1.
"English Disease": Historical Notes on Rickets, the Bone-Lung Link and Child Neglect Issues.
Zhang, M, Shen, F, Petryk, A, Tang, J, Chen, X, Sergi, C
Nutrients. 2016;(11)
Abstract
Nutritional or classical rickets (here labeled as "rickets") is a worldwide disease involving mostly infants and young children having inadequate sunlight exposure, often associated with a low dietary intake of Vitamin D. Rickets targets all layers of society independently of economic status with historical information spanning more than two millennia. Vitamin D is critical for the absorption of calcium and prevention of rickets in children as well as osteomalacia in adults. The initial and misleading paradigm of the 19th and 20th centuries that rickets may have been the consequence of infection has been, indeed, reversed following the identification of the Vitamin D molecule's important role in the function of the immune system. Although traditionally considered limited to osteopathology, Vitamin D deficiency is now known to be linked to infection, inflammation, and carcinogenesis. In this review, we consider the key historical (Whistler, pre-Whistler and post-Whistler descriptors) and social facts around rickets; highlight the osteo-pathological features of rickets and the pathology of the upper and lower respiratory tract, stressing the fact that lungs remain the main secondary organ affected by Vitamin D deficiency; and emphasize the public health role in identifying the cases of child neglect or abuse based on the evaluation of the costochondral region.
2.
Strand transfer inhibitors of HIV-1 integrase: bringing IN a new era of antiretroviral therapy.
McColl, DJ, Chen, X
Antiviral research. 2010;(1):101-18
Abstract
HIV-1 integrase (IN) is one of three essential enzymes (along with reverse transcriptase and protease) encoded by the viral pol gene. IN mediates two critical reactions during viral replication; firstly 3'-end processing (3'EP) of the double-stranded viral DNA ends and then strand transfer (STF) which joins the viral DNA to the host chromosomal DNA forming a functional integrated proviral DNA. IN is a 288 amino acid protein containing three functional domains, the N-terminal domain (NTD), catalytic core domain (CCD) and the C-terminal domain (CTD). The CCD contains three conserved catalytic residues, Asp64, Asp116 and Glu152, which coordinate divalent metal ions essential for the STF reaction. Intensive research over the last two decades has led to the discovery and development of small molecule inhibitors of the IN STF reaction (INSTIs). INSTIs are catalytic inhibitors of IN, and act to chelate the divalent metal ions in the CCD. One INSTI, raltegravir (RAL, Merck Inc.) was approved in late 2007 for the treatment of HIV-1 infection in patients with prior antiretroviral (ARV) treatment experience and was recently approved also for first line therapy. A second INSTI, elvitegravir (EVG, Gilead Sciences, Inc.) is currently undergoing phase 3 studies in ARV treatment-experienced patients and phase 2 studies in ARV naïve patients as part of a novel fixed dose combination. Several additional INSTIs are in early stage clinical development. This review will discuss the discovery and development of this novel class of antiretrovirals. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010.