Gene targeting in animal cells
R.M. Twyman in Gene Transfer to Animal Cells, 2004
This chapter discusses the principles of gene expression control as applied in transgenic systems and looks at the different regulatory elements that are available for expression construct design. It describes the inducible transcription systems allow transgene activity in cells and transgenic animals to be controlled by the application of a small molecule (an inducer) such as isopropyl-1-thio-ß-D-galactopyranoside, doxycycline, a synthetic hormone analog or an inducer of dimerization. Expression vectors are modular in nature and often contain a whole series of different elements with different functions. Transcription factors can act either positively or negatively and in most cases interact directly with the basal transcriptional apparatus, thus either stimulating or inhibiting the recruitment and activity of RNA polymerase and the other basal components. The cloning of viral regulatory elements provided the breakthrough in animal gene transfer, since transgenes could be expressed in many different host cells using a relatively small repertoire of promoters and enhancers.
Therapeutics in gynaecology
Andrea Akkad, Marwan Habiba, Justin Konje, David Taylor in EMQs in Obstetrics and Gynaecology, 2017
Metronidazole is the appropriate treatment for Trichomonas vaginalis and for bacterial vaginosis, whilst doxycycline is effective in chlamydial infections.
and related species
Peter M. Lydyard, Michael F. Cole, John Holton, William L. Irving, Nino Porakishvili, Pradhib Venkatesan, Katherine N. Ward in Case Studies in Infectious Disease, 2010
A 45-year-old woman was on vacation in Cape Cod, Massachusetts and decided to attend an outdoor music festival. In order to get there she walked 3 miles each way at night, through a dark, wooded, grassy area. Shortly thereafter she developed nonspecific symptoms that included fever, headache, muscle aches, mild neck stiffness, and joint pain. She also noticed an oval ‘bull’s eye’ rash on her right arm, which got larger and cleared in the center. Over the ensuing month she felt increasingly fatigued and developed facial paralysis ( Bell’s palsy ) ( Figure 1 ), which precipitated a visit to her family physician. She couldn’t remember being bitten by a tick but based on her description of the rash and her other symptoms her doctor suspected Lyme disease and took a blood sample for serology . Enzyme immunoassay and Western blot confirmed the presence of Borrelia burgdorferi -reactive antibodies. After confirming that the patient was not pregnant she was prescribed doxycycline 100 mg twice daily for 30 days.
Cutaneous side effects of doxycycline: a pediatric case series
Published in Cutaneous and Ocular Toxicology, 2017
Gulsum Iclal Bayhan, Sinan Akbayram, Goknur Ozaydin Yavuz, Ahmet Fayik Oner
Objective: Brucellosis is highly endemic in Turkey and doxycycline is commonly used for its treatment. The present study aimed at documenting the cutaneous side effects of doxycycline in pediatric brucellosis patients in Turkey. Materials and methods: Pediatric patients with brucellosis that were treated between February 2014 and January 2016 were analyzed retrospectively, and those that developed doxycycline-related cutaneous side effects were identified. Demographic data, epidemiological history, physical examination findings, laboratory test results, anti-brucellosis treatment regimen, duration of follow up and outcome were recorded. Results: Among the 189 brucellosis patients, 141 treated with doxycycline plus rifampicin. Seven patients (5%) (two female and five male) developed doxycycline-related cutaneous side effects. Mean duration of treatment before the onset of cutaneous side effects was 9.5 weeks. Doxycycline therapy was continued in five of these patients and was changed in two patients. In the patients that continued to receive doxycycline the cutaneous side effects gradually improved. Conclusions: Cutaneous side effects of doxycycline should always be a consideration, especially in regions in which brucellosis is endemic and doxycycline is commonly used to treat it.
Assessment of solid microneedle rollers to enhance transmembrane delivery of doxycycline and inhibition of MMP activity
Published in Drug Delivery, 2017
Abbie Omolu, Maryse Bailly, Richard M. Day
Many chronic wounds exhibit high matrix metalloproteinase (MMP) activity that impedes the normal wound healing process. Intradermal delivery (IDD) of sub-antimicrobial concentrations of doxycycline, as an MMP inhibitor, could target early stages of chronic wound development and inhibit further wound progression. To deliver doxycycline intradermally, the skin barrier must be disrupted. Microneedle rollers offer a minimally invasive technique to penetrate the skin by creating multiple microchannels that act as temporary conduits for drugs to diffuse through. In this study, an innovative and facile approach for delivery of doxycycline across Strat-MTM membrane was investigated using microneedle rollers. The quantity and rate of doxycycline diffusing through the micropores directly correlated with increasing microneedle lengths (250, 500 and 750 μm). Treatment of Strat-MTM with microneedle rollers resulted in a reduction in fibroblast-mediated collagen gel contraction and MMP activity compared with untreated Strat-MTM. Our results show that treatment of an epidermal mimetic with microneedle rollers provides sufficient permeabilization for doxycycline diffusion and inhibition of MMP activity. We conclude that microneedle rollers are a promising, clinically ready tool suitable for delivery of doxycycline intradermally to treat chronic wounds.
Doxycycline delivery from PLGA microspheres prepared by a modified solvent removal method
Published in Journal of Microencapsulation, 2012
Roshni S. Patel, Daniel Y. Cho, Cheng Tian, Amy Chang, Kenneth M. Estrellas, Danya Lavin, Stacia Furtado, Edith Mathiowitz
We report on the development of a modified solvent removal method for the encapsulation of hydrophilic drugs within poly(lactic-co-glycolic acid) (PLGA). Using a water/oil/oil double emulsion, hydrophilic doxycycline was encapsulated within PLGA spheres with particle diameters ranging from approximately 600 nm to 19 µm. Encapsulation efficiencies of up to 74% were achieved for theoretical loadings from 1% to 10% (w/w), with biphasic release over 85 days with nearly complete release at the end of this time course. About 1% salt was added to the formulations to examine its effects on doxycycline release; salt modulated release only by increasing the magnitude of initial release without altering kinetics. Fourier transform infrared spectroscopy indicated no characteristic differences between doxycycline-loaded and control spheres. Differential scanning calorimetry and X-ray diffraction suggest that there may be a molecular dispersion of the doxycycline within the spheres and the doxycycline may be in an amorphous state, which could explain the slow, prolonged release of the drug.