Living in an Extremely Polluted Environment: Clues from the Genome of Melanin-Producing Aeromonas salmonicida subsp. pectinolytica 34melT.

Aeromonas salmonicida subsp. pectinolytica 34mel(T) can be considered an extremophile due to the characteristics of the heavily polluted river from which it was isolated. While four subspecies of A. salmonicida are known fish pathogens, 34mel(T) belongs to the only subspecies isolated solely from the environment. Genome analysis revealed a high metabolic versatility, the capability to cope with diverse stress agents, and the lack of several virulence factors found in pathogenic Aeromonas. The most relevant phenotypic characteristics of 34mel(T) are pectin degradation, a distinctive trait of A. salmonicida subsp. pectinolytica, and melanin production. Genes coding for three pectate lyases were detected in a cluster, unique to this microorganism, that contains all genes needed for pectin degradation. Melanin synthesis in 34mel(T) is hypothesized to occur through the homogentisate pathway, as no tyrosinases or laccases were detected and the homogentisate 1,2-dioxygenase gene is inactivated by a transposon insertion, leading to the accumulation of the melanin precursor homogentisate. Comparative genome analysis of other melanogenic Aeromonas strains revealed that this gene was inactivated by transposon insertions or point mutations, indicating that melanin biosynthesis in Aeromonas occurs through the homogentisate pathway. Horizontal gene transfer could have contributed to the adaptation of 34mel(T) to a highly polluted environment, as 13 genomic islands were identified in its genome, some of them containing genes coding for fitness-related traits. Heavy metal resistance genes were also found, along with others associated with oxidative and nitrosative stresses. These characteristics, together with melanin production and the ability to use different substrates, may explain the ability of this microorganism to live in an extremely polluted environment.

Modulación de reflejos cutáneos locales después de lesión medular: implicaciones para la neuro-rehabilitación / Local cutaneous reflex modulation following spinal cord injury: implications for neurorehabilitation

Objetivo: Evaluar el estado de las vías inhibitorias medulares mediante la modulación de reflejos cutáneos locales (RCL) y normalizar su actividad mediante la aplicación de un estímulo vibratorio. Material y método: Se dividió el estudio en dos fases, 1: voluntarios sanos, pacientes con lesión medular incompleta (LMi) sin espasticidad y pacientes con LMi con espasticidad. 2: voluntarios sanos y pacientes con LMi. En ambas fases los sujetos realizaron un ejercicio continuo de tobillo con fases de reposo (REP) y de flexión plantar concéntrica (CON) e isométrica (ISO 50). Se evocaron RCL durante las tres fases del ejercicio registrando la actividad electromiográfica en tibial anterior (TA) y gemelo medial (GM). En la fase 2 se añadió un estímulo vibratorio en la planta del pie para comprobar su efecto sobre los RCL. Resultados: Los voluntarios sanos y el grupo sin espasticidad mostraron una inhibición del TA en las fases de movimiento mientras que en el grupo con espasticidad no hubo modulación de la respuesta. Conclusiones: La aplicación de estímulos vibratorios podría influir sobre mecanismos inhibitorios medulares alterados en pacientes con LMi con espasticidad (AU)

Objetive: To evaluate the general state of inhibitory spinal pathways measuring local cutaneous reflexes (LCR) modulation and normalize this activity through the application of vibratory stimuli. Methods: This study was performed in two phases. In phase 1, healthy volunteers and patients with incomplete spinal cord injury (iSCI) with or without spasticity were examined. In phase 2, healthy volunteers and patients with iSCI were examined. In both studies subjects performed an ankle continuous exercise with phases of rest (REP), concentric (CON) and isometric (ISO 50) plantarflexion. RCL activity was evoked during the three specific movements measuring electromyographic activity in the Tibialis Anterior (TA) and Gastrocnemious Medialis (GM). In the second study phase, vibratory stimuli were applied to the plantar surface of the foot to measure the effect on RCL activity. Results: In the phase I study, both the healthy and the patient group without spasticity revealed an inhibition of TA RCL activity in both plantarflexion exercises, while no such modulation was observed in the spasticity group. Conclusions: : The application of vibratory stimuli could mediate in inhibitory spinal mechanisms altered in patients with iSCI with spasticity (AU)

Crataegus laevigata decreases neutrophil elastase and has hypolipidemic effect: a randomized, double-blind, placebo-controlled trial.

Crataegus laevigata is a medicinal plant most commonly used for the treatment of heart failure and psychosomatic disorders. Based on previous experimental findings, this double-blind placebo-controlled study was aimed at finding beneficial effects of C. laevigata on biomarkers of coronary heart disease (CHD). The study included 49 diabetic subjects with chronic CHD who were randomly assigned to the treatment for 6 months with either a micronized flower and leaf preparation of C. laevigata (400 mg three times a day) or a matching placebo. Blood cell count, lipid profile, C-reactive protein, neutrophil elastase (NE) and malondialdehyde were analyzed in plasma at baseline, at one month and six months. The main results were that NE decreased in the C. laevigata group compared to the placebo group. In the C. laevigata group, baseline figures (median and interquartile range) were 35.8 (4.5) and in the placebo group 31 (5.9). At the end of the study, values were 33.2 (4.7) ng/ml and 36.7 (2.2) ng/ml, respectively; p<0.0001. C. laevigata, added to statins, decreased LDL cholesterol (LDL-C) (mean±SD) from 105±28.5 mg/dl at baseline to 92.7±25.1 mg/dl at 6 months (p=0.03), and non-HDL cholesterol from 131±37.5 mg/dl to 119.6±33 mg/dl (p<0.001). Differences between groups did not reach statistical significance at 6 months. No significant changes were observed in the rest of parameters. In conclusion, C. laevigata decreased NE and showed a trend to lower LDL-C compared to placebo as add-on-treatment for diabetic subjects with chronic CHD.

Arsenic- and mercury-induced phytotoxicity in the Mediterranean shrubs Pistacia lentiscus and Tamarix gallica grown in hydroponic culture.

Hg and As resistance and bioaccumulation were studied in hydroponically grown Pistacia lentiscus and Tamarix gallica plants. Both elements caused growth inhibition in roots and shoots, with mercury showing greater phytotoxicity than arsenic. Accumulation of both elements by plants increased in response to element supply, with the greatest uptake found in T. gallica. Both elements affected P and Mn status in plants, reduced chlorophyll a concentration and increased MDA and thiol levels. These stress indices showed good correlations with As and Hg concentration in plant tissues, especially in the roots. Toxic responses to mercury were more evident than for arsenic, especially in shoot tissues. T. gallica showed higher resistance to both Hg and As than P. lentiscus, as well accumulating more As and Hg.

Estatus pro-oxidante en niños del Valle de Mezquital, Hidalgo (México) / No disponible

El objetivo ha sido demostrar que el retraso en el crecimiento de la niñez está asociado a un estatus pro-oxidante. Se estudiaron niños indígenas con edades entre 9 y 11 años, residentes en el Valle del Mezquita!, Hidalgo, México. Las mediciones clínicas y antropométricas fueron realizadas utilizando técnicas estándares. En muestras de sangre se determinaron contenidos de vitaminas E y A, contenidos de metales (Cu, Mn, Fe, Zn y Se) y se determinaron los contenidos de sustancias reactivas al ácido tio-barbitúrico (SRATE1). Los niños del grupo experimental mostraron concentración disminuida de vitamina E (643.8 ± 11.3 y 529.3 .÷, 89 pgidL) y de vitamina A (28.9 ± 3.5 y 26.4 ± 2.5 wgidIL), con respecto a los niños del grupo control. La relación vitamina EiSF?A7-8 resultó más alta en el grupo control (1458.8 I- 736) comparado con el grupo experimental (1003 ± 535.3); las niñas presentaron valores más altos de este cociente que los niños. No se ha podido asociar la prosenda de un estatus pro-oxidante, ya que no se encontraron variaciones significativas. De los resultados SRATB y concentraciones de hierro resultaron más elevados en el grupo experimental que en el grupo control, pero no estadísticamente diferentes. Se propone considerar una suplementación de vitaminas antioxidantes para prevenir dicho estado y la capacidad potencial para inducir daño en células y tejidos finos. Se recomienda realizar otros estudios que permitan demostrar la capacidad antioxidante medida en suero. con determinaciones de capacidades antioxidantes de enzimas en estos niños. Se incrementa la posibilidad de que el estatus oxidante esté presente. dada la capacidad antioxidante disminuida por déficit de vitamina E y A y disminución de la relación SRATB/vitamina relacionado con el pobre desarrollo y la baja estatura (AU)

To test the hypothesis that growth retardation in early childhood might be associated to an oxidant stress status, 9-11 aged, living in Mezquita/ Valley (Hidalgo, México) were studied. Clinical and anth-ropometric measures were made using standard techniques. Blood samples were obtained by venous puncture. Vitamins E and C, copper, iron manganese, zinc: selenium and TBARS (thiobabituic acid reactive substances) were measured. Stunted children showed a decreased vitamin E (643.8 ± 11.3 to 529.3 -± 89 ug/dL) and A (28.9 ± a5 to 26.4 ± 2.5 pg/d/L) serum concentration than control group. The ratio Vitamin E/ TBARS were loo higher in control group (1458.8 ± 736) when was compared with stunted group (1003 ± 535.3). The girls showed higher values of this ratio than boys, in both control and stunted groups. From the data presented herein is not possible to associate the presence of oxidant stress status due the absence of statistical significances. In both, TBARS and iron the concentrations measure we-re higher in stunted group, but not statistically different compared with control group. Due the potential pre-oxidative stress status of student children, we propose to take in consideration the sup-plementation of antioxidant vitamins in those children in order to prevent the oxidative stress status, and its potential capacity for induce damage of cells and tissues and dysfunctional consequences. On the other hand, it is necessary to carry out other studies conducing to measured antioxidant serum capacity including antioxidant enzymes determinations in student children. Finally our data and observations raises the possibility that oxidative status due to decreased antioxidant capacity (vitamin E, A, TBRS/vitamin E) presented in stunted children, might be related with the low development of height in this children (AU)

Discrepancy between antibiotics administered in acute exacerbations of chronic bronchitis and susceptibility of isolated pathogens in respiratory samples: multicentre study in the primary care setting.

A national multicentre prevalence study was undertaken to determine the bacterial strains associated with mild-to-moderate acute exacerbations of chronic bronchitis (AECB) in the primary care setting and the susceptibility of isolated pathogens to different antimicrobials usually prescribed to these patients. All samples were processed by a central reference laboratory. Microdilution tests were carried out to establish the minimum inhibitory concentration (MIC) of various antimicrobials. A double-disk test was performed to establish the macrolide resistance phenotype in Streptococcus pneumoniae. Tests to detect the presence of beta-lactamase in Haemophilus influenzae and Moraxella catarrhalis and polymerase chain reaction to detect the presence of ermB and mefA genes in S. pneumoniae isolates were also performed. A total of 1537 patients were included in the trial and 468 microorganisms were isolated from sputum samples, with the most frequent isolates being S. pneumoniae (34.8%), M. catarrhalis (23.9%) and H. influenzae (12.6%). Resistance rates of pneumococci were 47.2% for penicillin, 1.2% for amoxicillin, 34.3% for macrolides (87.5% of which showed high-level resistance), 13.6% for cefuroxime/axetil and 4.2% for levofloxacin. No bacterial isolates showed resistance to telithromycin. Empirical antibiotic treatment was prescribed to 98.3% of patients, including macrolides to 36.6%, amoxicillin with or without clavulanic acid to 32.3% and fluoroquinolones to 16.1%. In conclusion, S. pneumoniae was the most frequently isolated bacteria in patients with mild-to-moderate AECB. Despite the high rates of resistance of pneumococci to macrolides, they continue to be the most widely used antibiotics in primary care to treat AECB.

Tratamiento anti-hormonal adyuvante en mujeres post-menopáusicas con diagnóstico de carcinoma de mama / Adjuvant anti-hormonal treatment of postmenopausal women with breast cancer

Durante las últimas décadas el tratamiento adyuvante anti-hormonal de elección para las pacientespost-menopáusicas con diagnóstico de carcinoma de mama localizado y con receptores hormonalespositivos ha sido el tamoxifeno al disminuir de una forma significativa el riesgo de muerte por tumor.Más recientemente, una serie de estudios comparativos utilizando tres agentes inhibidores aromatásicosde tercera generación y diferentes esquemas de administración, bien tras la cirugía inicial del primarioo después de 2-3 años o 5 años de tamoxifeno, han demostrado una ventaja en la supervivencialibre de enfermedad con respecto al tamoxifeno. Los efectos adversos acompañantes describen perfilesde toxicidad distintos entre ambos tipos de tratamiento anti-hormonal, siendo más comunes y frecuenteslos fenómenos osteo-musculares y cardiovasculares en el grupo de pacientes tratadas con inhibidoresaromatásicos así como los tromboembólicos y patología endometrial en el grupo tratado contamoxifeno. La mejor estrategia para la administración, la forma de prevenir los efectos adversos y eltipo de pacientes que más se pueden beneficiar de los inhibidores aromatásicos, quedan por ser definidoscon mayor precisión

Over the recent decades, tamoxifen has been considered the standard adjuvant treatment of postmenopausalwomen with hormone-receptor positive breast cancer based on its capacity to reduce the annualbreast cancer death. More recently, several major randomized controlled trials carried out with threedifferent new aromatase inhibitors used either from the time of primary surgery or after 2-3 or 5years of adjuvant tamoxifen therapy have shown a significant improvement in disease-free survivalwith respect to tamoxifen therapy. The described treatment-related side effects suggest different profilesof toxicity. Musculoskeletal disorders and cardiovascular events are the most serious side effectsassociated with the use of aromatase inhibitors, as well as the thromboembolic events and endometrialabnormalities are associated with tamoxifen therapy. An optimal treatment strategy for aromatase inhibitorsadministration, interventions to prevent or alleviate treatment-related side effects and identificationof women at higher risk having more benefit with aromatase inhibitors need to be addressed

Classical polymorphisms in Berbers from Moyen Atlas (Morocco): genetics, geography, and historical evidence in the Mediterranean peoples.

BACKGROUND: Mediterranean population relationships have recently been reviewed through the analysis of classical and DNA markers. The differentiation between Berbers and Arabic-speakers to the south, and the genetic impact of the seven centuries of Muslim domination in the Iberian Peninsula have been among the most interesting questions posed in these studies. AIM: The present study seeks to assess the degree of genetic affinity between the two main population groups of Morocco: Berbers and Arabic-speakers. Data from the Berber study population were also compared with published information on 20 circum-Mediterranean groups. SUBJECTS AND METHODS: A Berber sample of 140 individuals from Moyen Atlas (Morocco) has been characterized using 15 classical markers (ABO, Duffy, MNSs, Rh, ACPl, AKl, ESD, GLOI, 6-PGD, PGMl, GC, HP, PI, PLG and TF). RESULTS: Allele frequencies in the Berbers fit well into the general southern Mediterranean ranges, albeit with some peculiarities, such as the high FY*A, ACPl*C, and PI*S values. The general pattern of relationships among Mediterranean peoples tested by genetic variance analysis was compatible with a north-south geographical differentiation. Spatial auto-correlation analysis in the different geographical regions of the Mediterranean reveals that the highest degree of association between allele frequencies and geographical distances corresponds to the western (41% of significant correlograms) and northern Mediterranean populations (33%). When only southern Mediterranean groups were considered, the degree of geographical structure considerably decreases (11% of significant correlograms). CONCLUSIONS: The different loci studied revealed close similarity between the Berbers and other north African groups, mainly with Moroccan Arabic-speakers, which is in accord with the hypothesis that the current Moroccan population has a strong Berber background. Differences in the spatial pattern of allele frequencies also are compatible with specific population histories in distinct Mediterranean areas, rather than general population movements across the whole region.

[Progressive myoclonic epilepsy: clinical characteristics of 18 patients]. / Epilepsia mioclónica progresiva: caracterización clínica de 18 pacientes.

INTRODUCTION: The term progressive myoclonic epilepsy (PME) includes a groups of heterogeneous conditions, with genetic causes, characterized by having different types of seizures, basically myoclonic, and other neurological findings due to a progressive lesion of the central nervous system. OBJECTIVE: To demonstrate the aetiology and clinico-encephalographic changes seen in patients with PME. PATIENTS AND METHODS: A retrospective, descriptive study was done of patients attended for PME in the Instituto de Neurología y Neurocirugía de Cuba between 1990 and 1995. Eighteen patients were included. All were interviewed and had a physical examination, EEG and the specific complementary tests for each aetiology. RESULTS: There was a predominance of neural ceroid lipofuschinosis in 10 patients (55.5%), and in 9 of these the illness started before the age of 9 years. The second most frequent condition was myoclonic epilepsy with red-torn fibres (16.6%) and Unverricht-Lundborg disease (16.6%). The latter began in late childhood or adolescence. The most marked clinical characteristics were epilepsy, which was difficult to control and intellectual deterioration in 100%, followed by cerebellar signs in 88.8%. Myoclonias were the commonest type of seizures (94.4%) and many children presented with prior tonic-clonic seizures (88.8%). CONCLUSION: Response to treatment was poor but the best results were obtained using valproate either alone or associated with benzodiazepines.

The natriuretic effect of nifedipine gastrointestinal therapeutic system remains despite the presence of mild-to-moderate renal failure.

BACKGROUND: Calcium channel blockers facilitate the renal excretion of sodium and this effect is maintained during chronic administration of these drugs. However, it is unknown whether this natriuretic effect remains despite the presence of a decreased renal function. OBJECTIVE: To compare the natriuretic capacity of nifedipine gastrointestinal therapeutic system (GITS) and lisinopril in patients with mild-to-moderate chronic renal failure. METHODS: An open-label, randomized, comparative study was conducted to compare the natriuretic capacity of nifedipine GITS and lisinopril in the presence of mild-to-moderate renal failure (creatinine clearance 30-80 ml/min). After a wash-out period of 4 weeks an intravenous saline infusion (30 ml/kg of body weight of isotonic saline in 4 h) was performed and repeated after 4 weeks of active therapy. Two sex- and age-matched groups of hypertensive patients (n = 25) were included in the study. Renal failure was diagnosed as secondary to nephrosclerosis in all the patients. RESULTS: A significant increase in the renal capacity to excrete the sodium load was observed in patients receiving nifedipine GITS (n = 11) but not in those taking lisinopril (n = 13). Both drugs controlled blood pressure to a similar extent. No changes were observed in body weight, glomerular filtration rate and renal plasma flow (measured as inulin and paraaminohippurate clearances). A significant drop was observed in urinary albumin excretion after lisinopril, but not after nifedipine. Heart rate was higher in nifedipine group. CONCLUSION: The natriuretic capacity of nifedipine GITS remains despite the presence of mild-to-moderate chronic renal failure. Such an effect takes place in the absence of changes in renal hemodynamics, suggesting that it is caused by a direct tubular effect.