Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Dentistry, neurology and nephrology--what is the connection?

Case report A 28-year-old female patient was admitted because of painlessmacroscopic haematuria. Past history included severe mentalretardation and nystagmus. At age 17, a computed tomography(CT) scan of the brain showed an absent cerebellar vermis andcerebellar hypoplasia. There was no     

“Vinylogs” and “Acetylenylogs” of β-Adrenergic Agents

Vinylogous (Groups III and V ) and acetylenologous (Group IV ) analogs of the classical β-adrenergic agents — stimulants and blockers — were prepared in order to evaluate the effect of degree of saturation, position of unsaturation and rigidity of the chain linking the aromatic ring and the amino containing functional group on biological activity. Derivatives from Group III , which represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II , retained β₁-adrenoceptor antagonist activity albeit substantially less potent (50–200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group II compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists ( 5a, 5d, 5g ), with K_B's ranging from 73–93 nM while 3,4-dichloro substitution ( 5e ) markedly reduced antagonist potency (K_B = 2,400 nM). Agonist activity was also noted for 5b and 5d , suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the β₁-adrenoceptor confirming the importance of the spatial relationship between the hydroxyl and the amino nitrogen.     

Cytochrome P450-dependent arachidonic acid metabolism in human kidney

Cytochrome P450-dependent arachidonic acid metabolism in human kidney cortex from several postmortem subjects has been characterized. Using HPLC and GC/MS, four cytochrome P450-arachidonic acid metabolites were tentatively but not unequivocally identified as epoxyeicosatrienoic acid (EET), dihydroxyeicosatrienoic acid (DHT) and 19- and 20-hydroxyeicosatetraenoic acids, suggesting the involvement of two major cytochrome P450 enzymes, epoxygenase and omega/omega-1 hydroxylases. This pattern of metabolism was similar to that found in rabbit and rat kidneys. The formation of these metabolites was dependent on the presence of NADPH and inhibited by IgG of NADPH-cytochrome P450 (c) reductase. Immunologic studies of renal cytochrome P450 epoxygenase demonstrated that antibodies prepared against human-purified hepatic cytochrome P450 epoxygenase recognized renal enzyme protein and inhibited the enzyme activity by 92%. In contrast, control immunoglobulin did not inhibit renal cytochrome P450 epoxygenase. Antibody inhibition of renal cytochrome P450 epoxygenase demonstrated a degree of conservation of both enzyme proteins between liver and kidney. Antibodies against lauric acid omega/omega-1 hydroxylases (P450 omega) inhibited the formation of omega/omega-1 hydroxylase products, 19- and 20-HETEs. Identical qualitative patterns of arachidonic acid metabolites were observed in all cortical microsomes studied. Interindividual variations were observed in the cytochrome P450-dependent arachidonic acid metabolism, and the activities ranged from 0.031 to 5.027 nmol arachidonic acid converted/mg protein/30 min. which is about a 150-fold difference. However, when the specific activities for total cytochrome P450-dependent arachidonic acid metabolism were calculated, two separate groups could be distinguished, high and low metabolizers of arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Occupational therapy workforce needs: a model for demand-based studies.

PURPOSE: To provide a model for assessing occupational therapy workforce needs by using a demand-based approach to determine current workforce status in the Northwest region. Regional information may have implications for addressing national occupational therapy service needs. METHOD: A questionnaire was sent to a proportional random sample of 234 facilities that hire occupational therapy practitioners. Data were collected in July-August 2003 using structured mailing and follow-up procedures. RESULTS: Response rate was 79%. Twenty-four percent reported occupational therapy vacancies and 11% occupational therapy assistant vacancies; 48% predicted an increase in occupational therapy positions in the next 2 years and 41% an increase in occupational therapy assistant positions. Sixty-three percent of respondents reported difficulty in hiring. DISCUSSION: This study identifies an occupational therapy workforce shortage in the Northwest. Management of a shortage is critical, for even short-term adjustments could lead to permanent changes in service provision. This study demonstrates the importance of current information on the status of the national workforce and serves as a model for future studies.     

Potential roles of protease inhibitors in Alzheimer's disease

Recently, protease inhibitors have been recognized as potential contributors to the pathogenesis of Alzheimer's disease. In this role, they could mediate an exaggerated regenerative response in the brain, participate as acute phase reactants, or be involved in the aberrant proteolytic processing of the amyloid proteins. Protease inhibitors are, therefore, attractive targets for drug intervention in Alzheimer's disease.