Plasma oxysterols in drug-free patients with schizophrenia.

Evidence from clinical, genetic, and medical studies has shown the neuronal developmental disorder aspect of schizophrenia (SZ). Whereas oxysterols are vital factors in neurodevelopment, it is still unknown whether they are involved in the pathophysiology of SZ. The current study aims to explore the profile of oxysterols in plasma, ratio to total cholesterol (Tchol) and the association with clinical factors in patients with SZ. Forty men diagnosed with SZ and forty healthy controls matched for age and sex were included in the study. The ratios of cholestane-3ß,5α,6ß-triol, 27-hydroxycholesterol (27-OHC) and Cholestanol to Tchol increased in the schizophrenic group compared to controls. However, levels of 24S-hydroxycholesterol (24-OHC) were not significantly different between patients and controls. For the SZ patients, the plasma 24-OHC levels were positively correlated with the positive and negative syndrome total scores (PANSS) but negatively correlated with the Montreal Cognitive Assessment scores (MOCA). Moreover, the ratio Cholestanol to Tchol was negatively correlated with MOCA scores and positively correlated with PANSS general. The binary logistic regression analysis revealed that the ratio Cholestane-3ß,5α,6ß-triol/TChol could be considered as an independent risk factor for SZ. On the other hand, the receiver's operating characteristics analysis corresponding to potential biomarkers on SZ showed Areas Under the Curve (AUCs) of 82.1%; 69.7% and 77.6% for the ratio of Cholestane-3ß,5α,6ß-triol/TChol, 27-OHC/TChol and Cholestanol/TChol respectively. The relevance of Cholestane-3ß,5α,6ß-triol, 27-OHC and Cholestanol assays as biomarkers of this disease deserves further investigation.

Selected plasma oxysterols as a potential multi-marker biosignature panel for Behçet's Disease.

Clinical, genetic, and medical evidence has shown the inflammatory vasculitis aspect of Behçet's Disease (BD). Whereas oxysterols are vital factors in inflammation and oxidative stress, it is still unknown whether they are involved in the pathophysiology of BD. The current study aims to explore the profile of oxysterols in plasma of BD patients. Thirty patients diagnosed with BD and forty healthy controls matched for age and gender were included. Results showed that the cholestane-3ß,5α,6ß-triol, 27-hydroxycholesterol (27-OHC) and cholestanol levels were higher in BD than controls. In addition, plasma levels of 7-ketocholesterol (7-KC) and 25-hydroxycholesterol (25-OHC) were lower in BD patient. However, levels of 24S-hydroxycholesterol (24-OHC) did not significantly differ. For BD patients, the plasma 7-KC level was negatively correlated with the BD activity index (BDAI) while 27-OHC was positively correlated with high-sensitivity C-reactive protein (hs-CRP) in patients with active course of the disease. According to ROC analysis, a remarkable increase in the area under the curve (AUC) with a higher sensitivity (Se) and specificity (Sp) for 7-KC, 25-OHC and 27-OHC combined markers was observed. The present study indicated that the identification of the predictive value of these three-selected biomarkers related to oxidative stress and inflammation in patients should lead to a better identification of the etiological mechanism of BD.

Predictive value of oxidative stress biomarkers in drug-free patients with bipolar disorder.

OBJECTIVE: Oxidative stress is one of the primary etiological mechanisms of bipolar disorder (BD). METHODS: The present study was conducted over a period of 24 months on Tunisian on 34 drug­free male patients with BD (mean age: 34.5 years) and 101 age and gender matched controls (mean age: 34.20 years) were enrolled in the study. RESULTS: Plasma reduced glutathione (GSH) and total thiols levels were significantly decreased in patients compared to controls (respectively p < .001; p = .009). In addition, malondialdehyde (MDA), advanced oxidation protein products (AOPP), protein carbonyls (PC) and homocysteine (Hcys) concentrations and glutathione peroxidase (GSH-Px) activity were significantly increased in patients compared to controls (p = .002; p < .001; p = .001; p < .001 and p = .016, respectively). The binary logistic regression analysis revealed that MDA, AOPP and Hcys could be considered as independent risk factors for BD. When using CombiROC analysis, a remarkable increase in the area under the curve (AUC) with higher sensitivity (Se) and specificity (Sp) for MDA, AOPP, PC, GSH-Px and Hcys combined markers was observed. CONCLUSIONS: Overall, the identification of the predictive value of these five selected biomarkers related to oxidative stress in drug free patients should lead to a better identification of the etiological mechanism of BD.

Plasma oxysterols: Altered level of plasma 24-hydroxycholesterol in patients with bipolar disorder.

Cholesterol and its oxygenated metabolites, including oxysterols, are intensively investigated as potential players in the pathophysiology of brain disorders. Altered oxysterol levels have been described in patients with numerous neuropsychiatric disorders. Recent studies have shown that Bipolar disorder (BD) is associated with the disruption of cholesterol metabolism. The present study was aimed at investigating the profile of oxysterols in plasma, their ratio to total cholesterol and their association with clinical parameters in patients with BD. Thirty three men diagnosed with BD and forty healthy controls matched for age and sex were included in the study. Oxysterol levels were measured by isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry. Significantly higher levels were observed for cholestane-3ß,5α,6ß-triol, 27-hydroxycholesterol (27-OHC) and Cholestanol in patients with BD. The concentration of 24-hydroxycholesterol (24-OHC) was significantly lower in patients compared to controls. 24-OHC was also negatively correlated to MAS subscale score (r =-0.343; p = 0.049). In patients, 24-OHC was inversely correlated with age (r = -0.240; p = 0.045). Multivariate analysis found that BD acute decompensation was independently related to the rise in plasma 24-OHC (p = 0.002; OR = 0.966, 95 % CI [0.945 - 0.987]). However, the 24-OHC assay relevance as a biomarker of this disease deserves further investigation in other studies.

Acidic pretreatment as a chemical approach for enhanced Photorhabdus temperata bioinsecticide production from industrial wastewater.

The chemical treatment of the wastewater used for the bioinsecticide production by the bacterium Photorhabdus temperata was investigated in this study. An improvement of the volatile suspended solids (VSS) solubilization along with an increase in protein, carbohydrate, reducing sugar and nitrogen concentrations were demonstrated after alkali and thermo-alkali hydrolysis. In contrast, the application of acidic and thermo-acidic pretreatments reduced the organic matter hydrolysis. Compared to untreated wastewater, the chemical oxygen demand (COD) solubilization and the heavy metal concentration, except manganese, were enhanced in all the chemically pretreated wastewaters. Although its low contribution in the solubilization of the wastewater organic matter, the acidic-pretreated wastewater showed the highest performance in supporting P. temperata biopesticide production. Indeed, using the acidic-pretreated wastewater as a fermentation medium decreased the lag phase, enhanced the growth of the strain K122 to reach a final biomass production of 20 × 108 cells/mL, increased culturable cell count to 262 × 106 cells/mL and improved oral toxicity against Ephestia kuehniella larvae by 68.4%. Among chemical pretreatments performed, the acidic hydrolysis was demonstrated to be the unique promising one for P. temperata bioinsecticide production due to its ability to reduce aromatic compounds as shown by Gas Chromatography-Mass Spectrometry (GC-MS) analysis.

Predictive value of oxidative stress biomarkers in drug­free patients with schizophrenia and schizo-affective disorder.

Several studies have suggested that oxidative stress may represent one of the primary etiological mechanisms of schizophrenia (SZ) and schizoaffective disorder (SAD) which can be targeted by therapeutic intervention. The present study was conducted over a period of 24 months, between June 2016 and June 2018. All enrolled subjects were Tunisian, forty five drug­free male patients with SZ (mean age: 37.6 years), twenty one drug­free male patients with SAD (mean age: 28.8 years) and hundred and one age and gender matched controls (mean age: 34.2 years) were enrolled in the study. Plasma reduced glutathione (GSH) and Total thiols levels were significantly decreased in patients compared to controls (respectively p<0.001; p=0.050). In addition, malondialdehyde (MDA), advanced oxidation protein products (AOPP) and protein carbonyls (PC) concentrations and glutathione peroxidase (GSH-Px) activity were significantly increased in patients compared to controls (p<0.001; p<0.001; p<0.001 and p=0.003 respectively). The binary logistic regression analysis revealed that MDA, AOPP, PC and GSH-Px could be considered as independent risk factors for SZ and SAD. When using ROC analysis, a remarkable increase in the area under the curve (AUC) with higher sensitivity (Se) and specificity (Sp) for MDA, AOPP, PC and GSH-Px combined markers was observed. The present study indicated that the identification of the predictive value of this four-selected biomarkers related to oxidative stress in drug free patients should lead to a better identification of the etiological mechanism of SZ or SAD.

[Bipolar disorder vulnerability: The vitamin D path]. / Vulnérabilité au Trouble Bipolaire: La Piste de la Vitamine D.

OBJECTIVES: Bipolar disorder (BD) etiopathogenesis is still not well elucidated. It has recently been proven that 25-hydroxy vitamin D (25OHD) has an anti-inflammatory and neuroprotective role. Our objectives were to measure 25OHD plasma levels in patients with BD in acute decompensation and compare them with patients with schizophrenia (SCZ) or schizoaffective disorder (SAD) and with healthy controls. METHODS: This is a cross-sectional case-control study including male inpatients with a decompensation of their disease who were diagnosed with BD, SCZ or SAD according to DSM-5 criterias. The control group was constituted by unrelated healthy subjects, age-and-sex matched. RESULTS: The 25OHD level was significantly higher only in patients with BD compared to controls. 25OHD was also positively correlated to the PANSS scale (r = 0.282, p < 0.001) and to different MOCA scores (r = 0.326, p = 0.006) as well as aspects related to abstraction, attention and memory capacity. Multivariate analysis found that BD acute decompensation was independently related to the rise in plasma 25OHD (p = 0.012; OR =1.157, [1.032 -1.297]). CONCLUSION: Our study shows that BD acute decompensation is associated with the rise in plasma 25OHD synthesis. However, the vitamin D dosage relevance as a biomarker of this disease warrants a verification in other studies.

OBJECTIFS: L'étiopathogénie du trouble bipolaire (TB) demeure non encore bien élucidée. Récemment, il a été prouvé que la 25-hydroxy-vitamine D(25OHD) a un rôle anti-inflammatoire et neuroprotecteur. Nos objectifs étaient de mesurer les concentrations plasmatiques de la 25OHD chez des patients atteints de TB en décompensation aigue et de les comparer à celles de patients souffrant de schizophrénie (SCZ) ou de trouble schizo-affectif (TSA) et à celles de témoins sains. MÉTHODES: Il s'agissait d'une étude transversale de type cas-témoins qui a inclus des patients de sexe masculin hospitalisés pour une décompensation de leur maladie et chez qui les diagnostics de TB, SCZ, ou de TSA ont été retenus selon les critères du (DSM-5). Le groupe témoin a été constitué de sujets sains non apparentés, appariés selon l'age et le sexe. RÉSULTATS: La concentration de la 25OHD était significativement plus élevée uniquement chez les patients atteints de TB par rapport aux témoins. la 25OHD était aussi corrélée positivement à l'échelle PANSS (r = 0.282, p < 0.001) et aux différents scores de l'échelle MOCA (r = 0.326, p = 0.006) ainsi qu'aux dimensions concernant la capacité d'abstraction, d'attention et la mémoire . A l'analyse multivariée, la décompensation aigue du TB était liée de manière indépendante à l'élévation de la 25OHD plasmatique (p = 0.012; OR = 1.157, [1.032 -1.297]). CONCLUSION: Notre étude a montré que la décompensation aigue des TB était associée à une élévation de la synthèse de la 25OHD plasmatique. Toutefois, la pertinence du dosage de la vitamine D comme biomarqueur de cette maladie mérite d'être vérifiée par d'autres études.