Identification of Recurrent Mutations in the microRNA-Binding Sites of B-Cell Lymphoma-Associated Genes in Follicular Lymphoma.

Follicular lymphoma (FL) is a common indolent B-cell lymphoma that can transform into the more aggressive transformed FL (tFL). However, the molecular process driving this transformation is uncertain. In this work, we aimed to identify microRNA (miRNA)-binding sites recurrently mutated in follicular lymphoma patients, as well as in transformed FL patients. Using whole-genome sequencing data from FL tumors, we discovered 544 mutations located in bioinformatically predicted microRNA-binding sites. We then studied these specific regions using targeted sequencing in a cohort of 55 FL patients, found 16 recurrent mutations, and identified a further 69 variants. After filtering for QC, we identified 21 genes with mutated miRNA-binding sites that were also enriched for B-cell-associated genes by Gene Ontology. Over 40% of mutations identified in these genes were present exclusively in tFL patients. We validated the predicted miRNA-binding sites of five of the genes by luciferase assay and demonstrated that the identified mutations in BCL2 and EZH2 genes impaired the binding efficiency of miR-5008 and miR-144 and regulated the endogenous levels of messenger RNA (mRNA).

Effects on intestinal microbiota and immune genes of Solea senegalensis after suspension of the administration of Shewanella putrefaciens Pdp11.

The interaction host-intestinal microbiota is essential for the immunological homeostasis of the host. Probiotics, prebiotics and synbiotics are promising tools for the manipulation of the intestinal microbiota towards beneficial effects to the host. The objective of this study was to evaluate the modulation effect on the intestinal microbiota and the transcription of genes involved in the immune response in head kidney of Solea senegalensis after administration of diet supplemented with the prebiotic alginate and the probiotic Shewanella putrefaciens Pdp11 CECT 7627 (SpPdp11). The results showed higher adaptability to dietary changes in the intestinal microbiota of fish fed diet with alginate and SpPdp11 together compared to those fish that received an alginate-supplemented diet. The alginate-supplemented diet produced up-regulation of genes encoding proteins involved in immunological responses, such as complement, lysozyme G and transferrin, and oxidative stress, such as NADPH oxidase and glutation peroxidase. On the other hand, the administration of alginate combined with SpPdp11 resulted in a significant increase of the transcription of genes encoding for glutation peroxidase and HSP70, indicating a potential protective effect of SpPdp11 against oxidative stress. In addition, these effects were maintained after the suspension of the probiotic treatment. The relationship between the modulation of the intestinal microbiota and the expression of genes with protective effect against the oxidative stress was demonstrated by the Principal Components Analysis.

Vincristine pharmacokinetics pathway and neurotoxicity during early phases of treatment in pediatric acute lymphoblastic leukemia.

AIM: Vincristine is an important component of acute lymphoblastic leukemia (ALL) treatment protocols that can cause neurotoxicity. Patients treated with LAL/SHOP protocols often suffer from vincristine-related neurotoxicity in early phases of treatment. Recently, a genome-wide association study connected a SNP in CEP72, involved in vincristine pharmacodynamics, with neurotoxicity during later phases of therapy, which was not replicated during induction phase. These results, together with previous studies indicating that polymorphisms in pharmacokinetic genes are associated with drug toxicity, suggest that changes in the activity or levels of vincristine transporters or metabolizers could work as predictors of vincristine-related neurotoxicity in early phases of treatment in pediatric ALL. PATIENTS & METHODS: We analyzed 150 SNPs in eight key genes involved in vincristine pharmacokinetics and in 13 miRNAs that regulate them. We studied their correlation with neurotoxicity during induction phase in 152 ALL patients treated with LAL/SHOP protocols. RESULTS: The strongest associations with neurotoxicity were observed for two SNPs in ABCC2. The genotypes rs3740066 GG and rs12826 GG were associated with increased neurotoxicity. CONCLUSION: Polymorphisms in ABCC2 could be novel markers for vincristine-related neurotoxicity in pediatric ALL in early phases.

ECO-physiological response of S. vulgaris to CR(VI): Influence of concentration and genotype.

The objective of this work is to study the response of Silene vulgaris to a range of environmentally relevant concentrations of Cr(VI) in order to evaluate its potential use in the phytomanagement of Cr polluted sites. Cuttings of six homogenous genotypes from Madrid (Spain) have been used as plant material. The eco-physiological response of S. vulgaris to Cr(VI) changed with the genotype. The yield dose-response curve was characterized by stimulation at low doses of Cr(VI). The effects of metal concentration were quantified on root dry weight, water content and chlorophyll content, determined by SPAD index. The response was not homogeneous for all studied genotypes. At high doses of Cr(VI), plants increased micronutrient concentration in dry tissues which suggested that nutrient balance could be implicated in the alleviation of Cr toxicity. This work highlights the importance of studying the eco-physiological response of metallophytes under a range of pollutant concentrations to determine the most favorable traits to be employed in the phytomanagement process.

Facial lesions in frontal fibrosing alopecia (FFA): Clinicopathological features in a series of 12 cases.

BACKGROUND: Facial lesions in frontal fibrosing alopecia (FFA) have been poorly described in published series. OBJECTIVE: We sought to describe facial lesions in FFA. METHODS: We reviewed our series of 55 cases of FFA, selecting 12 cases with clinically significant facial lesions. We performed a histologic study of these lesions. RESULTS: In addition to the observations already described in the literature such as facial papules or follicular red dots, we observed perifollicular and diffuse erythema, sometimes with a reticular pattern, and the gradual appearance of pigmented macules on facial skin. Biopsy specimens from the areas with facial erythema showed perifollicular and interfollicular lymphocytic infiltrate and fibrosis around vellus hair follicles. Histologic evaluation of pigmented macules sometimes exhibited an increased epidermal pigmentation and on occasions, pigmentary incontinence. LIMITATIONS: More patients are needed to determine the prevalence of these lesions in FFA. CONCLUSION: On facial skin of patients with FFA, we can observe papules or perifollicular erythema secondary to vellus hair follicle involvement. We describe diffuse erythema, owing to follicular and interfollicular lichenoid infiltrate, and the gradual appearance of pigmented macules, which could be secondary to an increased epidermal pigmentation or to pigmentary incontinence.

Probiotic supplementation influences the diversity of the intestinal microbiota during early stages of farmed senegalese sole (Solea Senegalensis, Kaup 1858).

Ingestion of bacteria at early stages results in establishment of a primary intestinal microbiota which likely undergoes several stages along fish life. The role of this intestinal microbiota regulating body functions is crucial for larval development. Probiotics have been proved to modulate this microbiota and exert antagonistic effects against fish pathogens. In the present study, we aimed to determine bacterial diversity along different developmental stages of farmed Senegalese sole (Solea senegalensis) after feeding probiotic (Shewanella putrefaciens Pdp11) supplemented diet for a short period (10-30 days after hatching, DAH). Intestinal lumen contents of sole larvae fed control and probiotic diets were collected at 23, 56, 87, and 119 DAH and DNA was amplified using 16S rDNA bacterial domain-specific primers. Amplicons obtained were separated by denaturing gradient gel electrophoresis (DGGE), cloned, and resulting sequences compared to sequences in GenBank. Results suggest that Shewanella putrefaciens Pdp11 induces a modulation of the dominant bacterial taxa of the intestinal microbiota from 23 DAH. DGGE patterns of larvae fed the probiotic diet showed a core of bands related to Lactobacillus helveticus, Pseudomonas acephalitica, Vibrio parahaemolyticus, and Shewanella genus, together with increased Vibrio genus presence. In addition, decreased number of clones related to Photobacterium damselae subsp piscicida at 23 and 56 DAH was observed in probiotic-fed larvae. A band corresponding to Shewanella putrefaciens Pdp11 was sequenced as predominant from 23 to 119 DAH samples, confirming the colonization by the probiotics. Microbiota modulation obtained via probiotics addition emerges as an effective tool to improve Solea senegalensis larviculture.

Uptake of CeO2 nanoparticles and its effect on growth of Medicago arborea In vitro plantlets.

The present study analyzes some effects of nano-CeO2 particles on the growth of in vitro plantlets of Medicago arborea when the nanoceria was added to the culture medium. Various concentrations of nano-CeO2 and bulk ceric oxide particles in suspension form were introduced to the agar culture medium to compare the effects of nanoceria versus ceric oxide bulk material. Germination rate and shoot dry weight were not affected by the addition of ceric oxide to the culture media. Furthermore, no effects were observed on chlorophyll content (single-photon avalanche diode (SPAD) measurements) due to the presence of either nano- or micro-CeO2 in the culture medium. When low concentrations of nanoceria were added to the medium, the number of trifoliate leaves and the root length increased but the root dry weight decreased. Also the values of maximum photochemical efficiency of PSII (F(v)/F m) showed a significant decrease. Dark-adapted minimum fluorescence (F 0) significantly increased in the presence of 200 mg L(-1) nanoceria and 400 mg L(-1) bulk material. Root tissues were more sensitive to nanoceria than were the shoots at lower concentrations of nanoceria. A stress effect was observed on M. arborea plantlets due to cerium uptake.

The Presence of Mutations in the K-RAS Gene Does Not Affect Survival after Resection of Pulmonary Metastases from Colorectal Cancer.

Introduction. Our objective was to identify mutations in the K-RAS gene in cases of pulmonary metastases from colorectal cancer (CRC) and determine whether their presence was a prognostic factor for survival. Methods. We included all patients with pulmonary metastases from CRC operated on between 1998 and 2010. K-RAS mutations were investigated by direct sequencing of DNA. Differences in survival were explored with the Kaplan-Meier method log-rank tests and multivariate Cox regression analysis. Results. 110 surgical interventions were performed on 90 patients. Factors significantly associated with survival were disease-free interval (P = 0.002), age (P = 0.007), number of metastases (P = 0.001), lymph node involvement (P = 0.007), size of the metastases (P = 0.013), and previous liver metastasis (P = 0.003). Searching in 79 patients, K-RAS mutations were found in 30 cases. We did not find statistically significant differences in survival (P = 0.913) comparing native and mutated K-RAS. We found a higher rate of lung recurrence (P = 0.040) and shorter time to recurrence (P = 0.015) in patients with K-RAS mutations. Gly12Asp mutation was associated with higher recurrence (P = 0.022) and lower survival (P = 0.389). Conclusions. The presence of K-RAS mutations in pulmonary metastases does not affect overall survival but is associated with higher rates of pulmonary recurrence.

Integrating classical and molecular approaches to evaluate the impact of nanosized zero-valent iron (nZVI) on soil organisms.

Nanosized zero-valent iron (nZVI) is a new option for the remediation of contaminated soil and groundwater, but the effect of nZVI on soil biota is mostly unknown. In this work, nanotoxicological studies were performed in vitro and in two different standard soils to assess the effect of nZVI on autochthonous soil organisms by integrating classical and molecular analysis. Standardised ecotoxicity testing methods using Caenorhabditis elegans were applied in vitro and in soil experiments and changes in microbial biodiversity and biomarker gene expression were used to assess the responses of the microbial community to nZVI. The classical tests conducted in soil ruled out a toxic impact of nZVI on the soil nematode C. elegans in the test soils. The molecular analysis applied to soil microorganisms, however, revealed significant changes in the expression of the proposed biomarkers of exposure. These changes were related not only to the nZVI treatment but also to the soil characteristics, highlighting the importance of considering the soil matrix on a case by case basis. Furthermore, due to the temporal shift between transcriptional responses and the development of the corresponding phenotype, the molecular approach could anticipate adverse effects on environmental biota.

Dietary probiotic supplementation (Shewanella putrefaciens Pdp11) modulates gut microbiota and promotes growth and condition in Senegalese sole larviculture.

Probiotic supplementation in fish aquaculture has significantly increased in the last decade due to its beneficial effect on fish performance. Probiotic use at early stages of fish development may contribute to better face metamorphosis and weaning stress. In the present work, we studied the influence of Shewanella putrefaciens Pdp11 supplementation on growth, body composition and gut microbiota in Senegalese sole (Solea senegalensis) during larval and weaning development. S. putrefaciens Pdp11 was incorporated using Artemia as live vector (2.5 × 107 cfu mL⁻¹) and supplied to sole specimens in a co-feeding regime (10-86 DAH) by triplicate. Probiotic addition promoted early metamorphosis and a significantly higher growth in length at 24 DAH larvae. S. putrefaciens Pdp11 also modulated gut microbiota and significantly increased protein content and DHA/EPA ratios in sole fry (90 DAH). This nutritional enhancement is considered especially important after weaning, where significantly higher growth in length and weight was observed in probiotic fish. Moreover, a less heterogeneous fish size in length was detected since metamorphosis till the end of weaning, being of interest for sole aquaculture production. After weaning, fish showed significantly higher growth (length and weight) and less variable lengths in fish when supplemented with probiotics. Both the enhancement of nutritional condition and the decrease in size variability associated with probiotic addition are highly interesting for sole aquaculture production.

Determinación de grupo de bajo riesgo para tener nódulos metastásicos no detectados por tomografía axial computarizada en la cirugía de las metástasis pulmonares / Determination of a Low Risk Group for Having Metastatic Nodules Not Detected by Computed Tomography Scan in Lung Metastases Surgery

Introducción: En los últimos años existe un debate en relación con la exactitud diagnóstica de la tomografía axial computarizada (TAC) para identificar metástasis pulmonares y la necesidad de la palpación pulmonar para determinar el número de nódulos metastásicos. El objetivo del estudio fue determinar en qué pacientes era más eficaz la TAC para detectar todas las metástasis. Métodos: Se estudiaron todos los pacientes operados de metástasis pulmonar con intención curativa a través de toracotomía entre 1998 y 2012. Todos los casos fueron revisados preoperatoriamente por 2 radiólogos expertos en pulmón. Para el análisis estadístico se utilizó el programa Systat versión 13. Resultados: Ciento ochenta y tres pacientes (63,6% varones) con una edad media de 61,7 años a los que se les realizaron 217 intervenciones. La TAC acertó en 185 casos (85,3%). Discordancias observadas: 26 pacientes (11,9%) con más metástasis resecadas que las observadas y 6 casos (2,8%) con menos metástasis. Agrupando a los pacientes de origen colorrectal con una o 2 metástasis y metástasis única de cualquier origen, la probabilidad de resecar nódulos extras fue del 9,5%. En el resto la probabilidad fue del 27,8%, observándose diferencias estadísticamente significativas (p = 0,001). La edad media de los pacientes en los que no aparecieron nódulos no observados fue de 62,9 años, frente a 56,5 años de media en los pacientes que se escapaba alguna metástasis (p = 0,001). Conclusiones: Se consideró grupo con baja probabilidad de resecar más metástasis que las observadas a los pacientes mayores de 60 años con una o 2 metástasis de origen colorrectal o una de otro origen (AU)

Introduction: In recent years, there has been debate regarding the diagnostic accuracy of computed tomography (CT) in the identification of lung metastases and the need for lung palpation to determine the number of metastatic nodules. The aim of this study was to determine in which patients the CT scan was more effective in detecting all metastases. Methods: We studied all patients who underwent curative thoracotomy for pulmonary metastasis between 1998 and 2012. All cases were reviewed by two expert pulmonary radiologists before surgery. Statistical analyses were performed using Systat version 13. Results: The study included 183 patients (63.6% male) with a mean age of 61.7 years who underwent 217 interventions. The CT scan was correct in 185 cases (85.3%). Discrepancies observed: 26 patients (11.9%) with more metastases resected than observed and 6 cases (2.8%) with fewer metastases. In patients with one or two metastases of colorectal origin or a single metastasis of any other origin, the probability of finding extra nodules was 9.5%. In the remaining patients, the probability was 27.8%, with statistically significant differences (P=0.001). The mean age of the patients in whom no unobserved nodules were detected was 62.9 years compared to 56.5 years on average in patients who were free from any metastases (P=0.001). Conclusions: Patients older than 60 years, with one or two metastases of colorectal origin or a single metastasis from any other origin were considered to be the group with low probability of having more metastases resected than observed (AU)

Determination of a low risk group for having metastatic nodules not detected by computed tomography scan in lung metastases surgery.

INTRODUCTION: In recent years, there has been debate regarding the diagnostic accuracy of computed tomography (CT) in the identification of lung metastases and the need for lung palpation to determine the number of metastatic nodules. The aim of this study was to determine in which patients the CT scan was more effective in detecting all metastases. METHODS: We studied all patients who underwent curative thoracotomy for pulmonary metastasis between 1998 and 2012. All cases were reviewed by two expert pulmonary radiologists before surgery. Statistical analyses were performed using Systat version 13. RESULTS: The study included 183 patients (63.6% male) with a mean age of 61.7 years who underwent 217 interventions. The CT scan was correct in 185 cases (85.3%). Discrepancies observed: 26 patients (11.9%) with more metastases resected than observed and 6 cases (2.8%) with fewer metastases. In patients with one or two metastases of colorectal origin or a single metastasis of any other origin, the probability of finding extra nodules was 9.5%. In the remaining patients, the probability was 27.8%, with statistically significant differences (P=.001). The mean age of the patients in whom no unobserved nodules were detected was 62.9 years compared to 56.5 years on average in patients who were free from any metastases (P=.001). CONCLUSIONS: Patients older than 60 years, with one or two metastases of colorectal origin or a single metastasis from any other origin were considered to be the group with low probability of having more metastases resected than observed.

Letter: Photodistributed reticulated hyperpigmentation related to diltiazem.

Diltiazem is a calcium channel blocking agent used for the treatment of hypertension. Cutaneous adverse effects are uncommon. The most frequently reported are itching, urticaria, and maculopapular eruption. A peculiar, cutaneous photodistributed reticulated hyperpigmentation secondary to diltiazem has been recently reported. A 66-year-old white woman with a 2 year history of pruritic hyperpigmented lesions on her face was seen in the clinic. Past medical history was remarkable for hypertension, which had been treated with diltiazem. Physical examination showed slate-gray to brown reticulated hyperpigmentation in the photo-exposed areas of the face and neck. Histological examination revealed interface dermatitis with liquefactive degeneration of the basal layer, necrotic keratinocytes, lymphocytic inflammatory infiltrate, and melanophages in the superficial dermis. A diagnosis of diltiazem-induced hyperpigmentation was established and diltiazem was stopped. Gradual resolution of the hyperpigmentation was observed over the following months. Although diltiazem has been marketed for over 20 years, the first cases of this particular type of reticulated hyperpigmentation were described in 2001. Since then, to our knowledge, only 17 cases have been reported in the literature. In all cases, cutaneous lesions appeared at least 6 months after this treatment had been started. Hyperpigmentation was controlled by means of photoprotection and discontinuation of diltiazem. Diltiazem can produce a characteristic lichenoid dermatitis with reticulated hyperpigmentation on sun-exposed areas.

Habilidad de cuidado de cuidadores familiares principales de pacientes con ACV: Cartagena (Colombia) / Care abilities of familiy caregiver the principal of patients with VCA: Cartagena (Colombia)

El accidente cerebrovascular (ACV) es la enfermedad neurológica que más incapacidad e institucionalización origina. Su alta supervivencia no es pareja a una recuperación total, pues hasta el noventa por ciento sufre secuelas, lo cual genera una demanda de cuidados y la presencia de un cuidador para realizar las actividades básicas. Estos cuidadores están expuestos a padecer cambios en su vida que afectan sus diferentes roles, lo cual los convierte en una población vulnerable que requiere atención de los servicios de salud. Objetivo: Identificar las habilidades de cuidado de los cuidadores principales de los pacientes con secuelas de ACV en Cartagena. Método: Estudio descriptivo, realizado a 152 cuidadores de pacientes con secuelas de ACV en la ciudad de Cartagena. Se utilizaron dos instrumentos: Caracterización de los Cuidadores e Inventario de Habilidad de Cuidado, instrumento que mide la habilidad de cuidado en las dimensiones conocimiento, valor y paciencia. Resultados: Los cuidadores en su mayoría son mujeres en edad adulta, menores que el sujeto de cuidado, dedicadas al hogar, llevan más de 37 meses dedicados al cuidado, no son las únicas cuidadoras; primer grado de consanguinidad (51,3%), presentan habilidad de cuidado media. Las dimensiones de habilidad de cuidado, el conocimiento (75,7%) y la paciencia (87,5%) estuvieron en categoría alta y el valor en categoría alta (2,6%). Conclusiones: Los cuidadores de personas con ACV no cuentan con la habilidad necesaria para establecer la relación de cuidado, es necesario realizar intervenciones orientadas a disminuir los riegos del rol de cuidador.

Cerebrovascular accident (CVA) is the neurological disease that causes more disability and institutionalization. Its high survival is not even a full recovery, since until ninety percent suffer consequences, creating a demand for care and the presence of a caregiver to perform the basic activities. These caregivers are exposed to suffer changes in their lives that affect different roles, making them a vulnerable population that requires care from health services. Objective: Identify the skills of care from care givers of patients with sequelae of CVA in Cartagena. Method: Descriptive study, made to 152 caregivers of patients with sequelae of CVA in the city of Cartagena. It was used two instruments, Characterization of the care givers and Inventory Caregiver's Ability to Care, an instrument that measures the ability of care in the dimensions knowledge, courage and patience. Results: Caregivers are mostly women in adulthood, younger than the subject of care, homemakers. They have more than 37 months devoted to the care, generally there are more carers, they have first degree of consanguinity (51.3%), and average ability to care. The dimensions of caring ability, knowledge (75.7%) patience (87.5%) and courage (2.6%) were in the high category. Conclusions: Caregivers of people with ACV, do not have the skills necessary to establish the relationship of care, interventions are needed to reduce the risks of the caregiver role.

Intestinal microbiota diversity of the flat fish Solea senegalensis (Kaup, 1858) following probiotic administration.

Pleuronectiforms are an important group of fish, and one of their species, Solea senegalensis (Kaup 1858), has been extensively studied at different levels, although information about its intestinal microbiota and the effects of different factors on it is very scarce. Modern aquaculture industry demands strategies which help to maintain a microbiologically healthy environment and an environmentally friendly aquaculture. In this context, probiotics seem to offer an attractive alternative. The intake of probiotics could modify the composition of the intestinal microbiota, which is a key component in excluding potential invaders and maintaining health. The aim of this study was to evaluate by 16S rRNA gene analysis using polymerase chain reaction-denaturing gradient gel electrophoresis the effect of administering fresh or lyophilized cells of Pdp11 on the intestinal microbiota of farmed Senegalese sole, using sodium alginate to facilitate the incorporation of bacterial cells to the feed. The results obtained showed that the composition of fish intestinal microbiota was affected when fish received a diet supplemented with sodium alginate and fresh or lyophilized probiotic cells. In all cases, the dominant bacterial groups belonged to γ-Proteobacteria and mainly the Vibrio species. The use of sodium alginate reduced the incidence of populations with <97% 16S rRNA gene sequence identity to uncultured microorganisms in the intestinal microbiota until non-detected limits. On the other hand, the supplementation of the diet with probiotics produced an increase of the predominant species related to Vibrio genus.

Creatinina sérica elevada en el paciente hipotiroideo: miopatía o verdadera nefropatía?: propuesta de clasificación / Elevated serum creatinine in hypothyroidism: myopathy or real nephropathy?: classification proposal

En el paciente hipotiroideo la creatinina sérica puede aumentar no solo por fallo renal, sino también por miopatía en presencia de función renal normal. Se reportan 2 pacientes representativos de sendos tipos de la clasificación aquí propuesta sobre la asociación disfunción tiroidea / creatinina sérica. El primer enfermo presenta aumento de la creatinina sérica secundario a miopatía hipotiroidea con función renal normal, tipo I, esta se puede complicar con rabdomiolisis y causar insuficiencia renal aguda en hipotiroideos no diagnosticada. El otro paciente con creatina sérica alta mejoró su función renal al tratarse su hipotiroidismo, tipo 2. Ocasionalmente, este ha permanecido oculto y al ser diagnosticado y tratado, se mejora la función renal. El hipotiroidismo cursa con hipercolesterolemia y si no se valora la función tiroidea y se administran estatinas, se empeora el daño muscular del paciente. Lo mismo ha sucedido con el uso de gemfibrozil en condiciones similares. El tercer tipo de daño renal relacionado con hipotiroidismo es la proteinuria en rango de síndrome nefrótico, vinculada con suspensión de la levotiroxina. Las biopsias muestran lesiones histológicas de diversas glomerulopatías, que mejoran con la administración de levotiroxina. En pacientes con tiroiditis de Hashimoto aparecen otras glomerulopatías que responden a los glucocorticoides...

In patients with hypothyroidism is possible to find an increased serum creatinine not only due to renalfailure but to myopathy in presence of normal renal function. Two patients, each representing 1 type of a proposed classification regarding thyroid dysfunction and abnormal creatinine are presented, in order to communicate thisrelationship, until now based on isolated reports. The first individual had an increased serum creatinine withnormal renal function due to hypothyroid myopathy (type 1). Rhabdomyolysis related to this myopathy is pointed as a cause of acute renal failure. The 2nd patient had an increased serum creatinine with abnormal kidney function (type 2),which improved when he became euthyroid after levothyroxine administration. The diagnosis of hypothyroidism is often missed in patients with altered renal function, if it becomes evident and is properly treated the renal function will improve. As isknown hypothyroidism causes hypercholesterolemia, if such patient unknowingly receives statins or gemfibrozil, severe rhabdomyolysis and renal falilure may occur, as reported inthe literature. The 3d category of the classification is the occurrence of nephrotic syndrome in hypothyroid patients who discontinue T4 treatment due to thyroid cancer for further studies or by patient non adherence, developingsignificant proteinuria few months later. Kidney biopsy lesions vary from membranous glomerulopathy tomembranoproliferative glomerulonephritis. These findingswill resolve with the administration of levothiroxine, without glucocorticoids. However patients with nephrotic syndrome related to Hashimoto thyroiditis will improve withglucocorticoids.

Application of fluorescence in situ hybridization technique to detect simazine-degrading bacteria in soil samples.

We propose a new approach to evaluate the natural attenuation capacity of soil by using fluorescence in situ hybridization (FISH). A specific oligonucleotide probe AtzB1 was designed based on the sequence data of the atzB gene involved in the hydrolytic deamination of s-triazines; this gene, located in a multiple copy plasmid was detected by the optimized FISH protocol. Two agricultural soils (Lodi and Henares) with a history of simazine treatments, and two natural soils (Soto and Monza), without previous exposure to simazine, were studied. AtzB1 probe-target cells were found only in the agricultural soils and, in a greater percentage, in the Lodi soil, compared to the Henares one. Moreover, the greatest percentage of AtzB1 probe-target cells in Lodi was accompanied by a greater mineralization rate, compared to the Henares soil. The FISH method used in this study was suitable for the detection of simazine-degrading bacteria and could be a useful indicator of the potential of soil bioremediation.

[Expression of proteins associated with multidrug resistance and resistance to chemotherapy in lung cancer]. / Expresión de proteínas relacionadas con resistencia a múltiples fármacos y resistencia a la quimioterapia en el cáncer de pulmón.

OBJECTIVE: Membrane transporters are proteins that play a crucial role in resistance to chemotherapy. The aim of this study was to assess the influence of membrane transporter protein expression on chemotherapeutic response. MATERIAL AND METHODS: One hundred and forty seven samples of tumor tissue were collected from 143 patients; 35 samples were obtained by bronchoscopy and 112 were surgical specimens. A total of 101 samples from 99 patients were adequate for study. Cryopreserved samples were subjected to immunohistochemical analysis to detect 3 proteins associated with multidrug resistance: P-glycoprotein (Pgp), multidrug-resistance-associated protein 1 (MRP1), and lung resistance protein (LRP). RESULTS: In 16 cases none of the proteins were expressed. A single protein was expressed in 32 (3 Pgp, 11 MRP1, and 18 LRP); 2 in 34 cases (24 Pgp and LRP; 5 MRP1 and Pgp; 5 MRP1 and LRP); and all 3 in 17 cases. No significant relationship was found between age and the expression of Pgp (P=.74), MRP1 (P=.95), or LRP (P=.26). Nor were there significant differences in number (P=.72) or type of coexpressed proteins (P=.39) by sex, by tumor stage (number, P=.55; type, P=.21), or by tumor grade (number, P=.59; type, P=.51). There was a highly significant trend toward coexpression of Pgp and LRP (P< .01) but not of Pgp and MRP1 (P=.18) or MRP1 and LRP (P=.26). MRP1 was expressed less often in adenocarcinoma. LRP was expressed less often in squamous cell carcinoma than in adenocarcinoma and undifferentiated large cell carcinoma. Coexpression of Pgp, MRP1, and LRP was observed most often in squamous cell carcinoma. CONCLUSIONS: Proteins associated with multidrug resistance are commonly expressed in lung cancer. Of the 3 proteins studied, LRP was the one most often found. Coexpression of more than 1 of the proteins was found in a considerable percentage of patients. Pgp was mainly found to be coexpressed with LRP. Pgp expression and the number of coexpressed proteins seemed to have a negative impact on response to chemotherapy.