Background and objectives: This study evaluated the effect of chronic consumption of saccharin on important physiological and biochemical parameters in rats. Materials and Methods: Male Wistar rats were used in this study and were divided into four groups: A control group and three experimental groups (groups 1, 2, and 3) were treated with different doses of saccharin at 2.5, 5, and 10 mg/kg, respectively. Each experimental group received sodium saccharin once per day for 120 days while the control group was treated with distilled water only. In addition to the evaluation of body weight, blood samples [total protein, albumin, glucose, lipid profile, alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatinine, and uric acid] and urine (isoprostane) were collected in zero time, and after 60 and 120 days for biochemical evaluation. Liver (catalase activity) and brain (8-hydroxy-2’-deoxyguanosine, 8-OHdG) tissues were collected at time zero and after 120 days. Results: The data showed that saccharin at 5 mg/kg increased body weight of treated rats after 60 (59%) and 120 (67%) days of treatment. Increased concentration of serum glucose was observed after treatment with saccharin at 5 (75% and 62%) and 10 mg/kg (43% and 40%) following 60 and 120 days, respectively. The concentration of albumin decreased after treatment with saccharin at 2.5 (34% and 36%), 5 (39% and 34%), and 10 mg/kg (15% and 21%) after 60 and 120 days of treatment, respectively. The activity of LDH and uric acid increased proportionally with dosage levels and consumption period. There was an increased concentration of creatinine after treatment with saccharin at 2.5 (125% and 68%), 5 (114% and 45%), and 10 mg/kg (26% and 31%) following 60 and 120 days, respectively. Catalase activity and 8-OHdG increased by 51% and 49%, respectively, following 120 days of treatment with saccharin at 2.5 mg/kg. Elevation in the concentration of isoprostane was observed after treatment with saccharin at all doses. Conclusions: The administration of saccharin throughout the treatment period was correlated with impaired kidney and liver function. Both hyperglycemic and obesity-inducing side effects were observed. There was an increased oxidative status of the liver, as well as exposure to increased oxidative stress demonstrated through the increased levels of isoprostane, uric acid, 8-OHdG, and activity of catalase. Therefore, it is suggested that saccharin is unsafe to be included in the diet.

Mesial temporal lobe epilepsy (MTLE) is usually associated with drug-resistant seizures and cognitive deficits. Efforts have been made to improve the understanding of the pathophysiology of MTLE for new therapies. In this study, we used proteomics to determine the differential expression of proteins in the hippocampus of patients with MTLE compared to control samples. By using the two-dimensional electrophoresis method (2-DE), the proteins were separated into spots and analyzed by LC-MS/MS. Spots that had different densitometric values for patients and controls were selected for the study. The following proteins were found to be up-regulated in patients: isoform 1 of serum albumin (ALB), proton ATPase catalytic subunit A (ATP6V1A), heat shock protein 70 (HSP70), dihydropyrimidinase-related protein 2 (DPYSL2), isoform 1 of myelin basic protein (MBP), and dihydrolipoamide S-acethyltransferase (DLAT). The protein isoform 3 of the spectrin alpha chain (SPTAN1) was down-regulated while glutathione S-transferase P (GSTP1) and protein DJ-1 (PARK7) were found only in the hippocampus of patients with MTLE. Interactome analysis of the nine proteins of interest revealed interactions with 20 other proteins, most of them involved with metabolic processes (37%), presenting catalytic activity (37%) and working as hydrolyses (25%), among others. Our results provide evidence supporting a direct link between synaptic plasticity, metabolic disturbance, oxidative stress with mitochondrial damage, the disruption of the blood–brain barrier and changes in CNS structural proteins with cell death and epileptogenesis in MTLE. Besides this, the presence of markers of cell survival indicated a compensatory mechanism. The over-expression of GSTP1 in MTLE could be related to drug-resistance.

Background: Previous studies on saccharin and cyclamate were either limited to experimental animals or lacked evaluation of their long-term consumption effects in humans. Objectives: This study evaluated the effect of chronic consumption of saccharin and cyclamate on biochemical parameters in healthy individuals and patients with type 2 diabetes mellitus. Material and Methods: Healthy and diabetic individuals were classified into two groups based on whether they consumed sweeteners or not. The participants were classified according to the amount of sweetener consumed per day and duration of consumption. Serum catalase activity, peroxynitrite, ceruloplasmin, and malondialdehyde concentrations were determined. Glycated hemoglobin, fasting glucose, creatinine, alanine transaminase, and lipid profile were also evaluated. The results suggest that saccharin and cyclamate increased HbA1C (+11.16%), MDA (+52.38%), TG (+16.74%), LDL (+13.39%), and TC/HDL (+13.11%) in healthy volunteers. Diabetic patients consuming sweeteners showed increased FSG (+17.51%), ceruloplasmin (+13.17%), and MDA (+8.92%). Diabetic patients showed a positive correlation between the number of tablets consumed per day with FSG and serum creatinine. A positive correlation was found between the duration of sweetener consumption and FSG as well as TG. Conclusion: Consumption of saccharin and cyclamate affected biochemical parameters related to metabolic functions in a time and dose-dependent manner and appear to increase oxidative stress in healthy and diabetic type 2 patients.

In adult rats, the administration of lithium–pilocarpine (LiPilo) reproduces most clinical and neuropathological features of human temporal lobe epilepsy (TLE). Carisbamate (CRS) possesses the property of modifying epileptogenesis in this model. Indeed, about 50% of rats subjected to LiPilo status epilepticus (SE) develop non-convulsive seizures (NCS) instead of motor seizures when treated with CRS. However, the mechanisms underlying these effects remain unknown. The aim of this study was to perform a proteomic analysis in the hippocampus of rats receiving LiPilo and developing motor seizures or NCS following CRS treatment. Fifteen adult male Sprague–Dawley rats were used. SE was induced by LiPilo injection. CRS treatment was initiated at 1 h and 9 h after SE onset and maintained for 7 days, twice daily. Four groups were studied after video-EEG control of the occurrence of motor seizures: a control group receiving saline (CT n = 3) and three groups that underwent SE: rats treated with diazepam (DZP n = 4), rats treated with CRS displaying NCS (CRS-NCS n = 4) or motor seizures (CRS-TLE n = 4). Proteomic analysis was conducted by 2D-SDS-PAGE. Twenty-four proteins were found altered. In the CRS-NCS group, proteins related to glycolysis and ATP synthesis were down-regulated while proteins associated with pyruvate catabolism were up-regulated. Moreover, among the other proteins differentially expressed, we found proteins related to inflammatory processes, protein folding, tissue regeneration, response to oxidative stress, gene expression, biogenesis of synaptic vesicles, signal transduction, axonal transport, microtubule formation, cell survival, and neuronal plasticity. Our results suggest a global reduction of glycolysis and cellular energy production that might affect brain excitability. In addition, CRS seems to modulate proteins related to many other pathways that could significantly participate in the epileptogenesis-modifying effect observed.

Post-traumatic stress disorder (PTSD) is a multifaceted syndrome due to its complex pathophysiology. Signals of illness include alterations in genes, proteins, cells, tissues, and organism-level physiological modifications. Specificity of sensitivity to PTSD suggests that response to trauma depend on gender and type of adverse event being experienced. Individuals diagnosed with PTSD represent a heterogeneous group, as evidenced by differences in symptoms, course, and response to treatment. It is clear that the biochemical mechanisms involved in PTSD need to be elucidated to identify specific biomarkers. A brief review of the recent literature in Pubmed was made to explore the major biochemical mechanisms involved in PTSD and the methodologies applied in the assessment of the disease. PTSD shows pre-exposure vulnerability factors in addition to trauma-induced alterations. The disease was found to be associated with dysfunctions of the hypothalamic–pituitary–adrenal axis (HPA) and hypothalamus–pituitary–thyroid axis. Sympathetic nervous system (SNS) activity play a role in PTSD by releasing norepinephrine and epinephrine. Cortisol release from the adrenal cortex amplifies the SNS response. Cortisol levels in PTSD patients, especially women, are later reduced by a negative feedback mechanism which contributes to neuroendocrine alterations and promotes structural changes in the brain leading to PTSD. Gender differences in normal HPA responsiveness may be due to an increased vulnerability in women to PTSD. Serotonin and dopamine levels were found to be abnormal in the presence of PTSD. Mechanisms such as the induction of neuroinflammation and alterations of mitochondrial energy processing were also associated with PTSD.

The severity of post-traumatic stress disorder and its long-lasting effects among the Yazidi population has not yet been investigated. Objectives: This study evaluated the impact of PTSD severity and chronicity on physiological and anthropometric parameters in women survivors of the genocide- related events after the so-called Islamic State of Iraq and Syria (ISIS) attack in 2014. Methods: The diagnosis PTSD was assessed using PTSD Checklist for DSM-5 (PCL-5). Participants were divided into: External control (healthy individuals living outside the camps), Internal control (healthy individuals living in the camps), and PTSD group (individuals diagnosed with PTSD). The PTSD group was subdivided according to chronicity 5 years and subdivided according to PTSD severity into "Moderate", "Severe" and "Extreme". Systolic blood pressure (SBP), diastolic blood pressure (DBP), blood oxygen saturation (SPO2) and heart rate (HR) were evaluated. Weight, height and waist circumference were measured. Body mass index (BMI) and waist-to-height ratio (WHtR) were calculated. Results: The PTSD group showed significant increases in SBP, DBP, heart rate, BMI, WC, weight, and WHtR compared to the control groups. SPO2 values decreased in the PTSD group. As the disease progressed, there were further increases in SBP, DBP, heart rate, BMI, WC, WHtR, and weight. Similar increases were observed with the severity of the disease. Conclusion: Our data indicates that a long-term impact on physiological and anthropometric parameters is present in women diagnosed with PTSD which might be aggravated by the severity and chronicity of the disease.