Predictive value of the Global Activity Limitation Indicator (GALI) on all-cause mortality.

OBJECTIVES: The Global Activity Limitation Indicator (GALI) is an instrument that measures long-term overall disability. The objective of this study was to evaluate GALI's predictive value on mortality while examining variations according to sex, age, and educational level. STUDY DESIGN: Longitudinal study. METHODS: This longitudinal study was based on 42,991 individuals aged ≥15 years who participated in the 2011-2012 National Health Survey and the 2014 European Health Survey in Spain. These records were linked to mortality data up to December 2021. GALI assessed self-reported functional limitation in the past 6 months and classified individuals into three categories: severely limited, limited but not severely, and not limited. Incidence rate ratios (IRR) were calculated using Poisson regression models, adjusting for sociodemographic, lifestyle, and health status variables. RESULTS: Compared to individuals with no limitations, those with non-severe limitations had an IRR for mortality of 1.27 (95% CI: 1.16-1.38), and 2.04 (95% CI: 1.81-2.31) in those with severe limitations. Women with severe limitations exhibited a higher IRR (2.32; 95% CI: 1.98-2.71) compared to men (1.73; 95% CI: 1.45-2.08) (P for interaction = 0.005). Individuals <65 years with severe limitations showed a greater association (2.22; 95% CI: 1.58-3.10) than those ≥65 (1.49; 95% CI: 1.32-1.69) (P for interaction <0.001). Among individuals with lower educational attainment, the IRR was 2.08 (95% CI: 1.83-2.37), and 1.87 (95% CI: 1.37-2.56) for the higher education group (P for interaction = 0.017). CONCLUSIONS: GALI is a robust predictor of all-cause mortality in the general population and subgroups. The association is stronger in women, individuals <65 years, and those with lower educational levels.

Compact laser modulation system for a transportable atomic gravimeter.

Nowadays, atom-based quantum sensors are leaving the laboratory towards field applications requiring compact and robust laser systems. Here we describe the realization of a compact laser system for atomic gravimetry. Starting with a single diode laser operating at 780 nm and adding only one fiber electro-optical modulator, one acousto-optical modulator and one laser amplifier we produce laser beams at all the frequencies required for a Rb-87 atomic gravimeter. Furthermore, we demonstrate that an atomic fountain configuration can also be implemented with our laser system. The modulated system reported here represents a substantial advance in the simplification of the laser source for transportable atom-based quantum sensors that can be adapted to other sensors such as atomic clocks, accelerometers, gyroscopes or magnetometers with minor modifications.

Accurate temperature measurement of cold atoms in cesium fountain clocks.

We introduce a new approach to determine if a cloud of cold atoms has or not a unique, well-defined temperature. In the first case, the temperature can be determined using the width of the velocity distribution. However, the temperature in a cloud of cold atoms may not be well-defined if the velocity distribution does not turn out to be Gaussian. In this case, the width of the velocity distribution cannot be associated to a unique temperature, and additional considerations exposed here should be followed to measure the temperatures of two groups of atoms forming the whole cloud. Also an uncertainty evaluation is presented.

Endophytic fungi isolated from plants present in a mine tailing facility show a differential growth response to lead.

Plants growing in metal-polluted sites can be a source of micro-organisms suitable for bio-assisted phytoremediation strategies. In this work, three endophytic fungi from the roots of Poa stuckertii and Poa pratensis, two grasses that naturally colonize a Lead-Zinc tailing storage facility in Southern Chile, were isolated and identified. The leachate of the tailing sands showed a Pb content of 1·36 ± 0·71 ppm, and a pH of 7·3. By amplifying the ITS1/ITS4 region of fungal ribosomal DNA, the isolates were identified as Bjerkandera sp., Microdochium sp. and Sarocladium sp. When the growth media was supplemented with 50 ppm of Pb at pH 4·5, Microdochium sp. showed an 80% decrease in the biomass, but the biomass production of Bjerkandera sp. and Sarocladium sp. was not affected by the same treatment. The accumulation of Pb in Microdochium sp. increased as a function of the concentration of the metal in the growth media, between 48·3 and 241·3 µmol l-1 . We showed that two Poaceae plants growing on a Lead-Zinc tailing storage facility are a source of endophyte fungi and that Pb had a differential effect on the growth of the isolated fungi independent of the plant of origin.

Bone union formation in the rat mandibular symphysis using hydroxyapatite with or without simvastatin: effects on healthy, diabetic, and osteoporotic rats.

OBJECTIVE: The objective is to compare new bone formation in critical defects in healthy, diabetic, and osteoporotic rats filled with hydroxyapatite (HA) alone and HA combined with simvastatin (SV). MATERIALS AND METHODS: A total of 48 adult female Sprague-Dawley rats were randomized into three groups (n = 16 per group): Group, 1 healthy; Group 2, diabetics; and Group 3, osteoporotics. Streptozotocin was used to induce type 1 diabetes in Group 2, while bilateral ovariectomy was used to induce osteoporosis in Group 3. The central portion of the rat mandibular symphysis was used as a physiological critical bone defect. In each group, eight defects were filled with HA alone and eight with HA combined with SV. The animals were sacrificed at 4 and 8 weeks, and the mandibles were processed for micro-computed tomography to analyze radiological union and bone mineral density (BMD); histological analysis of the bone union; and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2). RESULTS: In all groups (healthy, diabetics, and osteoporotics), the defects filled with HA + SV presented greater radiological bone union, BMD, histological bone union, and more VEGF and BMP-2 positivity, in comparison with bone defects treated with HA alone. CONCLUSIONS: Combined application of HA and SV improves bone regeneration in mandibular critical bone defects compared with application of HA alone in healthy, diabetic, and osteoporotic rats. CLINICAL RELEVANCE: This study might help to patients with osteoporosis or uncontrolled diabetes type 1, but future studies should be done.

[An Early Obesity Prevention Program: HaViSa UC (2009-2019)]. / Un programa de prevención temprana de la obesidad: "HaViSa UC" (2009-2019).

INTRODUCTION: Prevention is the definitive solution to the serious nutritional epidemiological pro blem of children in our country and the world, obesity. OBJECTIVE: To describe the results of an obesi ty prevention program for infants and preschoolers, ten years after its implementation. SUBJECTS AND METHODS: Retrospective, and quasi-experimental study of the overweight and obesity prevalence, in children attending three nursery and preschool centers located at the Universidad Católica de Chile, since the implementation of a multidimensional program for early promotion of healthy lifestyle habits (HaViSa-UC) between 2009 and 2019. This study obtained ethical approval. Annual records of anthropometric assessment (WHO 2006) were analyzed using Minitab 17 software. The actions applied by the HaViSa-UC program were the assessment of nutritional status and communication with parents, delivery of healthy food, promotion of an active lifestyle, and education to encourage such healthy habits. RESULTS: The annual mean was 319 subjects, 14% younger than two years old, and 49.5% were girls. In March 2009 (baseline), 32.6% had overweight and 8.6% obesity; both figures decreased reaching 23.8% and 4.7% respectively, in March 2019. Normal weight increased from 56.9 to 67.4% and malnutrition presented no increase. In the same period, zW/H dropped from 0.84 ± 0.94 to 0.55 ± 0.87 (p: 0.00), and zH/A increased from -0.36 ± 0.87 to -0.32 ± 0.90 (p > 0.05). Con clusion: Since the implementation of the HaViSa-UC Program, the frequency of obesity decreased by 45.4% and overweight by 27.2% in this sample of infants and preschoolers, remaining stable after 10 years.

Plasmonic directional couplers using channel waveguides in random arrays of metal nanoparticles.

Plasmonic directional couplers based on channel waveguides embedded in random arrays of metal nanoparticles (NPs) operating in near-infrared are fabricated using electron-beam lithography and investigated experimentally characterizing their performance with leakage-radiation microscopy. The power exchange between coupled waveguides, its spatial period and efficiency, along with the overall power transmission, are determined in the wavelength range from 700 to 800 nm. We introduce a simple coupled-mode approach based on three coupled waveguides. The composite system considers a waveguide consisting of NP-filled stripe with characteristics distinctly different from those of the channel waveguides. Using this model, we describe the performance of investigated composite plasmonic configurations and obtain good qualitative agreement with experimental observations.

Utilization of naproxen by Amycolatopsis sp. Poz 14 and detection of the enzymes involved in the degradation metabolic pathway.

The pollution of aquatic environments by drugs is a problem for which scarce research has been conducted in regards of their removal. Amycolatopsis sp. Poz 14 presents the ability to biotransformation naphthalene at high efficiency, therefore, in this work this bacterium was proposed as an assimilator of naproxen and carbamazepine. Growth curves at different concentrations of naproxen and carbamazepine showed that Amycolatopsis sp. Poz 14 is able to utilize these drugs at a concentration of 50 mg L-1 as a source of carbon and energy. At higher concentrations, the bacterial growth was inhibited. The transformation kinetics of naproxen showed the total elimination of the compound in 18 days, but carbamazepine was only eliminated in 19.9%. The supplementation with cometabolites such as yeast extract and naphthalene (structure similar to naproxen) at 50 mg L-1, showed that the yeast extract shortened the naproxen elimination to 6 days and reached a higher global consumption rate compared to the naphthalene cometabolite. The biotransformation of carbamazepine was not improved by the addition of cometabolites. The partial sequencing of the genome of Amycolatopsis sp. Poz 14 detected genes encoding putative enzymes for the degradation of cyclic aromatic compounds and the activities of aromatic monooxygenase, catechol 1,2-dioxygenase and gentisate 1,2-dioxygenase exhibited their involving in the naproxen biodegradation. The HPLC-MS analysis detected the 5-methoxysalicylic acid at the end of the biotransformation kinetics. This work demonstrates that Amycolatopsis sp. Poz 14 utilizes naproxen and transforms it to 5-methoxysalicylic acid which is the initial compound for the catechol and gentisic acid metabolic pathway.

Oral status, quality of life, and anxiety and depression in hemodialysis patients and the effect of the duration of treatment by dialysis on these variables.

This study aimed is to evaluate the oral health status, quality of life, anxiety and depression among hemodialysis patients and to analyze the effect of the duration of dialysis on these variables. 120 patients on hemodialysis and 120 control subjects underwent oral examination, periodontal evaluation, xerostomia study using a Visual Analogue Scale (VAS), sialometry evaluation; quality of life (QOL) using the OHIP-14 questionnaire and anxiety/depression. Bleeding index, CPTIN, clinical attachment level, and probing depth were significantly higher in the hemodialysis group than the control group (p < 0.001). VAS scores were higher in patients on hemodialysis with significant differences in 6 of the 8 domains (p ≤ 0.05). Unstimulated whole saliva was significantly lower in hemodialysis patients than control subjects (p < 0.001). OHIP-14 scores showed significantly poorer QOL in patients on hemodialysis than control subjects (p = 0.042). Hemodialysis patients presented greater depression and anxiety than control (p < 0.001). Periodontal health was worse among the patients who had been in treatment >10 years, xerostomia and sialorrea was worse in patients treated for 5-9.9, and >10 years, QOL was worse in patients who had spent <1 year; depression and anxiety was greater among those treated for 1-2.9 years. In conclusion, Oral health, QOL, anxiety and depression are worse in patients on hemodialysis, and oral health deteriorates as the time spent in dialysis lengthens, but patients in treatment for <3 years presented the poorest QOL and the greatest anxiety and depression.

Short-term atorvastatin therapy improves arterial stiffness of middle-aged systemic lupus erythematosus patients with pathological pulse wave velocity.

Objectives Statins have been proposed as a potential treatment for systemic lupus erythematosus (SLE) due to their immunomodulatory properties, their role restoring endothelial function and preventing atherosclerosis. We evaluate the effect of a short period treatment with a low dose of atorvastatin and its withdrawal on early stage subclinical atherosclerosis. Methods Thirty-seven SLE females received 20 mg/day atorvastatin during eight weeks. At baseline, at the end of treatment and six months after atorvastatin withdrawal, disease activity, subclinical atherosclerosis -assessed by measuring carotid-femoral pulse wave velocity (PWV) - and quantification of circulating endothelial progenitor cells (EPC) - as a surrogate biological marker of subclinical atherosclerosis - were carried out. Results The group of SLE patients with baseline pathological arterial stiffness showed a significant decrease of PWV after atorvastatin therapy (8.43 ± 1.45 m/s vs 7.42 ± 1.06 m/s; p = 0.002) that is maintained six months after treatment finished. Only patients of the middle-aged group showed a nearly significant decrease in the PWV measured along the study (7.16 ± 1.23 m/s vs 6.76 ± 0.82 m/s; p = 0.05). Atorvastatin induced a significant decrease in the circulating EPC percentage (0.65 ± 0.67 vs 0.40 ± 0.31; p = 0.023) as well as a downward trend of disease activity that it is observed by a decrease in SLE disease activity index simultaneously with an increase in C3 complement and significant decrease in serum concentration of vascular endothelial grow factor (VEGF) and sVCAM-1. Conclusions Short-term atorvastatin therapy reduces arterial stiffness of SLE patients with baseline pathological PWV, who are mainly in the group of middle-aged patients. Further studies are needed to determine whether these patients would benefit from statin therapy in preventing cardiovascular events.

Antimicrobial activity of a new synthetic peptide loaded in polylactic acid or poly(lactic-co-glycolic) acid nanoparticles against Pseudomonas aeruginosa, Escherichia coli O157:H7 and methicillin resistant Staphylococcus aureus (MRSA).

Nanocarrier systems are currently being developed for peptide, protein and gene delivery to protect them in the blood circulation and in the gastrointestinal tract. Polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with a new antimicrobial GIBIM-P5S9K peptide were obtained by the double emulsion solvent extraction/evaporation method. PLA- and PLGA-NPs were spherical with sizes between 300 and 400 nm for PLA and 200 and 300 nm for PLGA and <0.3 polydispersity index as determined by dynamic light scattering and scanning electron microscopy), having the zeta potential of >20 mV. The peptide-loading efficiency of PLA-NP and PLGA-NPs was 75% and 55%, respectively. PLA- and PLGA-NPs released around 50% of this peptide over 8 h. In 10% human sera the size of peptide loaded PLA- and PLGA-NPs increased between 25.2% and 39.3%, the PDI changed from 3.2 to 5.1 and the surface charge from -7.15 to 14.6 mV. Both peptide loaded PLA- and PLGA-NPs at 0.5 µM peptide concentration inhibited the growth of Escherichia coli O157:H7 (E. coli O157:H7), methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. aeruginosa (P. aeruginosa). In contrast, free peptide inhibited at 10 µM but did not inhibit at 0.5 and 1 µM. These PLA- and PLGA-NPs presented <10% hemolysis indicating that they are hemocompatible and promising for delivery and protection system of GIBIM-P5S9K peptide.

Short-term association between environmental factors and hospital admissions due to dementia in Madrid.

BACKGROUND: Spain has one of the highest proportions of dementia in the world among the population aged 60 years or over. Recent studies link various environmental factors to neurocognitive-type diseases. This study sought to analyse whether urban risk factors such as traffic noise, pollutants and heat waves might have a short-term impact on exacerbation of symptoms of dementia, leading to emergency hospital admission. MATERIAL AND METHODS: We conducted a longitudinal ecological time-series study, with the dependent variable being the number of daily dementia-related emergency (DDE) hospital admissions to Madrid municipal hospitals (ICD-10 codes 290.0-290.2, 290.4-290.9, 294.1-294) from 01 to 01-2001 to 31-12-2009, as obtained from the Hospital Morbidity Survey (National Statistics Institute). The measures used were as follows: for noise pollution, Leqd, equivalent diurnal noise level (from 8 to 22h), and Leqn, equivalent nocturnal noise level (from 22 to 8h) in dB(A); for chemical pollution, mean daily NO2, PM2.5, PM1 as provided by the Madrid Municipal Air Quality Monitoring Grid; and lastly, maximum daily temperature (°C), as supplied by the State Meteorological Agency. Scatterplot diagrams were plotted to assess the type of functional relationship existing between the main variable of analysis and the environmental variables. The lags of the environmental variables were calculated to analyse the timing of the effect. Poisson regression models were fitted, controlling for trends and seasonalities, to quantify relative risk (RR). RESULTS: During the study period, there were 1175 DDE hospital admissions. These admissions displayed a linear functional relationship without a threshold in the case of Leqd. The RR of DDE admissions was 1.15 (1.11-1.20) for an increase of 1dB in Leqd, with impact at lag 0. In the case of maximum daily temperature, there was a threshold temperature of 34°C, with an increase of 1°C over this threshold posing an RR of 1.19 (1.09-1.30) at lag 1. The only pollutant to show an association with DDE hospital admissions was O3 at lag 5, with an RR of 1.09 (1.04-1.15) for an increase of 10µg/m3 CONCLUSIONS: Diurnal traffic noise, heat waves and tropospheric ozone may exacerbate the symptoms of dementia to the point of requiring emergency admission to hospital. Lowering exposure levels to these environmental factors could reduce dementia-related admissions in Madrid.

Asymmetric Michael Addition Organocatalyzed by α,ß-Dipeptides under Solvent-Free Reaction Conditions.

The application of six novel α,ß-dipeptides as chiral organocatalysts in the asymmetric Michael addition reaction between enolizable aldehydes and N-arylmaleimides or nitroolefins is described. With N-arylmaleimides as substrates, the best results were achieved with dipeptide 2 as a catalyst in the presence of aq. NaOH. Whereas dipeptides 4 and 6 in conjunction with 4-dimethylaminopyridine (DMAP) and thiourea as a hydrogen bond donor proved to be highly efficient organocatalytic systems in the enantioselective reaction between isobutyraldehyde and various nitroolefins.

One-Pot Lipase-Catalyzed Enantioselective Synthesis of (R)-(-)-N-Benzyl-3-(benzylamino)butanamide: The Effect of Solvent Polarity on Enantioselectivity.

The use of the solvent engineering has been applied for controlling the resolution of lipase-catalyzed synthesis of ß-aminoacids via Michael addition reactions. The strategy consisted of the thermodynamic control of products at equilibrium using the lipase CalB as a catalyst. The enzymatic chemo- and enantioselective synthesis of (R)-(-)-N-benzyl-3-(benzylamino)butanamide is reported, showing the influence of the solvent on the chemoselectivity of the aza-Michael addition and the subsequent kinetic resolution of the Michael adduct; both processes are catalyzed by CalB and both are influenced by the nature of the solvent medium. This approach allowed us to propose a novel one-pot strategy for the enzymatic synthesis of enantiomerically enriched ß-aminoesters and ß-aminoacids.

Spatial variability in threshold temperatures of heat wave mortality: impact assessment on prevention plans.

Spain's current heat wave prevention plans are activated according to administrative areas. This study analyses the determination of threshold temperatures for triggering prevention-plan activation by reference to isoclimatic areas, and describes the public health benefits. We subdivided the study area - the Madrid Autonomous Region (MAR) - into three, distinct, isoclimatic areas: 'North', 'Central' and 'South', and grouped daily natural-cause mortality (ICD-10: A00-R99) in towns of over 10,000 inhabitants (2000-2009 period) accordingly. Using these three areas rather than the MAR as a whole would have resulted in a possible decrease in mortality of 73 persons (38-108) in the North area, and in aborting unnecessary activation of the plan 153 times in the Central area and 417 times in the South area. Our results indicate that extrapolating this methodology would bring benefits associated with a reduction in attributable mortality and improved effectiveness of public health interventions.

Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

BACKGROUND AND OBJECTIVES: Obesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis. MATERIALS AND METHODS: Male C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay. RESULTS: Lentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects. CONCLUSIONS: Cathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity.

Metabolic syndrome is associated with decreased circulating endothelial progenitor cells and increased arterial stiffness in systemic lupus erythematosus.

OBJECTIVES: Metabolic syndrome (MetS) is highly prevalent in patients with systemic lupus erythematosus (SLE) and it has been associated with increased cardiovascular risk. We examined the contribution of MetS to inflammatory markers, arterial stiffness and circulating endothelial progenitor cells (EPCs) as surrogates of subclinical atherosclerosis. METHODS: Cardiovascular risk factors, SLE-specific factors and peripheral blood EPCs were assessed in 50 female SLE patients. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III. Simultaneously, atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by doppler velocimetry. RESULTS: Beyond the factors included in the definition, SLE patients with MetS have a significantly higher serum level of uric acid (6.88 ± 2.20 vs 4.45 ± 1.17, p < 0.001) and some inflammatory biomarkers such as homocysteine, IL-8, sICAM-1 or complement molecules. The presence of MetS in our patients was closely linked with a significantly increased patient organ damage score (3.20 ± 1.97 vs 1.60 ± 1.67, p = 0.008), a decreased percentage of circulating EPCs (0.53 ± 0.24 vs 0.85 ± 0.57, p = 0.007) and an increased arterial stiffness (9.89 ± 2.40 vs 7.13 ± 1.51, p < 0.001). CONCLUSIONS: MetS may contribute to the development of atherosclerosis by significantly increasing inflammation levels and arterial stiffness and decreasing circulating EPCs. This finding would justify close monitoring of these patients.

Comparison of two negative pressure systems and syringe irrigation for root canal irrigation: an ex vivo study.

AIM: To compare in a laboratory study two negative pressure systems and syringe irrigation, regarding the delivery of a contrast solution (CS) to working length (WL) and into simulated lateral canals and the effective volume of irrigant aspirated during negative pressure irrigation. METHODOLOGY: Twenty single-canaled incisor training models were constructed with six simulated lateral canals each (2, 4 and 6 mm to WL) and a size 40, 0.04 taper apical size canal. Each model underwent all irrigation procedures (EndoVac at WL (EndoVac-0) and WL-2 mm (EndoVac-2), iNP needle with negative pressure (iNPn) and syringe irrigation with the iNP needle (iNPs) and a 30-G side-slot needle placed at WL (SI0) and WL-2 (SI2) mm in a crossover design. CS was delivered at 4 mL min(-1) for 60 s with a peristaltic pump and a recovery device collected the volume (in mL) of irrigant suctioned by the negative pressure groups. The irrigation procedures were digitally recorded, and a still image of the 60-s time-point of irrigation was evaluated for CS distance to WL (in millimetres) after irrigation and penetration into lateral canals (3-point scale). Statistical tests used were Kruskal-Wallis and Dunn's test. RESULTS: EndoVac-0, iNPn and iNPs had median distances of CS to WL of 0 mm, followed by SI0 (0.2 mm), SI2 (0.7 mm) and EndoVac-2 (1.7 mm). There were no significant differences between EndoVac-0, iNPn, iNPs and SI0, but these were significantly different to SI2 and EndoVac-2 (P < 0.05). There were no significant differences between the volume of CS delivered by syringe irrigation and that collected by iNPn (4 mL), but these were significantly greater than EndoVac-0 (2.8 mL, P < 0.001) and EndoVac-2 (2.85 mL, P < 0.001), which were not different to each other (P = 1.0). The irrigation procedures were ineffective at penetration into lateral canals. CONCLUSION: iNPn, EndoVac-0, iNPs and SI0 achieved greater irrigant penetration to WL. iNPn was able to collect a median volume of CS (4 mL) similar to that delivered by syringe irrigation (iNPp, SI0 and SI2). An adequate irrigant penetration into lateral canals could not be achieved by any of the systems.

Synthesis and pharmaceutical properties of N-acyloxymethyl prodrugs of Allop with potential anti-trypanosomal activity.

We report herein the synthesis, and the physicochemical and pharmacokinetic properties of N-acyloxymethyl prodrugs of allopurinol (Allop) (2a-f). Allop is a compound with activity against Trypanosoma cruzi, a causative agent of Chagas disease. Its pathology leads to a huge number of infections and deaths per year, because in addition to many sufferers only having limited access to health services only an inefficient chemotherapy is available. Relevant pharmaceutical properties (pKa, stability, solubility, lipophilicity, in vitro permeability, binding protein, xanthine oxidase binding) were also determined. The results obtained showed that derivatives behave as prodrugs of Allop, since they exhibit improved physicochemical and pharmacokinetic properties relative to their precursor. This behavior turns these compounds into active reservoirs of Allop, and reduces its unfavorable characteristics, so 2a-f compounds are excellent candidates for the treatment of Chagas disease. This work is therefore an important contribution leading to the suppression of Chagas disease.