Pathway with single-dose long-acting intravenous antibiotic reduces emergency department hospitalizations of patients with skin infections.

Objectives: Emergency department (ED) patients with serious skin and soft tissue infections (SSTIs) are often hospitalized to receive intravenous (IV) antibiotics. Appropriate patients may avoid admission following a single-dose, long-acting IV antibiotic.

Methods: We conducted a preintervention versus postintervention design trial at 11 U.

Dalbavancin Reduces Hospital Stay and Improves Productivity for Patients with Acute Bacterial Skin and Skin Structure Infections: The ENHANCE Trial.

Introduction: Admissions for acute bacterial skin and skin structure infections (ABSSSI) are often prolonged because of intravenous (IV) antibiotics. Use of a long-acting IV antibiotic may reduce length of stay (LOS) on a hospitalist service. The ENHANCE ABSSSI trial sought to determine the impact on LOS and work productivity in patients treated with a long-acting IV antibiotic, dalbavancin, vs.

Radioprotective efficacy and toxicity of a new family of aminothiol analogs.

Purpose: A family of 17 new nucleophilic-polyamine and aminothiol structures was designed and synthesized to identify new topical or systemic radioprotectors with acceptable mammalian toxicity profiles. design elements included: (i) Length and charge of the DNA-interacting, alkylamine backbone, (ii) nucleophilicity of the reactive oxygen species (ROS)-scavenging group, and (iii) non-toxic drug concentration achievable in animal tissues.

Materials And Methods: Mouse maximum tolerated doses (MTD) were determined by increasing intraperitoneal (IP) doses.

ROS-scavenger and radioprotective efficacy of the new PrC-210 aminothiol.

To identify new aminothiol radioprotectors that are active when applied topically and have fewer side effects when administered systemically, a new family of aminothiol radioprotectors was designed and synthesized. Three key elements in the aminothiol design were, (1) small size for efficient transmembrane diffusion, (2) positive charged amines in alkyl backbone for strong ionic interaction with DNA backbone, and (3) a perpendicular, alkyl side-chain with a terminal thiol that is projected away from the DNA backbone to enable reactive oxygen species scavenging around DNA. Several in vitro assays were used to characterize the prototype aminothiol, PrC-210, for efficacy: protection against reactive oxygen species-induced plasmid DNA nicking, mass spectrometry to detect aminothiol-reactive oxygen species by-products, S.

Changes in clinical management and diagnosis following DaTscan SPECT imaging in patients with clinically uncertain parkinsonian syndromes: a 12-week follow-up study.

Background: An accurate diagnosis is important for timely and adequate treatment in patients with clinically uncertain parkinsonian syndrome (CUPS).

Objective: The objective of this study was to assess safety and changes in clinical management, diagnosis and quality of life (QoL) at 4 and 12 weeks following DaTscan (ioflupane [(123)I] injection) imaging in patients with CUPS.

Methods: This randomized, open-label, single-dose, multicenter trial was carried out in patients with CUPS who were randomized to either a DaTscan imaging group or to a control group without imaging.

Synthesis and growth regulatory activity of a prototype member of a new family of aminothiol radioprotectors.

The synthesis, growth inhibition and radioprotective activity of the PrC-210 aminothiol, 3-(methylamino)-2-((methylamino)methyl)propane-1-thiol, and its polyamine and thiolated polyamine progenitors are reported. All of the molecules significantly inhibited growth of cultured normal human fibroblasts. The combination of an ROS-scavenging thiol group and a positively charged alkyl-amine backbone provided the most radioprotective aminothiol molecule.

Characterization and Synthesis of a 6-Substituted Benzo[b]thiophene.

An impurity observed during the synthesis of zileuton (Zyflo) has been isolated and characterized as a benzo[b]thiophene derivative that has undergone electrophilic substitution in the 6 position (4). A nine-step synthesis confirms the structural assignment. Key steps in the synthesis include a regioselective Friedel-Crafts coupling between 2-hydroxythioanisole, 8, and 1-(benzo[b]thien-2-yl)ethanol, 1, and formation of a benzo[b]thiophene from an o-methylthiobenzaldehyde, 14, and chloroacetone.

Localization of alpha-tocopherol transfer protein in the brains of patients with ataxia with vitamin E deficiency and other oxidative stress related neurodegenerative disorders.

Vitamin E (alpha-tocopherol) is an essential nutrient and an important antioxidant. Its plasma levels are dependent upon oral intake, absorption and transfer of the vitamin to a circulating lipoprotein. The latter step is controlled by alpha-tocopherol transfer protein (alpha-TTP), which is a 278 amino acid protein encoded on chromosome 8, known to be synthesized in the liver.

Influence of thyroid hormone on ADP-ribosylation of nuclear proteins in cultured GH1 cells.

We present evidence that T3 can alter the ADP-ribosylation of chromatin associated proteins. Nuclei from GH1 cells were incubated with [adenylate-32P]NAD and the radioactivity incorporated into histone and non-histone proteins was quantitated and analyzed by gel electrophoresis and autoradiography. Incubation of GH1 cells for 24 h with T3 lowered by 40-70% the [32P]ADP-ribose incorporated into nuclear proteins.

Synthesis of two cyclopentenyl-3-deazapyrimidine carbocyclic nucleosides related to cytidine and uridine.

The cytosine analogue of neplanocin A, cyclopentenylcytosine (CPE-C, 3), has significant antitumor and antiviral activity commensurate with the drug's ability to produce a significant depletion of cytidine triphosphate (CTP) levels that result from the potent inhibition of cytidine triphosphate synthetase. Another important antitumor agent, previously identified as a potent inhibitor of the same enzyme, is 3-deazauridine (2). The synthesis of the cyclopentenyl nucleosides 3-deaza-CPE-C (5) and 3-deaza-CPE-U (6) was undertaken in order to investigate the effects of a modified 3-deaza pyrimidine aglycon moiety on the biological activity of the parent CPE-C.

Synthesis and biological activity of novel carbocyclic nucleosides.

The syntheses of several novel carbocyclic nucleosides which incorporate the cyclopentene moiety of neplanocin A will be presented. These include modified pyrimidine derivatives of the very potent antitumor agent cyclopentenyl cytosine and carbocyclic analogues of the ketohexose nucleosides psicofuranine and psicofuranosyl cytosine.

Identification of an adenosine 3',5'-monophosphate (cAMP)-responsive region in the rat growth hormone gene: evidence for independent and synergistic effects of cAMP and thyroid hormone on gene expression.

Rat GH gene expression is known to be stimulated by several factors, including thyroid hormone and GRF. This effect of GRF appears to be mediated by cAMP resulting from activation of adenylate cyclase by the peptide. The elements of the rat GH gene important for thyroid hormone stimulation and cell-specific expression have been previously mapped using gene transfection techniques.

Cholera toxin affects nuclear ADP-ribosylation in GH1 cells.

Incubation of GH1 cells with cholera toxin for 24 h inhibits [32P]ADP-ribose incorporation into histones and non-histone nuclear proteins by more than 50%. The toxin produces a generalized decrease of incorporation into all protein acceptors and into the poly(ADP-ribosyl)ated components excised from chromatin after micrococcal nuclease digestion. The cellular levels of NAD were also decreased (40 to 80%) after treatment with cholera toxin.

cis-acting elements of the rat growth hormone gene which mediate basal and regulated expression by thyroid hormone.

In GC cells, a growth hormone-producing rat pituitary cell line, 3,5,3'-triiodo-L-thyronine (L-T3) rapidly stimulates the transcription rate of the growth hormone gene which parallels the level of chromatin-associated L-T3-receptor complexes (Yaffe, B. M., and Samuels, H.

5'-Flanking DNA of the rat growth hormone gene mediates regulated expression by thyroid hormone.

Thyroid hormone has been shown to rapidly stimulate the rate of rat growth hormone gene transcription which parallels the kinetics of binding of 3,5,3'-triiodo-L-thyronine (L-T3) to its nuclear receptor (Yaffe, B. M., and Samuels, H.

Photoaffinity labeling of thyroid hormone nuclear receptors. Influence of n-butyrate and analysis of the half-lives of the 57,000 and 47,000 molecular weight receptor forms.

The thyroid hormone receptor is a nuclear-associated protein which appears to mediate the actions of 3,5,3'-triiodo-L-thyronine (L-T3) and 3,5,3',5'-tetraiodo-L-thyronine (L-T4) in mammalian cells. In a previous study we reported that N-2-diazo-3,3,3-trifluoropropionyl-3,5,3'-triiodo-L-thyronine (L-T3-PAL) serves as an effective photoaffinity label probe of the receptor in GH1 cells, a growth hormone producting rat pituitary cell line. Irradiation of cells at 254 nm covalently cross-links L-[125I]T3-PAL to two molecular weight (Mr) nuclear receptor forms, an abundant 47,000 Mr component and a less abundant 57,000 Mr species (Pascual, A.

Nutritional status of dairy cows indicated by analysis of blood.

A study of 395 cows in 21 herds tested the suitability of applying the normal distribution to 23 blood variables in setting reference ranges and the potential of multiple regression equations for predicting energy and nutrient intakes, milk and fat production, and reproductive variables from blood measurements. After adjustment for herd and lactational group within herd, deviations from the normal distribution were significant for nine blood variables: glucose, cholesterol, glycerol, triglyceride, acetoacetate, urea, uric acid, creatinine, and chloride. Multiple regressions were calculated for group-averages of ration variables on group-medians of blood variables, and for production and reproductive variables on blood variables in individual cows.

Vitamin A nutrition of the equine: growth, serum biochemistry and hematology.

Four diets were fed to pony fillies for 40 weeks. One group received a basal diet low in carotene, designated mildly deficient. Other groups were fed basal diet plus vitamin A propionate equivalent to 12 (control), 1,200 (mildly intoxicated) or 12,000 (severely intoxicated) microgram retinol/kg body weight/day.

Specificity of response in hamster cells induced to produce plasminogen activator by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate.

A phorbol ester promoting agent, 12-O-tetradecanoylphorbol-13-acetate, enhances plasminogen activator production in hamster cell lines that synthesize plasminogen activator immunologically identical with plasminogen activator of normal hamster lung cells. 12-O-Tetradecanoylphorbol-13-acetate exhibits a high degree of specificity in the type of plasminogen activator evoked, which is always of the lung form. No enhancement of plasminogen activator production was detected in hamster cell lines synthesizing plasminogen activator of different antigenic form, although in the presence of 12-O-tetradecanoylphorbol-13-acetate, cells of one such line initiated synthesis of plasminogen activator of the lung form.