The displacement study of 99m Tc-DTPA-Human serum albumin binding in presence of furosemide and metformin by using equilibrium dialysis and molecular docking.

The 99m Tc-DTPA (Technetium99m diethylenetriaminepentaacetic acid), is a radiopharmaceutical used in renal scintigraphy. The human serum albumin (HSA) binding site(s) for the 99m Tc-DTPA have never been characterized. This study will cover in vitro the binding rates of 99m Tc-DTPA on HSA and the 99m Tc-DTPA competition interactions with two drugs having known human serum albumin binding sites. Furosemide (FUR) and metformin (MET) were added to 99m Tc-DTPA solution (weight ratios 1/1 vol:vol) followed by the quantification of 99m Tc-DTPA binding rates to HSA (40 g/L) using equilibrium dialysis and the qualification of this binding using Molecular Modeling methods. The 99m Tc-DTPA binding rates to human serum albumin increased with the highest concentration. Both drugs FUR and MET displaced 99m Tc-DTPA binding. 99m Tc-DTPA could bind to human serum albumin in many locations in site I and I-II, but strongly bound to site I through hydrogen bonds.

Consumption of Argan Oil Improves Anti-Oxidant and Lipid Status in Hemodialysis Patients.

OBJECTIVE: Virgin Argan oil (VAO) is of interest in oxidative stress and lipid profile because of its fat composition and antioxidant compounds. We investigated the effect of VAO consumption on lipid profile and antioxidant status in hemodialysis patients after a 4-week period of consumption. METHODS: In a crossover, controlled trial, 37 patients (18 men, 19 women) with end-stage renal disease on maintenance hemodialysis, were randomly assigned to a 4-week VAO diet. Fasting plasma lipids, vitamin E and oxidized LDL (ox-LDL) were analyzed. Malondialdehyde (MDA) was determined before and after hemodialysis session. RESULTS: There was no significant change in serum total cholesterol and ox-LDL. However, VAO consumption decreased the levels of triglyceride (p = 0.03), total cholesterol (p = 0.02) and low-density lipoprotein (p = 0.03) and increased the levels of high-density lipoprotein (p = 0.01). Plasma vitamin E contents significantly increased from baseline only in VAO-group (p < 0.001). Hemodialysis session increased MDA levels, but the increase in VAO group was less than in control group. CONCLUSION: VAO consumption improved lipid profile and oxidative stress status in hemodialysis patients.

Characterization of Am IT, an anti-insect ß-toxin isolated from the venom of scorpion Androctonus mauretanicus.

In the present study, a 'novel' toxin, called Am IT from the venom of scorpion Androctonus mauretanicus is isolated and characterized. A detailed analysis of the action of Am IT on insect axonal sodium currents is reported. Am IT was purified through gel filtration followed by C18 reversed-phase HPLC. Toxicity of Am IT in vivo was assessed on male German cockroach (Blattella germanica) larvae and C57/BL6 mice. Cross-reactivity of Am IT with two ß-toxins was evidenced using (125)I-iodinated toxin-based radioimmunoassays with synaptosomal preparations from rat brain. The complete amino acid sequence of Am IT was finally determined by Edman sequencing. Am IT was observed to compete with AaH IT4 purified from the venom of scorpion Androctonus australis in binding assays. It was recognized by an antibody raised against a ß-type toxin, which indicated some structural similarity with ß-toxins (or related toxin family). The 'novel' toxin exhibited dual activity since it competed with anti-mammal toxins in binding assays as well as showed contracting activity to insect. The toxin competed with radio-labeled ß-toxin Css IV by binding to Na(+) channels of rat brain synaptosomes. Analysis of toxin amino acid sequences showed that Am IT shares high structural identity (92%) with AaH IT4. In conclusion, Am IT not only reveals an anti-insect compound properties secreted by 'Old World' scorpions, paralyzing insect larvae by binding to Na(+) channels on larvae's nerve-cell membranes, but also exerts toxic activity in mice, which is similar to anti-mammal toxins from 'New World' scorpions (North and South Americas). Therefore, Am IT appears to be structurally and functionally similar to AaH IT4.

[Toxicology of synthetic cannabinoids]. / Toxicologie des cannabinoïdes de synthèse.

Synthetic cannabinoids (CS), or synthetic endocannabinoid receptor agonists, were initially synthesized for basic research into exocannabinoid signaling pathways, as well as in clinical research for their analgesic properties. The use of CS for recreational purposes is a recent phenomenon, but one that has grown very quickly in recent years, since these molecules now represent the main category of new synthetic products (NPS). This literature review aims to bring together current data regarding the use and effects caused by CS in humans. The relationship between the structure and activity of these CSs, the pharmacology and adverse effects of these CSs and finally the different methods of analyzing CSs. A better understanding of this phenomenon is essential to raise awareness among stakeholders in the health field.

Genetic diversity and evolutionary dynamics of the Omicron variant of SARS-CoV-2 in Morocco.

Among the numerous variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that have been reported worldwide, the emergence of the Omicron variant has drastically changed the landscape of the coronavirus disease (COVID-19) pandemic. Here, we analyzed the genetic diversity of Moroccan SARS-CoV-2 genomes with a focus on Omicron variant after one year of its detection in Morocco in order to understand its genomic dynamics, features and its potential introduction sources. From 937 Omicron genomes, we identified a total of 999 non-unique mutations distributed across 92 Omicron lineages, of which 13 were specific to the country. Our findings suggest multiple introductory sources of the Omicron variant to Morocco. In addition, we found that four Omicron clades are more infectious in comparison to other Omicron clades. Remarkably, a clade of Omicron is particularly more transmissible and has become the dominant variant worldwide. Moreover, our assessment of Receptor-Binding Domain (RBD) mutations showed that the Spike K444T and N460K mutations enabled a clade higher ability of immune vaccine escape. In conclusion, our analysis highlights the unique genetic diversity of the Omicron variant in Moroccan SARS-CoV-2 genomes, with multiple introductory sources and the emergence of highly transmissible clades. The distinctiveness of the Moroccan strains compared to global ones underscores the importance of ongoing surveillance and understanding of local genomic dynamics for effective response strategies in the evolving COVID-19 pandemic.

Prevalence of Blastocystis sp. in Morocco: Comparative assessment of three diagnostic methods and characterization of parasite forms in Jones' culture medium.

Blastocystosis is an infection caused by Blastocystis sp., which colonizes the digestive tract of various hosts, including humans, although its pathogenicity is debated. It is crucial to detect and distinguish the different forms of Blastocystis to understand better its impact on human health and its epidemiological evolution. This study evaluated three diagnostic methods on 105 stool samples: direct examination, culture in Jones' medium, and conventional PCR. PCR is considered the gold standard and revealed a high prevalence of Blastocystis (67.62%) compared to direct examination (20.95%) and culture in Jones' medium (51.43%). Although the sensitivity of direct examination and culture was 31% and 76.1%, respectively, their specificity was 100%. No significant risk factors were identified. A statistically significant association was observed between Blastocystis infection and abdominal pain. Microscopic analysis revealed various morphological forms. Molecular diagnosis is an essential tool to determine the true prevalence of Blastocystis, and studying the different forms of this microorganism will contribute to a better understanding of its biological cycle and, therefore, the impact of this emerging infection on human health.

Title: Prévalence de Blastocystis sp. au Maroc : évaluation comparative de trois méthodes de diagnostic et caractérisation des formes parasitaires en milieu de culture Jones. Abstract: La blastocystose est une infection causée par Blastocystis sp., qui colonise le tractus digestif de divers hôtes, y compris l'homme, bien que son pouvoir pathogène soit débattu. Il est crucial de détecter et de distinguer les différentes formes de Blastocystis pour mieux comprendre son impact sur la santé humaine et son évolution épidémiologique. Cette étude a évalué trois méthodes de diagnostic sur 105 échantillons de selles : l'examen direct, la culture en milieu de Jones et la PCR conventionnelle. La PCR, considérée comme méthode de référence, a révélé une prévalence élevée de Blastocystis (67,62 %) par rapport à l'examen direct (20,95 %) et à la culture en milieu de Jones (51,43 %). Bien que la sensibilité de l'examen direct et de la culture soit respectivement de 31 % et 76,1 %, leur spécificité était de 100 %. Aucun facteur de risque significatif n'a été identifié. Une association statistiquement significative a été observée entre l'infection à Blastocystis et les douleurs abdominales. L'analyse microscopique a révélé diverses formes morphologiques. Le diagnostic moléculaire est un outil essentiel pour déterminer la véritable prévalence de Blastocystis, et l'étude des différentes formes de ce microorganisme contribuera à une meilleure compréhension de son cycle biologique et, par conséquent de l'impact de cette infection émergente sur la santé humaine.

Availability of antidotes in Moroccan hospitals: a national survey.

AIM: The lack of availability of antidotes is a challenge for hospitals all over the world. The objective of our study was to investigate the availability of antidotes in Moroccan hospitals. METHODS: A cross-sectional, questionnaire-based study was conducted from November 2018 to April 2019. The questionnaire was sent to 25 hospitals in order to investigate the availability of 42 selected antidotes based on the International Programme on Chemical Safety list. RESULTS: The survey response rate was 68%. Of the 42 selected antidotes, 38 (90.5%) were available depending on the hospitals included in the study. We found a strong correlation between the availability of antidotes and hospital bed capacity, and logistic regression analysis revealed that bed capacity is the only factor strongly associated with higher antidote stock levels. Some essential antidotes such as digoxin-specific antibody, protamine sulfate, flumazenil and glucagon were unavailable in many of the small- and medium-sized hospitals, and methylene blue, sodium nitroprussiate, Prussian blue and anti-snake venom were absent in all of the hospitals. CONCLUSION: Despite the great efforts that have been made to improve the availability of antidotes in Morocco, some of these vital products are still lacking in Moroccan hospitals.

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.

Significant Association of Polymorphisms in the TCF7L2 Gene with a Higher Risk of Type 2 Diabetes in a Moroccan Population.

BACKGROUND AND AIMS: Several studies have shown that genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) are highly associated with the development of type 2 diabetes mellitus (T2DM) and its associated complications in several populations. The aim of our study was to investigate the association of the rs7903146 (C/T) and rs12255372 (G/T) polymorphism in the TCF7L2 gene with the risk of developing T2DM in the Moroccan population. MATERIAL AND METHODS: A total of 150 T2DM patients and 100 healthy controls were recruited for various anthropometric, biochemical and genetic parameters. Genotyping was performed by using Real Time-PCR. The frequency of genotypes, alleles, anthropometric measures, glycemia, glycated hemoglobin (HbA1c) were evaluated in patients and control, while lipid profile was available only for T2DM group. RESULTS: Glycemia, HbA1c and body mass index (BMI) were significantly higher in T2DM group than control. Analysis of the distribution of the TCF7L2 rs7903146 genotype and allele revealed that the TT genotype was more frequent in T2DM group (24.0%) than in healthy controls (5%) (OR = 4.08, 95% confidence interval (CI = 1.95-11.80, p < 0.0001). The T allele was more frequent in diabetic patients (45.2%) than healthy control (34.5%) and it was associated with high risk of diabetes (OR = 2.13, 95% CI = 1.12-7.31, p = 0.005). The same results were found regarding rs12255372, TT genotype frequencies were 18,7% and 6.0% in T2DM and control group, respectively (OR = 3.11, 95% CI = 1.33-7.24, p = 0.004). The T allele was over-presented in diabetics compared to controls (45.3% and 38.0%, respectively) and increases the risk of T2DM (OR = 2.01, 95% CI = 1.04-3.10, p = 0.01). However, there was no significant difference between the three genotypes of rs7903146 and rs12255372 regarding age, BMI, glycemia, HbA1c and lipid profile. CONCLUSION: The present study confirmed a significant association of the TCF7L2 gene (rs7903146 (C/T) and rs12255372 (G/T) polymorphisms with a higher risk to T2DM in the Moroccan population. No significant difference in respect to anthropometric and metabolic parameters between different genotypes.

Lead concentrations in breast milk of Moroccan nursing mothers and associated factors of exposure: CONTAMILK STUDY.

The aim of CONTAMILK study was to estimate levels of contamination of breast milk (BM) of Moroccan nursing mothers by some xenobiotics including, lead (Pb), to identify associated factors of exposure and to determine the daily intake of newborns. Lead concentrations were determined in 70 samples of colostrum by ICPMS and a structured questionnaire was filled during milk collection to report participants' data. The median lead concentration was 908 µg/L (range 1.38-515,39 µg/L) and in 79 % of samples, levels were higher than the normal range reported by the World Health Organization (WHO) in BM (2-5 µg/L). Indeed, preterm delivery, frequency of use of cosmetic powders and lipsticks were significantly associated with the level of lead in BM. The estimated daily intake was greater than the tolerable daily intake (TDI) of the European food safety authority (0.5 µg/kg/day) for 39 babies and 6 babies according to the WHO (3.6 µg/kg/day).

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.

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.

Cannabis arteritis.

Cannabis is the most consumed psychoactive substance by young people. Chronic use of cannabis can lead to cannabis arteritis, which is a very rare peripheral vascular disease similar to Buerger's disease. It is affecting young adults, especially men, consuming cannabis. A 27-year old woman, with no particular past medical history except for long-term use of cannabis and tobacco developed a digital necrosis in the left hand. She denied using other illicit drugs. Doppler ultrasound examination of the upper limbs was unremarkable. Toxicological analysis revealed the presence of cannabis in both biological fluid and hair strand. Despite medical treatment, cessation of the cannabis and tobacco consumption and hyperbaric oxygen therapy, an amputation of necrotic parts was then required. This case shows the prolonged use of cannabis could be a risk factor for young adult arteritis. Faced with a rapidly progressive arteritis occurring in young adult, the physician should consider the history of use of cannabis. Hair analysis can be useful for confirmation of the chronic consumption of drugs.

Antioxidants status in type 2 diabetic patients in Morocco.

BACKGROUND/AIM: Type 2 diabetes is a heterogeneous and multifactorial metabolic disorder with some relationship to oxidative stress (OS). Since no studies were conducted in the Moroccan population, this clinical investigation aimed at evaluating the antioxidants status in Moroccan patients with type 2 diabetes. MATERIALS AND METHODS: Blood samples of 60 type 2 diabetic patients and 40 healthy controls subjects were analyzed for determination of glycemia, hemoglobin, CRP, glycated hemoglobin, lipid parameters, malondialdehyde (MDA), vitamins E and C, copper (Cu), zinc (Zn), and selenium (Se). RESULTS: CRP and triglycerides were higher in the diabetic group while high-density lipoprotein levels were significantly lower compared to the control group. Plasma MDA, Cu concentrations, and Cu/Zn ratio were found to be higher in diabetic patients compared to healthy subjects, while vitamin E, Zn, and Se concentrations were lower compared to the control group. No significant difference was found in vitamin C levels between the two groups. Plasma HbA1c was positively correlated to MDA levels. CONCLUSION: This study shows that antioxidant status is impaired in diabetics compared to healthy controls.

Whole-Genome Shotgun Sequences of Three Multidrug-Resistant Mycobacterium tuberculosis Strains Isolated from Morocco.

Tuberculosis is a contagious disease that usually attacks the lungs but sometimes attacks other parts of the body, such as the kidneys, glands, and bones. It is an endemic and major public health problem in Morocco. Tuberculosis is transmitted through the airways via the inhalation of microdroplets containing Mycobacterium tuberculosis We present here the whole-genome shotgun sequences of three multidrug-resistant M. tuberculosis strains isolated from Morocco.

Impact of improving quality of dialysis fluid on oxidative stress and lipid profile in hemodialysis patients.

The aim of this study was to evaluate the levels of malondialdehyde as an oxidative stress marker in the same hemodialysis patients after changing the quality of dialysate with ultrapure dialysis fluid. Methods. This prospective study concerns hemodialysis patients; all patients were in the first step treated with conventional dialysate, and in the second step (three months later) the same patients were treated with online produced ultrapure dialysis fluid. The malondialdehyde, C-reactive protein, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, fibrinogen, and albumin were quantified before the two steps. Results. Thirty-seven patients completed the study. Ultrapure dialysis fluid reduced but not significantly the malondialdehyde concentrations. Both dialysis fluids were associated with improvement in the malondialdehyde level before and after the hemodialysis session. In lipid parameters, there was a significant decrease with conventional dialysis fluid versus ultrapure dialysis fluid of triglycerides, total cholesterol, and high-density lipoprotein in patients' blood. Instead, the level of low-density lipoprotein, fibrinogen, albumin, and C-reactive protein does not change significantly. Conclusion. The lipid parameters were improved for triglycerides and total cholesterol. Malondialdehyde increases following the hemodialysis session, and the conventional dialysate increased malondialdehyde levels more than the ultrapure dialysis but the differences were not statistically significant.

[Development and validation of an assay method of the paraphenylene diamine by gas chromatography-mass spectrometry]. / Développement et validation d'une méthode de dosage de la paraphénylène diamine par chromatographie gazeuse couplée à la spectrométrie de masse.

Paraphenylenediamine is an aromatic amine used as a hair dye; it is responsible for poisoning characterized by respiratory distress involving life-threatening. The objective of this work is the development and validation of an assay of para-phenylenediamine in the whole blood. The method is based on the determination of paraphenylene diamine in whole blood by gas chromatography-mass spectrometry after liquid-liquid extraction and derivatization. The validation protocol has included the study of the recovery factor of extraction, the measurement range, accurency, repetability and intermediate precision. The calibration curve was linear between 98 and 1350 µg/L (r = 0.999), the limit of detection and quantification were 37 µg/L and 63 µg/L respectively. The accuracy were 94.7%. Coefficients of variation were (2.3/6.8/9.7%) for repeatability and (4.4/8.7/9.8%) for intermediate precision. The method is suitable for quantification of PPD in acute poisoning situations. A method for the determination of the paraphenylene diamine in the whole blood by gas chromatography coupled to mass spectrometry was developed. The validation of the method showed good linearity, good accuracy and low limit of quantification.