Estudios de acoplamiento molecular de nuevos análogos de quinolonas a la ADN girasa de Escherichia coli

Indexación: Scopus.Chemicals and CAS Registry Numbers: amino acid, 65072-01-7; ciprofloxacin, 85721-33-1; DNA topoisomerase (ATP hydrolysing); gatifloxacin, 112811-59-3, 180200-66-2; levofloxacin, 100986-85-4, 138199-71-0; lomefloxacin, 98079-51-7; moxifloxacin, 151096-09-2; nalidixic acid, 389-08-2; oxolinic acid, 14698-29-4; pipemidic acid, 51940-44-4; rufloxacin, 101363-10-4; sitafloxacin, 127254-12-0, 163253-35-8Context: Bacterial resistance to antibiotics is the inevitable consequence of the use of antimicrobial agents. Thus, quinolones are an important class of antibacterials; these agents generally consist of a 1-subtituted-1,4-dihydro-4-oxopyridine-3-carboxylic acid moiety combined with an aromatic or heteroaromatic ring fused at the 5- and 6-position. Aims: To determine the binding of quinolones to DNA gyrase of Escherichia coli. Methods: An analysis was performed using an in silico approach to determine, by docking calculations and energy descriptors, the conformer of 4‐oxo‐1,4‐dihydroquinoline skeleton that forms the most stable complex with DNA gyrase of E. coli. Results: The complex shows that the pose of the quinolones coincides with the amino acid residues Asp87, Thr88, Arg91 and Met92, which is expected to be critical in the binding of quinolones to DNA gyrase of E. coli. A series of quinolones were computationally designed, and the interactions between the quinolones and the amino acid residues of the DNA gyrase were calculated. Conclusions: Among the designed compounds, compounds 105 and 115 exhibit higher binding energy values and interact with amino acids Asp87, Thr88, Arg91 and Met92. © 2018 Journal of Pharmacy & Pharmacognosy Research.http://jppres.com/jppres/pdf/vol6/jppres18.368_6.5.386.pd

The raw material procurement at the Upper Palaeolithic settlements of the Côa Valley (Portugal): new data concerning modes of resource exploitation in Iberia

info:eu-repo/semantics/publishedVersio

VO2 indirect maximum and fitness age of sedentary and non-sedentary

El objetivo es: comparar la edad cronológica con la edad fitness obtenida por medio del VO2 máximo indirecto, de un grupo de personas sedentarias y no sedentarias. Método: 253 personas fueron evaluadas respecto a masa corporal, estatura, perímetro de cintura, frecuencia cardiaca basal y un cuestionario del modelo web "Fitness Calculator". Los resultados demostraron diferencias significativas en las variables antropométricas y fisiológicas entre personas sedentarias y no sedentarias (P<,001). Las personas no sedentarias tienen un mayor VO2máx en comparación con las personas sedentarias. Las personas sedentarias indican que presentan una edad fitness que se encuentra sobre 12 años cronológicos promedio de lo esperado. Conclusión: Las personas sedentarias tienen una mayor edad fitness, esto permite establecer que su cuerpo se deteriora más rápido que los no sedentarios. El bajo VO2 máx es un potente predictor de la capacidad cardiorrespiratoria y se establece como un predictor de enfermedades cardiovascularesThe purpose was to compare chronological age with fitness age obtained through indirect VO2max in a group of sedentary and non-sedentary people. Method: 253 people were evaluated for body mass, height, waist circumference, basal heart rate and a web model questionnaire "Fitness Calculator". The results: showed significant differences in anthropometric and physiological variables between sedentary and non-sedentary people (P <.001). Non- Sedentary people have a greater higher VO2máx group compared to sedentary people. This indicates that sedentary people have a fitness age 12 years over their expected chronological average age. Conclusion: Sedentary people have a higher fitness age; therefore your body deteriorates faster than the nonsedentary people. A low level of VO2máx is a powerful predictor of cardiorespiratory capacity and of cardiovascular diseasesEl estudio fue financiado por la Escuela de Kinesiología de la Universidad Bernardo O`higgin

Frankenstein’s problem

This text is based on an invited address presented at IFIP 8.2 ‘Living with Monsters’ in San Francisco, CA, 11 December 2018. Taking the 200th anniversary of Mary Wollstonecraft Shelley’s Frankenstein as a starting place, I explore questions of autonomy and control with respect to human/technology relations. I consider the ambivalence of these agencies, and recent initiatives in science and technology studies and related fields to reconceptualize the problem as matters of relation and care. While embracing this turn, I reflect as well upon the ambivalences of relation and care, and the need to address the resilient politics of alterity in our figurations (and celebrations) of the monstrous

Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarisations and fibrillation

Aims: Atrial fibrillation (AF) is increased in patients with heart failure resulting from myocardial infarction (MI). We aimed to determine the effects of chronic ventricular MI in rabbits on the susceptibility to AF, and underlying atrial electrophysiological and Ca2+-handling mechanisms. Methods and results: In Langendorff-perfused rabbit hearts, under beta-adrenergic-stimulation with isoproterenol (1 µM; ISO), 8 weeks MI decreased AF threshold, indicating increased AF-susceptibility. This was associated with increased atrial action potential duration-alternans at 90% repolarisation, by 147%, and no significant change in mean APD or atrial global conduction velocity (n=6-13 non-MI hearts, 5-12 MI). In atrial isolated myocytes, also under beta-stimulation, L-type Ca2+ current (ICaL) density and intracellular Ca2+-transient amplitude were decreased by MI, by 35% and 41%, respectively, and the frequency of spontaneous depolarisations (SDs) was substantially increased. MI increased atrial myocyte size and capacity, and markedly decreased transverse-tubule density. In non-MI hearts perfused with ISO, the ICaL-blocker nifedipine, at a concentration (0.02 µM) causing an equivalent ICaL-reduction (35%) to that from the MI, did not affect AF-susceptibility, and decreased APD. Conclusion: chronic MI in rabbits remodels atrial structure, electrophysiology and intracellular Ca2+-handling. Increased susceptibility to AF by MI, under beta-adrenergic-stimulation, may result from associated production of atrial APD-alternans and SDs, since steady-state APD and global conduction velocity were unchanged under these conditions, and may be unrelated to the associated reduction in whole-cell ICaL. Future studies may clarify potential contributions of local conduction changes, and cellular and sub-cellular mechanisms of alternans, to the increased AF-susceptibility

Treatment of secondary hyperparathyroidism in haemodialysis patients: a randomised clinical trial comparing paricalcitol and alfacalcidol

<p>Abstract</p> <p>Background</p> <p>Secondary hyperparathyroidism is a common feature in patients with chronic kidney disease. Its serious clinical consequences include renal osteodystrophy, calcific uremic arteriolopathy, and vascular calcifications that increase morbidity and mortality.</p> <p>Reduced synthesis of active vitamin D contributes to secondary hyperparathyroidism. Therefore, this condition is managed with activated vitamin D. However, hypercalcemia and hyperphosphatemia limit the use of activated vitamin D.</p> <p>In Denmark alfacalcidol is the primary choice of vitamin D analog.</p> <p>A new vitamin D analog, paricalcitol, may be less prone to induce hypercalcemia and hyperphosphatemia.</p> <p>However, a randomised controlled clinical study comparing alfacalcidol and paricalcitol has never been performed.</p> <p>The primary objective of this study is to compare alfacalcidol and paricalcitol. We evaluate the suppression of the secondary hyperparathyroidism and the tendency towards hyperphosphatemia and hypercalcemia.</p> <p>Methods/Design</p> <p>This is an investigator-initiated cross-over study. Nine Danish haemodialysis units will recruit 117 patients with end stage renal failure on maintenance haemodialysis therapy.</p> <p>Patients are randomised into two treatment arms. After a wash out period of 6 weeks they receive increasing doses of alfacalcidol or paricalcitol for a period of 16 weeks and after a further wash out period of 6 weeks they receive the contrary treatment (paricalcitol or alfacalcidol) for 16 weeks.</p> <p>Discussion</p> <p>Hyperparathyroidism, hypercalcemia and hyperphosphatemia are associated with increased cardiovascular mortality in patients with chronic kidney disease.</p> <p>If there is any difference in the ability of these two vitamin D analogs to decrease the secondary hyperparathyroidism without causing hypercalcemia and hyperphosphatemia, there may also be a difference in the risk of cardiovascular mortality depending on which vitamin D analog that are used. This has potential major importance for this group of patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT004695</p

Mineral analysis of complete dog and cat foods in the UK and compliance with European guidelines

Mineral content of complete pet food is regulated to ensure health of the companion animal population. Analysis of adherence to these regulatory guidelines has not been conducted. Here, mineral composition of complete wet (n = 97) and dry (n = 80) canine and feline pet food sold in the UK was measured to assess compliance with EU guidelines. A majority of foods complied with ≥8 of 11 guidelines (99% and 83% for dry and wet food, respectively), but many failed to provide nutritional minimum (e.g. Cu, 20% of wet food) or exceeded nutritional maximum (e.g. Se, 76% of wet food). Only 6% (6/97) of wet and 38% (30/80) of dry food were fully compliant. Some foods (20–30% of all analysed) had mineral imbalance, such as not having the recommended ratio of Ca:P (between 1:1 to 2:1). Foods with high fish content had high levels of undesirable metal elements such as arsenic. This study highlights broad non-compliance of a range of popular pet foods sold in the UK with EU guidelines (94% and 61% of wet and dry foods, respectively). If fed exclusively and over an extended period, a number of these pet foods could impact the general health of companion animals

Detection, Properties, and Frequency of Local Calcium Release from the Sarcoplasmic Reticulum in Teleost Cardiomyocytes

Calcium release from the sarcoplasmic reticulum (SR) plays a central role in the regulation of cardiac contraction and rhythm in mammals and humans but its role is controversial in teleosts. Since the zebrafish is an emerging model for studies of cardiovascular function and regeneration we here sought to determine if basic features of SR calcium release are phylogenetically conserved. Confocal calcium imaging was used to detect spontaneous calcium release (calcium sparks and waves) from the SR. Calcium sparks were detected in 16 of 38 trout atrial myocytes and 6 of 15 ventricular cells. The spark amplitude was 1.45±0.03 times the baseline fluorescence and the time to half maximal decay of sparks was 27±3 ms. Spark frequency was 0.88 sparks µm−1 min−1 while calcium waves were 8.5 times less frequent. Inhibition of SR calcium uptake reduced the calcium transient (F/F0) from 1.77±0.17 to 1.12±0.18 (p = 0.002) and abolished calcium sparks and waves. Moreover, elevation of extracellular calcium from 2 to 10 mM promoted early and delayed afterdepolarizations (from 0.6±0.3 min−1 to 8.1±2.0 min−1, p = 0.001), demonstrating the ability of SR calcium release to induce afterdepolarizations in the trout heart. Calcium sparks of similar width and duration were also observed in zebrafish ventricular myocytes. In conclusion, this is the first study to consistently report calcium sparks in teleosts and demonstrate that the basic features of calcium release through the ryanodine receptor are conserved, suggesting that teleost cardiac myocytes is a relevant model to study the functional impact of abnormal SR function

Evaluation of different bowel preparations for small bowel capsule endoscopy: a prospective, randomized, controlled study

To obtain an adequate view of the whole small intestine during capsule endoscopy (CE) a clear liquid diet and overnight fasting is recommended. However, intestinal content can hamper vision in spite of these measures. Our aim was to evaluate tolerance and degree of intestinal cleanliness during CE following three types of bowel preparation. PATIENTS AND METHODS: This was a prospective, multicenter, randomized, controlled study. Two-hundred ninety-one patients underwent one of the following preparations: 4 L of clear liquids (CL) (group A; 92 patients); 90 mL of aqueous sodium phosphate (group B; 89 patients); or 4 L of a polyethylene glycol electrolyte solution (group C; 92 patients). The degree of cleanliness of the small bowel was classified by blinded examiners according to four categories (excellent, good, fair or poor). The degree of patient satisfaction, gastric and small bowel transit times, and diagnostic yield were measured. RESULTS: The degree of cleanliness did not differ significantly between the groups (P = 0.496). Interobserver concordance was fair (k = 0.38). No significant differences were detected between the diagnostic yields of the CE (P = 0.601). Gastric transit time was 35.7 +/- 3.7 min (group A), 46.1 +/- 8.6 min (group B) and 34.6 +/- 5.0 min (group C) (P = 0.417). Small-intestinal transit time was 276.9 +/- 10.7 min (group A), 249.7 +/- 13.1 min (group B) and 245.6 +/- 11.6 min (group C) (P = 0.120). CL was the best tolerated preparation. Compliance with the bowel preparation regimen was lowest in group C (P = 0.008). CONCLUSIONS: A clear liquid diet and overnight fasting is sufficient to achieve an adequate level of cleanliness and is better tolerated by patients than other forms of preparation