Synthesis, design, in silico, in vitro and in vivo (streptozotocin-induced diabetes in mice) biological evaluation of novels N-arylacetamide derivatives.

The organic compounds 2-chloro-N-(aryl)acetamide (Ps13-Ps18) and 2-azido-N-(aryl)acetamide (148-153) were synthesized and analyzed using 1 H, 13C NMR. The acute oral toxicity study was carried out according to OECD guidelines, which approve that the compounds (Ps18 and 153) were nontoxic. In addition, the compounds were evaluated for its antidiabetic and antihyperglycemic properties (in vitro and in vivo) and for antioxidant activity by utilizing several tests as 1,1-diphenyl2-picrylhydrazyl DPPH, (2,2'-azino-bis(3-ethyl benzthiazoline-6-sulfonicacid) ABTS, reducing power test FRAP and hydrogen peroxide activity H2O2. The molecular docking studies were performed to investigate the antidiabetic activity of Ps18 and 153 and compared with the experimental results. These compounds are a potent antidiabetic from both the experimental and molecular docking results. Finally, the physicochemical, pharmacokinetic and toxicological properties of Ps18 and 153 have been evaluated by using in silico absorption, distribution, metabolism, excretion and toxicity analysis prediction.Communicated by Ramaswamy H. Sarma.

[Combined deficiency of clotting factor V and factor VIII: about three siblings]. / Déficit combiné en facteurs V et VIII de la coagulation: à propos d´une fratrie de trois cas.

Combined deficiency of clotting factor V and factor VIII (DF5F8) is a congenital autosomal recessive disorder. This study involved a family of four children born to consanguineous parents. The eldest daughter was referred for assessment of activated partial thromboplastin time and prothrombin time associated with hemorrhagic manifestations. Coagulation factor dosing showed combined deficiency of factor V and factor VIII as well as normal levels of other coagulation factors. DF5F8 was detected in two girls and a boy. Two protein coding genes LMAN1 (lectin, mannose binding 1) and MCFD2 (multiple coagulation factor deficiency2) were involved in the intracellular passage of Factor V and Factor VIII, including some mutations which caused deficiency of Factor V and VIII. The diagnosis of DF5F8 is routinely possible, especially in patients born to consanguineous parents with a suggestive clinico-biological condition.

[Profile of Von Willebrand factor antigen in pregnancy: descriptive study of 390 pregnant women in Morocco]. / Profil du facteur Von Willebrand dans la grossesse: étude descriptive chez 390 femmes enceintes au Maroc.

Von Willebrand factor (vWF) is a glycoprotein which plays an important role in hemostasis. Its quantitative or qualitative deficit results in von Willebrand's disease (vWD). The study aims to update the current understanding of the distribution of vWF rates in Moroccan pregnant women and their variability in function of the ABO blood group. We conducted a cross-sectional study of 390 pregnant women from the Rabat-Salé-Kenitra region. Sample size was calculated on the basis of a prevalence of 1%, corresponding to the global prevalence of vWD with a margin of error of 5% and a confidence level of 95%. There were 317 cases (81.28%) of elevated vWF levels (> 160%) out 390 pregnant women. The levels of factor VIII (FVIII) varied in parallel in a significant way (p < 0.001) with the levels of vWF (Pearson's r 0,597). The distribution of the ABO blood groups has had an influence on the level of vWF with a significant difference (p < 0.001) between the four groups: the lowest average level in the group O (188,54±57,02), followed by group A (203,19±54,46), then group AB (219±38,95) and finally group B (221,15±48,63). Our results confirm on the one hand an elevation of the levels of vWF during pregnancy and on the other hand the influence of ABO blood group on the levels of vWF.

[Epidemiological profile of hemoglobinopathies: a cross-sectional and descriptive index case study]. / Profil épidémiologique des hémoglobinopathies: étude transversale descriptive autour du cas index.

Hemoglobinopathies are congenital disorders resultimg from hemoglobin abnormalities. Major forms are often severe, their management is difficult and associated with a great psychosocial impact on patients and their families. They are classified as rare diseases and are still insufficiently known by health professionals. This lack of knowledge is at the origin of diagnostic errors, delay in their management and therefore high morbidity and mortality rate for these patients. In 2008, the World Health Organization (WHO) has published data on hemoglobinopathies epidemiology: more than 330.000 cases of hemoglobinopathy occur each year (83% of cases of sickle cell anemia, 17 % of cases of thalassemia). Hemoglobin disorders are responsible for approximately 3.4% of deaths among people under the age of 5. At the global level, approximately 7% of pregnant women would be carriers of a form of thalassemia and 1% of couples are at risk. However, they are relatively frequent in some regions of the globe where consanguineous marriages are common. We conducted a descriptive cross-sectional study based on two surveys, the first in May 2015 and the second in June of the same year. It was performed in the immunization days to deliver pneumococcal vaccine to the index cases and it was aimed to describe the epidemiological features of families at risk of hemoglobinopathies (index case study), whose index cases were treated in the Department of Pediatrics at the Provincial Hospital El Idrisi, Kenitra, Morocco. After having collected the epidemiological data from patients, laboratory tests were performed including: blood count with red blood cells morphological assessment using the MGG assay and automatic numbering of reticulocytes; hemoglobin electrophoresis at alkaline pH (8.8) and then at acid pH (5.4) on agarose gel and densitometric integration. 275 patients had laboratory profiles compatible with hemoglobinopathy. The majority of these patients were born to consanguineous marriages (83.1%) and came from the north regions of Morocco. This family survey allowed to identify families at risk with a high frequency of sickle cell anemia. Our results confirm the existence of hemoglobinopathies variants among Moroccan population.

[Epidemiological, clinical, cytologic and immunophenotypic aspects of acute leukemia in children: the experience at the hematology laboratory of IBN SINA University Hospital Center]. / Aspects épidémiologiques, cliniques, cytologiques et immunophénotypiques des leucémies aiguës chez les enfants: expérience du laboratoire d'hématologie du Centre Hospitalier Universitaire IBN Sina.

The aim of this study was to describe epidemiological, cytologic and immunophenotypic aspects of acute leukemias (AL) in children diagnosed at IBN SINA University Hospital Center and to determine the concordance between cytology and immunophenotyping results. This is a cross-sectional study conducted in the hematology laboratory of IBN SINA University Hospital Center between June 2012 and May 2014. Among the 104 cases with diagnosed AL, 52% were boys with a sex-ratio H/F= 1.32, the average age was 5.7 years. The distribution of different types of AL was: lymphoid AL (LAL) (74%), myeloid (AML) (20.2%), biphenotypic AL (BAL) (65.8%). Among the LALs, 78% were classified as B LAL and 22% as T LAL. Clinical signs were mainly presented with tumor syndrome (73.1%), fever (61%) and hemorrhagic syndrome (50%). The most common blood count abnormalities were: thrombopenia (89.4%), anemia (86.5%), hyperleukocytosis (79.8%). The rate of peripheral and bone marrow blasts was statistically higher for LAL than for AML and BAL (p <0.001). The rate of relapse and mortality was 21.2% and 16. 3% respectively. Concordance rate between the results of cytology and of immunophenotyping was 92.7% for LAL and 82.6% for AML. Diagnosis of AL is always based primarily on cytology. Immunophenotyping allowed us to make a better distinction between acute leukemias. The management of paediatric AL is a major health problem which requires specialized care centers.

[Evaluation of hemogram in patients with homozygous sickle cell disease: about 87 cases]. / Etude de l'hémogramme dans la drépanocytose homozygote: à propos de 87 patients.

Homozygous sickle cell disease is one of the most frequent haemoglobinopathies in Morocco. Sickle cell disease is characterized by a large clinical and biological expression variability which depends on modulating genetic and environmental factors. Clinical manifestation includes regenerative anemia whose severity may vary among individuals. In the absence of treatment, it results in premature death. Sickle cell disease is characterized by a large clinical and biological expression variability which depends on genetic and environmental factors. A severe clinical picture marked by high early transfusion frequency, severe infectious complications and early mortality. A constant inflammatory condition characterized by elevated inflammatory proteins and compromised nutritional status. The objective of this study is to determine the hematological parameters profile in moroccan patients with homozygous sickle cell (SS) disease during stationary phases. We conducted a cross-sectional descriptive study of 87 patients with sickle cell (SS) disease. We performed a biological study based on: Hemogram with morphological assessment of red blood cells stained with MGG and automated reticulocyte counting; Hemoglobin electrophoresis test performed on alkaline agarose gel (pH 8.8) and densitometric integration. The average age is 13.22 years ± 16.36, ranging betrween 0.6 and 36 years, with a sex ratio (M/F) of 1.175. Biological effects of anemia were intense in 88.5% of patients; 67.8% of patients had normocytic anemia compared with 29.9% with microcytosis, and 2.3% with macrocytosis. The degree of anisocytosis was related to the degree of anemia, very evocative in patients with homozygous S/S (95.4%). Reticulocytosis was observed in 81.6% of patients; 52.9% of patients had thrombocytosis. Leukocytosis was observed in 64.4% of patients; 80.5% of patients had neutropenia. The parameters of the hemogram will serve as a basis for comparison during crises and will make it possible to evaluate the effectiveness of patient management. High white blood cell count, platelets and MCHC seem to be determinant of sickle cell anemia severity in Morocco. The haematological profile of moroccan patients with sickle cell disease exhibits data similar to those reported in literature relating to patients with leucocytosis from Central Africa. The results of our study suggest that sickle cell anemia is the most common health problem in Morocco and they are similar to those for major sickle cell syndrome.

[Mantle cell lymphoma diagnosis]. / Diagnostic du lymphome du manteau.

Recent classifications of non-Hodgkin's lymphomas based on combination of morphologic, immunophenotypic, and cytogenetic criteria have individualized mantle cell lymphoma (MCL). This clinico-biological entity which accounts for 3 to 10% of all non-Hodgkin's lymphomas, now appears to be a biological and therapeutic model for the understanding and treatment of hematologic malignancies. The present study consisting of two cases of MCL collated at laboratory of hematology of Rabat Ibn Sina hospital. The morphological appearance of MCL is characterized by diffuse or nodular lymph infiltration in the mantle zone, the osteo-medullary biopsy shows an interstitial infringement characterized by the presence of lymphocytes resembling centrocytes with cleaved and angular nuclei, dispersed chromatin, inconspicuous nucleoli and scanty cytoplasm. The flow cytometry showed immunophenotype positive for surface Ig, CD19, CD20, CD22, CD79b, CD5 and cyclin D1, and negative for CD10, CD23 and CD25. In conclusion, the methods of diagnosis and prognosis evaluation of mantle cell lymphoma are based on the nodular, medullary and blood morphology, the immunophenotypic, cytogenetic and molecular study of neoplastic cells.