erythropoietin has been recently found to be increased in the vitreous fluid from ischemic retinal diseases such as proliferative diabetic retinopathy (PDR). The aims of the present study were 1) to measure erythropoietin levels in the vitreous fluid from patients with diabetic macular edema (DME), a condition in which the ischemia is not a predominant event, and 2) to compare erythropoietin mRNA expression between human retinas from nondiabetic and diabetic donors without retinopathy. RESEARCH DESIGN AND METHODS: Vitreous samples from 12 type 2 diabetic patients with DME without significant retinal ischemia and 12 PDR patients were prospectively analyzed. Ten nondiabetic patients with macular holes served as the control group. Erythropoietin was assessed by radioimmunoassay (milliunits per milliliter). Erythropoietin mRNA expression was measured by quantitative real-time RT-PCR analysis in the retina from eight nondiabetic and eight age-matched diabetic donors without diabetic retinopathy RESULTS: Intravitreal erythropoietin concentration was higher in both PDR and DME patients than in nondiabetic control subjects (PDR vs. control subjects: median 302 [range 117-1,850] vs. 30 mU/ml [10-75], P < 0.01; DME vs. control subjects: 430 [41-3,000] vs. 30 mU/ml [10-75], P < 0.01). However, no significant differences were found between DME and PDR patients. Erythropoietin mRNA expression was detected in the human retina, and it was higher in the retina from diabetic than from nondiabetic donors. CONCLUSIONS: As occurs in PDR, intravitreous erythropoietin concentrations are strikingly higher in DME. Erythropoietin is expressed in the human retina, and it is upregulated in diabetic patients even without retinopathy. These findings suggest that other factors apart from ischemia are involved in the overexpression of erythropoietin in diabetic retinopathy.     

Free insulin-like growth factor 1 in the vitreous fluid of diabetic patients with proliferative diabetic retinopathy: a case-control study

The aim of the study was to evaluate the vitreous levels of free insulin-like growth factor 1 (IGF-1) in patients with proliferative diabetic retinopathy (PDR). For this, a total of 36 diabetic patients with PDR (group A) and 28 non-diabetic patients (group B) in whom a vitrectomy was performed were compared. Both groups were matched by age, sex and serum-free IGF-1. In a subgroup of diabetic patients (n =21) and non-diabetic patients (n =13), vitreous and serum total IGF-1, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were also determined. Serum and vitreous levels of free IGF-1, total IGF-1, IGFBP-1 and IGFBP-3 were measured by immunological methods. Vitreal proteins were assessed by a turbidimetric method and adjusted for vitreous haemoglobin. Vitreous levels of free IGF-1 were elevated in group A (median, 0.16 ng/ml; range 0.06-0.57 ng/ml) in comparison with group B (median, 0.12 ng/ml; range 0.06-0.22 ng/ml; P <0.001); however, after adjusting for vitreal proteins, free IGF-1 levels were significantly lower in group A in comparison with group B [0.05 ng/mg (0.01-0.45 ng/mg) versus 0.15 ng/mg (0.07-0.66 ng/mg); P <0.001]. The relatively lower free IGF-1 level observed in group A could not be attributed to differences in the distribution of intravitreous IGFBP-1 and IGFBP-3 in relation to total IGF-1. Notably, the contribution of free IGF-1 to total IGF-1 in vitreous fluid was 10% in group A and 42% in group B; these percentages largely exceed that obtained in serum (<1%). Our results suggest that although there is an enhancement of intravitreous free IGF-1 in diabetic patients due to serum diffusion, a deficit in its intraocular production also exists. In addition, these findings support the concept that intraocular-produced free IGF-1 plays a relevant role in retinal homoeostasis.     

Evaluation of visual function and prognosis for patients with proliferative diabetic retinopathy with the low vision evaluator

Proliferative diabetic retinopathy (PDR) is a leading cause of visual loss in adults in industrialized countries. PDR patients with light perception (LP) or hand movement (HM) acuity due to severe vitreous hemorrhage require vitreous surgery. The purpose of this study was to determine whether the visual acuity of PDR patients with LP or HM can be graded into finer steps with the Low Vision Evaluator (LoVE). In addition, we determined whether the LoVE results are correlated with the amplitude of the electroretinogram (ERG), the presence of retinal detachment (RD), or postoperative visual prognosis. The LoVE instrument is a subjective device that measures the thresholds for light stimulus and is equipped with a pair of goggles with white light-emitting diodes as the stimulus. We measured the LoVE thresholds of 19 PDR patients, whose fundi could not be observed due to vitreous hemorrhage and whose visual acuity was LP or HM. The 13 patients with HM vision had LoVE thresholds that ranged from 25.0 and 40.0 dB, and the 6 patients with LP vision had LoVE thresholds that ranged from 20.0 and 40.0 dB. The LoVE thresholds of 9 patients with RD were significantly lower than those of 10 patients without RD (p < 0.001). The LoVE thresholds were correlated with the amplitude of the a- and b-waves of the ERG and the postoperative best-corrected visual acuity (BCVA) (a-wave: r = 0.70, p < 0.001; b-wave: r = 0.71, p < 0.001; postoperative BCVA: r = 0.46, p < 0.05). These results indicate that the LoVE is capable of grading the visual function of PDR patients with conventional LP and HM vision into finer steps. Thus, the LoVE is an invaluable device in predicting the postoperative visual acuity of patients with vitreous hemorrhage.     

体力活动对增生性糖尿病视网膜病变患者玻璃体积血的安全性分析

目的 通过对比发生玻璃体积血与无明显玻璃体积血增生性糖尿病视网膜病变（PDR）患者不同体力活动形式及强度的差异,探讨体力活动对PDR患者的安全性及潜在价值。方法 首次在开封市中心医院开封眼病医院就诊的无明显纤维组织增生的PDR患者67例,其中31例无明显玻璃体积血PDR患者为对照组,36例发生玻璃体积血（<1月）患者为研究组。采用国际体力活动量表（IPAQ）统计患者玻璃体积血发生前的体力活动。同时记录患者年龄、病程、最佳矫正视力（BCVA）、身高、体重指数（BMI）、糖化血红蛋白、血脂、血压。 调查出血诱因,比较两组间体力活动的差异。结果 36例发生玻璃体积血患者中未见体力活动直接诱发玻璃体积血病例;研究组大量患者部分体力活动缺失,中、重体力活动、总体力活动、能量消耗、休闲及运动相关体力活动时间及人数显著低于对照组(P＜0.05);研究组静坐时间显著延长,睡眠时间显著缩短,BMI、甘油三酯、收缩压显著高于对照组(P＜0.05)。结论 不同体力活动未见诱发玻璃体积血;不同体力活动对无明显纤维组织增生PDR患者可能是安全和有益的;减少静坐时间、改善睡眠质量值得提倡。     

微创23G和传统20G玻璃体切割术治疗玻璃体积血的临床对照研究

目的：比较微创23G经结膜无缝线玻璃体手术和传统20G玻璃体手术治疗玻璃体积血的临床效果。方法15例（15眼）患者接受微创23G玻璃体手术（A组）,20例（20眼）患者接受传统20G玻璃体手术（B组）,分析比较这两种手术建立三通道时间、关闭切口时间、术后最佳矫正视力、眼压、术后舒适度、术中术后的并发症及术后巩膜穿刺口的愈合情况等。结果两组建立三通道的时间、关闭切口的时间差异均有统计学意义（t分别=12.51、13.57,P均＜0.05）。 A组和B组术后与术前视力比较均有不同程度的提高,差异有统计学意义（χ2分别=8.85、10.40,P均＜0.05）,两组术后视力比较差异无统计学意义（χ2=0.22,P＞0.05）。两组术后1 d的平均眼压比较,差异有统计学意义（t=1.94,P＜0.05）,而术后3 d、7 d的平均眼压比较,差异均无统计学意义（t分别=0.45、1.11,P均＞0.05）。术后两组自觉舒适度、巩膜穿刺口愈合情况比较,差异均有统计学意义（χ2分别=9.94、7.69,P＜0.05）。两组术中无1例出现医源孔,均未发生严重并发症。3月后末次随访结果示两组均未发生玻璃体再次出血,未发生视网膜脱离。结论23G和20G玻璃体切割术都能有效治疗玻璃体积血的疾病。微创23G玻璃体手术在建立三通道时间、关闭切口的时间和减轻术后巩膜穿刺口的玻璃体嵌顿上有明显优势,且术后舒适度优于传统20G玻璃体手术,在术后视力提高方面,两组疗效相仿。     

增生型糖尿病视网膜病变玻璃体手术硅油填充影响因素分析

目的 探讨增生型糖尿病视网膜病变(PDR)玻璃体手术硅油填充的影响因素.方法 回顾性分析因PDR在我院行玻璃体手术的125例(150眼)患者的临床资料.按照玻璃体手术填充介质将患者分为硅油组[80例(98眼)]与非硅油组[45例(52眼)].分析两组患者的玻璃体手术疗效以及影响PDR玻璃体手术硅油填充的因素.结果 两组...     

玻璃体切除术后白内障超声乳化术

目的 探讨玻璃体切除术后白内障超声乳化术的临床疗效。方法 对41人43眼玻璃体切除术后白内障实行超声乳化手术．手术中单纯行白内障超声乳化9眼。白内障超声乳化I期植入后房型人工晶体15眼,前房型人工晶体4眼。白内障超声乳化联合再次玻璃体切除、硅油填充术8眼。白内障超声乳化联合再次玻璃体切除、惰性气体充填术3眼。白内障超声乳化、人工晶体植入联合小梁切除术1眼。白内障超声乳化、玻璃体腔硅油取出术3眼。结果玻璃体切除术后白内障手术难度大,前房深度不稳定．术后最佳矫正视力较术前视力有提高37眼（声6．04％）,视力未提高4眼（9．30％）,视力下降2眼（4．65％）。结论 玻璃体切除术后白内障采用超声乳化术,减少了并发症,保留了晶状体后囊膜,并可I期或Ⅱ期植入人工晶体,是玻璃体切除术后白内障摘除的较好的手术方式。     

Neurotrophic factor receptors in epiretinal membranes after human diabetic retinopathy

OBJECTIVE: Formation of epiretinal membranes (ERMs) in the posterior fundus results in progressive deterioration of vision. ERMs have been associated with numerous clinical conditions, including proliferative diabetic retinopathy (PDR), but its pathogenic mechanisms are still unknown. This study was conducted to determine whether neurotrophic factor receptors (tyrosine kinase receptors trkA, trkB, and trkC; low-affinity neurotrophin [NT] receptor p75 [p75(NTR)]; glial cell line-derived neurotrophic factor receptor-alpha1 [GFR alpha 1] and GFR alpha 2; and Ret) are involved in the formation of ERMs after PDR. RESEARCH DESIGN AND METHODS: ERM samples were obtained by vitrectomy from 19 subjects with PDR aged 57 +/- 8 years with 17 +/- 8 years of diabetes and 15 subjects with idiopathic ERM. They were processed for RT-PCR analysis. In addition, 11 ERM samples from PDR patients aged 47 +/- 18 years with 13 +/- 4 years of diabetes were processed for immunohistochemical analysis. RESULTS: Expressions of trkA, trkB, trkC, p75(NTR), and Ret mRNAs were similar in both groups. In contrast, GFR alpha 2 expression levels were significantly higher (17 of 19 vs. 2 of 15 subjects in idiopathic ERM, P < 0.0001) in PDR subjects. Accordingly, immunohistochemical analysis revealed expression of GFR alpha 2 protein in all of the 11 ERMs derived from PDR patients, and that region was double-labeled with glial cell-specific markers. On the other hand, GFR alpha 1 expression was lower (8 of 19 vs. 12 of 15 subjects with idiopathic ERM, P = 0.0258) in PDR subjects. CONCLUSIONS: These results suggest a possibility that glial cell line-derived neurotrophic factor receptor (GDNF) subtypes are differently involved in the formation of ERMs.     

Serum 1,25 dihydroxy vitamin D (1,25(OH)2D3), 25 hydroxy vitamin D (25(OH)D) and parathormone levels in diabetic retinopathy

OBJECTIVES: To investigate whether there is a relationship between serum 1,25 dihydroxy vitamin D3 [1,25(OH)2D3], which is an inhibitor of angiogenesis, concentrations and severity of diabetic retinopathy (DR). DESIGN AND METHODS: Serum 1,25(OH)2D3, 25 hydroxy vitamin D [25(OH)D] and parathormone (PTH) concentrations were measured in diabetic patients (n = 66) and nondiabetic healthy subjects (n = 20). RESULTS: The mean serum 1,25(OH)2D3 concentration in diabetic patients was lower than that in nondiabetics (57.3+/-21.44 vs. 89.4+/-18.01 pmol/L, p<0.001); mean 1,25(OH)2D3 concentrations fell with increasing severity of DR [being 63.4+/-17.26 pmol/L for background DR (BDR), 47.7+/-13.27 pmol/L for preproliferative DR (pre-PDR), and 43.1+/-19.45 pmol/L for proliferative DR (PDR)]. Compared with the control group, serum 25(OH)D concentrations were found to be decreased in diabetic patients (p<0.001).There were negative correlations between 1,25(OH)2D3 and age (r = -0.331, p<0.01) and duration of diabetes (r = -0.255, p<0.05). CONCLUSION: From these findings, it was found that there was an inverse relationship between the severity of the retinopathy, i.e., neovascularization, and serum 1,25(OH)2D3 concentrations, being the lowest in PDR and the highest in diabetic patients without retinopathy (NDR) patients. The measurement of serum 1,25(OH)2D3 concentrations might be helpful to predict severity of DR in patients with diabetes mellitus.     

Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure.

Human hepatocyte growth factor (hHGF) has been purified approximately 209,000-fold with 18% yield from plasma of a patient with fulminant hepatic failure. The purification involves heat treatment of plasma, ammonium sulfate precipitation, and chromatography on Affi-Gel Blue, heparin-Sepharose, and hydroxylapatite. Purified hHGF shows several bands with molecular weights between 76,000 and 92,000. Each band shows growth-stimulating activity on cultured hepatocytes which is proportional to the intensity of the band. After reduction of the sample with 2-mercaptoethanol, SDS-PAGE yields two chains with molecular weights of 31,500-34,500 and 54,000-65,000. The effect of hHGF on DNA synthesis by hepatocytes is half-maximal at 3.5 ng/ml. hHGF stimulates proliferation of cultured hepatocytes more effectively than human epidermal growth factor (hEGF) or insulin, and the effect of hHGF is additive or synergistic with the maximal effects of hEGF and insulin. These results suggest that hHGF is a new growth factor which is different from hEGF.     

High vitreous concentration of vascular endothelial growth factor in diabetic patients with proliferative retinopathy using statins

Background. Vascular endothelial growth factor (VEGF) plays an important role in the development of diabetic retinopathy. Previous studies have suggested that angiotensin‐converting enzyme (ACE) inhibitor therapy may reduce vitreous VEGF concentration in diabetic retinopathy. Also HMG CoA reductase inhibitors (statins), known for their beneficial effects on vascular endothelium, might influence vitreous VEGF concentration in diabetic retinopathy.

Aim. Vitreous VEGF concentration of diabetic patients with proliferative retinopathy using statin therapy and/or ACE inhibitor therapy was studied.

Methods. Fifty diabetic patients with proliferative diabetic retinopathy, 21 diabetic control patients without proliferative retinopathy, and 43 non‐diabetic control subjects underwent vitrectomy. Vitreous samples were collected at the beginning of surgery, and VEGF concentration was assessed using a chemiluminescent VEGF immunoassay.

Results. Vitreous VEGF concentration was significantly higher in diabetic patients with proliferative retinopathy using statins than in those not using statins. The diabetic patients with proliferative retinopathy were divided into subgroups according to use of ACE inhibitor and/or statin medication. These groups did not differ significantly in concentration of vitreous VEGF.

Conclusions. Statin therapy is associated with high vitreous VEGF concentration in diabetic patients with proliferative retinopathy. In contrast to previous reports, ACE inhibitor use did not significantly influence vitreous VEGF concentration in these patients.     

Association between subclinical hypothyroidism and proliferative diabetic retinopathy in type 2 diabetic patients: a case-control study

Subclinical hypothyroidism (SCH) is defined as an asymptomatic state characterized by normal serum levels of free thyroxine and elevated serum concentrations of thyrotropin (> 4.0 μU/ml). The association between SCH and type 2 diabetes has been well established. Proliferative diabetic retinopathy (PDR) that is characterized by neovascularization is a leading cause of visual loss in adults worldwide. However, whether SCH is related to PDR has not been studied. This study thus aimed to evaluate the relationship between SCH and PDR in type 2 diabetes. A total of 371 type 2 diabetic subjects were enrolled: 187 subjects with PDR and 184 subjects without diabetic retinopathy (with HbA1c above 6.5% and at least 10 years of diabetes duration). Subjects with PDR had higher blood pressure, higher serum levels of total cholesterol, low-density lipoprotein cholesterol and thyrotropin, and higher urinary albumin excretion rate. Of the 371 diabetics, 83 subjects (22.4%) were diagnosed as SCH (male 12.1% and female 29.9%). The prevalence of SCH in the PDR group (51/187, 27.3%) was higher than that in the subjects without diabetic retinopathy (32/184, 17.4%). Logistic regression analysis showed that after adjusting for compounding variables, SCH was independently related with PDR (p = 0.032, adjusted OR = 2.485). These results indicate that type 2 diabetic patients with PDR are at an increased risk of SCH. A routine screening for thyroid function may thus be considered advisable in PDR subjects. This may be helpful in investigating new strategies preventing or treating PDR in clinical practice.     

CD4(+) T helper cells engineered to produce latent TGF-beta1 reverse allergen-induced airway hyperreactivity and inflammation

T helper 2 (Th2) cells play a critical role in the pathogenesis of asthma, but the precise immunological mechanisms that inhibit Th2 cell function in vivo are not well understood. Using gene therapy, we demonstrated that ovalbumin-specific (OVA-specific) Th cells engineered to express latent TGF-beta abolished airway hyperreactivity and airway inflammation induced by OVA-specific Th2 effector cells in SCID and BALB/c mice. These effects correlated with increased concentrations of active TGF-beta in the bronchoalveolar lavage (BAL) fluid, demonstrating that latent TGF-beta was activated in the inflammatory environment. In contrast, OVA-specific Th1 cells failed to inhibit airway hyperreactivity and inflammation in this system. The inhibitory effect of TGF-beta-secreting Th cells was antigen-specific and was reversed by neutralization of TGF-beta. Our results demonstrate that T cells secreting TGF-beta in the respiratory mucosa can indeed regulate Th2-induced airway hyperreactivity and inflammation and suggest that TGF-beta-producing T cells play an important regulatory role in asthma.     

原发性视网膜脱离伴玻璃体积血的手术治疗

目的探讨原发性视网膜脱离伴玻璃体积血的手术方式及治疗效果。方法对36例（36眼）原发性视网膜脱离伴玻璃体积血的患者行玻璃体切除手术和眼内激光光凝封闭视网膜裂孔,结合环扎加压术或眼内惰性气体C3F8填充。结果术后随访6个月以上,36例（36眼）患者3眼视力无提高,其中1例患者术后再次发生视网膜脱离二次玻切术视网膜复位和硅油填充,2例因白内障加重视力下降,行超声乳化白内障摘除联合人工晶体植入术,术后视力均较术前提高。其余33眼术后视力均较术前提高,视网膜完全复位,裂孔封闭,无玻璃体积血复发。结论原发性视网膜脱离伴玻璃体积血时早期行玻璃体切除和眼内激光光凝封闭视网膜裂孔结合环扎加压术或眼内气体填充是有效的、可靠的方法,且疗效明显。