The cellular eff ect of lead poisoning and its clinical picture

Abstract Lead intoxication affects many systems of the body including the cardiovascular, renal, and reproductive systems. Its most detrimental effects occur in the nervous system, where lead blocks the receptor know as N-methyl-D-aspartate, an effective receptor involved in the maturation of brain plasticity. The toxicity of lead plays a major role in the communication between astrocytes and endothelial cells. By disrupting the blood-brain barrier, it causes encephalopathy and edema that primarily affects the cerebellum. Fetus' astrocytes in utero are at an especially high risk of lead intoxication because the immature endothelial cells that form the capillaries of the brain offer a decreased resistance to lead, and thereby easily allow Pb2+ to enter the brain. Intracellularly, lead replaces calcium as a second messenger, binding with calmodulin more readily than calcium, resulting in an alteration in protein conformation. This altered conformation leads protein kinases to phosphoylate and activate substrate molecules, which alter various cellular processes leading to the clinical picture of lead poisoning. In order to prevent the deleterious effects that Pb2+ has on the human system, it is important to understand the various means by which it is introduced into the body. Environmental and domestic sources of Pb2+ are the most often seen causes for the disease, but with proper precautionary measures, it is easily possible to adequately reduce the level of risk associated with lead poisoning

Characteristics of Patients With Antiphospholipid Antibody Positivity in the APS ACTION International Clinical Database and Repository

Objective To describe the baseline characteristics of patients with positivity for antiphospholipid antibodies (aPLs) who were enrolled in an international registry, the Antiphospholipid Syndrome (APS) Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository, overall and by clinical and laboratory subtypes. Methods The APS ACTION registry includes adults who persistently had positivity for aPLs. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and “non-criteria”) characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS only, obstetric APS only, and both thrombotic APS/obstetric APS). We assessed baseline characteristics of patients tested for the presence of three aPLs (lupus anticoagulant [LAC] test, anticardiolipin antibody [aCL], and anti-beta(2)-glycoprotein I [anti-beta(2)GPI]) antibodies by aPL profiles (LAC only, single, double, and triple aPL positivity). Results The 804 aPL-positive patients assessed in the present study had a mean age of 45 +/- 13 years, were 74% female, and 68% White; additionally, 36% had other systemic autoimmune diseases. Of these 804 aPL-positive patients, 80% were classified as having APS (with 55% having thrombotic APS, 9% obstetric APS, and 15% thrombotic APS/obstetric APS). In the overall cohort, 71% had vascular thrombosis, 50% with a history of pregnancy had obstetric morbidity, and 56% had experienced at least one non-criteria manifestation. Among those with three aPLs tested (n = 660), 42% were triple aPL-positive. While single-, double-, and triple aPL-positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup, which consisted of aCLs or anti-beta(2)GPI only. Conclusion Our study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter international cohort. Within single aPL positivity, LAC may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification