Action to protect the independence and integrity of global health research

Storeng KT, Abimbola S, Balabanova D, et al. Action to protect the independence and integrity of global health research. BMJ GLOBAL HEALTH. 2019;4(3): e001746

Case Report: Recurrent Respiratory Papillomatosis: A Report of two cases and review of literature

Background: Recurrent Respiratory Papillomatosis (RRP) is a non-cancerous tumour of the upper airway caused by the human papilloma virus, presenting as “wart-like” growth, which could be anywhere from the nose to the lungs commonly in the larynx.Design and Setting: Review of two cases at the National Hospital Abuja (NHA).Objectives: To highlight the challenges in the management of RRP.Subjects: Two patients diagnosed with RRP were referred to the paediatric respiratory clinic between 2009 and 2012. Case one is a four year old female who presented with persistent hoarseness of voice, breathing difficulty and noisy breathing of one year duration. She was born at term by spontaneous vertex delivery to a mother who had vaginal warty lesion excised during pregnancy. A neck X-ray showed opacities around the laryngeal region with total obliteration of air column with histological confirmation of squamous papilloma. She had eight excision surgeries within a two years period with treatment with oral acyclovir, interferon, and methotrexate and tracheotomy tube in situ. Case two, a six year old female presented with persistent hoarseness of voice that progressed to loss of voice, noisy and difficulty in breathing, snoring and frequent arousal from sleep of 1½ years. Histology was diagnostic of laryngeal Papillomatosis and she had two excisions surgeries and treatment with oral acyclovir and tracheotomy tube in place.Conclusion: RRP though a slow growing tumour, presently has no definitive cure. Excision surgeries provide temporal relief and antiviral agents adjuvant therapies. Prevention with vaccination is desirable.Keyword: Recurrent respiratory Papillomatosis, Human papilloma virus

Pattern of pathogens in ear discharge of HIV-infected children in Nnewi, Southeast Nigeria

No Abstract. Nigrian Journal of Clinical Practice Vol. 10 (2) 2007: pp. 130-13

CaMKIIα interacts with M4 muscarinic receptors to control receptor and psychomotor function

Muscarinic acetylcholine receptors (mAChRs) are widely expressed in the mammalian brain and are essential for neuronal functions. These receptors are believed to be actively regulated by intracellular signals, although the underlying mechanisms are largely unknown. In this study, we show that Ca2+/calmodulin-dependent protein kinase II (CaMKII) binds directly and selectively to one of five mAChR subtypes, M4 receptors (M4Rs), at their C-terminal regions of second intracellular loops. This binding relies on Ca2+ activation of the kinase and leads to the phosphorylation of M4Rs at a specific threonine site (Thr145). Complementary in vivo studies in rat striatal neurons enriched with M4Rs confirm that rising Ca2+ recruits CaMKIIα to M4Rs to potentiate receptor signalling, which controls behavioural sensitivity to dopamine stimulation in an activity-dependent manner. Our data identify a new model of protein–protein interactions. In a Ca2+-sensitive manner, CaMKIIα regulates M4R efficacy and controls the acetylcholine–dopamine balance in the basal ganglia and also the dynamics of movement

CaMKIIα, a modulator of M4 muscarinic acetylcholine receptors

G protein-coupled receptors (GPCRs) are subject to the regulation by protein kinases. By controlling the phosphorylation-dephosphorylation balance, protein kinases actively modify GPCR expression and function. In a recent study, we have identified a novel phosphorylation-dependent regulation of Gαi/o-coupled muscarinic acetylcholine receptors. A synapse-enriched protein kinase, Ca2+/calmodulin-dependent protein kinase II (CaMKIIα), binds directly and selectively to second intracellular loops of muscarinic M4 receptors (M4Rs). This Ca2+-sensitive binding enables CaMKIIα to phosphorylate M4Rs at a selective threonine residue. In rat striatal neurons which abundantly express M4Rs, rapid cytoplasmic Ca2+ rises enhance the association of CaMKIIα with M4Rs and increase threonine phosphorylation of the receptor. This CaMKIIα-mediated phosphorylation results in a potentiation of M4R activity, which is critical for controlling cellular and behavioral responsivity to dopamine stimulation. In sum, our data identify a novel kinase-GPCR interaction. Through a Ca2+/activity-sensitive manner, CaMKIIα contributes to maintaining acetylcholine-dopamine homeostasis in the basal ganglia