Drug delivery systems for potential treatment in intracellular bacterial infections

Despite the advent of a considerable number of new antibiotics, treatment of intracellular pathogens still represents a major pharmaceutical challenge. The antibiotic concentration in those specialized niches are often subtherapeutic, for which high doses of antibiotics must often be used. This is not only costly but may also increase localized or systemic side effects. There is therefore an urgent need for materials and methods to enable clinicians to achieve therapeutically effective intracellular concentration of those antibiotics which show good efficiency in vitro. In this setting, the possible use of drug delivery systems (DDS) loaded with antibiotics that exhibit a high in vitro bactericidal activity deserves to be considered. Entrapping or encapsulating the drug within a delivery system provides a greater control of the pharmacokinetic behavior of the active molecule. This more efficient use of antibiotics may diminish their drawbacks and provide the basis for shortening the current time required by classical treatments. This review will focus on the role of DDS as a potential tool against intracellular bacteria

Implicaciones del funcionamiento de un acuífero carbonatado fisurado complejo (Sierra de Lujar, Granada) en la variabilidad hidroquímica de su descarga natural

A hydrochemical study was carried out in a triassic carbonate aquifer located in a coastal mountain chain in the southern part of the Granada province (Sierra de Lújar, Alpujárride Complex, Betic Cordillera). This aquifer is made up of limestones and dolomites with marly and/or pelitic intercalations and sorne gypsum scattered or interbedded. Though the area is semid-arid, recharge by precipitation -rain or snow melt- is relatively high (over 600 mm/year) because of its mountainous nature up to near 1.900 m. The recharge of the aquifer also comes from the Guadalfeo river which crosses the permeable outcrops losing part of its stream flow. The carbonate rocks present dense microfissuration; the ground water regime is predominantly diffuse. The karstic forms are, in general, poorly developed either in the surface or at the level of speleological networks in the carbonate material. These characteristics influence the ground water chemistry, so the variability of physical-chemical parameters of water is very low, with single shaped histograms of these parameters. Although, in sorne points a larger variability was found related to mixing with streamwaters from the Guadalfeo river.Se ha llevado a cabo un estudio hidroquímico en un acuífero carbonatado triásico localizado en una cadena montañosa costera en el Sur de la provincia de Granada (Sierra de Lújar, Complejo Alpujárride, Cordillera Bética). Este acuífero está constituido por calizas y dolomías con intercalaciones margosas y/o pelíticas y yeso diseminado. Aunque el área es semiárida, la recarga por la precipitación (bien por la lluvia o por el agua de fusión niva!) es relativamente elevada (superior a 600 mm/año) debido a su naturaleza montañosa, cercana a los 1.900 m s.n.m. Además, el río Guadalfeo recarga al acuífero al perder parte de su caudal cuando atraviesa los afloramientos permeables. Las rocas carbonatadas presentan una densa microfisuración; el régimen de flujo es predominantemente difuso. Las formas kársticas están, por lo general, poco desarrolladas tanto en superficie como a nivel de redes espeleológicas. Estas características influyen en la química del agua subterránea, por lo que la variabilidad de los diferentes parámetros físicoquímicos del agua es reducida, con gráficos de distribución de frecuencias de dichos parámetros de formas, generalmente, unimodales. Sin embargo, se ha encontrado una mayor variabilidad en aquellos puntos en los que existe mezcla con aguas superficiales procedentes del río Guadalfeo

Assessment of the Evolution of a Landslide Using Digital Photogrammetry and LiDAR Techniques in the Alpujarras Region (Granada, Southeastern Spain)

In this work a detailed analysis of the temporal evolution of the Almegíjar landslide is presented. It is a rock slide located in the Alpujarras region (Granada, Spain) that has developed over the last 30 years. Six datasets and photogrammetric flights corresponding to the years 1956, 1984, 1992, 2001, 2008, and 2010 were surveyed. The more recent flight of 2010 combined an aerial digital camera and a LiDAR sensor and was oriented by means of in-flight data and tie points. This 2010 flight allowed for the generation of a reliable and high-precision Digital Terrain Model (DTM). The other flights were oriented using second-order ground control points transferred from the 2010 flight, and the corresponding DTMs were prepared by automatic matching and subsequent editing from the stereoscopic models. After comparing the DTMs of different dates, it has been observed that the landslide was triggered after 1984 and since then has evolved in an irregular pattern with periods of variable activity. On average, the ground surface dropped more than 8 m in depleted zones and rose nearly 4 m in the accumulation zones, with a velocity catalogued as very slow (about 15–30 cm/year) over a time span corresponding to a degree VIII of diachroneity. The total volume of the mobilized mass of this large contemporary slide was about 300 × 103 m3.This research was funded by the projects P06-RNM-02125 and RNM-06862 (ISTEGEO) funded by the Andalusian Research Plan, projects CGL2008-04854 and TIN2009-09939 funded by the Ministry of Science and Innovation of Spain and Research Groups TEP-213, and RNM 221 of the Andalusian Research Plan

Fasting plasma glucose is an independent predictor of survival in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy

Background: Diabetes is related with increased cancer mortality across multiple cancer types. Its role in lung cancer mortality is still unclear. We aim to determine the prognostic value of fasting plasma glucose (FPG) and diabetes mellitus in patients with locally advanced non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy. Methods: One-hundred seventy patients with stage III NSCLC received definitive concurrent chemoradiotherapy from 2010 to 2014. Clinico-pathological data and clinical outcome was retrospectively registered. Fifty-six patients (33%), met criteria for type 2 diabetes mellitus (T2DM) at baseline. The prognostic value of FPG and other clinical variables was assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and Cox proportional models and log-rank test were used. Results: With a median follow-up of 36 months, median PFS was 8.0 months and median OS was 15.0 months in patients with FPG ≥7 mmol/L compared to 20 months (HR 1.13; 95% CI 1.07-1.19, p  8.5%) (HR 4.53; 95% CI 2.21-9.30; p < 0.001) and those receiving insulin (HR 3.22; 95% CI 1.90-5.46 p < 0.001) had significantly independent worse OS. Conclusion: Baseline FPG level is an independent predictor of survival in our cohort of patients with locally advanced NSCLC treated with concurrent chemoradiotherapy. Studies in larger cohorts of patients are warranted to confirm this relevant association

Elevated Levels of the Complement Activation Product C4d in Bronchial Fluids for the Diagnosis of Lung Cancer

Molecular markers in bronchial fluids may contribute to the diagnosis of lung cancer. We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL) supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort). The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d) in bronchial fluids. C4d levels were determined in BAL supernatants from two independent cohorts: the CU cohort (25 cases and 26 controls) and the HUVR cohort (60 cases and 98 controls). A series of spontaneous sputum samples from 68 patients with lung cancer and 10 controls was also used (LCCCIO cohort). Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. C4d levels were significantly increased in BAL samples from lung cancer patients. The area under the ROC curve was 0.82 (95% CI = 0.71-0.94) and 0.67 (95% CI = 0.58-0.76) for the CU and HUVR cohorts, respectively. In addition, unlike the other markers, C4d levels in BAL samples were highly consistent across the CUN, CU and HUVR cohorts. Interestingly, C4d test markedly increased the sensitivity of bronchoscopy in the two cohorts in which cytological data were available (CUN and HUVR cohorts). Finally, in the LCCCIO cohort, C4d levels were higher in sputum supernatants from patients with lung cancer (area under the ROC curve: 0.7; 95% CI = 0.56-0.83). In conclusion, C4d is consistently elevated in bronchial fluids from lung cancer patients and may be used to improve the diagnosis of the disease