Background: The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for plague during pregnancy.
Methods: We searched 5 scientific literature databases for primary sources on the safety of 9 antimicrobials considered for plague during pregnancy (amikacin, gentamicin, plazomicin, streptomycin, tobramycin, chloramphenicol, doxycycline, sulfadiazine, and trimethoprim-sulfamethoxazole [TMP-SMX]) and abstracted data on maternal, pregnancy, and fetal/neonatal outcomes.
Results: Of 13 052 articles identified, 66 studies (case-control, case series, cohort, and randomized studies) and 96 case reports were included, totaling 27 751 prenatal exposures to amikacin (n = 9), gentamicin (n = 345), plazomicin (n = 0), streptomycin (n = 285), tobramycin (n = 43), chloramphenicol (n = 246), doxycycline (n = 2351), sulfadiazine (n = 870), and TMP-SMX (n = 23 602).
Background: Botulism is a rare, life-threatening paralytic illness. Equine-derived heptavalent botulinum antitoxin (HBAT), the only currently available treatment for noninfant botulism in the United States, was licensed in 2013. No reports have systematically examined safety and clinical benefit of HBAT among botulism patients.
View Article and Find Full Text PDFOsteoblast differentiation is regulated through the successive activation of signaling molecules by a complex interplay of extracellular signals such as bone morphogenetic protein (BMP) and Wnt ligands. Numerous studies have identified natural as well as synthetic compounds with osteogenic activity through the regulation of either BMP/SMADs or the Wnt/β-catenin pathway. Here, we attempted to isolate small molecules that concurrently activated both SMADs and β-catenin, which led to the discovery of a novel potent osteogenic compound, DMP-PYT.
View Article and Find Full Text PDFBackground: In 2013-2014, an outbreak of serogroup B meningococcal disease occurred among persons linked to a New Jersey university (University A). In the absence of a licensed serogroup B meningococcal (MenB) vaccine in the United States, the Food and Drug Administration authorized use of an investigational MenB vaccine to control the outbreak. An investigation of the outbreak and response was undertaken to determine the population at risk and assess vaccination coverage.
View Article and Find Full Text PDFHyperglycemia is a key feature in diabetes. Hyperglycemia has been implicated as a major contributor to several complications of diabetes. High glucose levels induce the release of proinflammatory cytokines.
View Article and Find Full Text PDFTranscription activator-like (TAL) effector nucleases (TALENs) can be readily engineered to bind specific genomic loci, enabling the introduction of precise genetic modifications such as gene knockouts and additions. Here we present a genome-scale collection of TALENs for efficient and scalable gene targeting in human cells. We chose target sites that did not have highly similar sequences elsewhere in the genome to avoid off-target mutations and assembled TALEN plasmids for 18,740 protein-coding genes using a high-throughput Golden-Gate cloning system.
View Article and Find Full Text PDFEvid Based Complement Alternat Med
January 2013
Diabetes is characterized by a proinflammatory state, and several inflammatory processes have been associated with both type 1 and type 2 diabetes and the resulting complications. High glucose levels induce the release of proinflammatory cytokines. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria), and is also widely distributed in fruits and vegetables.
View Article and Find Full Text PDFBackground: In response to the influenza A(H1N1)pdm09 (pH1N1) pandemic, peramivir, an investigational intravenous neuraminidase inhibitor, was made available for treatment of hospitalized patients with pH1N1 in the United States under an Emergency Use Authorization (EUA). The Centers for Disease Control and Prevention (CDC) implemented a program to manage peramivir distribution to requesting clinicians under EUA. We describe results of the CDC's peramivir program and 3 related surveys.
View Article and Find Full Text PDFAs the primary step for 'drug repositioning', we evaluated the effect of 2000 drugs and drug candidates on the commitment of bi-potential mesenchymal precursor C2C12 cells into osteoblasts in the presence of bone morphogenetic protein (BMP)-2 and found that butamben enhanced BMP-2-stimulated induction of alkaline phosphatase, a biomarker of osteoblastogenesis. Investigating the underlying mechanism of its anabolic actions, we found anabolic action of its derivative (compound 4) relies on BMP-2 signaling and mRNA induction of BMPs and voltage-gated potassium channels.
View Article and Find Full Text PDFThe receptor activator of nuclear factor-κB ligand (RANKL) is a key factor in regulating osteoclastogenesis and in maintaining the survival of mature osteoclasts. We screened differentially expressed genes in RAW264.7 cells in response to RANKL and found osteoclast stimulatory transmembrane protein (OC-STAMP) as one of the RANKL-induced genes of interest.
View Article and Find Full Text PDFIn this study, we demonstrate a stimulatory effect of tanshinone IIA isolated from the root of Salvia miltiorrhiza on the commitment of bi-potential mesenchymal precursor C2C12 cells into osteoblasts in the presence of bone morphogenetic protein (BMP)-2. At low concentrations, tanshinone IIA enhanced BMP-2-stimulated induction of alkaline phosphatase (ALP), an early phase biomarker of osteoblast differentiation, and mRNA expression of BMPs. ALP induction was inhibited by the BMP antagonist noggin, suggesting that tanshinone IIA enhances the osteogenic activity of BMP signaling.
View Article and Find Full Text PDFObjective: To provide a general description of the roles and contributions of three pharmacists from the Regulatory Affairs program (RA) at the Centers for Disease Control and Prevention (CDC) who are involved in emergency preparedness and response activities, including the 2009 pandemic influenza A (H1N1) public health emergency.
Setting: Atlanta, GA.
Practice Description: RA consists of a staff of nine members, three of whom are pharmacists.
Broad applications of zinc finger nuclease (ZFN) technology-which allows targeted genome editing-in research, medicine, and biotechnology are hampered by the lack of a convenient, rapid, and publicly available method for the synthesis of functional ZFNs. Here we describe an efficient and easy-to-practice modular-assembly method using publicly available zinc fingers to make ZFNs that can modify the DNA sequences of predetermined genomic sites in human cells. We synthesized and tested hundreds of ZFNs to target dozens of different sites in the human CCR5 gene-a co-receptor required for HIV infection-and found that many of these nucleases induced site-specific mutations in the CCR5 sequence.
View Article and Find Full Text PDFGenetic variations in the Calpain-10 gene, CAPN10, have been reported to be associated with the risk of type 2 diabetes mellitus (T2DM) in Mexican-Americans and Northern Europeans whereas these variations are not associated with T2DM in other populations. The aim of this study was to determine whether there is an association between specific CAPN10 diplotype (SNP-43, -19, and -63) and T2DM in the Korean population. Overall, 454 Korean patients with T2DM (male 230, female 224) and 236 non-diabetic controls (male 124, female 112) with no family history of diabetes were enrolled in this study.
View Article and Find Full Text PDFPatients with metabolic syndrome are at increased risk of developing cardiovascular disease. The combinations of the haplotype created by the alleles of three single nucleotide polymorphisms (SNPs): SNP-43, -19, and -63 of the Calpain-10 gene (CAPN10), have been reported to be associated with the risk of type 2 diabetes in many populations. The aim of this study was to examine the association of the CAPN10 polymorphism with metabolic syndrome in patients with type 2 diabetes in Korea.
View Article and Find Full Text PDFBackground: Previous studies demonstrating the efficacy of insulin gene therapy have mostly involved use of adenoviral vectors or naked DNA to deliver the insulin gene. However, this procedure may not guarantee long-term insulin production. To improve the performance, we prepared recombinant adeno-associated viral vectors (rAAV) harboring the gene encoding a furin-modified human insulin under the cytomegalovirus (CMV) promoter [rAAV-hPPI(F12)].
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