The chemokine receptor CXCR5 is pivotal for ectopic mucosa-associated lymphoid tissue neogenesis in chronic Helicobacter pylori-induced inflammation

Ectopic lymphoid follicles are a key feature of chronic inflammatory autoimmune and infectious diseases, such as rheumatoid arthritis, Sjögren's syndrome, and Helicobacter pylori-induced gastritis. Homeostatic chemokines are considered to be involved in the formation of such tertiary lymphoid tissue. High expression of CXCL13 and its receptor, CXCR5, has been associated with the formation of ectopic lymphoid follicles in chronic infectious diseases. Here, we defined the role of CXCR5 in the development of mucosal tertiary lymphoid tissue and gastric inflammation in a mouse model of chronic H. pylori infection. CXCR5-deficient mice failed to develop organized gastric lymphoid follicles despite similar bacterial colonization density as infected wild-type mice. CXCR5 deficiency altered Th17 responses but not Th1-type cellular immune responses to H. pylori infection. Furthermore, CXCR5-deficient mice exhibited lower H. pylori-specific serum IgG and IgA levels and an overall decrease in chronic gastric immune responses. In conclusion, the development of mucosal tertiary ectopic follicles during chronic H. pylori infection is strongly dependent on the CXCL13/CXCR5 signaling axis, and lack of de novo lymphoid tissue formation attenuates chronic immune responses

Induction of TLR-2 and TLR-5 Expression by Helicobacter pylori Switches cagPAI-Dependent Signalling Leading to the Secretion of IL-8 and TNF-α

Helicobacter pylori is the causative agent for developing gastritis, gastric ulcer, and even gastric cancer. Virulent strains carry the cag pathogenicity island (cagPAI) encoding a type-IV secretion system (T4SS) for injecting the CagA protein. However, mechanisms of sensing this pathogen through Toll-like receptors (TLRs) and downstream signalling pathways in the development of different pathologies are widely unclear. Here, we explored the involvement of TLR-2 and TLR-5 in THP-1 cells and HEK293 cell lines (stably transfected with TLR-2 or TLR-5) during infection with wild-type H. pylori and isogenic cagPAI mutants. H. pylori triggered enhanced TLR-2 and TLR-5 expression in THP-1, HEK293-TLR2 and HEK293-TLR5 cells, but not in the HEK293 control. In addition, IL-8 and TNF-α cytokine secretion in THP-1 cells was induced in a cagPAI-dependent manner. Furthermore, we show that HEK293 cells are not competent for the uptake of T4SS-delivered CagA, and are therefore ideally suited for studying TLR signalling in the absence of T4SS functions. HEK293 control cells, which do not induce TLR-2 and TLR-5 expression during infection, only secreted cytokines in small amounts, in agreement with T4SS functions being absent. In contrast, HEK293-TLR2 and HEK293-TLR5 cells were highly competent for inducing the secretion of IL-8 and TNF-α cytokines in a cagPAI-independent manner, suggesting that the expression of TLR-2 or TLR-5 has profoundly changed the capability to trigger pro-inflammatory signalling upon infection. Using phospho-specific antibodies and luciferase reporter assays, we further demonstrate that H. pylori induces IRAK-1 and IκB phosphorylation in a TLR-dependent manner, and this was required for activation of transcription factor NF-κB. Finally, NF-κB activation in HEK293-TLR2 and HEK293-TLR5 cells was confirmed by expressing p65-GFP which was translocated from the cytoplasm into the nucleus. These data indicate that H. pylori-induced expression of TLR-2 and TLR-5 can qualitatively shift cagPAI-dependent to cagPAI-independent pro-inflammatory signalling pathways with possible impact on the outcome of H. pylori-associated diseases

Multiple Peptidoglycan Modification Networks Modulate Helicobacter pylori's Cell Shape, Motility, and Colonization Potential

Helical cell shape of the gastric pathogen Helicobacter pylori has been suggested to promote virulence through viscosity-dependent enhancement of swimming velocity. However, H. pylori csd1 mutants, which are curved but lack helical twist, show normal velocity in viscous polymer solutions and the reason for their deficiency in stomach colonization has remained unclear. Characterization of new rod shaped mutants identified Csd4, a DL-carboxypeptidase of peptidoglycan (PG) tripeptide monomers and Csd5, a putative scaffolding protein. Morphological and biochemical studies indicated Csd4 tripeptide cleavage and Csd1 crosslinking relaxation modify the PG sacculus through independent networks that coordinately generate helical shape. csd4 mutants show attenuation of stomach colonization, but no change in proinflammatory cytokine induction, despite four-fold higher levels of Nod1-agonist tripeptides in the PG sacculus. Motility analysis of similarly shaped mutants bearing distinct alterations in PG modifications revealed deficits associated with shape, but only in gel-like media and not viscous solutions. As gastric mucus displays viscoelastic gel-like properties, our results suggest enhanced penetration of the mucus barrier underlies the fitness advantage conferred by H. pylori's characteristic shape

Epidemiology of neurodegenerative diseases in sub-Saharan Africa: a systematic review

BACKGROUND:Sub-Saharan African (SSA) countries are experiencing rapid transitions with increased life expectancy. As a result the burden of age-related conditions such as neurodegenerative diseases might be increasing. We conducted a systematic review of published studies on common neurodegenerative diseases, and HIV-related neurocognitive impairment in SSA, in order to identify research gaps and inform prevention and control solutions. METHODS: We searched MEDLINE via PubMed, 'Banque de Donnees de Sante Publique' and the database of the 'Institut d'Epidemiologie Neurologique et de Neurologie Tropicale' from inception to February 2013 for published original studies from SSA on neurodegenerative diseases and HIV-related neurocognitive impairment. Screening and data extraction were conducted by two investigators. Bibliographies and citations of eligible studies were investigated. RESULTS: In all 144 publications reporting on dementia (n=49 publications, mainly Alzheimer disease), Parkinsonism (PD, n=20), HIV-related neurocognitive impairment (n=47), Huntington disease (HD, n=19), amyotrophic lateral sclerosis (ALS, n=15), cerebellar degeneration (n=4) and Lewy body dementia (n=1). Of these studies, largely based on prevalent cases from retrospective data on urban populations, half originated from Nigeria and South Africa. The prevalence of dementia (Alzheimer disease) varied between <1% and 10.1% (0.7% and 5.6%) in population-based studies and from <1% to 47.8% in hospital-based studies. Incidence of dementia (Alzheimer disease) ranged from 8.7 to 21.8/1000/year (9.5 to 11.1), and major risk factors were advanced age and female sex. HIV-related neurocognitive impairment's prevalence (all from hospital-based studies) ranged from <1% to 80%. Population-based prevalence of PD and ALS varied from 10 to 235/100,000, and from 5 to 15/100,000 respectively while that for Huntington disease was 3.5/100,000. Equivalent figures for hospital based studies were the following: PD (0.41 to 7.2%), ALS (0.2 to 8.0/1000), and HD (0.2/100,000 to 46.0/100,000). CONCLUSIONS: The body of literature on neurodegenerative disorders in SSA is large with regard to dementia and HIV-related neurocognitive disorders but limited for other neurodegenerative disorders. Shortcomings include few population-based studies, heterogeneous diagnostic criteria and uneven representation of countries on the continent. There are important knowledge gaps that need urgent action, in order to prepare the sub-continent for the anticipated local surge in neurodegenerative diseases

Prise en charge de nouveau-ne apres cesarienne au bloc operatoire de la clinique de gynecologie et d’obstetrique du CHU Sylvanus Olympio de Lome

Objectifs: Déterminer la fréquence des accouchements par voie haute et leur indication, évaluer l’état clinique du nouveau-né et en déduire les éléments susceptibles d’améliorer la prise en charge de celui-ci.Patients et Méthodes: Il s’agit d’une étude prospective de 255 nouveau né extraits par césarienne à la maternité du CHU-Tokoin du 10 septembre au 10 novembre 2008. L’analyse des indications de césarienne, de la fréquence de l’anesthésie rachidienne et de l’anesthésie générale, de l’intervalle entre l’induction anesthésique et l’extraction du foetus, des scores d’APGAR, de la corrélation entre les indications et types de réanimation néonatale ont composé l’étude de la prise en du césariennes.Résultats: la fréquence des accouchements par voie haute (césarienne) est de 20,53% des cas. Cette étude a révélé que 70,2% des césariennes ont eu un âge gestationnel supérieur à 37 Semaines d’aménorrhée. La souffrance foetale aiguë (38,4%) ; l’utérus cicatriciel (22,4%) ; l’éclampsie et la prééclampsie (12,5%) ; présentation de siège (6,3%) sont les principales indications de la césarienne. La rachianesthésie est la technique anesthésique prioritairement pratiquée 4/5 contre 1/5 de l’anesthésie générale. L’AG est apparue plus dépresseur de la capacité adaptative néonatale que la rachianesthésie. Le protocole anesthésique I est le plus pratiquée (95,91%) et le plus dépresseur que le protocole II d’AG ; Les indictions de réanimation néonatale des césariennes a donné 66,7% de bon résultat.Conclusion: La prise en charge du nouveau né après césarienne ne doit pas être considéré comme un acte banal. Elle doit être précoce, adéquate et réalisée par un personnel qualifié pour prévenir les risques et agressions chez le nouveau né puis qu’elle souffre de manque de personnels qualifiés, d’une bonne organisation et de matériel adapté.Mots clés: Césarienne, nouveau né, LoméEnglish AbstractObjectives: To determine the frequency of high deliveries and their indication, evaluate the clinical status of the newborn and deduce the evidence to improve the management of it.Patients and methods: this is a prospective study of 255 new born by caesarean in the maternity of the Tokoin CHU from September 10 to November 10, 2008. Analysis of the indications of Cesarean section, the frequency of spinal anesthesia and general anesthesia, the interval between the anesthetic induction and the extraction of the fetus, APGAR scores, correlation between indications and types of neonatal resuscitation have composed the study of decision-making in the caesarean section.Results: the frequency of childbirth (cesarean section) high through is 20.53% of cases. The study found that 70.2% of caesarean section had a gestational age greater than 37 weeks of amenorrhea. Acute fetal distress (38.4%); the scar uterus (22.4%), eclampsia and pre-eclampsia (12.5%); presentation of seat (6.3%) are the main indications of Cesarean section. Spinal anesthesia is primarily practiced anesthetic technique 4/5 against 1/5 of the general anesthesia. The general anesthesia has appeared more depressant neonatal adaptive capacity than spinal anesthesia. The anesthetic protocol I is the most practiced (95.91%) and more depressing than the protocol II of general anesthesia. The signs of neonatal resuscitation of cesarean sections gave 66.7% of good results.Conclusion: support the new born after caesarean section should not be considered a banal act. It must be early, adequate and carried out by personnel qualified to prevent risks and attacks in new born then it suffers from lack of qualified, good organization and adapted equipment.Keywords: cesarean section, new born, Lom

Quality of antiretroviral drugs, stavudine and indinavir capsules available in the Tanzanian market

Background: The number of antiretroviral drugs (ARVs) available to HIV/AIDS patients in Tanzania is increasing due to a number of intervention programs such as PEPFAR and the Clinton Foundation. These ARVs are imported from a number of countries. However, currently there are no reports on the quality of these medicines imported into Tanzania. The sale of substandard and counterfeit drugs has been well documented particularly in developing countries. The marketing of counterfeit and substandard antiretroviral drugs has also been widely reported in Africa. It is therefore important to closely monitor the quality of ARVs marketed in Tanzania to ensure that substandard or fake products are uncovered before great harm is done to public health. Objective: To assess the quality of ARVs marketed in Tanzania. Methodology: A total of five samples of two generic drugs (stavudine and indinavir) from different manufacturers were randomly collected from various retail pharmacies. Assessment of package inserts and labels was carried out using the Tanzania Food and Drugs Authority (TFDA) specifications. The capsules were analyzed for the content of the active components using validated in-house methods Results: All samples of Indinavir and Stavudine investigated conformed to the packaging and labeling specifications. However, all Indinavir samples were found to contain excess amount of active ingredient (112.6% - 118%) compared to the official limit of 95 – 105%. One sample of stavudine capsules failed the dissolution test, releasing only 56% instead of the specified 80% of the active ingredient. Conclusion: The results of this study emphasize the need for careful monitoring of the quality of drugs to ensure their safety and efficacy. Keywords: Antiretroviral drugs, Quality, Substandard drugs. Tanzania Medical Journal Vol. 21 (1) 2006: pp. 8-1

Indications and outcomes of bone marrow aspiration cytology in a Nigerian tertiary hospital: The Federal Medical Centre, Yola experience

Background: Bone marrow aspiration (BMA) cytology is a useful investigative tool in the diagnosis of haematological and non- haematological disorders. The purpose of this work was to identify the main indications and diagnostic outcomes of BMA cytology in our facility. Methods: A retrospective review of all BMA cytology reports of patients that underwent this procedure in Federal Medical Centre, Yola from January 2018 to December 2019 was carried out. Results: A total of one hundred and four (104) patients underwent BMAs in the period under review. This comprised of 59 (56.7%) males&nbsp; and 45 (43.3%) females. Their ages ranged between 3 and 82 years with median age of 38 years and interquartile range (IQR): 22-55. The most common clinical indication for BMA was recurrent anaemia which accounted for 64.4% of all indications, while the most frequent diagnostic outcome was Megaloblastic Anaemia accounting for 34.6%. Conclusion: It is concluded that the commonest indication for BMA cytology in our facility is recurrent anaemia. The most frequent&nbsp; diagnostic outcome is megaloblastic anaemia. Considering its safety and cost-effectiveness, BMA cytology is a valuable diagnostic&nbsp; procedure among patients presenting with recurrent anaemia in our environmen

Human Immunodeficiency Virus in patients with lymphoma in Jos North-Central Nigeria

Background: Individuals with human immunodeficiency virus (HIV) infection have increased risk of developing malignancies including lymphoma despite adequate antiretroviral therapy. The study was conducted with the aim of determining the proportion of adults with HIV-associated lymphoma in Jos, Nigeria. Methods: Consecutive consenting adults diagnosed with lymphoma attending the Haematology clinics of Jos and Bingham University Teaching Hospitals in Jos between February, 2016 and December, 2017had their blood samples screened and confirmed for HIV after completing a questionnaire. Results: Sixty (60) patients which comprised of 37 (61.7%) males and 23 (38.3%) females with lymphoma aged between 18 and 75 years participated. Nine (15.0%) of them were positive for HIV, which comprised of 8 (13.3%) Non-Hodgkins lymphoma (NHL) and 1 (1.7%) Hodgkins lymphoma (p = 0.074). Conclusion: The study has demonstrated a high prevalence of HIV infection in patients with lymphoma in Jos. Keywords: Lymphoma, Human Immunodeficiency Virus, Jo