Detección de anticuerpos séricos contra Toxoplasma gondii (Nicolle y Manceaux, 1909) en llamas (Lama glama Linneaus, 1758) y alpacas (Lama pacos Linneaus, 1758 ) de Chile.

Sera samples from 113 Ilamas (Lama glama) and 127 alpacas (Lama pacos) from the IX and V Regions, respectively, of Chile were tested for Toxoplasma gondii antibodies. The modified agglutination test (MAT) was used in both species and titers 1:25 were considered diagnostically significant based in previously published data. Sera from 49 lamas (43.3%) and 15 alpacas (11.8%) were positive to T. gondii. Percentaje seropositivity in serum dilutions of 1:25, 1:50, 1:500 and 1:5000 was 17.6%; 7.9%; 14.1% and 3.5% in lamas and 0%; 2.3%; 0.7% and 8.6% in alpacas, respectively. The rather low prevalence in alpacas may be associated with geographical conditions, management practices or contacts with cats rather than different species susceptibility. As expected, older animals showed higher reactivity of T. gondii than young animals.Se obtuvieron 113 sueros de llamas y 127 de alpacas de criaderos ubicados en la IX y V Regiones del país respectivamente para determinar la presencia de infección de T. gondii. Para el análisis de los sueros se utilizó el "test" modificado de aglutinación (MAT) a diluciones 1:25; 1:50, 1:500; 1:5000. Del total de 113 sueros de llamas estudiados 49 (43,3%) de ellas presentaron anticuerpos contra T. gondii, mientras que en las alpacas 15 de las 127 (11,8%) fueron positivas. El número de animales positivos en las diluciones 1/25; 1/50; 1/500; 1/5000 fue de 20 (17,6%); 9 (7,9%); 16 (10,6%); 4 (3,5%) en las llamas, respectivamente. En las alpacas los valores fueron de 0 (0%); 3 (2,3%); 1 (0,7%); 11 (8,6%), respectivamente. Aunque no existen antecedentes clínicos de la infección en los establecimientos estudiados, su potencial implicancia en este tipo de patología debería ser considerada a base de los resultados del presente trabajo que demuestra que llamas y alpacas del centro-sur de Chile son reaccionantes a la infección por T. gondii

Solvents to Fragments to Drugs: MD Applications in Drug Design

Simulations of molecular dynamics (MD) are playing an increasingly important role in structure-based drug discovery (SBDD). Here we review the use of MD for proteins in aqueous solvation, organic/aqueous mixed solvents (MDmix) and with small ligands, to the classic SBDD problems: Binding mode and binding free energy predictions. The simulation of proteins in their condensed state reveals solvent structures and preferential interaction sites (hot spots) on the protein surface. The information provided by water and its cosolvents can be used very effectively to understand protein ligand recognition and to improve the predictive capability of well-established methods such as molecular docking. The application of MD simulations to the study of the association of proteins with drug-like compounds is currently only possible for specific cases, as it remains computationally very expensive and labor intensive. MDmix simulations on the other hand, can be used systematically to address some of the common tasks in SBDD. With the advent of new tools and faster computers we expect to see an increase in the application of mixed solvent MD simulations to a plethora of protein targets to identify new drug candidates

Hydrophobic waters in bromodomains

Targeting epigenetic proteins is a rapidly growing area for medicinal chemistry and drug discovery. Recent years have seen an explosion of interest in developing small molecules binding to bromodomains due to their implication in cancer, inflammation, and a plethora of diseases. Several small-molecule inhibitors and degraders that target bromodomains have entered the clinic, and many more are increasingly being used as chemical probes to describe bromodomain biology. From a structural point of view, crystallographic studies of bromodomains describe, as a common feature, five water molecules as an integral part of the acetyl-lysine binding pocket. These water molecules are essential in druggability and are described as a functional part of the protein [1,2]. In this framework, we focused our attention on the description of the hydrophilic/hydrophobic character of these molecules, which seem to create a favorable environment for the recognition of hydrophobic groups. To this end, and following fragment-based drug design techniques, here we describe a new family of small molecules with a 5-phenylthiazolo[2,3-c][1,2,4]triazol nucleus and probe the water site with various substituents at the 3-position endowing hydrophilic or hydrophobic properties. In this work, we present the theoretical calculations, the synthesis of the new compounds, the results of differential scanning fluorimetry (DSF) and isothermal titration calorimetry (ITC), and the crystal structures of three of our compounds with the target protein. The study sheds light on the counterintuitive behavior of the water molecules in this particular environment

Emergence of unusual human rotavirus strains in Salento, Italy, during 2006–2007

<p>Abstract</p> <p>Background</p> <p>In recent years, rotavirus genotyping by RT-PCR has provided valuable information about the diversity of rotaviruses (RV) circulating throughout the world.</p> <p>The purpose of the present study was to monitor the prevalence of the different G and P genotypes of rotaviruses circulating in Salento and detect any uncommon or novel types.</p> <p>Methods</p> <p>During the period from January 2006 to December 2007, a total of 243 rotavirus positive stool samples were collected from children with diarrhoea admitted to four Hospitals in the province of Lecce (Copertino, Galatina, Gallipoli and Tricase).</p> <p>All the specimens were tested for RV by real time PCR and genotyped for VP7 (G-type) and VP4 (P-type) gene by reverse transcription (RT) and multiplex PCR using different type specific primers.</p> <p>Results</p> <p>In course of this study we identified 4 common G&P combinations viz. G2P[8], G1P[8], G2P[4] and G9P[8] amongst 59.8% of the typeable rotavirus positives.</p> <p>Rotavirus G2P[8] was recognized as the most widespread genotype during the sentinel-based survey in Salento.</p> <p>The detection of other novel and unusual strains, such as G2P[10], G4P[10], G8P[4], G9P[11] and G10P[8] is noteworthy.</p> <p>Furthermore, a significant number of mixed infections were observed during the survey period but G3P[8] rotaviruses were not detected.</p> <p>Conclusion</p> <p>This study highlights the genetic diversity among rotaviruses isolated from children in Salento and the emergence of some novel strains. Therefore, it is highly essential to continuously monitor for these strains so as to assess the impact of vaccines on RV strains circulating in Salento and understand the effect of strain variation on efficacy of presently available vaccines.</p

Infection by the hepatitis C virus in chronic renal failure patients undergoing hemodialysis in Mato Grosso state, central Brazil: a cohort study

BACKGROUND: Hepatitis C virus (HCV) is a significant problem for patients undergoing hemodialysis therapy. This situation has never been studied in Mato Grosso state, central Brazil. This study was conducted aiming to estimate the prevalence of the anti-HCV and the incidence of seroconversion in the main metropolitan region of the state. METHODS: 433 patients from the six hemodialysis units were interviewed and anti-HCV was tested by a third-generation enzyme immunoassay. An open cohort of patients who tested negative for anti-HCV at the entry of the study was created and seroconversions was assessed monthly. The staff responsible for the units were interviewed to assess whether the infection control measures were being followed. Logistic and Cox regression analysis were performed in order to assess risk factor to HCV. RESULTS: The entry on the study took place between January 2002 and June 2005. 73 out of 433 (16.9%, CI95%: 13.3–20.8) was found to be anti-HCV reactive. The multivariate analysis indicated as risk factors associated to anti-HCV the duration of the hemodialysis treatment, the number of transfusions received, and the unit of treatment. An open cohort of 360 patients who tested negative for anti-HCV was created, with a following average of 24 (± 15) months. Forty seroconversions were recorded corresponding to an incidence density of 4.6/1000 patient-months, ranges 0 to 30 among the units. Cox regression indicated the time of hemodialysis (RR = 2.2; CI95%: 1.1–4.6; p < 0.05) and the unit where treatment was performed (RR = 42.4; CI95%: 9.9–180.5; p < 0.05) as risk factors for seroconversion. The three units with highest anti-HCV prevalence and incidence were identified as those that more frequently failed to apply control measures. CONCLUSION: The study demonstrated high prevalence and incidence of anti-HCV in some of the hemodialysis units. Time on hemodialysis therapy was an independent factor associated to HCV. Blood transfusion was associated with anti-HCV in initial survey but was not important in incident cases. Failure of applying control meaures was more evident in units with the highest HCV prevalence and incidence. The results suggest that nosocomial transmission was the main spread factor of HCV in the studied population

Miniatures from domestic contexts in Iron age Iberia

This article reviews a set of miniatures from domestic contexts in Iron Age eastern Iberia, and interprets them in terms of their role in forging social personae. After an introduction to the historical case under consideration, the miniatures are described in terms of their typology and their contexts of provenance are outlined. Though not abundant, they tend to occur in central places in the landscape; specifically, they are often found in houses of the powerful. The vast majority are miniatures of pottery and tools, though some miniature weapons are recorded. We contend that these objects were used as a means of enculturation and for the learning of values and norms. It is no coincidence that they emerge in the archaeological record of Iron Age Iberia at the same time as the rise of a social structure based on hereditary power

Acute hepatitis C virus infection assessment among chronic hemodialysis patients in the Southwest Parana State, Brazil

BACKGROUND: Chronic hemodialysis patients are at higher risk for acquiring hepatitis C virus (HCV). The prevalence varies among different countries and hemodialysis centers. Although guidelines for a comprehensive infection control program exist, the nosocomial transmission still accounts for the new cases of infection. The aim of this study was analyze the follow up of newly acquired acute hepatitis C cases, during the period from January 2002 to May 2005, in the Hemodialysis Center, located in the Southwest region of Parana State, Brazil and to analyze the effectiveness of the measures to restrain the appearance of new cases of acute hepatitis C. METHODS: Patients were analyzed monthly with anti-HCV tests and ALT measurements. Patients with ALT elevations were monitored for possible acute hepatitis C. RESULTS: During this period, 32 new cases were identified with acute hepatitis C virus infection. Blood screening showed variable ALT levels preceding the anti-HCV seroconversion. HCV RNA viremia by PCR analysis was intermittently and even negative in some cases. Ten out of 32 patients received 1 mcg/kg dose of pegylated interferon alfa-2b treatment for 24 weeks. All dialysis personnel were re-trained to strictly follow the regulations and recommendations regarding infection control, proper methods to clean and disinfect equipment were reviewed and HCV-positive patients were isolated. CONCLUSION: Laboratory tests results showed variable ALT preceding anti-HCV seroconversion and intermittent viremia. The applied recommendations contributed importantly to restrain the appearance of new cases of acute hepatitis C in this center and the last case was diagnosed in May 2004

Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb/V and dialysis in Spanish clinical practice – preliminary data Vie-KinD study

Poster presentatio

Mechanically assisted electrochemical degradation of alumina-TiC composites

Alumina-TiC composite material is a tough ceramic composite with excellent hardness, wear resistance and oxidation resistance in dry and high-temperature conditions. In aqueous conditions, however, it is likely to be electrochemically active facilitating charge transfer processes due to the conductive nature of TiC. For application as an orthopedic biomaterial, it is crucial to assess the electrochemical behavior of this composite, especially under a combined mechanical and electrochemical environment. In this study, we examined the mechanically assisted electrochemical performance of alumina-TiC composite in an aqueous environment. The spontaneous electrochemical response to brushing abrasion was measured. Changes in the magnitude of electrochemical current with abrasion test conditions and possible causal relationship to the alteration in surface morphology were examined. Results showed that the alumina matrix underwent abrasive wear with evidence of microploughing and grain boundary damage. Chemical analysis revealed TiO2 formation in the abraded region, indicating oxidation of the conductive TiC domain. Furthermore, wear debris from alumina abrasion appeared to affect reaction kinetics at the composite-electrolyte interface. From this work, we established that the composite undergoes abrasion assisted electrochemical degradation even in gentle abrasive conditions and the severity of degradation is related to temperature and conditions of test environment

Thermodynamics of Aryl-Dihydroxyphenyl-Thiadiazole Binding to Human Hsp90

The design of specific inhibitors against the Hsp90 chaperone and other enzyme relies on the detailed and correct understanding of both the thermodynamics of inhibitor binding and the structural features of the protein-inhibitor complex. Here we present a detailed thermodynamic study of binding of aryl-dihydroxyphenyl-thiadiazole inhibitor series to recombinant human Hsp90 alpha isozyme. The inhibitors are highly potent, with the intrinsic Kd approximately equal to 1 nM as determined by isothermal titration calorimetry (ITC) and thermal shift assay (TSA). Dissection of protonation contributions yielded the intrinsic thermodynamic parameters of binding, such as enthalpy, entropy, Gibbs free energy, and the heat capacity. The differences in binding thermodynamic parameters between the series of inhibitors revealed contributions of the functional groups, thus providing insight into molecular reasons for improved or diminished binding efficiency. The inhibitor binding to Hsp90 alpha primarily depended on a large favorable enthalpic contribution combined with the smaller favorable entropic contribution, thus suggesting that their binding was both enthalpically and entropically optimized. The enthalpy-entropy compensation phenomenon was highly evident when comparing the inhibitor binding enthalpies and entropies. This study illustrates how detailed thermodynamic analysis helps to understand energetic reasons for the binding efficiency and develop more potent inhibitors that could be applied for therapeutic use as Hsp90 inhibitors