scholarly journals Oxidative stress and gut-derived lipopolysaccharides in children affected by Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections.

2020 ◽  
Author(s):  
Lorenzo Loffredo ◽  
Alberto Spalice ◽  
Francesca Salvatori ◽  
De Castro Giovanna ◽  
Cristiana Alessia Guido ◽  
...  

Abstract Background: paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to evaluate serum NOX2 levels, as well as 8-iso-prostaglandin F2α (8-iso-PGF2α) and lipopolysaccharide (LPS) of PANDAS patients. Methods: in this study we wanted to compare serum levels of soluble NOX2-dp (sNOX-2-dp), iso-PGF2α and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used as intestinal permeability assay.Results: compared with CT, PANDAS children had increased serum levels of sNOX-2-dp, 8-iso-PGF2α and LPS. Bivariate analysis showed that serum sNOX2-dp was significantly correlated with LPS (Rs=0.359; p=0.005), zonulin (Rs=0.444; p<0.001) and 8-iso-PGF2α (Rs=0.704; p<0.001). Serum LPS significantly correlated with zonulin (Rs=0.610; p<0.001), and 8-iso-PGF2α (Rs=0.591; p=0.001). Finally, a multiple linear regression analysis showed that serum 8-iso-PGF2α and zonulin were the only independent variables associated with sNOX2-dp (R2=68%).Conclusion: this study shows that children affected by PANDAS have high circulating levels of sNOX2-dp, isoprostanes and of LPS that could be involved in the process of neuroinflammation.

2020 ◽  
Author(s):  
Lorenzo Loffredo ◽  
Alberto Spalice ◽  
Francesca Salvatori ◽  
De Castro Giovanna ◽  
Cristiana Alessia Guido ◽  
...  

Abstract Background: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to assess NOX2 levels, as well as serum 8-iso-prostaglandin F2α (iso-PGF2α) and lipopolysaccharide (LPS) derived from Gram-negative bacteria in the gut of patients with PANDAS. Methods: a cross sectional study was performed to compare serum levels of soluble NOX2-dp (sNOX-2-dp), isoprostanes and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used to assess gut permeability. Results: compared with CT, PANDAS children had higher values of sNOX-2-dp, 8-iso-PGF2-alpha and LPS. Simple linear regression analysis showed that sNOX2-dp was significantly correlated with serum LPS (Rs=0.359; p=0.005), zonulin (Rs=0.444; p<0.001) and iso-PGF2α (Rs=0.704; p<0.001). LPS significantly correlated with serum zonulin (Rs=0.610; p<0.001), and iso-PGF2α (Rs=0.591; p=0.001). A multiple linear regression analysis was performed to define the independent predictors of sNOX-2-dp. Isoprostanes and zonulin emerged as the only independent predictive variables associated with sNOX2-dp (R2=68%). Conclusion: this study provides evidences that children affected by PANDAS have high circulating levels of sNOX2-dp, isoprostanes and of LPS that could be potentially implicated in the process of neuroinflammation.


2020 ◽  
Author(s):  
Lorenzo Loffredo ◽  
Alberto Spalice ◽  
Francesca Salvatori ◽  
De Castro Giovanna ◽  
Cristiana Alessia Guido ◽  
...  

Abstract Background: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to evaluate serum NOX2 levels, as well as 8-iso-prostaglandin F2α (iso-PGF2α) and lipopolysaccharide (LPS) of PANDAS patients. Methods: a cross sectional study was performed to compare serum levels of soluble NOX2-dp (sNOX-2-dp), isoprostanes and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used as intestinal permeability assay. Results: compared with CT, PANDAS children had increased values of sNOX-2-dp, 8-iso-PGF2-alpha and LPS. Simple linear regression analysis showed that sNOX2-dp was significantly correlated with serum LPS (Rs=0.359; p=0.005), zonulin (Rs=0.444; p<0.001) and iso-PGF2α (Rs=0.704; p<0.001). Serum LPS significantly correlated with zonulin (Rs=0.610; p<0.001), and iso-PGF2α (Rs=0.591; p=0.001). Finally, a multiple linear regression analysis was performed to define the independent predictors of sNOX-2-dp. Serum isoprostanes and zonulin resulted as the only independent predictive variables associated with sNOX2-dp (R2=68%). Conclusion: this study shows that children affected by PANDAS have high circulating levels of sNOX2-dp, isoprostanes and of LPS that could be potentially implicated in the process of neuroinflammation.


2020 ◽  
Author(s):  
Lorenzo Loffredo ◽  
Alberto Spalice ◽  
Francesca Salvatori ◽  
De Castro Giovanna ◽  
Cristiana Alessia Guido ◽  
...  

Abstract Background: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to assess NOX2 levels, as well as serum 8-iso-prostaglandin F2α (iso-PGF2α) and lipopolysaccharide (LPS) derived from Gram-negative bacteria in the gut of patients with PANDAS. Methods: a cross sectional study was performed to compare serum levels of soluble NOX-2-dp (sNOX-2-dp), isoprostanes and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used to assess gut permeability. Results: compared with CT, PANDAS children had higher values of sNOX-2-dp, 8-iso-PGF2-alpha and LPS. Simple linear regression analysis showed that sNOX2-dp was significantly correlated with serum LPS (Rs=0.359; p=0.005), zonulin (Rs=0.444; p<0.001) and iso-PGF2α (Rs=0.704; p<0.001). LPS significantly correlated with serum zonulin (Rs=0.610; p<0.001), and iso-PGF2α (Rs=0.591; p=0.001). A multiple linear regression analysis was performed to define the independent predictors of sNOX-2-dp. Isoprostanes and zonulin emerged as the only independent predictive variables associated with sNOX2-dp (R2=68%). Conclusion: this study provides evidences that children affected by PANDAS have high circulating levels of sNOX2-dp, isoprostanes and of LPS that could be potentially implicated in the process of neuroinflammation.


2019 ◽  
Author(s):  
Lorenzo Loffredo ◽  
Alberto Spalice ◽  
Francesca Salvatori ◽  
De Castro Giovanna ◽  
Cristiana Alessia Guido ◽  
...  

Abstract Backgroundpaediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to assess NOX2 activity, as well as serum 8-iso-prostaglandin F2α (iso-PGF2α) and lipopolysaccharide (LPS) derived from Gram-negative bacteria in the gut of patients with PANDAS. Methodsa cross sectional study was performed to compare serum activity of soluble NOX-2-dp (sNOX-2-dp), blood levels of isoprostanes and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used to assess gut permeability. Resultscompared with CT, PANDAS children had higher values of sNOX-2-dp, 8-iso-PGF2-alpha and LPS. Simple linear regression analysis showed that sNOX2-dp was significantly correlated with serum LPS (Rs=0.359; p=0.005), zonulin (Rs=0.444; p<0.001) and iso-PGF2α (Rs=0.704; p<0.001). LPS significantly correlated with serum zonulin (Rs=0.610; p<0.001), and iso-PGF2α (Rs=0.591; p=0.001). A multiple linear regression analysis was performed to define the independent predictors of sNOX-2-dp. Isoprostanes and zonulin emerged as the only independent predictive variables associated with sNOX2-dp (R2=68%).Conclusionthis study provides the first report attesting that children affected by PANDAS have high NOX2 activation, oxidative stress and circulating levels of LPS that could be potentially implicated in the process of neuroinflammation.


2021 ◽  
Vol 9 ◽  
Author(s):  
Adriana Prato ◽  
Mariangela Gulisano ◽  
Miriam Scerbo ◽  
Rita Barone ◽  
Carmelo M. Vicario ◽  
...  

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are clinical conditions characterized by the sudden onset of obsessive–compulsive disorder and/or tics, often accompanied by other behavioral symptoms in a group of children with streptococcal infection. PANDAS-related disorders, including pediatric acute-onset neuropsychiatric syndrome (PANS), childhood acute neuropsychiatric symptoms (CANS), and pediatric infection triggered autoimmune neuropsychiatric disorders (PITANDs), have also been described. Since first defined in 1998, PANDAS has been considered a controversial diagnosis. A comprehensive review of the literature was performed on PubMed and Scopus databases, searching for diagnostic criteria and diagnostic procedures of PANDAS and related disorders. We propose a test panel to support clinicians in the workout of PANDAS/PANS patients establishing an appropriate treatment. However, further studies are needed to improve our knowledge on these acute-onset neuropsychiatric conditions.


Author(s):  
Mohammad O AL fattani ◽  
Asmaa M Al Refaie ◽  
Shuruq Hassan Alsulami ◽  
Najia Al Hojaili

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a rear disease in pediatric age group which constitute a unique manifestation associated with obsessive-compulsive disorder (OCD) and tic disorder in children. However, this diagnosis has carried a lot of controversies, related mainly to its management. Here we are presenting one case of PANDAS syndrome who was treated successfully with full coarse of antibiotic for 10 days, where all his symptoms disappeared completely in subsequent days including suicidal attempts. PANDAS should be considered in children with neuropsychiatric disorders (tics, obsessive behavior etc.) especially if symptoms associated within a period of infection such as febrile illness or sore throats.


1992 ◽  
Vol 263 (6) ◽  
pp. E1164-E1170
Author(s):  
A. A. Portale ◽  
B. P. Halloran ◽  
S. T. Harris ◽  
D. D. Bikle ◽  
R. C. Morris

We tested the hypothesis that in humans, metabolic acidosis can disorder the metabolism of 1,25-dihydroxyvitamin D [1,25(OH)2D] by impairing the capacity for a sustained physiological stimulus to increase renal production of this hormone. Specifically, in seven healthy men in whom restriction of dietary phosphorus had doubled their serum concentration of 1,25(OH)2D, we induced metabolic acidosis of moderate severity with oral NH4Cl, administered for 7 days. With induction of acidosis, the serum concentration of 1,25(OH)2D decreased sharply and remained decreased and near constant throughout the period of acidosis, the decrease amounting to one-half of the increment induced by phosphorus restriction alone. The serum concentration of free 1,25(OH)2D also decreased, since the measured free fraction of 1,25(OH)2D was unaffected by NH4Cl. The decrease in serum 1,25(OH)2D was accounted for by a 16% increase in its metabolic clearance rate and by a 19% decrease in its production rate. Metabolic acidosis induced a modest increase in the concentrations of blood ionized calcium and serum phosphorus. Multiple linear regression analysis revealed that serum levels of 1,25(OH)2D varied inversely and significantly with those of plasma hydrogen ion (R = -0.77, P < 0.001), but not with those of blood ionized calcium or serum phosphorus. These data demonstrate in humans that metabolic acidosis can substantially reverse the increase in serum concentration of 1,25(OH)2D induced by phosphorus restriction. The data provide evidence that acidosis can restrict the increase in renal production and serum concentration of 1,25(OH)2D effected by a sustained physiological stimulus.


2017 ◽  
Vol 41 (S1) ◽  
pp. s781-s782
Author(s):  
A. Pozza

IntroductionPaediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a subgroup of conditions including obsessive-compulsive disorder (OCD), tic disorders, pre-pubertal and sudden onset, temporal association between streptococcal infections and associated neurological abnormalities. Some strategies were developed, including the use of antibiotic prophylaxis to prevent streptococcal-triggered exacerbations, and immunomodulatory interventions for the management of acute symptoms. Cognitive-behavioral therapy (CBT), which has been demonstrated to be the first-line treatment for OCD, can be a valid adjuvant during the difficult course of PANDAS to target acute symptoms and prevent exacerbations.ObjectivesThe study presented a case of a patient with PANDAS treated with antibiotic medication and CBT as augmentation.MethodsThe 11-year-old patient (Y-BOCS pre-test score = 32), had been hospitalized for three weeks for acute onset of PANDAS. The clinical picture consisted of asthenia, contamination fears and washing compulsions, separation anxiety, severe depression and anxiety. Pharmacotherapy involved risperidone 2 mg/die and sertraline 250 mg/die for five months combined with antibiotic prophylaxis for two years. The CBT intervention started at discharge from hospital and included psycho-education on anxiety, intensive exposure and response prevention (2 hour sessions three times a week) for twelve months, cognitive restructuring, diffusion and mindfulness for the subsequent twelve months.ResultsAnxiety and OCD symptoms substantially improved. The patient gradually started school again. Post-test score was 11 on the Y-BOCS.ConclusionsAlong with psychiatric and antibiotic medications, CBT may be a valid augmentation strategy for PANDAS to reduce risk of exacerbations and enhance symptom improvement. Limitations are discussed.Disclosure of interestThe author has not supplied his/her declaration of competing interest.


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