Metabolic dysfunction in lymphocytes promotes postoperative morbidity

2015 ◽  
Vol 129 (5) ◽  
pp. 423-437 ◽  
Author(s):  
Mark R. Edwards ◽  
Pervez Sultan ◽  
Ana Gutierrez del Arroyo ◽  
John Whittle ◽  
Shamir N. Karmali ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Postoperative Morbidity ◽  
Infectious Complications ◽  
Metabolic Dysfunction ◽  
Normal Lymphocyte ◽  
Nlrp1 Inflammasome ◽  
Increased Risk

Acquired/established lymphopenia is associated with an increased risk of infectious complications and characterized by reduced oxidative phosphorylation and impaired glycolysis. This hypometabolic phenotype triggered by glucocorticoid-induced mitochondrial dysfunction activating the NLRP1 inflammasome prevents normal lymphocyte functionality and increases apoptosis.

scholarly journals Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chun Chen ◽  
David McDonald ◽  
Alasdair Blain ◽  
Ashwin Sachdeva ◽  
Laura Bone ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Dopaminergic Neurons ◽  
Neuronal Response ◽  
Proteomic Profiling ◽  
Mass Cytometry ◽  
And Control

AbstractHere we report the application of a mass spectrometry-based technology, imaging mass cytometry, to perform in-depth proteomic profiling of mitochondrial complexes in single neurons, using metal-conjugated antibodies to label post-mortem human midbrain sections. Mitochondrial dysfunction, particularly deficiency in complex I has previously been associated with the degeneration of dopaminergic neurons in Parkinson’s disease. To further our understanding of the nature of this dysfunction, and to identify Parkinson’s disease specific changes, we validated a panel of antibodies targeting subunits of all five mitochondrial oxidative phosphorylation complexes in dopaminergic neurons from Parkinson’s disease, mitochondrial disease, and control cases. Detailed analysis of the expression profile of these proteins, highlighted heterogeneity between individuals. There is a widespread decrease in expression of all complexes in Parkinson’s neurons, although more severe in mitochondrial disease neurons, however, the combination of affected complexes varies between the two groups. We also provide evidence of a potential neuronal response to mitochondrial dysfunction through a compensatory increase in mitochondrial mass. This study highlights the use of imaging mass cytometry in the assessment and analysis of expression of oxidative phosphorylation proteins, revealing the complexity of deficiencies of these proteins within individual neurons which may contribute to and drive neurodegeneration in Parkinson’s disease.

scholarly journals Epilepsy in Mitochondrial Diseases—Current State of Knowledge on Aetiology and Treatment

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 532
Author(s):  
Dorota Wesół-Kucharska ◽  
Dariusz Rokicki ◽  
Aleksandra Jezela-Stanek
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Clinical Picture ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Mitochondrial Diseases ◽  
Energy Deficit ◽  
Atp Production ◽  
Current State

Mitochondrial diseases are a heterogeneous group of diseases resulting from energy deficit and reduced adenosine triphosphate (ATP) production due to impaired oxidative phosphorylation. The manifestation of mitochondrial disease is usually multi-organ. Epilepsy is one of the most common manifestations of diseases resulting from mitochondrial dysfunction, especially in children. The onset of epilepsy is associated with poor prognosis, while its treatment is very challenging, which further adversely affects the course of these disorders. Fortunately, our knowledge of mitochondrial diseases is still growing, which gives hope for patients to improve their condition in the future. The paper presents the pathophysiology, clinical picture and treatment options for epilepsy in patients with mitochondrial disease.

ID: 3522307 LIVER TRANSPLANT PATIENTS WITH INTRAHEPATIC STRICTURES ARE AT INCREASED RISK OF POST-ERCP INFECTIOUS COMPLICATIONS

2021 ◽  
Vol 93 (6) ◽  
pp. AB133
Author(s):  
Ian Holmes ◽  
Muhammad Bashir ◽  
Thomas E. Kowalski ◽  
David E. Loren ◽  
Anand Kumar ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Infectious Complications ◽  
Transplant Patients ◽  
Increased Risk

Abstract P233: Diabetic Cardiomyopathy is Reversed by Increased Mitochondrial Bioenergetics Due to PGC-1α Activation by EET Treatment of Obese Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jian Cao ◽  
John A McClung ◽  
Shailendra P Singh ◽  
Lars Bellner ◽  
Maayan Waldman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Systolic Function ◽  
Control Group ◽  
Protein Markers ◽  
Obesity And Diabetes

Introduction: Obesity and diabetes are associated with progressive cardiac fibrosis that, sequentially, results in diastolic dysfunction, reduced contractility, and ultimately heart failure. Contributing factors include hyperglycemia, insulin resistance, mitochondrial dysfunction, and a reduction in AMPK signaling. PGC-1α activates mitochondrial biogenesis and oxidative phosphorylation and is decreased in patients with diabetes mellitus (DM). We hypothesize that an epoxyeicosatrienoic acids (EETs) agonist (EET-A) will increase PGC-1α levels in a db mouse model of DM attenuate cardiomyopathy, and prevent heart failure. Methods: Db mice (4-wks), were allowed to acclimatize for 16-wks and were then divided into 3 treatment groups for an additional 16 wks: A) control, B) EET-A 1.5mg/100g BW 2 weeks and C) EET-A-Ln-PGC-1α shRNA. Ln-PGC-1α shRNA suppressed PGC-1α protein in heart tissue by 40-50%. Oxygen consumption (VO 2 ), and blood glucose was determined. Heart tissues were harvested to measure PGC-1α, HO-1, pAMPK, PGC-1α, echocardiographic fractional shortening, mitochondrial oxidative phosphorylation (OXPHOS) and mitofusion protein markers. Results: All mice developed heart failure by the end of 16 weeks and were characterized by a decrease in myocardial contractility, an increase in insulin resistance and blood pressure, decreased VO 2 , the appearance of mitochondria dysfunction and a decrease in AMPK and downstream PGC-1α signaling. Mice treated with EET-A demonstrated an increase in PGC-1α levels, improved mitochondrial function and oxidative phosphorylation (p<0.01 vs control), increased NO bioavailability (p<0.05 vs control), and normalization of glucose metabolism, insulin levels, VO 2 and LV systolic function (p<0.05 vs control). All of these findings were suppressed by PGC-1α inhibition which was accompanied by the onset of even more severe LV dysfunction than in the control group. Conclusion: Increased EET levels result in activation of PGC-1α-HO-1 which reverses diabetes induced insulin resistance, mitochondrial dysfunction, and cardiomyopathy. EET may have potential as a powerful agent for therapeutic application in the treatment of diabetic cardiomyopathy.

scholarly journals Female offspring born to obese and insulin-resistant dams are not at increased risk for obesity and metabolic dysfunction during early development

2018 ◽  
Vol 96 (1) ◽  
pp. 97-102 ◽  
Author(s):  
Hanin Aburasayn ◽  
Rami Al Batran ◽  
Keshav Gopal ◽  
Malak Almutairi ◽  
Amina Eshreif ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Female Offspring ◽  
Metabolic Dysfunction ◽  
Insulin Resistant ◽  
The Metabolic Syndrome ◽  
Rate Versus ◽  
Increased Risk ◽  
Study Completion ◽  
Reduced Rate

The percentage of women who are obese at the time of conception or during pregnancy is increasing, with animal and human studies demonstrating that offspring born to obese dams or mothers are at increased risk for obesity and the metabolic syndrome. Our goal was to confirm in an experimental model of metabolic syndrome in the dam, whether the offspring would be at increased risk of obesity. Conversely, we observed that male offspring born to dams with metabolic syndrome had no alterations in their body mass profiles, whereas female offspring born to dams with metabolic syndrome were heavier at weaning, but exhibited no perturbations in energy metabolism. Moreover, they gained weight at a reduced rate versus female offspring born to healthy dams, and thus weighed less at study completion. Hence, our findings suggest that factors other than increased adiposity and insulin resistance during pregnancy are responsible for the increased risk of obesity in children born to obese mothers.

scholarly journals Is Nighttime Really Not the Right Time for a Laparoscopic Cholecystectomy?

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Anna C. M. Geraedts ◽  
Meindert N. Sosef ◽  
Jan Willem M. Greve ◽  
Mechteld C. de Jong
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
Postoperative Morbidity ◽  
Time Of Day ◽  
Outcome Data ◽  
Emergency Procedure ◽  
Out Of Hours ◽  
Increased Risk ◽  
The Right ◽  
The Impact ◽  
Univariate Analyses

Purpose. The impact of an out-of-hours laparoscopic cholecystectomy on outcome is controversial. We sought to determine the association between an out-of-hours procedure and postoperative complications within 90 days. Methods. Between 2014 and 2016, 1553 laparoscopic cholecystectomies were performed. Therapeutic, operative, and outcome data were prospectively collected and analyzed. We defined out of hours as during weekends, national holidays, and daily between 5PM and 8AM. Results. Most patients operated on were female (n=988; 63.6%) and the majority of procedures were electives (n=1341; 86.3%). Although all procedures were performed with a laparoscopic intent, 42 (2.7%) were converted to open procedure. In total, 145 (9.3%) procedures were out of hours, all nonelective, and in most cases for acute cholecystitis (n=111; 7.1%). Overall, there were 212 complications in 191 patients (12.3%), most (n=153; 9.9%) classified as minor. The conversion rate in the out-of-hours group was significantly higher (9.7% vs 2.0%; p<0.001). While univariate analyses revealed out-of-hours procedure (OR=1.83; p=0.008) to be associated with an increased risk of complications, when controlling for confounding factors by multivariate analysis, this association was not found. However, operation by surgical staff (OR=1.71) and conversion to laparotomy (OR=3.74) were found to be independently associated with an increased risk of complications (both p<0.05), while an emergency procedure tended to be associated with postoperative morbidity (OR=1.82; p=0.069). Conclusion. An out-of-hours laparoscopic cholecystectomy was not found to be an independent risk factor for developing postoperative morbidity and time of day should therefore only be a relative contraindication.

Since blood transfusion is linked to the magnitude of the surgical procedure, comparing transfused patients to untransfused patients will always be confounded by infection risks due to factors related to the procedure. To control for these factors one must compare patients transfused with red cells from different sources or prepared in a manner which minimize infection risk. Patients transfused with homologous blood have infection rates several fold higher than recipients of equal values of autologous blood undergoing the same operative procedure (20-23). Homologous blood recipients have significantly longer hospital stays attributed to treating infections. The cost of a blood transfusion exceeds the cost of collection, storage and administration because of transfusion's association with length of stay. In this era of cost-containment the association with prolonged stay may ultimately curtail the use of blood. Homologous blood can be filtered to remove donor leukocytes which may be contributing to immune suppression and infection risk. A prospective randomized trial comparing the infection rates among colorectal cancer patients receiving filtered and unfiltered blood has been conducted (9). There were 17 infectious complications among the 56 recipients of whole blood and one infectious complication among the 48 recipients of filtered blood. Infections were prevented by the seemingly simplistic addition of a $25/filter to every bag of blood transfused. These clinical studies are very convincing: homologous blood transfusion is associated with increased risk of infection in every clinical situation examined. In multivariate analyses transfusion was a significant predictor of infection after consideration of other variables measured and in the majority of those studies transfusion was the single most significant factor. Patients receiving homologous blood exhibited an incidence of infectious complications that was approximately four times higher than patients receiving autologous blood. The association of transfusion with infection is found among patients undergoing surgery for cardiac, orthopedic and gastrointestinal disorders and for trauma as well as among unoperated patients transfused for bums and gastrointestinal bleeding. The observation that nosocomial infections are increased in these studies argues strongly that the association of transfusion with infection is not simply a reflection of transfusion as a marker of tissue destruction and contamination. Infections that develop in transfused patients away from the site of trauma or in the absence of trauma, cannot be attributed to the quantity of tissue destroyed or to the degree of bacterial contamination. Filtered blood can remove leukocytes and prevent postoperative infections. Since filtering blood can significantly reduce the incidence of infection among transfused patients, all transfused blood will be passing through filters in the very near future. EXPERIMENTAL STUDIES RELATING BLOOD TRANSFUSION TO INCREASED RISK OF INFECTION Patients are extremely heterogeneous and even in prospective randomized trials, factors which influence patients' participation affect the outcome despite double-blinding and randomization. In animal studies using syngeneic strains with identical housing, lighting, access to food and water, control over the extent of injury, use of antibiotics and exposure to other variables the influence of a single variable such as blood transfusion can be measured. Dr. Waymack's laboratory has intensively studied parameters which interact with transfusion in

1995 ◽  
pp. 296-296
Keyword(s):  
Blood Transfusion ◽  
Autologous Blood ◽  
Experimental Studies ◽  
Infection Risk ◽  
Infectious Complications ◽  
Risk Of Infection ◽  
Infection Rates ◽  
Homologous Blood ◽  
Increased Risk ◽  
The Cost

scholarly journals Efficiency and safety of using a peritoneal dialysis catheter weighted with a stainless steel ballast : the Limousin experience

2019 ◽  
Vol 2 (4) ◽  
pp. 193-200
Author(s):  
Bénédicte Larivière-Durgueil ◽  
Rémi Boudet ◽  
Marie Essig ◽  
Stéphane Bouvier ◽  
Ali Abdeh ◽  
...  
Keyword(s):  
Stainless Steel ◽  
Peritoneal Dialysis ◽  
Infectious Complications ◽  
Control Group ◽  
Peritoneal Dialysis Catheter ◽  
Causal Factors ◽  
Catheter Migration ◽  
Mechanical Complications ◽  
Increased Risk ◽  
One Year

Objective: To assess the recurrence of PD catheter migration after the introduction of a walnut ballast. Materials and Methods: Retrospective study from 1999 to 2014 of PD patients followed in Limousin. Were compared two groups: ballast group (patients who benefited from the establishment of stainless steel ballast at the intraperitoneal catheter extremity) with 26 patients and control group with 204 patients. The primary endpoint was the occurrence of an episode catheter’s migration after ballast’s establishment. Secondary objectives were (i) to determine the causal factors leading to the catheter weighting, (ii) to ensure the safety of the procedure on the following criteria: infectious complications, mechanicals complications, epurations criteria, and catheter’s survival. Results: More than one year after the implementation of the ballast, no recurrent migration was observed in 86.6% of cases. It wasn’t found an increased risk of infections (OR = 0.5, 95% CI [0.22, 1.13]) or mechanical complications (OR = 1.77- 95% CI [0.77, 4.05]) between the two groups. The adequation criteria were similar: KT / V total : 2.37 in the control group and 2.28 in the ballast group (p = 0.63). The survival of the ballast catheter was comparable among the two groups (p = 0.983). Three causal factors that led to the ballast were identified: automated peritoneal dialysis (APD) (OR = 0.38, 95% CI [0.16, 0.9]), the failure from the first use of the catheter (OR = 19.48, CI 95 % [7.67, 49.48]) and the incarceration of the omentum (OR = 15.84, 95% CI [5.81, 43.21]). Conclusion: The ballast used in these study appears to prevent recurrence of migration, without any impact in terms of infectious or mechanical complications, or on the dialysis criteria or on catheter’s survival. However this catheter does currently not have an EC authorization

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