Copper, zinc and selenium imbalance in Moroccan haemodialysis patients and its correlation to lipid peroxidation

Background: Haemodialysis patients are at risk of developing trace elements imbalance and lipid peroxidation. The present study was aimed to assess plasma levels of copper (Cu), zinc (Zn), selenium (Se) and malondialdehyde (MDA) of haemodialysis patients and to investigate the possible effect of haemodialysis on these trace elements and MDA imbalance.Methods: Blood samples of fifty hemodialysis patients and forty healthy controls subjects were analyzed for determination of hemoglobin, albumin, creatinine, urea and high-sensitivity C-reactive protein (hs-CRP). Cu, Zn and Se were determined in plasma (before and after hemodialysis) and erythrocytes and MDA in plasma before and after hemodialysis.Results: The study showed that, plasma Zn and Se concentrations were lower in haemodialysis patients compared to that of healthy controls, while plasma Cu, MDA and Cu/Zn ratio were higher.  Plasma Cu/Zn ratios were positively correlated to MDA and weakly correlated to hs-CRP levels whereas plasma Se concentrations were inversely correlated to MDA. In addition, MDA levels increased after haemodialysis session.Conclusions: Based on the results of the present study regarding the imbalance of trace elements in haemodialysis patients, it seems reasonable to periodically assess the trace elements status and consider possible correctional therapy in case of deficiency.

Carbimazol and acenocoumarol, where is the problem?

Acenocoumarol and carbimazole are two drugs widely prescribed, they can sometimes be used in the same time. There is no known drug interaction between the two drugs but we report a case of a serious hemorrhagic complication following the concomitant use of the acenocoumarol and carbimazole. A 70-year old man treated by acenocoumarol for an aortic and mitral valve replacement. For a clinical and biological hyperthyroidism, he began treatment with carbimazole, ten days before admission. Three days later, he developed a mucocutaneous icterus with major hemorrhagic syndrome. The outcome was favourable after stopping medication and the use of vitamin K

Evaluation of selected trace elements in the Moroccan type 2 diabetic patients

Background: Several trace elements have been implicated in the etiology of type 2 diabetes, they can influence the onset or pathogenesis of diabetes in various ways including disruption of normal metabolism of glucose and insulin. The purpose of this work is to evaluate the serum status of copper, zinc, selenium, chromium and manganese in Moroccan type 2 diabetics compared to control group.Methods: Blood samples from 100 type 2 diabetics and 90 control subjects were analyzed for blood glucose, glycated hemoglobin (only for diabetics), lipid status and serum trace elements concentrations.Results: Glucose and triglyceride values were statistically higher in diabetics; while those of HDL-cholesterol were lower. Concentrations of zinc, selenium, chromium, and manganese were lower in diabetics compared to controls. In contrast, copper concentrations were higher.Conclusions: The status of trace elements is impaired in type 2 diabetics compared to a control group

Serum vitamin D and vitamin D receptor gene polymorphism in Moroccan patients with systemic lupus erythematosus

Background: Vitamin D plays an important role in the immunomodulation and could be involved in the development of autoimmune diseases such as systemic lupus erythematous (SLE). The study of the polymorphism of the Vitamin D Receptor (VDR) gene may be of interest in explaining the pathophysiology of SLE.Methods: In this study, we aimed to examine the characteristics of VDR gene BsmI polymorphism for the first time in Moroccan patients with SLE and their relationship with clinical manifestations of the disease. We also measured the serum level of 25-hyroxyvitamin D3 to assess its relation to such polymorphism.Results: The study included 66 SLE patients and 91 healthy controls. Our results showed that there were no differences observed in VDR genotypes and allelic distribution within the two groups. Both groups were in Hardy-Weinberg equilibrium, with no significant P values for the observed and expected genotype frequencies. 25-hyroxyvitamin D3 serum levels were the same in the two groups.Conclusions: Based on the results of the present study. We cannot verify any association between VDR gene BsmI polymorphism and SLE. This polymorphism could not be regarded as a genetic marker of the SLE. A larger study examining BsmI and other VDR gene polymorphisms is needed

Serum levels of Selenium and C-reactive protein in comatose patients with severe traumatic brain injury during the first week of hospitalization: case-control study

Introduction: Mortality and morbidity related to traumatic brain injuries still remain high in patients. Many authors reported the importance of Selenium in maintaining the integrity of brain functions. This fact is supported by clinical evidence that therapy with selenium supplementation could help patients suffering from brain disorders like neurodegenerative diseases. The aim of our study was to assess the relationship between Selenium concentration in serum and evolution of comatose patients with severe traumatic brain injury, in the first week of admission, and the correlation between selenium and C-reactive protein. Methods: This case-control study was conducted with 64 comatose patients with TBI, in the Department of Anesthesiology and Reanimation, IbnSina University Hospital and Hospital of specialties in Rabat-Morocco, and healthy volunteers recruited in Blood transfusion center of Rabat. Blood sampling was collected from TBI patients, in the first week (3h after admission and each 48h during one week), and from healthy volunteers one time. Concentration of Se in serum was determined by electrochemical atomic absorption spectrometry. Statistical analysis was performed using Statistical software (SPSS) and the cases and controls were compared using the Mann- Whitney U test. A P-value < 0.05 was considered to be statistically significant. Results: Comparison selenium concentration in the first day (D0), third day (D2) and fifth day according to the death and survival statue in patients did not show statistical significance (p > 0.05). Selenium concentration of D0 in patients and Selenium concentration in control group also did not show statistical significance (p > 0.05). Similarly, we did not report a correlation between selenium and C-reactive protein. Conclusion: According to our data selenium and CRP may not play a role in progression of coma state in patients with severe traumatic brain injury

The Influence of Heavy Metals and Trace Elements on Comatose Patients with Severe Traumatic Brain Injury in the First Week of Admission

Purpose. The aim of this study is to investigate the possible role of heavy metals (lead and cadmium) and imbalance of trace elements (chromium, iron, zinc, copper, and manganese) in death among patients with severe traumatic brain injury. Material and Methods. A case-control study was conducted with 64 comatose patients with severe TBI, in the Department of Anesthesiology and Reanimation, Ibn Sina University Hospital and Hospital of Specialties in Rabat, Morocco; 22 healthy volunteers were recruited in Blood Transfusion Center of Rabat. Blood samples were collected from TBI patients, in the first week (3h after admission and each 48h during one week) and from healthy volunteers one time. Concentration of heavy metals and trace elements in serum was determined by electrochemical atomic absorption spectrometry. Statistical analysis was performed using Statistical software (SPSS) and the cases and controls were compared using the Mann–Whitney U test and Student’s t-test for cadmium according to gender and final evolution. A P-value <0.05 was considered to be statistically significant. Results. Our data showed that the difference of heavy metals concentration (lead and cadmium) between patients and healthy subjects was not statistically significant. However, the difference of some trace elements concentration (iron, copper, chromium, and selenium) between patients and healthy subjects was statistically significant. According to the final evolution, the concentration of manganese was higher in dead patients and statistically significant (p = 0.04) for heavy metals; the concentration of lead was not statistically significant while the concentration in cadmium was statistically significant (p = 0.004). By sex, lead and cadmium were statistically significant, respectively p = 0.02, p = 0.001, and cadmium was higher in women, while lead was higher in men. Conclusion. Among all studied heavy metals (lead and cadmium) and trace elements (iron, zinc, copper, selenium, chromium, and manganese), manganese and cadmium may play a role in the death of patients from severe traumatic brain injury

Preclinical Evaluation of panobinostat and ONC201 for the treatment of diffuse intrinsic pontine glioma (DIPG)

Diffuse intrinsic pontine glioma (DIPG) also referred as paediatric high-grade glioma (pHGG) is a fast-growing and aggressive type of childhood brain cancer. Recent studies investigating the molecular pathogenesis of DIPG have identified new therapeutic targets, paving the way for a new line of drugs mainly HDAC inhibitors. However, despite long years of trials, no significant results have been generated yet. Panobinostat is a HDAC inhibitor that has shown promising preclinical cytotoxicity in DIPG but failed so far in clinical trials. This study aims to re-evaluate the efficacy of Panobinostat in DIPG in vitro using patient-derived DIPG cell cultures obtained directly from patients. ONC201 is another potentially effective drug in DIPG. This apoptotic agent has been considered in a few clinical trials in diffuse glioma including DIPG. Our results reveal a dose-dependent response to Panobinostat and ONC201 in DIPG cells. However, Panobinostat caused a significant reduction in the mean percentage cell viability at a lower concentration compared to ONC201. Panobinostat caused significant decreases in DIPG cell viability at concentrations greater than or equal to 0.002 μM (p<0.05), the response reached a plateau after 0.1 μM, which reduced cell viability to 32.81 % ± 0.25 % (p = 6.74E−06) when compared to control cells. ONC201 only significantly induced apoptosis at concentrations equal or higher than 0.01 μM (p<0.05), with its effect plateauing after 0.2 μM. This pre-clinical study supports the effectiveness of Panobinostat as a potential therapeutic agent for DIPG compared to ONC201, with no apparent synergistic effect observed in combination

Targeted Gene Panel Sequencing Unveiled New Pathogenic Mutations in Patients With Breast Cancer

The increasing commercialization of new gene panels based on next-generation sequencing for clinical research has significantly improved our understanding of breast cancer genetics and has led to the discovery of new mutation variants. The study included 16 unselected Moroccan breast cancer patients tested with multi-gene panel (HEVA screen panel) using Illumina Miseq, followed by Sanger sequencing to validate the most relevant mutation. Mutational analysis revealed the presence of 13 mutations (11 single-nucleotide polymorphisms [SNPs] and 2 indels), and 6 of 11 identified SNPs were predicted as pathogenic. One of the 6 pathogenic mutations was c.7874G>C, a heterozygous SNP in HD-OB domain of BRCA2 gene, which led to the arginine to threonine change at codon 2625 of the protein. This work describes the first case of a patient with breast cancer harboring this pathogenic variant and analyzes its functional impact using molecular docking and molecular dynamics simulation. Further experimental investigations are needed to validate its pathogenicity and to verify its association with breast cancer