Synthesis, characterization and antifungal assessment of optically active bis-organotin compounds derived from (S)-BINOL diesters

Background: Organotin(IV) derivatives have appeared recently as potential biologically active metallopharmaceuticals exhibiting a variety of therapeutic activities. Hence, it is important to study the synthesis of new organotin compounds with low toxicity that may be of pharmacological interest.Objectives:This study focuses on the synthesis of new bis-stannylated derivatives with C2 symmetry that could be tested as antifungal agents against two clinical important fungal species, Cryptococcus neoformans and Candida albicans.Methods:The radical addition of triorganotin hydrides (R3SnH) and diorganotin chlorohydrides (R2ClSnH) to bis-α,β-unsaturated diesters derived from (S)-BINOL led to the corresponding new bis-stannylated derivatives with C2 symmetry. Nine pure organotin compounds were synthesized with defined stereochemistry. Four of them were enantiomerically pure and four were diastereoisomeric mixtures.Results:All new organotin compounds were fully characterized, those with phenyl ligands bonded to tin were the most active compounds against both the strains (Cryptococcus neoformans and Candida albicans), with activity parameters of IC50 close to those of the reference drug (amphotericin B).Conclusion:Nine pure organotin compounds with C2 symmetry were synthesized with defined stereochemistry and their antifungal properties were tested against two clinical important fungi with IC values close to those of the reference drug. The structure-containing preferably two or three phenyl groups joined to the tin atom were highly active against both the strains compared with those possessing tri-n-butyl groups.Fil: Costantino, Andrea Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Neudörfl, Jörg M.. Universitat zu Köln; Alemania. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Ocampo, Romina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Svetaz, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Zacchino, Susana Alicia Stella. Universitat zu Köln; AlemaniaFil: Koll, Liliana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; ArgentinaFil: Mandolesi, Sandra Delia. Universidad Nacional del Sur; Argentin

Stepwise synthesis of RNA conjugates carrying peptide sequences for RNA interference studies

Oligoribonucleotide conjugates carrying nuclear localization peptide sequences at the 3?-end were prepared stepwise on a single support. The siRNA duplex carrying the nuclear localization peptide sequence at the 3?-end of the passenger strand has similar inhibitory properties as those of unmodified or cholesterol-modified RNA duplexes.Oligoribonucleotide conjugates carrying nuclear localization peptide sequences at the 3?-end were prepared stepwise on a single support. The siRNA duplex carrying the nuclear localization peptide sequence at the 3?-end of the passenger strand has similar inhibitory properties as those of unmodified or cholesterol-modified RNA duplexes.Peer reviewe

Engineering Iron Oxide Nanoparticles for Clinical Settings

Iron oxide nanoparticles (IONPs) occupy a privileged position among magnetic nanomaterials with potential applications in medicine and biology. They have been widely used in preclinical experiments for imaging contrast enhancement, magnetic resonance, immunoassays, cell tracking, tissue repair, magnetic hyperthermia and drug delivery. Despite these promising results, their successful translation into a clinical setting is strongly dependent upon their physicochemical properties, toxicity and functionalization possibilities. Currently, IONPs-based medical applications are limited to the use of non-functionalized IONPs smaller than 100 nm, with overall narrow particle size distribution, so that the particles have uniform physical and chemical properties. However, the main entry of IONPs into the scene of medical application will surely arise from their functionalization possibilities that will provide them with the capacity to target specific cells within the body, and hence to play a role in the development of specific therapies. In this review, we offer an overview of their basic physicochemical design parameters, giving an account of the progress made in their functionalization and current clinical applications. We place special emphasis on past and present clinical trials

Co-Existence of blaNDM-1, blaOXA-23, blaOXA-64, blaPER-7 and blaADC-57 in a Clinical Isolate of Acinetobacter baumannii from Alexandria, Egypt

The increasing rates of antimicrobial resistance among carbapenem-resistant Acinetobacter baumannii in the Middle East and North Africa are one of the major concerns for healthcare settings. We characterised the first A. baumannii isolate harbouring five β-lactamases identified in Egypt. The isolate Ale25 was obtained from an ICU patient of a hospital from Alexandria. The isolate was phenotypically and genotypically screened for carbapenemase genes. The isolate was resistant to carbapenems, aminoglycosides, fluoroquinolones and cefiderocol. Whole-Genome Sequencing identified five β-lactamase genes, blaNDM-1, blaOXA-23, blaOXA-64, blaPER-7 and blaADC-57, together with other antibiotic resistance genes, conferring resistance to sulfonamides, macrolides, tetracyclines, rifamycin and chloramphenicol. Virulome analysis showed the presence of genes involved in adhesion and biofilm production, type II and VI secretion systems, exotoxins, etc. Multi-Locus Sequence Typing analysis identified the isolate as Sequence Types 113Pas and 2246Oxf, belonging to International Clone 7. Sequencing experiments revealed the presence of four plasmids of 2.7, 22.3, 70.4 and 240.8 Kb. All the β-lactamase genes were located in the chromosome, except the blaPER-7, gene which was found within the plasmid of 240.8 Kb. This study highlights the threat of the emergence and dissemination of these types of isolates.This research was funded by the MINISTRY OF SCIENCE AND INNOVATION (MCIN/AEI/10.13039/501100011033), grant number PID2020-116495RB-I00; the DEPARTMENT OF EDUCATION OF THE BASQUE GOVERNMENT (Research Groups of the Basque University System 2021), grant number Group IT1578-22, GIC21/18; and the ARAB ACADEMY FOR SCIENCE, TECHNOLOGY AND MARITIME TRANSPORT, grant number 2072

Utilidad de las fórmulas CDK-EPI y MDRD-4 para estimar el índice de filtración glomerular en pacientes con patología glomerular

More than 40 formulas have been developed to estimate the glomerular filtration rate (GFR) involving creatinine concentration (Cr) as well as demographic and anthropometric variables. Modification of Diet in Renal Disease (MDRD-4) is the most recommended one. However, several studies state that Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation improves the results obtained with MDRD-4. Our aim was to compare the results of the estimated GFR (eGFR) obtained with both formulas in patients with glomerular pathology. We studied 32 individuals with glomerulopathies, age (mean±SD): 34±8 years old, 24 females (F) and 8 males (M). Cr was assessed by an automated method. Results were expressed as mean±SD. eGFR (ml/min) with CKD-EPI and MDRD-4 were 102±41 and 105±51 respectively; no significant differences were obtained between both formulas (p>0.05). Correlation coefficient between both equations was highly significant (r=0.93; p0.05). We conclude that both formulas could be used indistinctly as estimators of GFR in patients with glomerular pathology. For GFR values > normal values, eGFR with both equations would tend to a poorer correlation, then stratification and comparison of these values with those obtained from Cr clearance are suggested in order to determine which equation would be the best analytical predictor in patients with glomerulopathy and glomerular hyperfiltration.Fil: Pezzarini, Eleonora. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; ArgentinaFil: Rossi, María F. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; ArgentinaFil: Rossi, María F. Provincia de Santa Fe. Hospital Provincial del Centenario. Servicio de Nefrología; ArgentinaFil: Balbi, Bárbara. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; ArgentinaFil: Monje, Adriana L. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; ArgentinaFil: Monje, Adriana L. Provincia de Santa Fe. Hospital Provincial del Centenario. Servicio de Nefrología; ArgentinaFil: Ocampo Alzate, Carlos. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; ArgentinaFil: Basiglio, Cecilia Lorena. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; ArgentinaFil: Basiglio, Cecilia L. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET); ArgentinaFil: Rodenas, M. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; ArgentinaFil: Rodenas, M. Provincia de Santa Fe. Hospital Provincial del Centenario. Servicio de Nefrología; Provincia de Santa Fe. Hospital Provincial del Centenario. Servicio de Nefrología; ArgentinaFil: Daniele, Stella Maris. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; ArgentinaFil: Arriaga, Sandra Mónica María. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; ArgentinaFil: Pelusa, Héctor Fabián. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; Argentin

Utilidad de las fórmulas CDK-EPI y MDRD-4 para estimar el índice de filtración glomerular en pacientes con patología glomerular

More than 40 formulas have been developed to estimate the glomerular filtration rate (GFR) involving creatinine concentration (Cr) as well as demographic and anthropometric variables. Modification of Diet in Renal Disease (MDRD-4) is the most recommended one. However, several studies state that Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation improves the results obtained with MDRD-4. Our aim was to compare the results of the estimated GFR (eGFR) obtained with both formulas in patients with glomerular pathology. We studied 32 individuals with glomerulopathies, age (mean±SD): 34±8 years old, 24 females (F) and 8 males (M). Cr was assessed by an automated method. Results were expressed as mean±SD. eGFR (ml/min) with CKD-EPI and MDRD-4 were 102±41 and 105±51 respectively; no significant differences were obtained between both formulas (p>0.05). Correlation coefficient between both equations was highly significant (r=0.93; p0.05). We conclude that both formulas could be used indistinctly as estimators of GFR in patients with glomerular pathology. For GFR values > normal values, eGFR with both equations would tend to a poorer correlation, then stratification and comparison of these values with those obtained from Cr clearance are suggested in order to determine which equation would be the best analytical predictor in patients with glomerulopathy and glomerular hyperfiltration.Fil: Pezzarini, Eleonora. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; ArgentinaFil: Rossi, María F. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; ArgentinaFil: Rossi, María F. Provincia de Santa Fe. Hospital Provincial del Centenario. Servicio de Nefrología; ArgentinaFil: Balbi, Bárbara. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; ArgentinaFil: Monje, Adriana L. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; ArgentinaFil: Monje, Adriana L. Provincia de Santa Fe. Hospital Provincial del Centenario. Servicio de Nefrología; ArgentinaFil: Ocampo Alzate, Carlos. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; ArgentinaFil: Basiglio, Cecilia Lorena. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; ArgentinaFil: Basiglio, Cecilia L. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET); ArgentinaFil: Rodenas, M. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; ArgentinaFil: Rodenas, M. Provincia de Santa Fe. Hospital Provincial del Centenario. Servicio de Nefrología; Provincia de Santa Fe. Hospital Provincial del Centenario. Servicio de Nefrología; ArgentinaFil: Daniele, Stella Maris. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; ArgentinaFil: Arriaga, Sandra Mónica María. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; ArgentinaFil: Pelusa, Héctor Fabián. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Bioquímica Clínica; Argentin

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO