Clinical Approach to Fever in the Neurosurgical Intensive Care Unit: Focus on Drug Fever.

Clinical approach to fever in the neurosurgical intensive care unit: Focus on drug fever.

Surg Neurol Int. 2013; 4(Suppl 5): S318-22
Cunha BA

As fever is one of the cardinal signs of infection, the presence of fever in a patient in the neurosurgical intensive care unit (NSICU) raises the question of whether it is infectious in etiology. Infectious and noninfectious causes of fever in the NSICU may be determined based upon assessment of clinical signs and symptoms, the degree of temperature elevation, the relationship of the pulse to the fever (e.g., an infectious process resulting in hyperpyrexia and bradycardia), and when the fever occurs (e.g., related to the length of stay in the NSICU). There are many noninfectious disorders which contribute to temperatures >102°F in the NSICU; these include drug fevers, deep vein thrombosis, phlebitis/pulmonary embolism, acute myocardial infarction, atelectasis, dehydration, acute gout flare, malignancy, acute pancreatitis, transfusion associated hepatitis, and hemorrhage. Infectious rather than noninfectious disorders, however, are more typically associated with high-grade fevers (>102°F.) in the NSICU, and nosocomial pneumonia, (synonymous with ventilator-associated pneumonia [VAP]), is the leading culprit, followed by nosocomial infections and Clostridium difficile. HubMed – drug

An amino acids mixture improves the hepatotoxicity induced by acetaminophen in mice.

J Amino Acids. 2013; 2013: 615754
Di Pierro F, Rossoni G

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but at high dose it leads to undesirable side effects, such as hepatotoxicity and nephrotoxicity. The aim of this study was to evaluate the protective role of DDM-GSH, a mixture of L-cysteine, L-methionine, and L-serine in a weight ratio of 2?:?1?:?1, in comparison to N-acetylcysteine (NAC), against acetaminophen- (APAP-) induced hepatotoxicity in mice. Toxicity was induced in mice by the intraperitoneal (ip) administration of low dose (2?mmol/kg) or high dose (8?mmol/kg) of APAP. DDM-GSH (0.4 to 1.6?mmol/kg) was given ip to mice 1?h before the APAP administration. The same was done with NAC (0.9 to 3.6?mmol/kg), the standard antidote of APAP toxicity. Mice were sacrificed 8?h after the APAP injection to determine liver weight, serum alanine aminotransferase (ALT), and total glutathione (GSH) depletion and malondialdehyde (MDA) accumulation in liver tissues. DDM-GSH improved mouse survival rates better than NAC against a high dose of APAP. Moreover, DDM-GSH significantly reduced in a dose-dependent manner not only APAP-induced increases of ALT but also APAP-induced hepatic GSH depletion and MDA accumulation. Our results suggest that DDM-GSH may be more potent than NAC in protecting the liver from APAP-induced liver injury. HubMed – drug

Lifting the veil on amyloid drug design.

Elife. 2013; 2: e01089
Tiller KE, Tessier PM

High resolution structures and computational methods have been used to identify compounds that prevent amyloid fibrils associated with Alzheimer’s disease from dissociating into toxic species. HubMed – drug

Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity of amyloid beta.

Elife. 2013; 2: e00857
Jiang L, Liu C, Leibly D, Landau M, Zhao M, Hughes MP, Eisenberg DS

Amyloid protein aggregates are associated with dozens of devastating diseases including Alzheimer’s, Parkinson’s, ALS, and diabetes type 2. While structure-based discovery of compounds has been effective in combating numerous infectious and metabolic diseases, ignorance of amyloid structure has hindered similar approaches to amyloid disease. Here we show that knowledge of the atomic structure of one of the adhesive, steric-zipper segments of the amyloid-beta (A?) protein of Alzheimer’s disease, when coupled with computational methods, identifies eight diverse but mainly flat compounds and three compound derivatives that reduce A? cytotoxicity against mammalian cells by up to 90%. Although these compounds bind to A? fibers, they do not reduce fiber formation of A?. Structure-activity relationship studies of the fiber-binding compounds and their derivatives suggest that compound binding increases fiber stability and decreases fiber toxicity, perhaps by shifting the equilibrium of A? from oligomers to fibers. DOI: HubMed – drug