Disruption of spermatogenesis in testicular adult Wistar rats after short-term exposure to high dose of glyphosate based-herbicide: Histopathological and biochemical changes.

Glyphosate is an endocrine disruptor and can act on the activity of certain enzymes of metabolism subsequently altering some functions such as reproduction. The goal of the present study is to evaluate the involvement of glyphosate based-herbicide (GBH) in spermatogenesis disruption and to investigate which cells of the adult Wistar rat testis are most affected by short-term exposure to GBH. Treated groups received a diluted solution of GBH orally for 21 days (D1: 102.5 mg/Kg; D2: 200 mg/Kg; D3: 400 mg/Kg). The control group (C) received water in the same manner. Hormone levels, oxidative stress markers were evaluated, histological and morphometric analysis were performed, AR and p53 expression was conducted. Seminiferious epithelium sloughing associated to erosion of Sertoli and spermatogonia from the basement of the seminiferous tubules, with intraluminal exfoliated cells among with immature spermatids were observed. A significant change in morphometric measurement and significant decrease in AR expression in Sertoli cells were noted for all treated groups. A significant increase in NO level and p53 expression in Leydig cells were showed for animals treated with 200 and 400 mg/kg BW/day. These data demonstrate that short-term exposure to high doses of GBH has led to a disruption of certain parameters that could disturb spermatogenesis. The treatment showed that both Leydig and Sertoli cells are affected in the same manner by GBH, the activation of p53 expression in both Leydig cells and peritubular myloid cells nuclei, and the reduction in AR expression in Sertoli cells, which resulted in important testicular damage.

Lung function data of North-African patients with rheumatoid arthritis: a comparative study between anti-citrullinated peptides antibodies positive and negative patients.

INTRODUCTION: Although lung damages are among the leading causes of death from Rheumatoid Arthritis (RA), few studies have assessed the spirometric and plethysmographic data and profile of patients with RA, particularly those with Anti-Citrullinated Peptides Antibodies Positive (ACPA+). AIM: To compare the spirometric and plethysmographic data and profile of RA patients ACPA+ and ACPA-. METHODS: This comparative pilot study was performed over a two-year period (2018-2019) in Algiers (Algeria). The study included two groups of RA non-smoker patients: 26 ACPA+ and 33 ACPA-.RA was diagnosed according to the ACR/EULAR 2010 RA classification criteria. Spirometry and plethysmography were performed. The following definitions were applied: Obstructive Ventilatory Impairment (OVI): FEV1/FVC z-score < -1.645; Restrictive Ventilatory Impairment (RVI): Total Lung Capacity (TLC) z-score< -1.645; Mixed Ventilatory Impairment (MVI): FEV1/FVC z-score < -1.645 and TLC z-score < -1.645; lung- hyperinflation: residual volume z-score > +1.645; Nonspecific Ventilatory Impairment (NSVI): FEV1z-score < -1.645, FVC z-score < -1.645, FEV1 /FVC z-score ≥ -1.645, and TLC z-score ≥ -1.645. RESULTS: The ACPA-group was older than the ACPA+ one by ~ 10 years (63±13 vs. 53±12 years, p=0.0025; respectively). The ACPA+ and ACPA-groups included comparative percentages of patients having RVI, MVI, and NSVI (23.1 vs. 45.5%, p=0.0745; 3.8 vs. 3.0%, p=0.8654; and 7.7 vs. 6.1%, p=0.8086; respectively). Compared to the ACPA- group, the ACPA+ group included a higher percentage of patients having OVI and lung-hyperinflation (9.1 vs. 38.5%, p=0.0069; 9.1 vs. 42.3%, p=0.0029; respectively). CONCLUSION: Compared to the ACPA-group, the ACPA+ one had more lung-hyperinflation and OVI, and comparative percentages of RVI, MVI, and NSVI.

Clinical, immunological, molecular and therapeutic findings in monogenic immune dysregulation diseases: Middle East and North Africa registry.

Monogenic immune dysregulation diseases (MIDD) are caused by defective immunotolerance. This study was designed to increase knowledge on the prevalence and spectrum of MIDDs, genetic patterns, and outcomes in Middle East and North Africa (MENA). MIDD patients from 11 MENA countries (Iran, Turkey, Kuwait, Oman, Algeria, Egypt, United Arab Emirates, Tunisia, Jordan, Qatar, and Azerbaijan) were retrospectively evaluated. 343 MIDD patients (58% males and 42% female) at a median (IQR) age of 101 (42-192) months were enrolled. The most common defective genes were LRBA (23.9%), LYST (8.2%), and RAB27A (7.9%). The most prevalent initial and overall manifestations were infections (32.2% and 75.1%), autoimmunity (18.6% and 41%), and organomegaly (13.3% and 53.8%), respectively. Treatments included immunoglobulin replacement therapy (53%), hematopoietic stem cell transplantation (HSCT) (14.3%), immunosuppressives (36.7%), and surgery (3.5%). Twenty-nine (59.2%) patients survived HSCT. Along with infectious complications, autoimmunity and organomegaly may be the initial or predominant manifestations of MIDD.

Algerian Registry for Inborn Errors of Immunity in Children: Report of 887 Children (1985-2021).

INTRODUCTION: Inborn errors of immunity (IEI) represent a heterogeneous large group of genetic disorders characterized by susceptibility of affected individuals to recurrent infections, autoimmune/inflammatory diseases, allergy, and malignancy. We aimed to report for the first time the Algerian registry for IEI in children. METHODS: We described the characteristics of IEI in Algerian children from the data collected in the Algerian registry for IEI between 1985 and 2021. RESULTS: Over a period of 37 years, we included 887 children (530 male, 59.6%) with a mean age at diagnosis of 3.23 years and a mean diagnosis delay of 2 years. The prevalence rate was estimated at 1.97/100,000 inhabitants or 5.91/100,000 children. The parental consanguinity was found in 52.6%. The most prevalent category was combined immunodeficiencies (CID) (35.5%), followed by predominantly antibody deficiencies (24.5%) and CID with syndromic features (18.3%). The most predominant diseases were severe CID (134 cases), MHC II deficiency (99 cases), agammaglobulinemia (82 cases), common variable immunodeficiency (78 cases), hyper IgE syndromes (61 patients), ataxia-telangiectasia (46 patients), Wiskott-Aldrich syndrome (40 patients) and chronic granulomatous disease (39 cases). The clinical presentation was dominated by lower respiratory tract infections (69%), failure to thrive (38.3%), and chronic diarrhea (35.2%). Genetic analysis was performed in 156 patients (17.6%). The global mortality rate was 28.4% mainly caused by CID. CONCLUSION: This is the first report of the Algerian registry for IEI in children. Data is globally similar to that of the Middle East and North African (MENA) registries with high consanguinity, predominance of CID, and significant mortality. This registry highlights the weak points that should be improved in order to provide better patient care.

Severity factors in Algerian patients hospitalized for COVID-19.

INTRODUCTION: Determining the profile of COVID-19 patients with low pulsed hemoglobin saturation in oxygen (SpO2) could help clinicians identify those with a poor prognosis. AIM: To identify and to compare the clinical, biological and radiological data of Algerian patients hospitalized for COVID-19 and divided according to the SpO2 measured at admission, at rest, and in ambient air. METHODS: A prospective study was carried out on Algerian patients hospitalized for COVID-19 during the period from March 9 to April 30, 2020. The general characteristics of the patients and the clinical, biological and radiological data were determined. RESULTS: 86 patients were included in the study [G1: SpO2 >95% (n=51) and G2: SpO2 ≤95% (n=35)]. Compared to G1, G2 was older (48±14 vs. 61±12 years, p=0.0001), included more patients aged ≥ 50 years (37.2 vs. 80.0%, p=0.0001), having an arterial-hypertension (21.6 vs. 45.7%, p=0.0180), a cancer (0.0 vs. 14.3%, p=0.0054), an anemia (25.6 vs. 56.3%, p=0.0069), a leukocytosis (4.7 vs. 21.9%, p=0.0236), a biological inflammatory syndrome (82.5 vs. 100%, p=0.0142), a hyper-uremia (7.0 vs. 37.5%, p=0.0185), a hyper-creatininaemia (4.7 vs. 18.8%, p=0.0356), a tissue damage (41.0 vs. 66.7%, p=0.0341), a diffuse ground-glass opacity (52.0 vs. 71.4%, p=0.0397), band condensations (30.0 vs. 54.3%, p=0.0244), a severe extension (2.0 vs. 25.7%, p=0.0008), and included fewer patients who complained from diarrhea (49.0 vs. 22.9%, p=0.0145), having a nodular ground-glass (66.0 vs. 40.0%, p=0.0177) and a slight extension (78.0 vs. 40.0%, p=0.0004). CONCLUSION: Criteria associated with low SpO2 in hospitalized COVID-19 patients were advanced age, a history of arterial-hypertension and cancer, high frequencies of certain biological abnormalities or radiological signs. The diarrhea symptom, the radiological appearance of nodular ground glass, and a slight extension of the radiological lesions appear as protective elements.

Functional analysis of splicing mutations and of an exon 2 polymorphic variant of SERPING1/C1NH.

Several sequence changes have been reported in hereditary angioedema patients in intron 2 of the SERPING1/C1NH gene, but their consequences on splicing have not been determined. We examined in cell transfection assays the consequences at the mRNA level of splicing mutations affecting either the +3 or the +5 donor site positions, or the conserved canonical splicing signals of exon 2, using mutant C1 inhibitor minigene constructs. Both intron 2 mutations, c.51+3A>G and c.51+5G>A, resulted in marked exon 2 skipping in these assays, but also yielded a large fraction of normal transcripts. We show that the c.51+3A>G mutation cosegregates with low C1 inhibitor protein levels in one family. Moreover, the second base of exon 2 of the SERPING1/C1NH gene is the site of a polymorphic variant, which has been proposed as a modifier of disease severity. We found that the c.-21C allele at this position yields low but significant levels of exon 2 skipping in transfected Hep G2 or Hep 3B cells, suggesting that this allele may contribute, at the RNA level, to more severe forms of angioedema. Furthermore, we describe a previously not detected alternative splicing of exon 3, found in peripheral blood cell mRNA but not in the liver or in hepatoma cell lines and we show that, in cultured monocytes of a patient carrying the c.51+3A>G mutation, this alternative splicing is shifted from exon 3 exclusion to skipping of both exons 2 and 3. The latter finding suggests that mutations affecting splicing of exon 2 of the SERPING1/C1NH gene may have different consequences in monocytes versus other cell types.