In vitro synergistic effect of amphotericin B and allicin on Leishmania donovani and L. infantum.

Current monotherapy against visceral leishmaniasis has serious side effects, and resistant Leishmania strains have been identified. Amphotericin B (AmB) has shown an extraordinary antileishmanial efficacy without emergence of resistance; however, toxicity has limited its general use. Results obtained showed, using a fixed-ratio analysis, that the combination of diallyl thiosulfinate (allicin) and AmB ranged from moderately synergic to synergic at low concentrations (0.07 µM AmB plus 35.45 µM allicin induced 95% growth inhibition). None of the treatments, alone or in combination, had noticeable adverse effects on macrophages (M) in the concentration range examined (allicin, 0.5, 1, 5 and 10 µM; AmB, 0.05, 0.075, and 0.1 µM). Allicin, AmB, or the combination did not affect the infection rate (percentage of infected M) of Leishmania. Allicin enhanced the activity of AmB on intracellular amastigotes of Leishmania donovani and L. infantum (ca. 45% reduction of amastigote burden with 0.05 µM AmB plus 10 µM allicin); this represented nearly a 2-fold reduction in the 50% inhibitory concentration (IC50) of the antibiotic added alone. Results point toward the possible utility of testing this combination in vivo to reduce the toxicity associated with monotherapy with AmB.

NADPH oxidase 4 (Nox4) deletion accelerates liver regeneration in mice.

Liver is a unique organ in displaying a reparative and regenerative response after acute/chronic damage or partial hepatectomy, when all the cell types must proliferate to re-establish the liver mass. The NADPH oxidase NOX4 mediates Transforming Growth Factor-beta (TGF-ß) actions, including apoptosis in hepatocytes and activation of stellate cells to myofibroblasts. Aim of this work was to analyze the impact of NOX4 in liver regeneration by using two mouse models where Nox4 was deleted: 1) general deletion of Nox4 (NOX4-/-) and 2) hepatocyte-specific deletion of Nox4 (NOX4hepKO). Liver regeneration was analyzed after 2/3 partial hepatectomy (PH). Results indicated an earlier recovery of the liver-to-body weight ratio in both NOX4-/- and NOX4hepKO mice and an increased survival, when compared to corresponding WT mice. The regenerative hepatocellular fat accumulation and the parenchyma organization recovered faster in NOX4 deleted livers. Hepatocyte proliferation, analyzed by Ki67 and phospho-Histone3 immunohistochemistry, was accelerated and increased in NOX4 deleted mice, coincident with an earlier and increased Myc expression. Primary hepatocytes isolated from NOX4 deleted mice showed higher proliferative capacity and increased expression of Myc and different cyclins in response to serum. Transcriptomic analysis through RNA-seq revealed significant changes after PH in NOX4-/- mice and support a relevant role for Myc in a node of regulation of proliferation-related genes. Interestingly, RNA-seq also revealed changes in the expression of genes related to activation of the TGF-ß pathway. In fact, levels of active TGF-ß1, phosphorylation of Smads and levels of its target p21 were lower at 24 h in NOX4 deleted mice. Nox4 did not appear to be essential for the termination of liver regeneration in vivo, neither for the in vitro hepatocyte response to TGF-ß1 in terms of growth inhibition, which suggest its potential as therapeutic target to improve liver regeneration, without adverse effects.

Developing strategies to reduce spray drift in pneumatic spraying in vineyards: Assessment of the parameters affecting droplet size in pneumatic spraying.

Pneumatic sprayers are widely used in vineyards due to their very fine droplet size, which makes the drift risk to become an important problem to be considered. The aim of this study was to assess the effect of the spout diameter at the release point on the spray droplet size and uniformity achieved for different liquid flow rates (LFR) and air flow rates (AFR). A test bench was developed to simulate a real pneumatic sprayer under laboratory conditions, and it was empirically adjusted to match the air pressure conditions as closely as possible to real working conditions. Two positions of insertion of the liquid hose, the conventional position (CP) and an alternative position (AP), were tested for three LFRs, 1.00, 1.64, and 2.67Lmin-1, and four AFRs, 0.280, 0.312, 0.345, and 0.376m3s-1. The air speed decrease between the two insertion points of the liquid hose was measured. A Malvern SprayTec® instrument was used to measure the droplet size, and the D50, D10, and D90 parameter values were obtained. The relative SPAN factor (RSF) was also calculated. A model to predict variations in D50 was fitted using the aforementioned parameters. The results show that variations in the diameter of the spout significantly change the droplet size, producing a mean increase of 59.45% in D50 and similar increases in D10 and D90. The model developed to predict variations in D50 has a very high degree of accuracy (R2=0.945). The relative decrease in the air speed along the spout did not present significant differences for the different airflow rates tested. The results of the study show that the droplet size produced in pneumatic spraying can be modified easily by varying the air spout dimensions. This should be taken into account by manufacturers from a design point of view.

[Palatine tonsil lipoma]. / Lipoma de amígdala palatina.

Lipomatous tumors represent an unfrequent cause for upper aerodigestive tract neoplasms, specially concerning the palatine tonsils, that should be included in their differential diagnosis. A case of palatine tonsil lipoma in a 11 year-old girl is reported and a revision of the available literature and some considerations about this condition are provided.

[Horizontal supraglottic laryngectomy. A study of 83 cases]. / Laringectomía horizontal supraglótica. Un estudio de 83 casos.

We present the results obtained in 83 patients with supraglottic laryngeal carcinoma treated by supraglottic laryngectomy. We studied the results, complications and the survival of these patients treated with this conservative surgery. We concluded that this surgical technique improved the survival rates in supraglottic carcinomas.

[Study of Cyfra 21-1 as a new tumor marker for the diagnosis of epidermoid carcinoma of the head and neck]. / Estudio del Cyfra 21-1 como un nuevo marcador tumoral en el diagnóstico del carcinoma epidermoide de cabeza y cuello.

Serum concentrations of Cyfra 21-1, a soluble cytokeratin fragment, were evaluated in 157 healthy patients, 66 patients with benign ear, nose or throat disease, and 102 patients with untreated epidermoid carcinoma of the head and neck. The technique had a sensitivity of 53.9% and specificity of 98.4% for a cutoff value of 1.5 ng/ml. Cyfra 21-1 levels differed significantly with tumor location (p < 0. 005) and tumor stage (p < 0.005), but not with the degree of histological differentiation.

[Iris abscess after bacterial endocarditis in a patient with leukaemia. Differential diagnosis]. / Absceso iridiano tras endocarditis bacteriana en un paciente con leucemia. Diagnóstico diferencial.

PURPOSE: To report a case of iris abscess due to bacterial endocarditis. CASE REPORT: A 46-year-old male under diagnosis of promielocitic leukemia and endocarditis presented with decreased vision in left eye (OS). Ophthalmic exploration revealed iris abscess and hypopyon with fibrinous exudate in iris of the left eye and tyndall +1 in right eye (OD). Blood culture and anterior chamber paracentesis was positive for methicillin-sensitive Staphylococcus aureus and negative for blastic cells in citology. Treatment with systemic antibiotic was initiated with total resolution of inflammation. CONCLUSION: Iris abscess is an unusual septic focus in bacterial endocarditis. It is crucial to rule out an extramedullary metastasis in a patient with leukemia due to the general prognosis.

Soil management systems and short term CO2 emissions in a clayey soil in southern Spain.

The soil in general and that destined for agricultural use, more specifically, can act as a source or sink of carbon, hence its direct involvement in strategies for mitigating climate change. A large proportion of this mitigation potential is produced by the sequestration of carbon by soils and, to a lesser extent, by a reduction in emissions from the soil. The most effective practices for increasing the organic carbon in the soils are generally those linked to conservation agriculture, which includes practices of no tillage or minimum tillage and the use of cover crops. During the farming seasons of 2006/07, 2007/08, 2008/09 and 2009/10, a trial was conducted in which the carbon dioxide emissions in soil with a high percentage of clay in the Vega de Carmona (Seville) were estimated, and it was determined how climate conditions and the adoption of conservation agriculture practices vs. the use of traditional tillage influenced the flux of gas into the atmosphere.

Mitochondrial genome depletion dysregulates bile acid- and paracetamol-induced expression of the transporters Mdr1, Mrp1 and Mrp4 in liver cells.

BACKGROUND AND PURPOSE: Mitochondria are involved in the toxicity of several compounds, retro-control of gene expression and apoptosis activation. The effect of mitochondrial genome (mtDNA) depletion on changes in ABC transporter protein expression in response to bile acids and paracetamol was investigated. EXPERIMENTAL APPROACH: Hepa 1-6 mouse hepatoma cells with 70% decrease in 16S/18S rRNA ratio (Rho cells) were obtained by long-term treatment with ethidium bromide. KEY RESULTS: Spontaneous apoptosis and reactive oxygen species (ROS) generation were decreased in Rho cells. Following glycochenodeoxycholic acid (GCDCA) or paracetamol, Rho cells generated less ROS and were more resistant to cell death. Apoptosis induced by GCDCA and Fas was also reduced. The basal expression of Mdr1 was significantly enhanced, but this was not further stimulated by GCDCA or paracetamol, as observed in wild-type (WT) cells. Basal expression of Mrp1 and Mrp4 was similar in WT and Rho cells, whereas they were up-regulated only in WT cells after GCDCA or paracetamol, along with the transcription factors Shp and Nrf2, but not Fxr or Pxr. Increased expression of Nrf2 was accompanied by its enhanced nuclear translocation. Glycoursodeoxycholic acid failed to cause any of the effects observed for GCDCA or paracetamol. CONCLUSIONS AND IMPLICATIONS: The Nrf2-mediated pathway is partly independent of ROS production. Nuclear translocation of Nrf2 is insufficient to up-regulate Mdr1, Mrp1 and Mrp4, which requires the participation of other regulatory element(s) whose activation in response to GCDCA and paracetamol is impaired in Rho cells and hence probably sensitive to ROS.

Osce: un nuevo método evaluativo: informe preliminar de su aplicación / Osce: a new evaluative method: preliminary report of their application

Se presentan los resultados preliminares de la aplicación por primera vez en Cuba de un novedoso metodo evaluativo, conocido internacionalmente por las siglas de Osce "Examen clinico objetivamente estructurado", que el colectivo de profesores de Ciencias Clinicas de la Facultad de Ciencias Medicas de Cienfuegosllevó a cabo en la rotación final de medicina interna a un grupo de 28 estudiantes del sexto año de la carrera de medicina, curso 1990-1991. Se definen los objetivos a lograr con su aplicación y se describen los recursos utilizados y la estrategia seguida. A continuación se detallan las ventajas y desventajas del método utilizado, a través de la comparación que se realiza con los resultados del método tradicionalmente aplicado. Finalmente se arriba a conclusiones cualitativamente superiores en la aplicación de dicho método sustentado en: su factibilidad de implementación, su capacidad de evaluar en un período de tiempo corto un mayor número de objetivos educativos e instructivos, a grupos numerosos de estudiantes con un mínimo de profesores, sin dejar de cumplir con los principios y funciones de la evaluación