scholarly journals A Hypercaloric Diet Induces Early Podocyte Damage in Aged, Non-Diabetic Rats

2021 ◽  
Vol 55 (S4) ◽  
pp. 96-112

Background/Aims: The number of patients of older age with metabolic syndrome, obesity, and associated kidney disease, which is characterized by podocyte damage, glomerular hypertrophy, and focal segmental glomerulosclerosis (FSGS), is increasing worldwide. Animal models that would reflect the development of such kidney diseases could facilitate the testing of drugs. We investigated the renal effects of a long-term high caloric diet in aged rats and the potential effects of drugs used to treat metabolic syndrome. Methods: We analyzed nine-month-old male and female Sprague Dawley rats fed five months with a normal diet (control group) or high-fat-high-carbohydrate diet (HFHCD group). Two additional groups were fed with HFHCD and treated with drugs used in patients with metabolic syndrome, i.e., the glucagon-like peptide receptor 1 agonist liraglutide (HFHCD+liraglutide group) or metformin (HFHCD+metformin group). Results: Except an increase of waist circumference as a sign of visceral obesity, the HFHCD diet did not induce metabolic syndrome or obesity. There were no significant changes in kidney function and all groups showed similar indices of glomerular injury, i.e., no differences in glomerular size or the number of glomeruli with FSGS or with FSGS-precursor lesions quantified by CD44 expression as a marker of parietal epithelial cell (PEC) activation. Analysis of ultrastructural morphology revealed mild podocyte stress and a decrease of glomerular nestin expression in the HFHCD group, whereas podocin and desmin were not altered. HFHCD did not promote fibrogenesis, however, treatment with liraglutide led to a slightly increased tubulointerstitial damage, immune cell infiltration, and collagen IV expression compared to the control and HFHCD groups. Conclusion: A five-month feeding with HFHCD in aged rats induced mild podocyte injury and microinflammation, which was not alleviated by liraglutide or metformin.

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A F Bestavashvili ◽  
A L Bestavashvili ◽  
I Dhif ◽  
D Tuter ◽  
D Gognieva ◽  
...  

Abstract Introduction Metabolic syndrome (MS) as a “cluster” of interrelated disorders, including insulin resistance, visceral obesity, dyslipidemia, and hypertension, is an serious clinical problem that is a high risk factor for the development of type 2 diabetes, acceleration of the development and progression of cardiovascular diseases, and such increasingly common liver damage like non-alcoholic fatty liver disease. According to a number of authors, metabolic syndrome is a reversible condition, and with early diagnosis and treatment, a reduction in the severity of manifestations of this syndrome can be achieved. A significant role in the treatment of MS and obesity is played by non-drug methods – dosed physical activity, diet, various physiotherapeutic procedures, as well as interval hypoxic-hyperoxic training (IHHT). Objective Evaluation of the effect of interval hypoxic-hyperoxic training (IHHT) on the components of metabolic syndrome, and the possibility of their reversal recovery. Materials and methods The study included 65 patients (33 men) with metabolic syndrome, aged 29–66 years. The patients were divided into 2 groups: study and control (the groups were matched by sex, age, presence of MS components and number of comorbidities). Initially, anthropometric, laboratory and instrumental studies were carried out. The patients of the main group underwent a course of IHHT for 3 weeks, 5 days a week (15 workouts). Patients in the control group underwent a course of training simulating IHHT (placebo), which also consisted of 15 trainings. The duration of one procedure was 40 minutes. Next day after the end of the training course, the changes in all initial parameters were assessed. Results The statistical significance of changes after the IGGT course was assessed using the Wilcoxon test as p<0.05 and was detected in the main group according to the following parameters: reduction in arterial stiffness, measured using CAVI (Cardio-Ankle Vascular Index, on the Fukuda Denshi ap.), a decrease in the stage of liver fibrosis and stiffness of liver tissue (was realized by a non-invasive method, a liver elastometry, on the FibroScan ap. Echosense), a decrease in high-sensitivity C-reactive protein, heat shot protein-70, a decrease in total cholesterol, low density lipoproteins, triglycerides levels. According to nitric oxide, transforming growth factor beta-1, heart-type fatty acid binding protein, there was no significant dynamics after the IHHT course in both groups. There was also a tendency towards a decrease in the indices of the abdominal/hip circumference, weight, and in blood pressure, but this results was not statistically significant, due to the insufficient power of the study (a small number of patients). Conclusions IHHT is a safe, well-tolerated procedure and is recommended in the therapeutic and prophylactic plan for patients with metabolic syndrome, and is effective in correcting and minimizing the components of this syndrome. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers “Digital biodesign and personalized healthcare”


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Wiwit A. W. Setyaningsih ◽  
Nur Arfian ◽  
Akbar S. Fitriawan ◽  
Ratih Yuniartha ◽  
Dwi C. R. Sari

Background. Diabetes mellitus (DM) is marked by oxidative stress, inflammation, and vascular dysfunction that caused diabetic nephropathy that resulted in end-stage renal disease (ESRD). Vascular dysfunction is characterized by an imbalance in vasoconstrictor and vasodilator agents which underlies the mechanism of vascular injury in DM. Additionally, diminished podocytes correlate with the severity of kidney injury. Podocyturia often precedes proteinuria in several kidney diseases, including diabetic kidney disease. Centella asiatica (CeA) is known as an anti-inflammatory and antioxidant and has neuroprotective effects. This research aimed to investigate the potential effect of CeA to inhibit glomerular injury and vascular remodeling in DM. Methods. The DM rat model was induced through intraperitoneal injection of streptozotocin 60 mg/kg body weight (BW), and then rats were divided into 1-month DM (DM1, n = 5), 2-month DM (DM2, n = 5), early DM concurrent with CeA treatment for 2 months (DMC2, n = 5), and 1-month DM treated with CeA for 1-month (DM1C1, n = 5). The CeA (400 mg/kg BW) was given daily via oral gavage. The control group (Control, n = 5) was maintained for 2 months. Finally, rats were euthanized and kidneys were harvested to assess vascular remodeling using Sirius Red staining and the mRNA expression of superoxide dismutase, podocytes marker, ACE2, eNOS, and ppET-1 using RT-PCR. Results. The DM groups demonstrated significant elevation of glucose level, glomerulosclerosis, and proteinuria. A significant reduction of SOD1 and SOD3 promotes the downregulation of nephrin and upregulation of TRPC6 mRNA expressions in rat glomerular kidney. Besides, this condition enhanced ppET-1 and inhibited eNOS and ACE2 mRNA expressions that lead to the development of vascular remodeling marked by an increase of wall thickness, and lumen wall area ratio (LWAR). Treatment of CeA, especially the DMC2 group, attenuated glomerular injury and showed the reversal of induced conditions. Conclusions. Centella asiatica treatment at the early stage of diabetes mellitus ameliorates glomerulosclerosis and vascular injury via increasing antioxidant enzymes.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Kayoko Miyata ◽  
Ryousuke Satou ◽  
Akemi Sato ◽  
Dale Seth ◽  
Allison Davis ◽  
...  

The development of glomerulonephritis causes glomerular injury and reduced renal function and is associated with increased renin release. The aims of this study were to demonstrate activation of intrarenal RAS in glomerulonephritis and determine the effects of DRI with aliskiren on progression of glomerulonephritis associated renal injury induced by administration of an anti-Thy1.1 antibody. We divided rats into 3 groups; control group, anti-Thy1.1 glomerulonephritis group and anti-Thy1.1 glomerulonephritis treated with aliskiren (30 mg/kg/day) group. In the anti-Thy1.1 rats, protein excretion and micro albumin excretion levels increased markedly after anti-Thy1.1 antibody injection. The increases in protein (94.7 ± 13.0 mg/day) and micro albumin (7.5 ± 2.6 mg/day) excretions were attenuated by aliskiren treatment (43.6 ± 4.5 mg/day of protein and 2.6 ± 0.7 mg/day of micro albumin). The glomerular expansion score was significantly higher in the anti-Thy1.1 group compared to the control group. The anti-Thy1.1 group also showed elevation of intrarenal TGF-β and PAI-1 mRNA levels compared with control rats. The progression of glomerular expansion and elevation of these mRNA levels was prevented by aliskiren. Importantly, the anti-Thy1.1 group had markedly increased urinary angiotensinogen (AGT) excretion at days 3 (3102.9 ± 683.8 ng/day), but these changes were markedly suppressed by aliskiren treatment (441.3 ± 104.8 ng/day). AGT protein expression in the kidney was significantly lower in the aliskiren treatment group compared with anti-Thy1.1 group (western blot, 0.8 ± 0.04 and immunohistochemistry, 0.7 ± 0.11 relative to anti-Thy1.1 group). Furthermore, plasma renin activity (PRA) and plasma angiotensin (Ang) II levels were significantly increased in the anti-Thy1.1 group and aliskiren treatment prevented the elevation of PRA and plasma Ang II. Anti-Thy1.1 antibody also elicited left ventricular hypertrophy and fibrosis, which were not ameliorated by aliskiren. These results demonstrate that DRI prevents or reduces intrarenal RAS activation and glomerular injury in progressive glomerulonephritis. Accordingly, DRI may be an effective approach to treat glomerulonephritis as well as other intrarenal RAS associated kidney diseases.


2016 ◽  
Vol 73 (10) ◽  
pp. 910-920 ◽  
Author(s):  
Gordana Petrovic ◽  
Goran Bjelakovic ◽  
Daniela Benedeto-Stojanov ◽  
Aleksandar Nagorni ◽  
Vesna Brzacki ◽  
...  

Introduction/ aim. Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease of a broad histological spectrum, characterized by the accumulation of triglycerides in more than 5% of hepatocytes in the absence of consuming alcohol in quantities harmful to the liver. The aim of our study was to determine the importance of anthropometric and laboratory parameters as well as metabolic syndrome (MS) for the diagnosis of NAFLD and to estimate their influence on the degree of liver steatosis as evaluated by ultrasound (US). Methods. The study included 86 participants, 55 of whom had fatty liver diagnosed by ultrasound and they comprised the study group. The control group consisted of 31 control subjects. During the course of hospitalization at the Clinic of Gastroenterology and Hepatology, Clinical Centre Nis, the patients had their anamnesis taken, and anthropometric measurements as well as biochemical blood analyses and abdominal ultrasound were performed. Results. The patients with NAFLD had statistically higher values of body mass index (BMI), waist circumference (WC), systolic (SBP) and diastolic blood pressure (DBP), levels of alanin and aspartate aminotransferase (ALT, AST), gamma-glutamyl transpeptidase (GGT) (p<0.001), low-density lipoprotein cholesterole (LDL), total bilirubin (TBIL) (p<0.05), total cholesterol (p<0.01), triglycerides (TGL), urates, C-reactive protein (CRP), ferritin, fibrinogenes, fasting blood glucose (FBG), insulin and Homeostasis Model Assessment (HOMA-IR) (p<0.001), whereas the levels of high-density lipoprotein cholesterol (HDL) were higher in the control group (p<0.05). In the NAFLD group, there were statistically significantly more patients with hypertension (72.73% vs. 12.90%, p<0.001) and type 2 diabetes mellitus (DM) (47.27%). Metabolic syndrome was determined in 48 (87.27%) patients of the study group. An equal number of patients, 16 of them (29.09%), had 3, 4 and 5 components of MS. In the NAFLD group there were 17 overweight (30.91%) (BMI from 25 kg/m2 to 29.9 kg/m2) and 38 (69.09%) obese patients. (BMI ? 30.0 kg/m2). The largest number of patients in the obesity group, 22 (40.00%) of them, had the first degree obesity (BMI from 30 kg/m2 to 34.99 kg/m2). The largest number of the NAFLD group patients - 23 (41.82%), had an ultrasound finding of grade 3 fatty liver, 20 patients (36.36%) had grade 2 and 12 (21.82%) grade 1 fatty liver. Kruskal-Wallis test and ANOVA analysis showed statistically significant differences between groups with different US grade for insulin, LDL-cholesterol, WC, BMI (p<0.05), as well as HOMA-IR and body weight (BW) (p<0.01). Metabolic syndrome was statistically more present in patients with US finding grades 2 and 3 (p<0.01) in relation to grade 1 US finding, as well as obesity, hypertension and DM type 2 (p<0.05). Conclusion. The results of our study have confirmed that a high percentage of patients with high risk factors (DM, MS, dyslipidemia, hypertension) have NAFLD.


Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 293 ◽  
Author(s):  
Ana Santos ◽  
Ana Santos ◽  
Clara Castro ◽  
Luís Raposo ◽  
Sofia Pereira ◽  
...  

The determinants for gastroenteropancreatic neuroendocrine tumors (GEP-NET) recent burden are matters of debate. Obesity and metabolic syndrome (MetS) are well established risks for several cancers even though no link with GEP-NETs was yet established. Our aim in this study was to investigate whether well-differentiated GEP-NETs were associated with obesity and MetS. Patients with well-differentiated GEP-NETs (n = 96) were cross-matched for age, gender, and district of residence with a control group (n = 96) derived from the general population in a case-control study. Patients presented gastro-intestinal (75.0%) or pancreatic (22.9%) tumors, grade G1 (66.7%) or G2 (27.1%) with localized disease (31.3%), regional metastasis (16.7%) or distant metastasis (43.8%) at diagnosis, and 45.8% had clinical hormonal syndromes. MetS was defined according to Joint Interim Statement (JIS) criteria. Well-differentiated GEP-NETs were associated with MetS criteria as well as the individual components’ waist circumference, fasting triglycerides, and fasting plasma glucose (p = 0.003, p = 0.002, p = 0.011 and p < 0.001, respectively). The likelihood of the association was higher when the number of individual MetS components was greater than four. MetS and some individual MetS components including visceral obesity, dyslipidemia, and increased fasting glucose are associated with well-differentiated GEP-NET. This data provides a novel insight in unraveling the mechanisms leading to GEP-NET disease.


2018 ◽  
Vol 26 (1) ◽  
pp. 86-95
Author(s):  
D. K. Muhabbatov ◽  
M. K. Gulov ◽  
B. M. Hamroev

Aim of work: to study the incidence of components of metabolic syndrome in patients with anal fistulae, to analyze combinations of different components of metabolic syndrome and types of pararectal fistulae. Materials and Methods. A clinical examination of 508 patients (85.2% – men; 21.5% at the age of 20-39 years, 43.9% – 40-59 years, 34.6% – ≥60 years) with anal fistulae (of them 48.0% were transsphincteric and 29.3% – extrasphincteric fistulae) who underwent treatment in the department of coloproctology of municipal clinical hospital №5 of Dushanbe in the period from 2010 to 2015, was conducted with the aim of identification of components of metabolic syndrome. Results. In 282 patients (55.5% of the total number of patients with anal fistulae, 90.8% of them being men) components of metabolic syndrome were identified: obesity – in 229 patients (45.1% of the total patients with anal fistulae), arterial hypertension – in 115 patients (22,6%), type 2 diabetes mellitus – in 58 patients (11.4%), IHD – in 8 patients (1.6%). In the presence of components of metabolic syndrome the recurrent forms of fistulae were recorded in 16.3% of cases (in the absence – in 12.8% of cases), and complicated forms – extrasphincteric (29.3%) predominated over intrasphincteric forms (22.7%); in control group the proportion of the mentioned forms was 24.8% and 29.2%, respectively. Transsphincteric forms were most common in both groups (48.0% and 46.0%). Conclusions. Components of metabolic syndrome in different combinations were identified in more than half (55.5%) the patients with anal fistulae (obesity – 45.1%, arterial hypertension – 22.6%, 2 type diabetes mellitus – 11.4%, IHD – 1.6%). A tendency was recorded to a more common recurrence of anal fistulae and to a more complicated forms of anal fistulae in patients with components of metabolic syndrome.


2018 ◽  
Vol 26 (1) ◽  
pp. 86-95 ◽  
Author(s):  
D. K. Muhabbatov ◽  
M. K. Gulov ◽  
B. M. Hamroev

Aim of work: to study the incidence of components of metabolic syndrome in patients with anal fistulae, to analyze combinations of different components of metabolic syndrome and types of pararectal fistulae. Materials and Methods. A clinical examination of 508 patients (85.2% – men; 21.5% at the age of 20-39 years, 43.9% – 40-59 years, 34.6% – ≥60 years) with anal fistulae (of them 48.0% were transsphincteric and 29.3% – extrasphincteric fistulae) who underwent treatment in the department of coloproctology of municipal clinical hospital №5 of Dushanbe in the period from 2010 to 2015, was conducted with the aim of identification of components of metabolic syndrome. Results. In 282 patients (55.5% of the total number of patients with anal fistulae, 90.8% of them being men) components of metabolic syndrome were identified: obesity – in 229 patients (45.1% of the total patients with anal fistulae), arterial hypertension – in 115 patients (22,6%), type 2 diabetes mellitus – in 58 patients (11.4%), IHD – in 8 patients (1.6%). In the presence of components of metabolic syndrome the recurrent forms of fistulae were recorded in 16.3% of cases (in the absence – in 12.8% of cases), and complicated forms – extrasphincteric (29.3%) predominated over intrasphincteric forms (22.7%); in control group the proportion of the mentioned forms was 24.8% and 29.2%, respectively. Transsphincteric forms were most common in both groups (48.0% and 46.0%). Conclusions. Components of metabolic syndrome in different combinations were identified in more than half (55.5%) the patients with anal fistulae (obesity – 45.1%, arterial hypertension – 22.6%, 2 type diabetes mellitus – 11.4%, IHD – 1.6%). A tendency was recorded to a more common recurrence of anal fistulae and to a more complicated forms of anal fistulae in patients with components of metabolic syndrome.


2012 ◽  
Vol 15 (2) ◽  
pp. 84 ◽  
Author(s):  
Canturk Cakalagaoglu ◽  
Cengiz Koksal ◽  
Ayse Baysal ◽  
Gokhan Alici ◽  
Birol Ozkan ◽  
...  

<p><b>Aim:</b> The goal was to determine the effectiveness of the posterior pericardiotomy technique in preventing the development of early and late pericardial effusions (PEs) and to determine the role of anxiety level for the detection of late pericardial tamponade (PT).</p><p><b>Materials and Methods:</b> We divided 100 patients randomly into 2 groups, the posterior pericardiotomy group (n = 50) and the control group (n = 50). All patients undergoing coronary artery bypass grafting surgery (CABG), valvular heart surgery, or combined valvular and CABG surgeries were included. The posterior pericardiotomy technique was performed in the first group of 50 patients. Evaluations completed preoperatively, postoperatively on day 1, before discharge, and on postoperative days 5 and 30 included electrocardiographic study, chest radiography, echocardiographic study, and evaluation of the patient's anxiety level. Postoperative causes of morbidity and durations of intensive care unit and hospital stays were recorded.</p><p><b>Results:</b> The 2 groups were not significantly different with respect to demographic and operative data (<i>P</i> > .05). Echocardiography evaluations revealed no significant differences between the groups preoperatively; however, before discharge the control group had a significantly higher number of patients with moderate, large, and very large PEs compared with the pericardiotomy group (<i>P</i> < .01). There were 6 cases of late PT in the control group, whereas there were none in the pericardiotomy group (<i>P</i> < .05). Before discharge and on postoperative day 15, the patients in the pericardiotomy group showed significant improvement in anxiety levels (<i>P</i> = .03 and .004, respectively). No differences in postoperative complications were observed between the 2 groups.</p><p><b>Conclusion:</b> Pericardiotomy is a simple, safe, and effective method for reducing the incidence of PE and late PT after cardiac surgery. It also has the potential to provide a better quality of life.</p>


2007 ◽  
Vol 30 (4) ◽  
pp. 95
Author(s):  
Valerie Taylor ◽  
Glenda M. MacQueen

Bipolar disorder and major depression are life-shortening illnesses. Unnatural causes such as suicide and accidents account for only a portion of this premature mortality1 Research is beginning to identify that mood disordered patients have a higher incidence of metabolic syndrome, an illness characterized by dyslipidemia, impaired glucose tolerance, hypertension and obesity.2 Metabolic syndrome is associated with an increased risk for a variety of physical illnesses. Hypothesis: Never treated patients with mood disorders have preexisting elevations in the prevalence of the component variables of metabolic syndrome. Central obesity will be especially elevated, predicting increased premature mortality. Methods: We assessed never treated patients with mood disorders for metabolic syndrome and its component variables. Patients were assessed at baseline and followed up at 6-month intervals. All psychiatric pharmacotherapy was documented. Body mass index (BMI) was also obtained and the percentage of deaths attributable to overweight and obesity was calculated using the population attributable risk (PAR). [PAR= ∑[P (RR-1)/RR] Results: Prior to the initiation of treatment, patients did not differ from population norms with respect to metabolic syndrome or BMI. At 2-year follow-up, BMI had increased for unipolar patients 2.02 points and 1.92 points for bipolar patients. (p < .001) This increase in BMI predicted an increase in mortality of 19.4%. Conclusion: An increase in visceral obesity is often the first component of metabolic syndrome to appear and may indicate the initiation of this disease process prematurely in this group. The increase in BMI places patients with mood disorders at risk for premature mortality and indicates a need for early intervention. References 1.Osby U, Brandt L, Correia N, Ekbom A & Sparen P. Excess mortability in bipolar and Unipolar disorder rin Sweden. Archives of General Psychiatry, 2001;58: 844-850 2.Toalson P, Saeeduddin A, Hardy T & Kabinoff G. The metabolic syndrome in patients with severe mental illness. Journal of Clinical Psychiatry, 2004; 6(4): 152-158


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