Classification Framework and Structure-Activity-Relationship (SAR) of Tetracycline-Structure-Based Drugs

By studying the literature about Tetracyclines (TCs), it becomes clearly evident that TCs are very dynamic molecules. In some cases, their structure-activity-relationship (SAR) are known, especially against bacteria, while against other targets, they are virtually unknown. In other diverse yields of research, such as neurology, oncology and virology the utility and activity of the tetracyclines are being discovered and are also emerging as new technological fronts. The first aim of this paper is classify the compounds already used in therapy and prepare the schematic structure in which include the next generation of TCs. The aim of this work is introduce a new framework for the classification of old and new TCs, using a medicinal chemistry approach to the structure of that drugs. A fully documented Structure-Activity-Relationship (SAR) is presented with the analysis data of antibacterial and nonantibacterial (antifungal, antiviral and anticancer) tetracyclines. Lipophilicity of functional groups and conformations interchangeably are determining rules in biological activities of TCs.Comment: 13 pages, 3 figures, 2 schemes, 1 table; http://www.mdpi.com/2079-6382/1/1/

Risks of hospitalization and drug consumption in children and young adults with diagnosed celiac disease and the role of maternal education: A population-based matched birth cohort study

Background: Celiac disease (CD) may affect healthcare use in children and young adults. Socio-economic factors may act as a confounder or effect modifier. We assessed such hypotheses in a population-based birth cohort of young celiac subjects and references matched by maternal education. Methods: The cohort included all newborns recorded in the Medical Birth Register of Friuli-Venezia Giulia Region (Italy) between 1989 and 2011. CD incident cases were identified through pathology reports, hospital discharges and copayment exemptions and matched with up to five references by sex, year of birth and maternal education. Cox regression models were used to estimate Hazard Ratios (HRs) for major causes of inpatient diagnosis and drug prescription occurring after diagnosis in CD patients compared to references, stratifying by time of first event and maternal education. Results: We identified 1294 CD cases and 5681 references. CD cases had a higher risk of hospital admission for any cause (HR: 2.34; 95 % CI 2.08-2.63) and for all major ICD9-CM categories except obstetric complications, skin and musculoskeletal diseases, and injuries and poisoning. Prescription of all major ATC drug categories, except dermatologicals and genito-urinary medications, was significantly increased in CD subjects. For most outcomes, HRs were highest in the first year after CD diagnosis but remained significant after five or more years. HRs were similar across different categories of maternal education. Conclusions: Diagnosed CD subjects had a higher risk of hospitalization and medication use compared to the general population, even five or more years after diagnosis, with no effect modification of maternal education

Current and evolving approaches for improving the oral permeability of BCS Class III or analogous molecules

The Biopharmaceutics Classification System (BCS) classifies pharmaceutical compounds based on their aqueous solubility and intestinal permeability. The BCS Class III compounds are hydrophilic molecules (high aqueous solubility) with low permeability across the biological membranes. While these compounds are pharmacologically effective, poor absorption due to low permeability becomes the rate-limiting step in achieving adequate bioavailability. Several approaches have been explored and utilized for improving the permeability profiles of these compounds. The approaches include traditional methods such as prodrugs, permeation enhancers, ion-pairing, etc., as well as relatively modern approaches such as nanoencapsulation and nanosizing. The most recent approaches include a combination/hybridization of one or more traditional approaches to improve drug permeability. While some of these approaches have been extremely successful, i.e. drug products utilizing the approach have progressed through the USFDA approval for marketing; others require further investigation to be applicable. This article discusses the commonly studied approaches for improving the permeability of BCS Class III compounds

Phytotherapy in zoo animals

Phytotherapy is one of the oldest medical disciplines and was traditionally based on empiricism (Reichling et al., 2008). Nowadays, its use as an additional integral component of evidence based medicine is well accepted in human medicine (Finkelmann, 2009). Herbal remedies are generally characterised by a broad therapeutic index. They consist of multicomponent mixtures and act as multi-target drugs with pleiotropic effects. In Switzerland, veterinary phytotherapy has been relaunched in 2006 as a subunit of the Swiss Medical Society for Phytotherapy (SMGP-vet). Since 2012, the certificate of qualification in veterinary phytotherapy has been approved by the Swiss Veterinary Association (GST/SVS). Historically, one of the common approaches to gain insight into the medical effects of plants was self-medication. In non-human animals, self medication remains a controversial subject, because evidence is mostly anecdotal. A few experimentally verified cases of self-medication support the theoretical expectation that animals can and do make specific foraging decisions that function specifically to remediate illness (Huffman and Caton, 2001; Villalba et al., 2006; Singer et al., 2009). In zoological medicine, this concept has first been implemented by primate keeping institutions. Permanent access to selected medicinal plants suggested self medication and helped maintain the health of certain primate species (Cousins, 2006)

The RCSB Protein Data Bank: views of structural biology for basic and applied research and education.

The RCSB Protein Data Bank (RCSB PDB, http://www.rcsb.org) provides access to 3D structures of biological macromolecules and is one of the leading resources in biology and biomedicine worldwide. Our efforts over the past 2 years focused on enabling a deeper understanding of structural biology and providing new structural views of biology that support both basic and applied research and education. Herein, we describe recently introduced data annotations including integration with external biological resources, such as gene and drug databases, new visualization tools and improved support for the mobile web. We also describe access to data files, web services and open access software components to enable software developers to more effectively mine the PDB archive and related annotations. Our efforts are aimed at expanding the role of 3D structure in understanding biology and medicine

Elevated serum levels of macrophage migration inhibitory factor and stem cell growth factor β in patients with idiopathic and systemic sclerosis associated pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) can be idiopathic or secondary to autoimmune diseases, and it represents one of the most threatening complications of systemic sclerosis (SSc). Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with proinflammatory functions that appears to be involved in the pathogenesis of hypoxia-induced PH. In SSc patients, high serum levels of MIF have been associated with the development of ulcers and PAH. Stem cell growth factor β (SCGF β) is a human growth factor that, together with MIF, is involved in the pathogenesis of chronic spinal cord injury. The aim of our study was to measure serum levels of MIF in patients with idiopathic and SSc-associated PAH. We enrolled 13 patients with idiopathic PAH and 15 with SSc-associated PAH. We also selected 14 SSc patients without PAH and 12 normal healthy controls, matched for sex and age. PAH was confirmed by right hearth catheterism (mPAP>25 mmHg). MIF and SCGF β levels were measured by ELISA. We found significantly higher circulating levels of MIF and of SCGF β in patients with idiopathic PAH (P=0.03 and P=0.004) and with PAH secondary to SSc (P=0.018 and P=0.023) compared to SSc patients without PAH. Higher levels of MIF were found in those patients with an higher New York Heart Association (NYHA) class (P=0.03). We can hypothesize that MIF and SCGF β are able to play a role in PAH, both idiopathic or secondary, and in the future they may be evaluated as useful biomarkers and prognostic factors for this serious vascular disease

Drug-therapy networks and the predictions of novel drug targets

Recently, a number of drug-therapy, disease, drug, and drug-target networks have been introduced. Here we suggest novel methods for network-based prediction of novel drug targets and for improvement of drug efficiency by analysing the effects of drugs on the robustness of cellular networks.Comment: This is an extended version of the Journal of Biology paper containing 2 Figures, 1 Table and 44 reference

Recent advances in smart biotechnology: Hydrogels and nanocarriers for tailored bioactive molecules depot

Over the past ten years, the global biopharmaceutical market has remarkably grown, with ten over the top twenty worldwide high performance medical treatment sales being biologics. Thus, biotech R&D (research and development) sector is becoming a key leading branch, with expanding revenues. Biotechnology offers considerable advantages compared to traditional therapeutic approaches, such as reducing side effects, specific treatments, higher patient compliance and therefore more effective treatments leading to lower healthcare costs. Within this sector, smart nanotechnology and colloidal self-assembling systems represent pivotal tools able to modulate the delivery of therapeutics. A comprehensive understanding of the processes involved in the self assembly of the colloidal structures discussed therein is essential for the development of relevant biomedical applications. In this review we report the most promising and best performing platforms for specific classes of bioactive molecules and related target, spanning from siRNAs, gene/plasmids, proteins/growth factors, small synthetic therapeutics and bioimaging probes.Istituto Italiano di Tecnologia (IIT)COST Action [CA 15107]People Program (Marie Curie Actions) of the European Union's Seventh Framework Program under REA [606713 BIBAFOODS]Portuguese Foundation for Science and Technology (FCT) [PTDC/AGR-TEC/4814/2014, IF/01005/2014]Fundacao para a Ciencia e Tecnologia [SFRH/BPD/99982/2014]Danish National Research Foundation [DNRF 122]Villum Foundation [9301]Italian Ministry of Instruction, University and Research (MIUR), PRIN [20109PLMH2]"Fondazione Beneficentia Stiftung" VaduzFondo di Ateneo FRAFRAinfo:eu-repo/semantics/publishedVersio