Objective To observe the effect of pigment epithelium-derived factor (PEDF）on glutamate metabolism in diabetic rat retina. Methods 78 Sprague-Dawley rats were randomly divided into the model group, model control group, PEDF intervention group and intervention control group. There were some dead and euglycemia rats at the end of experiment, so only 12 rats in each group were included in the statistical analysis. The diabetic retinopathy rat model of the model, PEDF intervention and intervention control group were induced with streptozotocin injection. The rats in the model group were not intervened. The monthly-age matched normal rats of model group were in the model control group. The left eyes of rats were received intravitreal injection with 5 mu;l (0.1 mu;g/mu;l) PEDF (PEDF intervention group) or 5 mu;l phosphate buffer solution (intervention control group). The expressions of L-glutamate/L-aspartate transporter in retina were analyzed by western blot and real time RT-PCR techniques and glutamate content in retina was analyzed by high-pressure liquid chromatography (HPLC). Cultured rat Muuml;ller cells were divided into the control,experimental, PEDF intervention and intervention control group, GLAST expressions were detected by fluorescence immunofluorescence and real-time RT-PCR techniques. The glutamate up-take activity of Muuml;ller cells was determined by intracellular [3H] labeled D, L-glutamate concentration with scintillation counting. Results Western blot and real-time RT-PCR showed that GLAST expression decreased (real-time RT-PCR：t=8.86,Plt;0.01；Western blot：t=3.42,P＜0.05), glutamate content increased（t=4.01,P＜0.05）in model group compared with the model control group; GLAST expression increased (real-time RT-PCR：t=3.56,P＜0.05；Western blot：t=3.52,P＜0.05), glutamate content decreased（t=4.36,P＜0.05）in the PEDF intervention group compared with the intervention control group. Real-time RT-PCR and fluorescence immunofluorescence showed that high glucose down-regulate GLAST expressions in Muuml;ller cells (rea-time RT-PCR：t=3.48,P＜0.05；fluorescence immunofluorescence：t=4.72,P＜0.05 ) and impair glutamate uptake activity of Muuml;ller cells (t=3.81, Plt;0.05). Under high glucose conditions, PEDF up-regulated GLAST expression significantly (real-time RT-PCR：t=6.82,P＜0.01；fluorescence immunofluorescence：t=3.72,P＜0.05) and ameliorated the glutamate up-take activity of Muuml;ller cells（t=4.14, Plt;0.05). Conclusions In diabetic rats, PEDF may improve the activity of GLAST in Muuml;ller cells, thus ameliorate retinal glutamate metabolism and inhibit death of retinal ganglion cells.
Objective
To detect the difference of the light sensitivity in the central visual field between normal people and type Ⅱ diabetic patients without diabetic retinopathy, and evaluate the effect of perimetric examination in early diagnosis of diabetic retinopathy.
Methods
The light sensitivity at the 80 locations in the central field was measured by Dicon field analyzer (model TKS-4000) in 76 normal eyes of 44 normal volunteers aged from 45 to 72 years and 75 eyes of 40 type Ⅱ diabetic patients without retinopathy aged from 46 to 71 years.
Results
For the diabetic patients without diabetic retinopathy, the light sensitivity of locations decreased by 4-8 dB,and there were some decreased light sensitivity areas. The mean light sensitivity of three zones of the central field had significant reduction in the diabetic patients as compared with the control group(Plt;0.001).
Conclusion
The retinal neurosensory function of diabetic patients is damaged in some degrees before diabetic retinopathy occured, and no relationship is found between the decrease of retinal light sensitivity and localized blood-retinal barrier leakage. It is suggested that examination of central field with computerized perimetry has certain clinical significance in early diagnosis of diabetic retinopathy.
(Chin J Ocul Fundus Dis, 2002, 18: 218-220)
Objective To analyze the causes of missed diagnosis of sleep apnea hypopnea syndrome ( SAHS) . Methods 42 missed diagnosed cases with SAHS from May 2009 to May 2011 were retrospectively analyzed and related literatures were reviewed. Results The SAHS patients often visited the doctors for complications of SAHS such as hypertension, diabetes mellitus, metabolic syndrome, etc. Clinical misdiagnosis rate was very high. Lack of specific symptoms during the day, complicated morbidities, and insufficient knowledge of SAHS led to the high misdiagnosis rate and the poor treatment effect of patients with SAHS. Conclusion Strengthening the educational propaganda of SAHS, detail medical history collection, and polysomnography monitoring ( PSG) as early as possible can help diagnose SAHS more accurately and reduce missed diagnosis.
ObjectiveTo investigate the establishment of rat models with chronic obstructive pulmonary disease (COPD) combined with type 2 diabetes mellitus (DM).
MethodsEighty Sprague-Dawley (SD) male rats were randomly divided into four groups:COPD group (n=20), DM group (n=20), COPD combined with DM group (n=20) and normal group (n=20). COPD rats were established by cigarette smoke. Type 2 diabetes rats were modeled by streptozotocin injection. COPD combined with DM rats were modeled by cigarette smoking and streptozotocin injection at the same time. Pathological examination and blood glucose were tested after three months.
ResultsBronchial epithelium was seriously shedding in COPD+DM group, with alveolar structure damaged and some alveolar fused into bullae. The blood glucose level in COPD+DM group was (27.1±1.1) mmol/L, which was statistically different from other groups (P<0.05).
ConclusionRat model of COPD combined with type 2 DM could be established by cigarette smoking and streptozotocin injection, which can provide an animal model for further medical research.
ObjectiveTo systematically review the preventive effect of breastfeeding intensity and duration on progression to pre-diabetes mellitus (DM) and DM among females with prior gestational diabetes mellitus (GDM).MethodsPubMed, Web of Science, CNKI, and WanFang Data databases were electronically searched to collect cohort studies on the correlation of GDM and breastfeeding from inception to January 8th, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Meta-analysis was then performed using Stata 16.0 software.ResultsA total of 29 cohort studies were included. The results of the meta-analysis showed that breastfeeding could lower the risk of pre-DM (RR=0.64, 95%CI 0.57 to 0.71, P<0.001) and DM (RR=0.75, 95%CI 0.66 to 0.86, P<0.001) among females with prior GDM. Subgroup analysis showed that breastfeeding exhibited protective effects against pre-DM after 0 to 6 months as well as 6 to 12 months. Both breastfeeding for 0 to 6 months and over 12 months could decrease the risk of DM. These effects became prominent with the extension of the follow-up period. However, no significant association was observed between breastfeeding and recurrence of GDM (RR=0.72, 95%CI 0.47 to 1.09, P=0.14).ConclusionsBreastfeeding may be a major contributor in protecting against pre-DM and DM among females with prior GDM history. Due to limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusions.
ObjectiveTo observe and analyze the correlation between macular microvascular parameters and urinary albumin to creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM). MethodsA cross-sectional study. From October 2017 to April 2018, 100 eyes of 100 patients (T2DM) and 27 eyes of 27 healthy controls (the control group) were enrolled in Xuzhou First People’s Hospital. All subjects underwent anterior segment examination via slit-lamp biomicroscopy, dilated fundus examination, 7-field fundus photographs, OCT angiography (OCTA), the fasting glucose test, glycosylated hemoglobin (HbA1c), urinary albumin, urinary creatinine and UACR levels determination. Height and weight measurement were taken for calculating body mass index (BMI). Diabetic retinopathy was ruled out by fundoscopic examinations and 7-field fundus photographs in T2DM patients. According to the UACR, patients in the T2DM group were subdivided into A1 group (UACR< 30 mg/g), A2 group (UACR 30-300 mg/g), and A3 group (UACR>300 mg/g), with 38 cases and 38 eyes respectively , 40 cases with 40 eyes, 22 cases with 22 eyes. A 6 mm×6 mm scanning area centered on the macular fovea were scanned for right eye using a frequency domain OCTA instrument, which were divided into three concentric circles centered on the macular fovea by the software automatically. The foveal zone was defined as a circular area measuring 1 mm in diameter, the parafoveal zone was described as a middle circle area measuring 1-3 mm in diameter, and the perifoveal zone was an outer circle area measuring 3-6 mm in diameter. The vessel density of superficial capillary plexus (SCP) and deep capillary plexus (DCP), foveal avascular area (FAZ) and perimeter (PERIM), non-circularity index (AI) were measured. The correlation between the macular vessel density, FAZ and UACR was analyzed by Spearman correlation analysis. ResultsA1 group, A2 group, A3 group, and normal control group. The macular area SCP and DCP (F=13.722, 5.644), foveal area (F=4.607, 4.719), parafoveal area (H=23.142, F=2.904), the blood flow density of the area around the fovea (F=12.292, H=10.946), the difference was statistically significant (P＜0.05); with the increase of UACR, the blood flow density of each area of SCP and DCP showed a downward trend. The results of correlation analysis showed that the blood flow density of the whole SCP, parafoveal area, and surrounding area of T2DM patients was negatively correlated with UACR (r=－0.376, －0.240, －0.364, －0.347, P＜0.05). There were no correlation among fasting plasma glucose, HbAlc and UACR (r=0.179, 0.085, P＞0.05). There were no correlation among blood flow density in BMI, SCP foveal area, DCP and UACR (|r|＜0.3, P＞0.05). ConclusionThe whole, parafovea and perifovea vessel density values of SCP in T2DM eyes without DR are negatively correlated with UACR.
Objective To observe the effect of intravitreal injection of mouse nerve growth factor (NGF) on interphotoreceptor retinoid-binding protein (IRBP) in the vitreous of diabetic rats at early stages. Methods Ninety-six male Sprague Dawley (SD) rats were divided into control group (group A, 24 rats) and experimental group (72 rats). The rats in experimental group were induced with streptozotocin injection for diabetic retinopathy model, and then randomly divided into positive control group (group B), normal saline group (group C) and NGF group (group D), 24 rats in each group. The rats in the group A and B were not intervened. The rats were received intravitreal injection with 4mu;l normal saline (group C) or 4 mu;l (0.5 mu;g/mu;l) NGF (group D). At 2, 4, 6 and 8 weeks after injection, IRBP levels were detected by enzymelinked immunosorbent assay (ELISA); hematoxylin-eosin (HE) staining and light microscope were used to observe the morphological changes of the retina; transmission electron microscope was used to observe the retinal ultrastructure.Results At 2 weeks after injection, there was no significant difference in IRBP expression between group A,B,C and D (F=2.833，P=0.052). At 4, 6, 8 weeks after injection, the differences of IRBP expression between group A, B, C and D were significant (F=22.252, 108.459, 105.726; P=0.000). At different time points after injection, there was no significant difference in IRBP expression of group A (F=1.462, P=0.241), but there were significant differences in IRBP expression of group B, C and D (F=150.98, 63.519, 64.604; P=0.000). Light microscope found that the retinal structure was clear in group A and in group B, C, D at 2, 4 weeks after injection; the retinal thickness were thinner in group B, C, D at 8 weeks after injection. Transmission electron microscope displayed that the structure of rod outer segments was clear in group A and in group B, C, D at 2 weeks after injection; partly unclear structure of rod outer segments and slightly enlarged gap were observed in group B, C, D at 4, 8 weeks after injection. Conclusion Intravitreal injection with NGF can stabilize the IRBP expression in the vitreous of diabetic rats at early stages effectively.
Objective The bone marrow mesenchymal stem cells (BMSCs) have the capacity to differentiate into insul in-producing cells (IPCs) in vitro. However, low differentiation efficiency and poor maturity are the main obstacles. To investigate the feasibil ity of BMSCs differentiation into IPCs in diabetic pancreatic microenvironment of pigs. Methods BMSCs were isolated and purified from the bone marrow of a 4-week-old male pig. Fifteen female pigs (aged 8 to 10 weeks, weighing 8 to 10 kg) were randomly divided into 3 groups: normal control group (group A, n=5), diabetic control group (group B, n=5), and BMSCs transplanted group (group C, n=5). The pigs of groups B and C were treated by auris vein injections of styeptozocin and alloxan for 3 days to induce diabetes mell itus (DM) model, whose blood glucose level 2 days all greater than 17 mmol/L was successful DM model. A total of 1.1 mL of the 3rd passage BMSCs labeled with enhanced green fluorescent protein (EGFP), with cell density of 5 × 107/ mL, were injected into subcapsular pancreas of group C at multi ple points, normal saline at the same dosage into those of groups A and B. After 30 days of monitoring blood glucose, the histological analysis of islet number and size were done; the immunofluorescence staining was used to detect the protein expression of insul in in the new-formed islets. The EGFP+ cells were collected from the sections using laser-capture microdissection; RT-PCR was used to detect insulin mRNA and pancreatic and duodenal homeobox factor 1 (PDX1) mRNA expressions from EGFP+ cells, and the insul in and sexdetermining region of the Y chromosome (SRY) genes were detected by fluorescence in situ hybridization (FISH). Results The blood glucose level decreased significantly in group C when compared with that in group B from 18 days and gradually decreased with time (P lt; 0.05). The histological observation showed that the number of islets was increased significantly in group C when compared with that in group B (10.9 ± 2.2 vs. 4.6 ± 1.4, P lt; 0.05), and there was no significant difference when compared with that in group A (10.9 ± 2.2 vs.12.6 ± 2.6, P gt; 0.05). The size of new-formed islets in group C was significantly smaller than that in group A [(47.2 ± 19.6) μm vs. (119.6 ± 27.7) μm, P lt; 0.05]. The immunofluorescence staining showed that new-formed islets of group C expressed insulin protein. RT-PCR showed that the microdissected EGFP+ cells of group C expressed insulin mRNA and PDX-1 mRNA. FISH showed that the new-formed islet cells of group C contained SRY gene in Y chromosome and insulin double positive cells. Conclusion BMSCs can differentiate into IPCs in diabetic pancreatic microenvironment of pigs.
【Abstract】ObjectiveTo investigate the effects of cholecystokinin （CCK） on diabetes mellitus with cholecystolithiasis. MethodsRelevant literatures of recent years were reviewed. ResultsCCK exists widely in human body．On the one hand, CCK enhances cholecystolithiasis by causing diabetes. On the other hand, its pathological changes can also lead to cholecystolithiasis. Besides, it is possibility that the CCKrelated gene abnormality is the common cause of diabetes and cholecystolithiasis. ConclusionCCK plays an important role in diabetes mellitus complicated with cholecystolithiasis. However, there is much yet to be known about CCK．
Purpose
To investigate the status of proliferation and activation of vascular endothelial cells in preretinal neovascular membranes from patients with insulin dependent diabetetes mellitus(IDDM)by means of immunohistochemical techniques.
Methods
Status of vascular endothelial cells in 18 preretinal neovascular membranes from 18 patients with IDDM was studied by double-immunofluorescence technique and the alkaline phosphataes-anti-alkaline phosphatase(APAAP)technique and compared the findings with the main clinical features of the patients.
Results
Of 18 vascularized membranes,16(88.9%)contained proliferating endothelial cells (positive for proliferating vascular endothelial cell marker EN 7/44) and 14 (77.8%) were positive for endothelial cell activation marker anti-VCAM-1;furthermore,by using a double staining technique,we found that in 14 of the 16 cases(87.5%) the proliferating vascular endothelial cells were activated (expressing VCAM-1).
Conclusion
The proliferation and activation of the vascular endothelial cells of the newly formed vessels in preretinal neovascular membranes suggests the significance of the vascular endothelial cells in the pathophysiology and the progress of proliferative diabetic retinopathy.
(Chin J Ocul Fundus Dis,1998,14:141-143)
