Mutation in Ribosomal Protein S5 Leads to Spectinomycin Resistance in Neisseria Gonorrhoeae.

Mutation in ribosomal protein S5 leads to spectinomycin resistance in Neisseria gonorrhoeae.

Front Microbiol. 2013; 4: 186
Ilina EN, Malakhova MV, Bodoev IN, Oparina NY, Filimonova AV, Govorun VM

Spectinomycin remains a useful reserve option for therapy of gonorrhea. The emergence of multidrug-resistant Neisseria gonorrhoeae strains with decreased susceptibility to cefixime and to ceftriaxone makes it the only medicine still effective for treatment of gonorrhea infection in analogous cases. However, adoption of spectinomycin as a routinely used drug of choice was soon followed by reports of spectinomycin resistance. The main molecular mechanism of spectinomycin resistance in N. gonorrhoeae was C1192T substitution in 16S rRNA genes. Here we reported a Thr-24?Pro mutation in ribosomal protein S5 (RPS5) found in spectinomycin resistant clinical N. gonorrhoeae strain, which carried no changes in 16S rRNA. In a series of experiments, the transfer of rpsE gene allele encoding the mutant RPS5 to the recipient N. gonorrhoeae strains was analyzed. The relatively high rate of transformation [ca. 10(-5) colony-forming units (CFUs)] indicates the possibility of spread of spectinonycin resistance within gonococcal population due to the horizontal gene transfer (HGT). HubMed – drug

Dare to Delay? The Impacts of Adolescent Alcohol and Marijuana Use Onset on Cognition, Brain Structure, and Function.

Front Psychiatry. 2013; 4: 53
Lisdahl KM, Gilbart ER, Wright NE, Shollenbarger S

Throughout the world, drug and alcohol use has a clear adolescent onset (Degenhardt et al., 2008). Alcohol continues to be the most popular drug among teens and emerging adults, with almost a third of 12th graders and 40% of college students reporting recent binge drinking (Johnston et al., 2009, 2010), and marijuana (MJ) is the second most popular drug in teens (Johnston et al., 2010). The initiation of drug use is consistent with an overall increase in risk-taking behaviors during adolescence that coincides with significant neurodevelopmental changes in both gray and white matter (Giedd et al., 1996a; Paus et al., 1999; Sowell et al., 1999, 2002, 2004; Gogtay et al., 2004; Barnea-Goraly et al., 2005; Lenroot and Giedd, 2006). Animal studies have suggested that compared to adults, adolescents may be particularly vulnerable to the neurotoxic effects of drugs, especially alcohol and MJ (see Schneider and Koch, 2003; Barron et al., 2005; Monti et al., 2005; Cha et al., 2006; Rubino et al., 2009; Spear, 2010). In this review, we will provide a detailed overview of studies that examined the impact of early adolescent onset of alcohol and MJ use on neurocognition (e.g., Ehrenreich et al., 1999; Wilson et al., 2000; Tapert et al., 2002a; Hartley et al., 2004; Fried et al., 2005; Townshend and Duka, 2005; Medina et al., 2007a; McQueeny et al., 2009; Gruber et al., 2011, 2012; Hanson et al., 2011; Lisdahl and Price, 2012), with a special emphasis on recent prospective longitudinal studies (e.g., White et al., 2011; Hicks et al., 2012; Meier et al., 2012). Finally, we will explore potential clinical and public health implications of these findings. HubMed – drug

Alternative functional in vitro models of human intestinal epithelia.

Front Pharmacol. 2013; 4: 79
Kauffman AL, Gyurdieva AV, Mabus JR, Ferguson C, Yan Z, Hornby PJ

Physiologically relevant sources of absorptive intestinal epithelial cells are crucial for human drug transport studies. Human adenocarcinoma-derived intestinal cell lines, such as Caco-2, offer conveniences of easy culture maintenance and scalability, but do not fully recapitulate in vivo intestinal phenotypes. Additional sources of renewable physiologically relevant human intestinal cells would provide a much needed tool for drug discovery and intestinal physiology. We compared two alternative sources of human intestinal cells, commercially available primary human intestinal epithelial cells (hInEpCs) and induced pluripotent stem cell (iPSC)-derived intestinal cells to Caco-2, for use in in vitro transwell monolayer intestinal transport assays. To achieve this for iPSC-derived cells, intestinal organogenesis was adapted to transwell differentiation. Intestinal cells were assessed by marker expression through immunocytochemical and mRNA expression analyses, monolayer integrity through Transepithelial Electrical Resistance (TEER) measurements and molecule permeability, and functionality by taking advantage the well-characterized intestinal transport mechanisms. In most cases, marker expression for primary hInEpCs and iPSC-derived cells appeared to be as good as or better than Caco-2. Furthermore, transwell monolayers exhibited high TEER with low permeability. Primary hInEpCs showed molecule efflux indicative of P-glycoprotein (Pgp) transport. Primary hInEpCs and iPSC-derived cells also showed neonatal Fc receptor-dependent binding of immunoglobulin G variants. Primary hInEpCs and iPSC-derived intestinal cells exhibit expected marker expression and demonstrate basic functional monolayer formation, similar to or better than Caco-2. These cells could offer an alternative source of human intestinal cells for understanding normal intestinal epithelial physiology and drug transport. HubMed – drug

Is abeta a sufficient biomarker for monitoring anti-abeta clinical studies? A critical review.

Front Aging Neurosci. 2013; 5: 25
Moreth J, Mavoungou C, Schindowski K

Amyloid-beta (A?) in Alzheimer’s disease (AD) appeared to be a promising target for disease-modifying therapeutic strategies like passive immunotherapy with anti-A? monoclonal antibodies (mAbs). Biochemical markers in cerebrospinal fluid (CSF) include alterations of A? that allow the diagnosis of AD. Biomarker strategies, such as the levels of A? in CSF and plasma, currently play an important role in early clinical trials for AD. Indeed, these strategies have a relevant impact on the outcome of such studies, since the biomarkers are used to monitor the bioactivity of anti-A? mAbs. The clinical trials of Solanezumab were mainly based on the readout of A? levels in CSF and plasma, whereas those of Bapineuzumab were based on cognition; however, little is known about the mechanisms altering these biomarker levels, and no biomarker has yet been proven to be a successful predictor for AD therapy. In addition, the A? biomarkers allow for the determination of free and bound anti-A? mAb in order to monitor the available amount of bioactive drug and could give hints to the mechanism of action. In this review, we discuss clinical A? biomarker data and the latest regulatory strategies. HubMed – drug