No abstract

Gentamicin blood levels were monitored in 86 patients. Twenty-one patients had valley levels over 2 ,ig/ml and 36% of these patients developed abnormal serum creatinine or a further rise in creatinine. No patient had a rise in creatinine without a valley level over 2. The peak levels in patients with valleys over 2 were above 10 ug/ml in only one case, whereas four patients had peaks over 10 4g/ml without nephrotoxicity. The mean peak blood levels in patients with a normal creatinine were dose related. An initial dose of 2.0, 1.5, and 1.3 or less mpk (mg/kg) yielded mean peak blood levels of 5.2, 4.7, and 3.7, respectively. To assure an initial peak blood level over 4 ug/ml a loading dose of 2 mpk was required. A rise in peak and valley levels during therapy appeared dose related, being observed in all patients treated with 4.5 mpk daily but not in those receiving 3.0 mpk daily. A radioenzymatic assay was used to validate the standard agar diffusion assay method. The results from the two assays were statistically identical. Valley blood levels of gentamicin may be useful for predicting accumulation of gentamicin which in tum may be correlated with early renal impairment before potentially toxic serum levels of gentamicin develop.

Nurse case management results in more appropriate management of older women with breast cancer.

Abnormalities in brain glucose metabolism and accumulation of abnormal protein deposits called plaques and tangles are neuropathological hallmarks of Alzheimer’s disease (AD), but their relationship to disease pathogenesis and to each other remains unclear. Here we show that succinylation, a metabolism-associated post-translational protein modification (PTM), provides a potential link between abnormal metabolism and AD pathology. We quantified the lysine succinylomes and proteomes from brains of individuals with AD, and healthy controls. In AD, succinylation of multiple mitochondrial proteins declined, and succinylation of small number of cytosolic proteins increased. The largest increases occurred at critical sites of amyloid precursor protein (APP) and microtubule-associated tau. We show that in vitro, succinylation of APP disrupted its normal proteolytic processing thereby promoting Aβ accumulation and plaque formation and that succinylation of tau promoted its aggregation to tangles and impaired microtubule assembly. In transgenic mouse models of AD, elevated succinylation associated with soluble and insoluble APP derivatives and tau. These findings indicate that a metabolism-linked PTM may be associated with AD.

Proteomic analysis of membrane proteins is challenged by the proteins solubility and detergent incompatibility with MS analysis. No single perfect protocol can be used to comprehensively characterize the proteome of membrane fraction. Here, we used cow milk fat globule membrane (MFGM) proteome analysis to assess six sample preparation procedures including one in-gel and five in-solution digestion approaches prior to LC-MS/MS analysis. The largest number of MFGM proteins were identified by suspension trapping (S-Trap) and filter-aided sample preparation (FASP) methods, followed by acetone precipitation without clean-up of tryptic peptides method. Protein identifications with highest average coverage was achieved by Chloroform/MeOH, in-gel and S-Trap methods. Most distinct proteins were identified by FASP method, followed by S-Trap. Analyses by Venn diagram, principal-component analysis, hierarchical clustering and the abundance ranking of quantitative proteins highlight differences in the MFGM fraction by the all sample preparation procedures. These results reveal the biased proteins/peptides loss occurred in each protocol. In this study, we found several novel proteins that were not observed previously by in-depth proteomics characterization of MFGM fraction in milk. Thus, a combination of multiple procedures with orthologous properties of sample preparation was demonstrated to improve the protein sequence coverage and expression level accuracy of membrane samples.