scholarly journals Methylglyoxal-Induced Retinal Angiogenesis in Zebrafish Embryo: A Potential Animal Model of Neovascular Retinopathy

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Li ◽  
Yantao Zhao ◽  
Shengmin Sang ◽  
TinChung Leung

Methylglyoxal (MG) is an intermediate of glucose metabolism and the precursor of advanced glycation end products (AGEs) found in high levels in blood or tissue of diabetic patients. MG and AGEs are thought to play a major role in the pathogenesis of diabetic retinopathy. In order to determine if zebrafish is valuable to help us understand more about retinopathy, we evaluate if MG induces abnormal vascular change and angiogenesis in zebrafish in a short incubation period. We also used an inhibitor of VEGFR (PTK787) to explore the mechanistic role of VEGF in MG-induced pathogenesis. A transgenic Tg(flk1:GFP) zebrafish line was used, and the embryos were incubated with MG solution and in combination with glucose (to mimic hyperglycemia). Retinal vascular structure visible with fluorescence signal was imaged using fluorescence microscopy. The percentage of vascular area was calculated and found elevated in the MG treatment groups than that in the control group (p<0.01) which indicated increased angiogenesis induced by MG treatment. PTK787 blocked the proangiogenic effects of MG treatment. This study suggests that MG has a potential proangiogenic effect via VEGF signaling in the retina of zebrafish embryos. Therefore, this zebrafish model may be used to study neovascular retinopathy.

Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 18
Author(s):  
Laura Toma ◽  
Camelia Sorina Stancu ◽  
Anca Volumnia Sima

Diabetes and its vascular complications affect an increasing number of people. This disease of epidemic proportion nowadays involves abnormalities of large and small blood vessels, all commencing with alterations of the endothelial cell (EC) functions. Cardiovascular diseases are a major cause of death and disability among diabetic patients. In diabetes, EC dysfunction (ECD) is induced by the pathological increase of glucose and by the appearance of advanced glycation end products (AGE) attached to the plasma proteins, including lipoproteins. AGE proteins interact with their specific receptors on EC plasma membrane promoting activation of signaling pathways, resulting in decreased nitric oxide bioavailability, increased intracellular oxidative and inflammatory stress, causing dysfunction and finally apoptosis of EC. Irreversibly glycated lipoproteins (AGE-Lp) were proven to have an important role in accelerating atherosclerosis in diabetes. The aim of the present review is to present up-to-date information connecting hyperglycemia, ECD and two classes of glycated Lp, glycated low-density lipoproteins and glycated high-density lipoproteins, which contribute to the aggravation of diabetes complications. We will highlight the role of dyslipidemia, oxidative and inflammatory stress and epigenetic risk factors, along with the specific mechanisms connecting them, as well as the new promising therapies to alleviate ECD in diabetes.


2019 ◽  
Vol 3 (1) ◽  
pp. 23-27
Author(s):  
Edy Soesanto ◽  
Edi Dharmana ◽  
Soeharyo Hadisaputro ◽  
Siti Fatimah Muis

Introduction: Bamboo shoot Gigantochloa apus extract has antioxidant compounds that act as lipid peroxidation inhibitors and reduce free radical formation so that it can be used as an anti-inflammatory and anti-oxidative stress in the atherosclerosis. Aim: Knowing the effect of bamboo shoot Gigantochloa apus extract in reducing MDA levels and IL-10 increasing levels in rabbits given atherogenic diet. Methods: This experiment used randomized pre-test and post-test with control group design, in 24 New Zealand White rabbits divided into 4 groups randomly. MDA and IL-10 levels were examined by the ELISA method. Results and conclusion: Bamboo shoot Gigantochloa apus extract can reduce MDA levels and increase IL-10 levels significantly in accordance with increasing doses. The increase of MDA levels in the control group with all treatment groups was different (p = 0.0001), and between the treatment groups and other treatment groups there were also differences (p


1995 ◽  
Vol 268 (6) ◽  
pp. S49 ◽  
Author(s):  
R L Walker ◽  
M E Olson

Because of the increased concern over use of human body fluids in physiology teaching laboratories, we developed an exercise in renal function that utilizes laboratory rats. The purpose is to demonstrate the role of the kidneys in the homeostatic control of extracellular fluid volume, plasma ionic concentrations, and osmolarity. Three treatment groups are utilized: a volume-expanded (access to 1 g/100 ml sucrose) group, a volume-expanded and salt-loaded (access to 0.9 g/100 ml NaCl) group, and a volume-depleted (water-deprived) group. A normovolemic control group (access to tap water) is also included. Rats are housed individually in metabolic cages that allow accurate measurement of fluid intake and urine output. Blood samples are removed via cardiac puncture. The animals recover from this procedure and can be reutilized within 2-3 wk. When class data are pooled, clear trends are seen that demonstrate the volume-, osmo-, and ionoregulatory abilities of the kidneys.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Anousakis-Vlachochristou ◽  
K Toutouzas ◽  
M Kyriakidou ◽  
E Varela ◽  
A Kapelouzou ◽  
...  

Abstract Background Advanced glycation end products (AGPs) promote human aortic smooth muscle cell calcification in vitro. Moreover, reduction of AGPs levels and inhibition of RAGE signaling decrease vascular calcification in vivo in animal studies. The role of AGPs in aortic valve calcification has not been investigated. Purpose We sought to investigate the role of AGPs in aortic valve calcification, in the absence of diabetes mellitus (DM). Methods We used human and animal cohorts. Firstly, we obtained aortic valves from patients without DM that underwent aortic valve replacement due to aortic valve stenosis. We studied the valves with Fourier-Transformed Infrared spectroscopy (FT-IR, Nicolet 6700 spectrometer, with Attenuated Total Reflection-ATR accessory, each spectrum consisted of 120 co-added spectra) in order to evaluate chemical changes. In the animal cohort, New Zealand male rabbits where randomized in calcification diet (normal chow+cholesterol 0,5%+3500 IU ergocalciferol/kg daily) and control group and sacrificed at 2, 4, 6, 8 10 and 12 weeks. The valves were longitudinally assessed with FT-IR. Results A total of 200 human aortic valves were studied (age 64–78). All patients demonstrated characteristic vibrations at the area about 1165 cm-1, where the C-O-C bonds absorb, attributed to AGPs. Thirty six rabbit valves were used, 3 per group. Glucose levels were within normal range and did not differ between groups. The FT-IR spectra of the rabbit aortic valves showed increasing intensity of the C-O-C band at 1165 cm-1 in experimental group in comparison to control group. The band at 1744 cm-1 is attributed to aldehyde formation due to oxidative stress and inflammation. Shifts and shape changes were detected at the bands of amide I and II at 1650 cm-1 and 1550 cm-1, respectively, concerning protein misfolding, fiber formation and sclerosis. The bands in the region 1299–900 cm-1 correspond to phosphate groups of phospholipidsand the formed calcium phosphate salts and non-biological hydroxyapatite Ca3(PO4)2 formation. All vibrations increased significantly longitudinally during experimental diet period. Representative FT-IR spectra of valves Conclusions Advanced glycation end products are detected in human calcified aortic valves irrespectively of DM. Moreover, AGPs correlate with presence and gradual development of aortic valve calcification in experimental rabbit model, along with acidosis, oxidation and protein secondary misfolding. Accumulation of AGPs in valve tissue is implicated in mechanisms of disease development.


2012 ◽  
Vol 108 (8) ◽  
pp. 1435-1442 ◽  
Author(s):  
Andréa Name Colado Simão ◽  
Marcell Alysson Batisti Lozovoy ◽  
Larissa Danielle Bahls ◽  
Helena Kaminami Morimoto ◽  
Tathiana Name Colado Simão ◽  
...  

The aim of the present study was to verify the effects of fish oil and a soya-based product on inflammatory markers and endothelial function measured by NO in women with the metabolic syndrome (MetS). A total of sixty-five women (mean age: 47·9 (sd9·98) years) were studied in a 90-d parallel, randomised design. A control group maintained their usual diet; the second group received 29 g/d of soyabean (kinako); the third group received 3 g/d of fish oiln-3 fatty acids; and the fourth group received fish oil (3 g/d) and kinako (29 g/d). Anthropometric, blood pressure (BP), inflammatory markers, anti-inflammatory marker (adiponectin) and NO concentrations were evaluated. In relation to the baseline values, the group that received fish oil and kinako concomitantly presented a statistically significant decrease in systolic BP (SBP;P < 0·05), whereas there was a significant decrease in diastolic BP (DBP) in the control group (P < 0·05), kinako group (P < 0·01) and fish oil group (P < 0·01) after 90 d. There was a significant increase in adiponectin (P < 0·01) and NO values (P < 0·05) after 90 d in the kinako and fish oil groups. Differences between treatment groups verified a significant decrease (P < 0·05) in DBP in the kinako group after 90 d when compared to the results obtained from the fish oil and kinako groups. In conclusion, the findings of increased serum adiponectin and NO metabolite levels after 90 d, both in the fish oil and soya groups, reinforce the importance of the influence of adiponectin and NO levels on BP decrease in patients with the MetS.


Author(s):  
Lilik Maslachah ◽  
Rahmi Sugihartuti

<p>Background <br />Leukocytes play an important role in the elimination of malaria infection. The leukocyte profile upon elimination of the malaria parasites that have been exposed to antimalarials and are subsequently capable of faster growth has not been researched. The aim of this research was to evaluate the role of mouse leukocytes in the elimination of parasites as shown by the leukocyte profile.</p><p>Methods <br />An experimental research with post test only control group design was conducted involving 24 male mice of the Swiss Albino strain weighing 20 g -30 g, and 2.5 months old. They were randomized into four groups: two control groups (K1, KP) and two treatment groups (P1, P4). Artemisinin at a dose of 0.04 mg/g body weight was given to the mice for 3 days, starting 2 days after infection. The leukocyte profile was observed on the 2nd, 5th, 8th, and 10th day after infection. The results were analyzed by two-way Anova.</p><p>Results <br />As shown in treatment control group KP and treatment group P4, P. berghei that had been passaged in the mice and were still viable after repeated exposure to artemisinin, may cause changes in leukocyte profile. On the 10th day of infection, the neutrophil percentage in group P1 showed a significantly different decrease when compared with the other groups (K1, KP and P4) (p&lt;0.05).</p><p>Conclusion <br />Repeated exposure to artemisinin of mice infected with P. berghei can cause changes in neutrophil profile in mice.</p>


2018 ◽  
Vol 6 (2) ◽  
pp. 131-138
Author(s):  
Ariani Ariani ◽  
Gemala Anjani ◽  
Muchlis Achsan Udji Sofro ◽  
Kis Djamiatun

Background : Sago worm flour (Rhyinchophorus ferrugineus)is a coconut beetle larvae that is processed into flour.This flour contains antioxidants as well as arginine, both of which play a role in modulating oxidative stress including NO involved in immunopathology of cerebral malaria.Objectives : To prove the immunomodulator role of sago worm flour in decreasing circulation  NO level at mice  who received standard antimalarial therapy  Dihydroartemisinin Piperaquine (DHP)Methods : This study was randomized control group post test only design by using 23 Swiss mice which divided into 5 group consist of : K(-) normal mice; K(+) inoculated woth Plasmodium berghei ANKA (PbA); X1 received DHP; X2 received sago worm flour; X3 received both of sago worm flour and DHP. All treatment groups X1,X2 and X3 were inoculated by PbA before treatmen were given. Serum circulation NO level was assessed by ELISA. statistical analysis used was One Way ANOVA followed by Bonferroni post hoc test.Results : The mean  NO level in K(-), K(+), X1, X2, and X3 were 1.008 μmol/mL, K(+) 1.338 μmol/mL; while at treatment X1 1.143 μmol/mL, X2 1.410 μmol/mL, dan X3 0.886 μmol/mL. One way ANOVA showed that they were significantly different (p=0.001). Bonferroni post hoc test of X2 was  proportional to K(+) (p=1.000), whole had NO level lower than either K(+)(p=0.009) or X2 (p=0.002). Conclusion : The immunomodulatory effects of sago worm flour (Rhyinchophorus ferrugineus) reduced circulating NO levels in standard antimalarial therapy recipients.


2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Masayoshi Takeuchi ◽  
Jun-ichi Takino ◽  
Sho-ichi Yamagishi

Diabetic complications are a leading cause of acquired blindness, end-stage renal failure, and accelerated atherosclerosis, which are associated with the disabilities and high mortality rates seen in diabetic patients. Continuous hyperglycemia is involved in the pathogenesis of diabetic micro- and macrovascular complicationsviavarious metabolic pathways, and numerous hyperglycemia-induced metabolic and hemodynamic conditions exist, including increased generation of various types of advanced glycation end-products (AGEs). Recently, we demonstrated that glyceraldehyde-derived AGEs, the predominant structure of toxic AGEs (TAGE), play an important role in the pathogenesis of angiopathy in diabetic patients. Moreover, recent evidence suggests that the interaction of TAGE with the receptor for AGEs (RAGE) elicits oxidative stress generation in numerous types of cells, all of which may contribute to the pathological changes observed in diabetic complications. In this paper, we discuss the pathophysiological role of the TAGE-RAGE system in the development and progression of diabetic retinopathy.


Author(s):  
Pavithra D ◽  
Praveen D ◽  
Vijey Aanandhi M

Aim and Objective: The aim of the study was to evaluate the role of Vitamin E supplementation in Type II diabetes mellitus (DM), to determines whether people with Type II DM treated with hypoglycemic agents alone, with or without Vitamin E, to determines the drug interaction in such treatment regimen, and to evaluates the Safety of the regimen.Methods: Type II DM patients with or without complications were included in this study along with serum glycated hemoglobin (HbA1c) concentration between 7.5% and 9.5%. They are divided into test group (which received hypoglycemic agent along with Vitamin E 4000 IU) and control group. Body mass index (BMI) status, fasting blood sugar (FBS), and post-prandial blood sugar (PPBS) were noted once in a month, HbA1c percentage, total cholesterol level (TC), and serum Vitamin E level were estimated and noted for every 3 months at total 9 months of this study. Patients with other comorbid conditions were prominent in this study.Results: It is perceptible with the analysis of obtained data that FBS, PPBS, HbA1c percentage, TC level, and BMI status of the patients were declined gradually in test group (patients with Vitamin E supplementation along with their hypoglycemic agents). Thus, antioxidant therapy is highly propitious whereby delaying the onset of complications in patients with DM. This development would be highly helpful for diabetic patients.


1987 ◽  
Author(s):  
C Boschetti ◽  
A Vicari ◽  
E Cofrancesco ◽  
A Della Volpe ◽  
G Moreo ◽  
...  

When heparin is injected i.v. as a bolus, PF4 but not (β-throm boglobulin ((βTG) is released immediately. HR-PF4 is not liberated from platelets but from the endothelial cells of vessels which serve as storage sites. The role of platelet activation in diabetic microvascular disease is still controversial, however there is experimental evidence of vascular injury and hemostatic activation preceding the appearance of microvascular disease. The contradictory results so far obtained in man may be partly attributed to the heterogeneity of the diabetic patients studied. We studied 20 insulin-dependent diabetics (age 21-40) in stable metabolic equilibrium (mean HbAlc=7.6%). 10 without fluoroangiographic evidence of retinopathy (Group l) and 10 with retinopathy (Group 2). None had signs or symptoms of macrovascular disease. The control group consisted of 10 healthy volunteers (age 22-39). No medication except insulin was taken for at least 10 days preceding the study. 12 h before the study all subjects received aspirin 500 mg p.o. Plasma (βTG and PF4 were determined before (basal) and 5,30,90 min after a heparin bolus i.v. (5000 U). Protein C, factor VIIIR:Ag and tissue plasminogen activator were also measured in plasma.


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