MO628IMPACT OF INDUCTION OF AUTOPHAGY BY RAPAMYCIN AND METFORMIN ON NATURAL HISTORY OF DIABETIC NEPHROPATHY IN RATS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Samar Ahmed ◽  
Emad Samaan ◽  
Dina Abdallah Ibrahim ◽  
Nagy Sayed-Ahmed ◽  
Hussein Sheashaa

Abstract Background and Aims Impaired autophagy in the kidney resulted in podocyte loss and massive proteinuria in diabetic nephropathy. Improvement of autophagy by activation of mTORC1 and reduction of AMPK and Sirt1 may be a novel therapeutic option for the suppression of diabetic nephropathy. Method This experimental work was carried out on 48 adult male Sprague dawely rats. The total duration of the study was 10 weeks. All investigation and intervention were carried out at 3 time points, 3 weeks, 6 weeks, 10 weeks. The rats were randomly divided into healthy control group (n = 12) and 3 induced diabetic groups (n = 12 each), the three groups were the non-treated, treated with rapamycin and treated with rapamycin and metformin. To study autophagy, we use electron microscopy and immunohistochemical staining of kidney tissue with LC3 antibody Results Diabetic rats treated with rapamycin alone or rapamycin and metformin showed lower level of proteinuria and almost normal serum creatinine through all intervals of the study. Also, their Kidney tissue showed increased autophagosomes and high expression of LC3 compared to diabetic rats. There are no significant differences between both treated groups in terms of induction of autophagy during the experiment period. Conclusion we concluded that using a small dose of rapamycin for short duration in early diabetic rats is beneficial in halting the course of diabetic nephropathy, adding metformin to rapamycin aiming to potentiate its effect on autophagy seems to be less beneficial.

2020 ◽  
Vol 22 (9) ◽  
pp. 657-662 ◽  
Author(s):  
Mustafa Celik ◽  
Alper Şen ◽  
İsmail Koyuncu ◽  
Ataman Gönel

Aim and Objective:: To determine the mechanisms present in the etiopathogenesis of nasal polyposis. It is not clear whether amino acids contribute in a causal way to the development of the disease. Therefore, the aim of this study was to determine the plasma-free amino acid profile in patients with nasal polyposis and to compare the results with a healthy control group. Materials and Methods:: This was a prospective controlled study that took place in the Otolaryngology Department at the Harran University Faculty of Medicine between April 2017 and April 2018. Plasmafree amino acid profile levels were studied in serum samples taken from a patient group and a healthy control group. Patients who were diagnosed with bilateral diffuse nasal polyposis and were scheduled for surgical interventions were included in this study. Individuals whose age, gender, and body mass index values were compatible with that of the patient group and who did not have any health problems were included in the control group. All the participants whose levels of plasma-free amino acid were thought to be affected by one or more of the following factors were excluded from the study: smoking and alcohol use, allergic rhinitis presence, the presence of acute or chronic sinusitis, a history of endoscopic sinus surgery, unilateral nasal masses, a history of chronic drug use, systemic or topical steroid use in the last three months for any reason, and liver, kidney, hematological, cardiovascular, metabolic, neurological, or psychiatric disorders or malignancies. Results: In patients with nasal polyposis, 3-methyl histidine (3-MHIS: nasal polyposis group (ng) = 3.22 (1.92 – 6.07); control group (cg) = 1.21 (0.77 – 1.68); p = 0.001); arginine (arg: ng = 98.95 (70.81 – 117.75); cg = 75.10 (54.49 – 79.88); p = 0.005); asparagine (asn: ng = 79.84 (57.50 – 101.44); cg = 60.66 (46.39 – 74.62); p = 0.021); citrulline (cit: ng = 51.83 (43.81 – 59.78); cg = 38.33 (27.81 – 53.73); p = 0.038); cystine (cys: ng = 4.29 (2.43 – 6.66); cg = 2.41 (1.51 – 4.16); p = 0.019); glutamic acid (glu: ng = 234.86 (128.75 – 286.66); cg = 152.37 (122.51 – 188.34); p = 0.045); histidine (his: ng = 94.19 (79.34 – 113.99); cg = 74.80 (62.76 – 98.91); p = 0.018); lysine (lys: ng = 297.22 (206.55 – 371.25); cg = 179.50 (151.58 – 238.02); p = 0.001); ornithine (ng = 160.62 (128.36 – 189.32); cg = 115.91 (97.03 – 159.91); p = 0.019); serine (ser: ng = 195.15 (151.58 – 253.07); cg = 83.07 (67.44 – 92.44); p = 0.001); taurine (tau: ng = 74.69 (47.00 – 112.13); cg = 53.14 (33.57 – 67.31); p = 0.006); tryptophan (trp: ng = 52.31 (33.81 – 80.11); cg = 34.44 (25.94 – 43.07); p = 0.005), homocitrulline (ng = 1.75 (1.27 – 2.59); cg = 0.00 (0.00 – 0.53); p = 0.001); norvaline (ng = 6.90 (5.61 – 9.18); cg = 4.93 (3.74 – 7.13); p = 0.021); argininosuccinic acid (ng = 14.33 (10.06 – 25.65); cg = 12.22 (5.77 – 16.87) p = 0.046); and plasma concentrations were significantly higher than in the healthy control group (p <0.05). However, the gamma-aminobutyric acid (gaba: ng = 0.16 (0.10 – 0.24); cg = 0.21 (0.19 – 0.29); p = 0.010) plasma concentration was significantly lower in the nasal polyposis group than in the healthy control group. Conclusion: In this study, plasma levels of 15 free amino acids were significantly higher in the nasal polyposis group than in the healthy control group. A plasma level of 1 free amino acid was found to be significantly lower in the nasal polyposis group compared to the healthy control group. Therefore, it is important to determine the possibility of using the information obtained to prevent the recurrence of the condition and to develop effective treatment strategies. This study may be a milestone for studies of this subject. However, this study needs to be confirmed by further studies conducted in a larger series.


2020 ◽  
Vol 20 (2) ◽  
pp. 833-840
Author(s):  
Erhan Onalan ◽  
Yusuf Doğan ◽  
Ebru Onalan ◽  
Nevzat Gozel ◽  
Ilay Buran ◽  
...  

Backround: Elabela (ELA) is a hormone that is secreted at high levels in the kidneys of a healthy adult. This study aims to investigate whether serum ELA levels of patients with Type 2 Diabetes vary with the severity of renal damage. Methods: Our study included 50 healthy control subjects and 100 diabetic patients, who were categorized into groups based on urine albumin/creatinine ratios (ACR). Patients included in the study were assigned to four groups: Group 1 (healthy control), Group 2 (ACR<29mg/g), Group 3 (ACR=30-299 mg/g), and Group 4 (ACR>300 mg/g normal or high serum creatinine). Physical examination findings, demographic characteristics of the study group were recorded, and serum ELA levels and other laboratory parameters were assessed using appropriate methods. Results: The results of the study indicated that ELA levels determined in healthy individuals gradually decreased through stages of normal albuminuria, microalbuminuria, and macroalbuminuria. Moreover, ELA had a significant negative corre- lation with LDL-C (r=-0.201, p=0.014), glucose (r=-0.437, P<0.001), retinopathy (r=-0.222, P=0.006), serum BUN (r=- 0.161, P=0.049), and a positive correlation with eGFR (r=0.250, P=0.002). Conclusions: The fact that ELA levels are higher in healthy individuals compared to diabetic patients without microalbu- minuria, and higher in diabetic patients without microalbuminuria compared to patients with advanced albuminuria and kidney damage, suggests that the ELA level can be an important clinical prognostic variable and even a promising agent for the treatment of diabetic nephropathy patients. Keywords: Elabela, diabetes, diabetic kidney disease, albuminuria.


2021 ◽  
Author(s):  
Laura S. van Velzen ◽  
Yara J. Toenders ◽  
Aina Avila-Parcet ◽  
Richard Dinga ◽  
Jill A. Rabinowitz ◽  
...  

AbstractDespite numerous efforts to predict suicide risk in children, the ability to reliably identify youth that will engage in suicide thoughts or behaviors (STB) has remained remarkably unsuccessful. To further knowledge in this area, we apply a novel machine learning approach and examine whether children with STB could be differentiated from children without STB based on a combination of sociodemographic, physical health, social environmental, clinical psychiatric, cognitive, biological and genetic characteristics. The study sample included 5,885 unrelated children (50% female, 67% white) between 9 and 11 years old from the Adolescent Brain Cognitive Development (ABCD) study. Both parents and youth reported on children’s STB and based on these reports, we divided children into three subgroups: 1. children with current or past STB, 2. children with psychiatric disorder but no STB (clinical controls) and 3. healthy control children. We performed binomial penalized logistic regression analysis to distinguish between groups. The analyses were performed separately for child-reported STB and parent-reported STB. Results showed that we were able to distinguish the STB group from healthy controls and clinical controls (area under the receiver operating characteristics curve (AUROC) range: 0.79-0.81 and 0.70-0.78 respectively). However, we could not distinguish children with suicidal ideation from those who attempted suicide (AUROC range 0.49-0.59). Factors that differentiated the STB group from the clinical control group included family conflict, prodromal psychosis symptoms, impulsivity, depression severity and a history of mental health treatment. Future research is needed to determine if these variables prospectively predict subsequent suicidal behavior.


Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 88
Author(s):  
Anna Baran ◽  
Paulina Kiluk ◽  
Julia Nowowiejska ◽  
Tomasz W. Kaminski ◽  
Magdalena Maciaszek ◽  
...  

Galectin-3 (gal-3) is a multifunctional regulator of various biological processes and diseases, which are common comorbidities in psoriasis. Data regarding potential diagnostic role of gal-3 in psoriasis are insufficient. Serum gal-3 levels were evaluated before and after twelve weeks of treatment with acitretin or methotrexate in 31 patients with plaque-type psoriasis and compared to 11 healthy control group. The mean serum galectin-3 level in patients with psoriasis was significantly higher compared to the control group (p < 0.01). In patients with obesity and long-lasting psoriasis (>20 years) positive relations of gal-3 and PASI were noted. In psoriatics with low gal-3 levels, positive correlations between the gal-3 and BMI, glucose level, and with the latter in short-lasting psoriasis (<20 years) were noted. In the long history of psoriasis, gal-3 was negatively correlated with lipids levels. The Gal-3 level might be a multifaceted modulator of the course of psoriasis and predictive factor of cardiometabolic comorbidities’ development, especially in patients with a long history of the disease or obesity. Patients with low serum gal-3 and short history of psoriasis are presumably at greater risk of diabetes. In patients with long-lasting psoriasis and concomitant obesity, gal-3 may exert a protective role against dyslipidemia or perhaps further CMD development.


Author(s):  
Mariam A. Atiia ◽  
Yasser M. Hafez ◽  
Maaly M. Mabrouk ◽  
Medhat A. Ghazy

Background: Interleukin-19 (IL-19) is a newly discovered cytokine belonging to the Interleukin-10 (IL-10) family. IL-19 has indispensable functions in many inflammatory processes and also can induce the angiogenic potential of endothelial cells. The purpose of present study was to assess the level of serum interleukin-19 (IL-19) in patients with diabetic nephropathy (DN). Our Study Aimed to assess the level of serum IL-19 in patients with diabetic nephropathy. Methods: In this cross-sectional study, we tested 90 subjects; 30 healthy control and 60 diabetic nephropathy patients recruited from outpatient clinics and wards of Internal Medicine department, Tanta university hospitals, Egypt. Patients were subdivided into 3subgroup according to the urinary albumin creatinine ratio (ACR). Results: The serum IL-19 levels in DN patients were significantly higher than the control group. The mean serum IL-19 level was 15.45±4.34 Pg/ml, 32.66±8.05 Pg/ml, 56.03±7.89 Pg/ml and 71.41±12.37 Pg/ml dL for control, normoalbuminuria group, microalbuminuria group and macroalbuminuria group respectively. Conclusions: Serum IL-19 level was significantly elevated in patients with diabetic nephropathy and was associated with the marker of inflammation CRP (C -reactive protein). So


2020 ◽  
Vol 10 (3) ◽  
pp. 244-257
Author(s):  
Abdollah Akbari ◽  
◽  
Vahid Tadibi ◽  
Naser Behpoor ◽  
◽  
...  

Objective: Diabetes is a chronic disease associated with a wide range of liver diseases. The levels of liver enzymes such as Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) are changed following a liver disease The purpose of this study is to investigate the effect of aerobic exercise combined with Stevia extract supplementation on the levels of ALT and AST enzymes in diabetic rats. Methods: In this experimental study, 40 males wistar rats weighing 150-220 g were used. Animals were randomly divided into five groups; healthy control , diabetic control, diabetic + exercise, diabetic + stevia, and diabetic + exercise + stevia. The extract was administered by oral gavage for 6 weeks. The aerobic exercise program was performed for six weeks, 5 days per week. At the end of the intervention, blood samples were collected from the heart of rats to measure the levels of ALT and AST. Data were analyzed by one-way ANOVA and Tukey’s post hoc test. Results: The levels of ALT and AST enzymes decreased significantly in all experimental groups compared to diabetic control group (P<0.05). Conclusion: Aerobic exercise combined with stevia extract supplementation can improve the liver function in streptozotocin-induced diabetic rats


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Arash Karimi ◽  
Hamid Reza Niazkar ◽  
Pouria Sefidmooye Azar ◽  
Helda Tutunchi ◽  
Mozhde Karimi ◽  
...  

Purpose Herbal medicine has been used for the management of complications of diabetes. The purpose of this paper is to examine the anti-diabetic effects of Achillea millefolium extract on diabetic rats. Design/methodology/approach To this aim, 32 male Wistar rats were randomly assigned into four groups in which each group comprised eight rats. The four experimental groups were as follows: control group, diabetic control (DC) group (STZ; 50 mg/kg), diabetic rats, receiving 250 mg/kg hydro-alcoholic extract of the A. millefolium (DAM) and diabetic rats, receiving 5 mg/kg glibenclamide (DG). After 21 days of the treatment course, tissues of the kidney and blood samples were collected for histopathological, biochemical and molecular analysis. Findings The concentration of malondialdehyde (MDA) and glucose serum were markedly reduced in the DC group while significantly increased in DG and DAM groups (1.11 ± 0.57 to 19.4 ± 3.5 and 17.8 ± 1.2 p = 0.002 and 325 ± 0.18 to 223 ± 0.11 and 211 ± 0.32 p = 0.02, respectively). Also, the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were markedly reduced in the DC group while significantly increased in DAM and DG groups (9.1 ± 2.21 to 18.7 ± 3.81 and 14.9 ± 3.1 p = 0.03 and p = 0.02, respectively). The concentrations of creatinine, blood urea nitrogen (BUN) and urea were substantially decreased in DAM and DG groups as compared with the DC group (0.49 ± 0.02 to 0.27 ± 0.01 and 0.25 ± 0.01 p = 0.01, 15.6 ± 2.1 to 7.2 ± 0.68 and 8.6 ± 1.2 p = 0.02 and 114 ± 9.4 to 59.8 ± 5.2 and 64 ± 5.2 p = 0.03, respectively). Also, Bcl-2-associated X protein (BAX) expression was significantly decreased in DAM and DG groups as compared with the DC group (1.3 ± 0.32 to 0.91 ± 0.03 and 0.93 ± 0.02 p = <0.01) and Bcl-2 expression were significantly increased in DAM and DG groups as compared with the DC group (0.42 ± 0.05 to 0.88 ± 0.07 and 0.85 ± 0.06 p = 0.01). Originality/value Diabetes led to degenerative damages in the kidney of rats and increased the mRNA level of Bax, while treatment with A. millefolium could protect the kidney tissue against diabetes complications and increased the mRNA expression of Bcl-2. This study indicated that A. millefolium extracts not only improves renal function as a result of anti-oxidant activity but also modulates some biochemical factors in diabetic rats.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Maha Safwat Abd-elrahman Elsheemy ◽  
Ahmed Abdel-Salam M Elmelegy ◽  
Lobna Fouad Abd Elaziz ◽  
Nadia Galal M El hefnawy ◽  
Mohammad Mahmoud El shaer ◽  
...  

Abstract Background & Aim Diabetic nephrectomy (DN) is a chronic progressive disorder that complicates long standing diabetes. Albuminuria is a prominent clinical feature of DN. Ursodeoxycholic acid (UDCA) is a physiologic hydrodrophillic bile acid that is therapeutically used in the treatment of primary biliary cirrhosis. It is known to alleviate endoplasmic reticulum (ER) stress in podocytes. In comparison to Ramipril as a standard ACEI therapy of DN, the present study was designed to investigate the effect of UDCA treatment on DN in association with renal biomarkers changes. Method Four groups of male Wister rats (6 per group) were designed; Normal control group, DN untreated group (High fat diet + STZ injection of 45 mg/kg + uninephrectomy), DN/Ramipril group; (1 mg/kg/d orally for 12 weeks) and DN/UDCA group (40 mg/kg/d orally for 12 weeks). Results DN rats treated with UDCA for 12 weeks exhibited significant decrease in ER stress marker, ATF6 with mean percentage value of 73.8% and improvement of podocyte structural deformities that is accompanied by a significant reduction in albuminuria by mean percentage value of 43.8% comparatively to Ramipril that caused reduction in ATF6 level with mean percentage value of 65.5% and reduction in albuminuria by mean percentage value of 50.2%. The remarkable improvement in metabolic profile and the neutral effect on blood pressure in UDCA treated group could explain the renoprotection at histopathological basis rather than the proved hemodynamic effect of ramipril. Conclusion Participation of ER stressmediated apoptosis in the pathophysiology of diabetic nephropathy make the UDCA a potential therapeutic option or add-on therapy due to its anti-apoptotic property apart from classic metabolic and hemodynamic aspects.


2012 ◽  
Vol 18 (5) ◽  
pp. 799-808 ◽  
Author(s):  
Deborah Arguedas ◽  
Robyn Langdon ◽  
Richard Stevenson

AbstractOlfactory hallucinations (OHs) are present in a significant minority of people with schizophrenia, yet these symptoms are under-researched and poorly understood. This study aimed to identify the neuropsychological impairments that associate with OHs in schizophrenia. Patients with schizophrenia or schizoaffective disorder were classified into an OH group and a group with auditory-verbal hallucinations (AVHs) and no lifetime history of OHs. Patients were age- and gender-matched to a healthy control group. All participants were assessed using: a test of odor identification; decision-making and socio-emotional tests of orbitofrontal cortex (OFC) and amygdala function; and a battery of standardized executive tests. Patients, as a whole, performed more poorly than controls on the tests of odor identification, emotion processing and executive function, consistent with previous research. Only two tests of OFC functioning: the Object Alternation Task, taken from Oscar-Berman and Zola-Morgan's (1980a, 1980b) Comparative Neuropsychological Tasks, and a test of “faux pas” understanding discriminated between the OH and AVH patients. Findings provide the first preliminary support for OH-specific neuropsychological impairments associated with OFC dysfunction in schizophrenia. (JINS, 2012, 18, 1–10)


2014 ◽  
Vol 34 (2) ◽  
pp. 127-134 ◽  
Author(s):  
E Altinoz ◽  
Z Oner ◽  
H Elbe ◽  
Y Cigremis ◽  
Y Turkoz

The reactive oxygen species take role in pathogenesis of many diseases including hypoxia, hypercholesterolemia, atherosclerosis, nephropathy, hypertension, ischemia–reperfusion damage, and heart defects. The aim of this study was to evaluate whether crocin administration could protect kidney injury from oxidative stress in streptozotocin-induced diabetic rats. The rats were randomly divided into 3 groups each containing 10 animals as follows: group 1, control group; group 2, diabetes mellitus (DM) group; and group 3, DM + crocin group. At the end of the study, trunk blood was collected to determine the plasma levels of blood urea nitrogen (BUN) and creatinine (Cr). The kidney tissue was removed, and biochemical and histological changes were examined. Diabetes caused a significant increase in malondialdehyde (MDA) and xanthine oxidase (XO) activities and a decrease in glutathione (GSH) contents (  p < 0.01) when compared with control group in the rat kidneys. Crocin given to DM rats significantly decreased MDA (  p < 0.01) and XO (  p < 0.05) activities and elevated GSH (  p < 0.05) contents when compared with DM group. Plasma levels of BUN and Cr were significantly higher in the DM group when compared with the control group (  p < 0.01). Pretreatment of the DM animals with crocin decreased the high level of serum Cr and BUN. Control group was normal in histological appearance, but congestion, severe inflammation, tubular desquamation, tubular necrosis, and hydropic degeneration in tubular cells were observed in the DM group. Histopathological changes markedly reduced, and appearance of kidney was nearly similar to control group in DM + crocin group. Our results show that crocin could be beneficial in reducing diabetes-induced renal injury.


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