Les fracture-luxations transolécraniennes

Les fracture-luxations transolécraniennes sont une entité rare des fracture-luxations du coude. Il s'agit d'une lésion complexe qui peut compromettre le pronostic fonctionnel du coude. Dix patients étaient diagnostiqués dans notre service entre janvier 2005 et novembre 2012. Tous nos patients étaient de sexe masculin, l'âge moyen était de 29 ans. Les fractures de l'olécrane étaient complexes et comminutives dans sept cas et simples chez trois patients. Deux cas étaient associés à des fractures de la tête radiale (Mason III) et deux autres à des fractures de l'apophyse coronoïde. Les résultats étaient évalués après un recul moyen de trois ans et demi par le score de BROBERG et MORREY: trois cas étaient excellents, quatre bons, deux moyens et un mauvais. Cette lésion complexe nécessite une bonne reconstruction de la surface articulaire et une réparation des lésions associées pour permettre une rééducation précoce, seul garant d'une bonne  récupération fonctionnelle.Key words: Transolécranienne, fracture–luxation, Coude, olécran

Virtual screening and pharmacokinetics analysis of inhibitors against tuberculosis: Structure and ligand-based approach

Life-threatening diseases like tuberculosis have raised concerns in the medical and scientific communities. The damage-causing disease makes the scientific community employ the in-silico approach for design of new inhibitors that can inhibit or retard the havoc caused by this deadly disease. The insilico approach was used in this study to create a mathematical model with promising molecular properties, and receptors from the library were used to screen compounds and estimate the kinetic ability of the screened inhibitors that can cure this disease. 2D molecular properties evolved in the built model with high predictive ability. Three inhibitors x, y, and z emerged with better and higher molecular properties, the lowest binding energy (and higher binding affinity), and a better pharmacokinetic assessment compared to the template used in designing the effective compounds, with binding affinities of -15.56 kcal/mol, -18.51 kcal/mol, and -18.58 kcal/mol, respectively. Virtual screening of these compounds showed that they have good binding energy and excellent docking positions with the inhibiting potential of the receptor. Also, pharmacokinetic predictions and ADMET, depict orally active ability of the inhibitors, possess good human intestinal absorption, and violate none of the RO5 as potential drug candidates to cure this disease. Hence, further laboratory tests are recommended for these to determine their toxicities and biological assays

Contribution to the Evaluation of Physicochemical Properties, Total Phenolic Content, Antioxidant Potential, and Antimicrobial Activity of Vinegar Commercialized in Morocco

Vinegar is a natural product widely used in food and traditional medicine thanks to its physicochemical properties and its richness in bioactive molecules. However, its direct use by consumers can have complications and undesirable effects. Therefore, this study contributes to investigating the physicochemical and biological properties of eleven vinegars marketed in Morocco. Determination of pH, acetic acid, conductivity, total soluble solids and alcohol content in vinegar was carried out. The polyphenols (TP), flavonoids (TF), and condensed tannins (CT) content was determined, and their antioxidant activities were evaluated using 2,2-diphenyl-1-picryl Hydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP) and Phosphomolybdenum Reduction Assay (TAC). Then, the antimicrobial activity was studied against four pathogenic bacteria and two fungal strains, using the disk diffusion and the microdilution method. This study showed a wide range of acetic acid values from 0.65 ± 0.29 to 5.15 ± 0.20%. The high value of TP, TF, and CT in our samples V10, V9, and V4 was 655.00 ± 22.2 µgGAE/mL, 244.53 ± 11.32 µgQE/mL and 84.63 ± 1.00 µgTAE/mL, respectively. The tested strains showed variable sensitivities to the different samples with inhibition zones ranging from 6.33 ± 2.08 to 34.33 ± 0.58 mm. The lowest minimum inhibition concentrations were recorded against Staphylococcus aureus ATCC29213 ranging from 1.95 to 7.81 µL/mL. While Aspergillus niger ATCC16404 showed resistance against all of the analyzed samples. In general, vinegar commercialized in Morocco presents a variable range of products with variable properties. Indeed, must take into account this diversity when using it. A future study is needed to identify the phytochemical composition that will further the comprehension of this variability and contribute to its valorization

GC/MS Profiling, In Vitro Antidiabetic Efficacy of <i>Origanum compactum</i> Benth. Essential Oil and In Silico Molecular Docking of Its Major Bioactive Compounds

Diabetes is a global health concern with significant implications for individuals and healthcare systems. Finding effective and safe antidiabetic agents is crucial for the management of this chronic disease. Natural products have emerged as potential alternatives to allopathic drugs, offering a vast source of bioactive compounds. In this study, we conducted an assessment of the antidiabetic potential of Origanum compactum essential oil, employing a two-pronged approach, i.e., experimental investigation and computational docking analysis. The results of gas chromatography–mass spectrometry (GC-MS) showed that thymol (54.6%), carvacrol (23.18%), and p-cymene (7.12%) were the major compounds. Experimental assessments revealed higher IC50 values (150 µg/mL for α-amylase; 120 µg/mL for α-glucosidase) of O. compactum oil, compared to the control drug acarbose. In silico analysis revealed the best binding affinity of the oil components (carvacrol and thymol) with human NADPH oxidase, while the lysosomal acid-α-glucosidase and salivary amylase also demonstrated good binding affinity towards carvacrol and thymol. Our findings highlight the translational potential of O. compactum oil-based treatment for diabetes mellitus and provide a basis for further studies on the modulation of NADPH oxidase, amylase inhibition, and α-glucosidase by antidiabetic natural products. However, further in vivo investigations are strongly required to confirm the results of in vitro antidiabetic effect of O. compactum EO

3D-QSAR, ADME-Tox In Silico Prediction and Molecular Docking Studies for Modeling the Analgesic Activity against Neuropathic Pain of Novel NR2B-Selective NMDA Receptor Antagonists

A new class of selective antagonists of the N-Methyl-D-Aspartate (NMDA) receptor subunit 2B have been developed using molecular modeling techniques. The three-dimensional quantitative structure&ndash;activity relationship (3D-QSAR) study, based on comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models, indicate that steric, electrostatic and hydrogen bond acceptor fields have a key function in the analgesic activity against neuropathic pain. The predictive accuracy of the developed CoMFA model (Q2 = 0.540, R2 = 0.980, R2&nbsp;pred = 0.613) and the best CoMSIA model (Q2 = 0.665, R2 = 0.916, R2&nbsp;pred = 0.701) has been successfully examined through external and internal validation. Based on ADMET in silico properties, L1, L2 and L3 ligands are non-toxic inhibitors of 1A2, 2C19 and 2C9 cytochromes, predicted to passively cross the blood&ndash;brain barrier (BBB) and have the highest probability to penetrate the central nervous system (CNS). Molecular docking results indicate that the active ligands (L1, L2 and L3) interact specifically with Phe176, Glu235, Glu236, Gln110, Asp136 and Glu178 amino acids of the transport protein encoded as 3QEL. Therefore, they could be used as analgesic drugs for the treatment of neuropathic pain

Phytochemical and physicochemical studies of different apple varieties grown in Morocco

The apple is an important part of the human diet and is one of the most popular fruits in Morocco, with varieties that are now suitable for human consumption. This study aims to clarify several aspects of apples, such as their physical and chemical compositions and nutrient profiles. Total polyphenols, flavonoids, tannins, and anthocyanins were determined using spectrophotometer and organic acid compounds were identified by high-performance liquid chromatography-ultraviolet. The results show a significant difference between the several varieties under study in terms of their physico-chemical and phyto-chemical characteristics. In general, the studied apples are juiciness, with a percentage ranging from 60 to 71%. The pH values demonstrate how acidic the apples are. The Brix parameter denotes values greater than 13°Brix. Total polyphenols and condensed tannins (1154.65 ± 13.54 µg EAG/g and 514.09 ± 32.40 µg EAT/g, respectively) are more present in the Ahjjani variety than they are in other varieties. This demonstrates their good nutritional quality while not being consumable. However, the Story variety has a predominance of flavonoids (75.074 ± 2.309 µg QE/g) and flavones (45.074 ± 2.09 µg QE/g). The detection of organic acids has shown that the acid succinic is the most abundant in all the varieties of studied apple fruits. These results allow us to infer that non-consumable varieties are also important dietary sources of bioactive molecules, notably for polyphenols. The fact that these kinds can be used to produce other byproducts is therefore highly intriguing

In-silico screening based on molecular simulations of 3,4-disubstituted pyrrolidine sulfonamides as selective and competitive GlyT1 inhibitors

A systematic in-silico study based on molecular modeling techniques was conducted on thirty 3,4-disubstituted pyrrolidine sulfonamides derivatives to identify the drug candidate for treating schizophrenia and impairments associated with NMDA receptor hypofunction, through selective and competitive inhibition of GlyT1. QSAR analysis demonstrates that geometric and constitutional descriptors have a key function in human GlyT1 activity. The in-silico study concluded that the most active ligand labeled C19 was predicted to be a non-toxic inhibitor, with a desired ADME-Toxicity profile and a significant probability to penetrate the central nervous system (CNS). Molecular docking simulations confirmed that the C19 compound was docked to the active sites of drosophila melanogaster dopamine transporter (DAT) protein, creating a variety of chemical bonds towards TYR 124, ASP 475, GLU 480, ALA 479, and VAL 120 amino acids residues. The molecular dynamic (MD) technique combined with the MMGBSA approach confirmed that produced intermolecular interactions for the (DAT protein–C19 ligand) complex remain so stable during 100 ns of MD simulation time. Consequently, the C19 ligand is highly recommended for the treatment of schizophrenia and other disabilities linked to the hypofunction of glutaminergic NMDA receptors

Design of novel anti-cancer agents targeting COX-2 inhibitors based on computational studies

The overexpression of cyclooxygenase-2 (COX-2) was clearly associated with carcinogenesis, and COX-2 as a possible target has long been exploited for cancer therapy. A group of 29 derivatives of 1, 5-diarylpyrazole was used to study its structural requirements using three-dimensional quantitative structure–activity relationship (3D-QSAR), the density functional theory method, molecular docking, and molecular dynamics. Four 3D-QSAR models were developed, and the predictive capability of the four selected models was also successfully tested using different validation methods. The contribution contours of the comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models effectively illustrate the relationships between the various chemical characteristics and their biological activities. Using the density functional theory method with the 6-31G (d, p) basis set and the Becke, 3-parameter, Lee-Yang-Parr (B3LYP) function to evaluate chemical reactivity properties, the results obtained from energy gaps of 3.431, 3.446, and 2.727 ev for molecules numbers 21, 22, and 23 indicate that these three molecules have good chemical stability and reactivity and select the most reactive regions in the three molecules studied. Molecular docking results revealed that the active sites of the COX-2 protein (PDB code: 3PGH) were residues ARG222, THR212, HIS386, HIS207, TYR148, and ASP382, in which the most active ligands and now ligands can inhibit the COX-2 enzyme. Based on the various results obtained by molecular modeling, four new compounds (N1, N2, N3, and N4) were proposed with significant predicted activity by different 3D-QSAR models. A molecular docking study and molecular dynamics simulations of the proposed new molecules (N1 and N2) and the most active molecule over 100 ns revealed that all three molecules establish multiple hydrogen interactions with several residues and also exhibit frequent stability throughout the simulation period. As a result, it is strongly recommended to consider the two newly proposed molecules, N1 and N4, as promising candidates for novel anti-cancer agents specifically designed to target COX-2 inhibition

In-silico investigations of novel tacrine derivatives potency against Alzheimer's disease

Tacrine was originally used as a palliative treatment for Alzheimer's disease (AD). But early applications soon revealed a number of its side effects on human health. That's why we decided to examine the effectiveness of novel tacrine derivatives known for their potent inhibition of GluN2B-NMDA receptors, to discover the leading candidates for treating AD in terms of safety and molecular stability towards NMDA receptors. As a result, CoMFA and CoMSIA models were generated using 3-dimensional quantitative structure-activity relationships (3D-QSARs) study, indicating that Electrostatic, Hydrophobic, and Steric fields have a vital function in the NMDAR-antagonizing activities. The predictive exactitude of the generated CoMFA model (Q2cv = 0.699, R2 training = 0.980, R2 test = 0.737) and the top model of CoMSIA (Q2cv = 0.646, R2 training = 0.867, R2 test = 0.761) has been successfully tested in both internal and external validations. The pharmacokinetics properties of in-silico ADME-Toxicity confirm the safety of C24 and C27 compounds, which were discovered to be free from any skin allergy toxicity and hepatotoxic effects, and would be able to passively break through the blood-brain barrier and ultimately penetrate the central nervous system with a very good level of absorption (HIA exceeding 95 %). The molecular docking results indicate that non-toxic inhibitors interact specifically with Gln110, Ser132, and Tyr109 amino acid residues as the main active sites of the transport protein encoded as 5EWJ.pdb. At last, the intermolecular mechanisms detected by the examined ligands labeled C24, and C27, revealed excellent levels of molecular stability towards the targeted protein along one hundred nano-seconds of molecular dynamics time.Therefore, C24 and C27 chemical compounds are strongly recommended to treat AD, due to their considerable similarity to drug candidates and high levels of molecular stability