scholarly journals Serum Amyloid Beta42 Is Not Eliminated by the Cirrhotic Liver: A Pilot Study

2021 ◽  
Vol 10 (12) ◽  
pp. 2669
Author(s):  
Reiner Wiest ◽  
Thomas S. Weiss ◽  
Lusine Danielyan ◽  
Christa Buechler
Keyword(s):  
Liver Cirrhosis ◽  
Hepatic Clearance ◽  
Protective Role ◽  
Tissue Growth ◽  
Cirrhotic Liver ◽  
Diabetic Patients ◽  
Peripheral Clearance ◽  
End Stage ◽  
The Brain

Amyloid-beta (Aβ) deposition in the brain is the main pathological hallmark of Alzheimer disease. Peripheral clearance of Aβ may possibly also lower brain levels. Recent evidence suggested that hepatic clearance of Aβ42 is impaired in liver cirrhosis. To further test this hypothesis, serum Aβ42 was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS), and hepatic venous serum (HVS) of 20 patients with liver cirrhosis. Mean Aβ42 level was 24.7 ± 20.4 pg/mL in PVS, 21.2 ± 16.7 pg/mL in HVS, and 19.2 ± 11.7 pg/mL in SVS. Similar levels in the three blood compartments suggested that the cirrhotic liver does not clear Aβ42. Aβ42 was neither associated with the model of end-stage liver disease score nor the Child–Pugh score. Patients with abnormal creatinine or bilirubin levels or prolonged prothrombin time did not display higher Aβ42 levels. Patients with massive ascites and patients with large varices had serum Aβ42 levels similar to patients without these complications. Serum Aβ42 was negatively associated with connective tissue growth factor levels (r = −0.580, p = 0.007) and a protective role of Aβ42 in fibrogenesis was already described. Diabetic patients with liver cirrhosis had higher Aβ42 levels (p = 0.069 for PVS, p = 0.047 for HVS and p = 0.181 for SVS), which is in accordance with previous reports. Present analysis showed that the cirrhotic liver does not eliminate Aβ42. Further studies are needed to explore the association of liver cirrhosis, Aβ42 levels, and cognitive dysfunction.

scholarly journals Protective role of melatonin in early‐stage and end‐stage liver cirrhosis

2019 ◽  
Vol 23 (11) ◽  
pp. 7151-7162 ◽  
Author(s):  
Chenxia Hu ◽  
Lingfei Zhao ◽  
Jingjing Tao ◽  
Lanjuan Li
Keyword(s):  
Liver Cirrhosis ◽  
Early Stage ◽  
Protective Role ◽  
End Stage

scholarly journals Genetic Variants of Lipoprotein Lipase and Regulatory Factors Associated with Alzheimer’s Disease Risk

2020 ◽  
Vol 21 (21) ◽  
pp. 8338
Author(s):  
Kimberley D. Bruce ◽  
Maoping Tang ◽  
Philip Reigan ◽  
Robert H. Eckel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipoprotein Lipase ◽  
Genetic Variants ◽  
Disease Risk ◽  
Lipoprotein Metabolism ◽  
Protective Role ◽  
Direct Role ◽  
The Brain

Lipoprotein lipase (LPL) is a key enzyme in lipid and lipoprotein metabolism. The canonical role of LPL involves the hydrolysis of triglyceride-rich lipoproteins for the provision of FFAs to metabolic tissues. However, LPL may also contribute to lipoprotein uptake by acting as a molecular bridge between lipoproteins and cell surface receptors. Recent studies have shown that LPL is abundantly expressed in the brain and predominantly expressed in the macrophages and microglia of the human and murine brain. Moreover, recent findings suggest that LPL plays a direct role in microglial function, metabolism, and phagocytosis of extracellular factors such as amyloid- beta (Aβ). Although the precise function of LPL in the brain remains to be determined, several studies have implicated LPL variants in Alzheimer’s disease (AD) risk. For example, while mutations shown to have a deleterious effect on LPL function and expression (e.g., N291S, HindIII, and PvuII) have been associated with increased AD risk, a mutation associated with increased bridging function (S447X) may be protective against AD. Recent studies have also shown that genetic variants in endogenous LPL activators (ApoC-II) and inhibitors (ApoC-III) can increase and decrease AD risk, respectively, consistent with the notion that LPL may play a protective role in AD pathogenesis. Here, we review recent advances in our understanding of LPL structure and function, which largely point to a protective role of functional LPL in AD neuropathogenesis.

Physical activity as a protective factor for successful aging

2019 ◽  
Vol 29 (87) ◽  
pp. 47-52
Author(s):  
Andrzej Jopkiewicz ◽  
Monika Królicka–Czerniak ◽  
Anita Zaręba
Keyword(s):  
Physical Activity ◽  
Prefrontal Cortex ◽  
Cognitive Processes ◽  
Cognitive Aging ◽  
Successful Aging ◽  
Protective Factor ◽  
Protective Role ◽  
Factors Affecting ◽  
The Brain

To divide the types of aging (successful, usual and impaired), as well as factors affecting this process, the protective role of physical activity was discussed in the literature. It was emphasized that physical activity is also a very important protective factor for cognitive aging - mainly executive function and memory. The prefrontal cortex and hippocampus, i.e. the regions of the brain responsible for the control and course of cognitive processes, show susceptibility to stimulation, which is movement exercises, which are prevention of degenerative changes within the brain.

scholarly journals Investigation of Bacteremia due toAeromonasSpecies and Comparison with That due to Enterobacteria in Patients with Liver Cirrhosis

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Toru Shizuma ◽  
Chiharu Tanaka ◽  
Hidezo Mori ◽  
Naoto Fukuyama
Keyword(s):  
Liver Cirrhosis ◽  
Japanese Patients ◽  
Meld Score ◽  
Short Term ◽  
E Coli ◽  
End Stage Liver Disease ◽  
Short Term Mortality ◽  
Clinical Background ◽  
End Stage

Background. The role ofAeromonasspecies (sp.) in bacteremia in Japanese patients with liver cirrhosis is poorly understood.Aim. To establish the importance ofAeromonassp. as a cause of bacteremia in patients with liver cirrhosis.Methods. Clinical and serological features and short-term prognosis were retrospectively investigated and compared in Japanese patients with bacteremia due toAeromonassp. () and due to enterobacteria (E. coli, Klebsiellasp., andEnterobactersp.) ().Results. There were no significant differences in patients’ clinical background, renal dysfunction, or short-term mortality rate between the two groups. However, in theAeromonasgroup, the model for end-stage liver disease (MELD) score and Child-Pugh score were significantly higher than in the enterobacteria group.Conclusion. These results indicate that the severity of liver dysfunction inAeromonas-induced bacteremia is greater than that in enterobacteria-induced bacteremia in Japanese patients with liver cirrhosis.

scholarly journals Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Mina Thabet Kelleni ◽  
Entesar Farghaly Amin ◽  
Aly Mohamed Abdelrahman
Keyword(s):  
Caspase 3 ◽  
Chemotherapy Regimen ◽  
Serum Levels ◽  
Protective Role ◽  
Diabetic Patients ◽  
Cardiac Protection ◽  
Immunohistochemical Expression ◽  
Sod Activity ◽  
Remarkable Improvement

Doxorubicin (DOX) is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. The aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in DW p.o. for seven days) and sitagliptin (10 mg/kg dissolved in DW p.o. for seven days) in a model of DOX-induced (single dose 15 mg/kg i.p. at the fifth day) cardiotoxicity in rats. Results of our study revealed that pretreatment with metformin or sitagliptin produced significant (P<0.05) cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group. These results may suggest using metformin and/or sitagliptin as preferable drugs for diabetic patients suffering from cancer and receiving DOX in their chemotherapy regimen.

scholarly journals Possible protective role of metformin therapy on colonic polyps in acromegaly: an exploratory cross-sectional study

2021 ◽  
Vol 184 (3) ◽  
pp. 423-429
Author(s):  
M Albertelli ◽  
E Nazzari ◽  
A Dotto ◽  
L F Grasso ◽  
S Sciallero ◽  
...  
Keyword(s):  
Acetylsalicylic Acid ◽  
Disease Duration ◽  
Colonic Polyps ◽  
Cross Sectional Study ◽  
Protective Role ◽  
Diabetic Patients ◽  
Sectional Study ◽  
Cross Sectional ◽  
Acid Intake

Context Colonic polyps occur in 30–40% of acromegalic patients, increasing the risk of colon carcinoma. Although debated, there is emerging evidence that metformin may play a protective role in diabetic and non-diabetic patients with colonic polyps and its use in chemoprevention is currently explored. Objective Evaluate the prevalence of colonic polyps in acromegalic patients treated or not with metformin and explore its possible protective role. Design Exploratory cross-sectional study in two tertiary Italian referral centres. Met hods: Out of 153 acromegalic patients, we selected 58 patients (36–82 years; f: 33) who had at least one colonoscopy performed within the first 2 years of diagnosis. Presence of colonic polyps/cancer and related risk factors, current metformin and acetylsalicylic acid intake, disease duration, therapies for acromegaly, hormonal and metabolic parameters were assessed. Results An overall prevalence of 36% polyps was found. Based on the presence of polyps, we identified two groups, comparable for age, BMI, disease duration, glucose, insulin, HOMA-IR, HbA1c, GH and IGF-I levels. Of the patients with polyps (including three adenocarcinomas) only 24% were treated with metformin vs 57% of patients without polyps. Multivariate analysis confirmed a significant negative association between colonic polyps and metformin intake (OR: 0.22, 95% CI: 0.06-0.77, P = 0.01), whereas no significant association was found between polyps and age (P = 0.10), overweight/obesity (P = 0.54), smoking (P = 0.15), acetylsalicylic acid intake (P = 0.99), disease duration (P = 0.96), somatostatin analogues treatment (P = 0.70). Conclusions These findings, though deriving from an exploratory study, could suggest a protective role of metformin on the development of colonic polyps in acromegaly, and need to be confirmed in an extended study population.

scholarly journals ROLE OF INSULIN IN BRAIN: DELVE INTO THE MOLECULAR MECHANISMS

2021 ◽  
Author(s):  
Sofia Khanam
Keyword(s):  
Molecular Mechanisms ◽  
Insulin Signalling ◽  
Diabetic Patients ◽  
Functional Activities ◽  
Mitochondrial Alterations ◽  
Age Related ◽  
The Brain ◽  
And Oxidative Stress

We have learned over the last several decades that the brain is an important target for insulin action. In central nervous system (CNS) it mainly affects feeding behaviour and various aspects of memory and cognition. Insulin signalling in CNS has emerged as a novel field of research since decreases brain insulin levels and signalling were associated to impaired learning, memory and age-related neurodegenerative diseases. Alterations of these functional activities may contribute to the manifestation of several clinical entities, such as central insulin resistance, type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). A close alliance between T2DM and AD has been reported, to the extent that AD is twice more frequent in diabetic patients. There are links between T2DM and AD through mitochondrial alterations and oxidative stress, altered energy and glucose metabolism, cholesterol modifications, dysfunctional protein O-GlcNAcylation, formation of amyloid plaques, altered Aβ metabolism and tau hyperphosphorylation. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: T2DM and AD, both in terms of intracellular signalling and potential therapeutic approach.

CD133+ Pluripotent Stem Cells for the Treatment of Chronic Liver Failure.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1185-1185
Author(s):  
Lucia Catani ◽  
Stefania Lorenzini ◽  
Rosaria Giordano ◽  
Paolo Caraceni ◽  
Maria Rosa Motta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Chronic Liver ◽  
Peripheral Blood Stem Cells ◽  
End Stage Liver Disease ◽  
End Stage

Abstract Abstract 1185 Background. The potential role of bone marrow (BM)-derived stem cells (SCs) in patients with end-stage liver disease has been addressed by our group in four studies. Main objectives were: 1) to assess stem/progenitor cell mobilization in 24 patients receiving orthotopic liver transplantation (OLT); 2) to evaluate whether G-CSF can be safely administered to patients with liver cirrhosis in order to expand and mobilize BM-derived SCs; 3) to investigate the effects of transplantation of human G-CSF-mobilized CD34+ and CD133+ SCs in mice with chronic liver injury and fibrosis; 4) to evaluate the feasibility and the safety of the purification and intrahepatic reinfusion of increasing numbers of autologous BM-derived G-CSF-mobilized CD133+ SCs in patients with end-stage liver disease. Methods. 1) Flow cytometry analysis, clonogenic assays and RT-PCR have been performed after OLT; 2) 18 patients with advanced liver disease were consecutively treated with increasing doses of G-CSF starting from 2 μg/kg/daily; 3) C57BL/6N mice received CCl4 by inhalation for thirteen weeks and were treated with Cyclosporin-A. Transplantation was performed by injection (tail vein) of 106 CD34+ or CD133+ SCs of three cirrhotic patients. After four weeks from transplantation all mice were sacrificed; 4) G-CSF at 7.5μg/Kg/b.i.d. is administered subcutaneosly (sc) from day 1 until the completion of peripheral blood stem cells (PBSC) collection. Collection of PBSC will begin on day + 4 only if the concentration of CD133+ cells is 38/mL. PB mononuclear cells obtained from mobilized standard-volume leukapheresis will be incubated with Macs colloidal superparamagnetic CD133 microbeads. CliniMacs device is used for the positive selection of CD133+ SCs under GMP conditions. At least 4 weeks after SC mobilization, collection and cryopreservation, highly purified autologous G-CSF-mobilized CD133+ cells are re-infused through the hepatic artery by transfemoral or transbranchial arteriography. CD133+ cells are administered to patients starting from 5×104/Kg patient's body weight and increased every 3 patients. The maximum infused cell dose will be 1×106/kg. G-CSF at 5μg/Kg/day is administered sc for 3 days after the reinfusion of SCs for their expansion and to induce a selective proliferative advantage of reinfused cells in vivo. Results and Discussion. 1) We demonstrated that both early subsets of the hematopoietic SC compartment (CD34+/CD90+ cells) and more mature committed progenitors (CFU-C) were mobilized into PB after OLT. We also demonstrated the release from the BM of liver-committed HSCs co-expressing epithelial markers after OLT; 2) We show that the administration of G-CSF to patients with liver cirrhosis is safe and feasible and allows the mobilization and collection of BM-derived SCs at the dose of 15 mg/kg/day. 3) We demonstrated that mice transplanted with either CD133+ or CD34+ human cells appear to have less fibrotic septa than mice without SC transplantation, suggesting the potential therapeutic role of human SCs on the recovery of liver fibrosis. 4) Up to date, three patients with end stage liver disease have been successfully mobilized with G-CSF and highly purified autologous CD133+ SCs have been re-infused. The number of collected CD133+ SCs is 0,7, 0,2 and 0.35×106/Kg, respectively. The number of the re-infused highly purified CD133+ SCs is 4.7, 5.0 and 5.4×104/Kg, respectively. No adverse events have been recorded during mobilization or intrahepatic SCs re-infusion. Updated results on current patients and future patients will be presented at the Meeting. Disclosures: No relevant conflicts of interest to declare.

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