Antimicrobial Stewardship and the Infection Control Practitioner: A Natural Alliance.

Antibiotic overuse and misuse has contributed to rising rates of multidrug-resistant organisms and Clostridioides difficile. Decreasing antibiotic misuse has become a national public health priority. This review outlines the goals of antimicrobial stewardship, essential members of the program, implementation strategies, approaches to measuring the program's impact, and steps needed to build a program.

Biotin deficiency enhances the inflammatory response of human dendritic cells.

The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation.

Changing epidemiology of methicillin-resistant Staphylococcus aureus in the Veterans Affairs Healthcare System, 2002-2009.

Purpose: The epidemiology of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) is changing. Temporal trends and differences between healthcare settings must be described in order to better predict future risk factors associated with this dangerous bacterial infection.

Methods: A national MRSA-infected cohort was identified from 2002 to 2009 in the Veterans Affairs Healthcare System of the United States: hospital (HOS), long-term care (LTC), and outpatient (OPT).

In vitro activity of tigecycline in combination with gentamicin against biofilm-forming Staphylococcus aureus.

We investigated the activity of tigecycline in combination with gentamicin for the treatment of biofilm-forming methicillin-resistant and sensitive Staphylococcus aureus in an in vitro pharmacodynamic model. Tigecycline monotherapy demonstrated bacteriostatic activity throughout 48 h (-0.24 +/- 0.

In vitro activities of telavancin and vancomycin against biofilm-producing Staphylococcus aureus, S. epidermidis, and Enterococcus faecalis strains.

We investigated the activities of telavancin and vancomycin against biofilm-producing Staphylococcus and Enterococcus strains. At clinically attainable concentrations, telavancin was active against bacteria embedded in biofilm (minimal biofilm eradication concentration [MBEC], 0.125 to 2 microg/ml) and inhibited biofilm formation at concentrations below the MIC.

Pancreatic beta cells and islets take up thiamin by a regulated carrier-mediated process: studies using mice and human pancreatic preparations.

Thiamin is essential for the normal function of the endocrine pancreas, but very little is known about uptake mechanism(s) and regulation by beta cells. We addressed these issues using mouse-derived pancreatic beta-TC-6 cells, and freshly isolated primary mouse and human pancreatic islets. Results showed that thiamin uptake by beta-TC-6 cells involves a pH (but not Na+)-dependent carrier-mediated process that is saturable at both the nanomolar (apparent K(m) = 37.

Transgenic overexpression of pregnancy-associated plasma protein-A increases the somatic growth and skeletal muscle mass in mice.

Although IGFs are indispensable to skeletal muscle development, little information is available regarding the mechanisms regulating the local action of IGFs in skeletal muscle tissues. Here we tested the hypothesis that pregnancy-associated plasma protein-A (PAPP-A), a member of the metalloproteinase superfamily, promotes skeletal muscle formation in vivo through degrading IGF binding proteins (IGFBPs), which increases the bioavailability of IGFs. Expression of PAPP-A is significantly increased in muscle five days after muscle injury in mice.

Alcohol ingestion by donors amplifies experimental airway disease after heterotopic transplantation.

Rationale: Obliterative bronchiolitis (OB) after lung transplantation is triggered by alloimmunity, but is ultimately mediated by transforming growth factor (TGF)-beta(1)-dependent airway fibrosis.

Objectives: Chronic alcohol use increases TGF-beta(1) expression and renders the lung susceptible to injury. Therefore, we hypothesized that donor alcohol abuse could prime the lung allograft for OB, as many organ donors have a history of alcohol abuse.

Molecular mechanisms involved in the adaptive regulation of human intestinal biotin uptake: A study of the hSMVT system.

Biotin, a water-soluble micronutrient, is vital for cellular functions, including growth and development. The human intestine utilizes the human sodium-dependent multivitamin transporter (hSMVT) for biotin uptake. Evidence exists showing that the intestinal biotin uptake process is adaptively regulated during biotin deficiency.

Pregnancy-associated plasma protein-A increases osteoblast proliferation in vitro and bone formation in vivo.

Pregnancy-associated plasma protein (PAPP)-A, a protease for IGF binding protein (IGFBP)-2, -4, and -5, may enhance IGF action by increasing its bioavailability. Here we have determined the role and mechanism of action of PAPP-A in the regulation of osteoblast proliferation in vitro and bone metabolism in vivo. Recombinant PAPP-A (100 ng/ml) significantly increased osteoblast proliferation and free IGF-I concentration.

Developmental abnormalities in multiple proliferative tissues of Apc(Min/+) mice.

Germ-line mutation of the Apc gene has been linked to familial adenomatous polyposis (FAP) that predisposes to colon cancer. Apc(Min/+) mice, heterozygous for the Apc gene mutation, progressively develop small intestinal tumours in a manner that is analogous to that observed in the colon of patients with FAP (Su et al. 1992; Fodde et al.

Role of reduced folate carrier in intestinal folate uptake.

Studies from our laboratory and others have characterized different aspects of the intestinal folate uptake process and have shown that the reduced folate carrier (RFC) is expressed in the gut and plays a role in the uptake process. Little, however, is known about the actual contribution of the RFC system toward total folate uptake by the enterocytes. Addressing this issue in RFC knockout mice is not possible due to the embryonic lethality of the model.

Moraxella catarrhalis in chronic obstructive pulmonary disease: burden of disease and immune response.

Rationale: Moraxella catarrhalis is frequently present in the sputum of adults with chronic obstructive pulmonary disease (COPD). Little is known about the role of M. catarrhalis in this common disease.

The effect of poststroke cognitive impairment on rehabilitation process and functional outcome.

Objectives: To determine whether cognitive impairment affects access to, or quality of, rehabilitation services, and to examine the effects of functional outcomes in stroke patients.

Design: Secondary analysis of prospective cohort of stroke patients followed for 6 months after stroke.

Settings: Eleven large-volume US Department of Veterans Affairs hospitals nationwide.

Characterization of the 5'-regulatory region of the human thiamin transporter SLC19A3: in vitro and in vivo studies.

Transcriptional regulation of expression of the human thiamin transporter-2 (the product of the SLC19A3 gene) is unknown. In this study, we cloned the 5'-regulatory region of the human SLC19A3 gene (2,016 bp), identified the minimal promoter region required for basal activity, demonstrated a critical role for specific cis-regulatory elements in determining the promoter activity, and confirmed activity and physiological relevance of the cloned SLC19A3 promoter in vivo. With the use of transiently transfected human intestinal epithelial Caco-2 cells and 5'-deletion analysis, the minimal promoter region required for basal activity of the SLC19A3 promoter was found to be encoded in a sequence between -77 and +59 by using the start of transcription initiation as position 1.

Acarbose attenuates experimental non-alcoholic steatohepatitis.

The alpha-glucosidase inhibitor acarbose is beneficial in the prevention of type 2 diabetes. To determine whether it attenuates the commonly associated non-alcoholic steatohepatitis (NASH), we used an experimental NASH model. Rats were fed ad libitum a nutritionally adequate high fat diet (71% of calories as fat) with or without acarbose (200 mg/1000 calories) for 3 weeks.

Expression and functional contribution of hTHTR-2 in thiamin absorption in human intestine.

The aim of this study was to investigate expression and relative contribution of human thiamin transporter (hTHTR)-2 toward overall carrier-mediated thiamin uptake by human intestinal epithelial cells. Northern blot analysis showed that the message of the hTHTR-2 is expressed along the native human gastrointestinal tract with highest expression being in the proximal part of small intestine. hTHTR-2 protein was found, by Western blot analysis, to be expressed at the brush-border membrane (BBM), but not at the basolateral membrane, of native human enterocytes.

Characterization of human brain nicotinamide 5'-mononucleotide adenylyltransferase-2 and expression in human pancreas.

NMNAT (nicotinamide 5'-mononucleotide adenylyltransferase; EC 2.7.7.

Effects of treatment of rats with indole-3-carbinol on apoptosis in the mammary gland and mammary adenocarcinomas.

Induction of apoptosis is an approach to suppress carcinogenesis. The effects of a 12-week treatment of female Sprague-Dawley rats with indole-3-carbinol (I3C), beta-naphthoflavone or vehicle (40% ethanol in corn oil), by oral gavages starting 3 weeks after initiation of mammary tumorigenesis with 7,12-dimethylbenz[alpha]anthracene, on apoptotic activities in the mammary adenocarcinomas were examined. Apoptotic cells in tumor sections were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and quantitated by light microscopy and an Image-Plus Program.

A carrier-mediated mechanism for pyridoxine uptake by human intestinal epithelial Caco-2 cells: regulation by a PKA-mediated pathway.

Vitamin B6 is essential for cellular functions and growth due to its involvement in important metabolic reactions. Humans and other mammals cannot synthesize vitamin B6 and thus must obtain this micronutrient from exogenous sources via intestinal absorption. The intestine, therefore, plays a central role in maintaining and regulating normal vitamin B6 homeostasis.

Ontogenic regulation of folate transport across rat jejunal brush-border membrane.

Folate is an essential micronutrient that in mammals must be obtained from exogenous sources via intestinal absorption. Previous studies from our laboratory and others have demonstrated that folate absorption from the small intestine is mediated via the reduced-folate carrier (RFC). The goal of this study was to determine whether the initial step of folate uptake by intestinal epithelial cells, i.

Lycopene attenuates arachidonic acid toxicity in HepG2 cells overexpressing CYP2E1.

Arachidonic acid (AA) was shown to be toxic to HepG2 cells expressing cytochrome P4502E1 (CYP2E1) because of oxidative stress. The aim of this study was to investigate whether lycopene, a carotenoid with high anti-oxidant capacity, protects HepG2 cells expressing CYP2E1 against AA toxicity. In preliminary experiments, lycopene as well as placebo (vehicle) were not toxic in the three types of cells tested: HepG2 cells, HepG2 cells transfected with pCI-neo (Neo) or pCI-neo/2E1 (2E1).

Biotin uptake by human intestinal and liver epithelial cells: role of the SMVT system.

It has been well established that human intestinal and liver epithelial cells transport biotin via an Na+-dependent carrier-mediated mechanism. The sodium-dependent multivitamin transport (SMVT), a biotin transporter, is expressed in both cell types. However, the relative contribution of SMVT toward total carrier-mediated uptake of physiological (nanomolar) concentrations of biotin by these cells is not clear.