Molecular Adaptations of BDNF/NT-4 Neurotrophic and Muscarinic Pathways in Ageing Neuromuscular Synapses.

Age-related conditions, such as sarcopenia, cause physical disabilities for an increasing section of society. At the neuromuscular junction, the postsynaptic-derived neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NT-4) have neuroprotective functions and contribute to the correct regulation of the exocytotic machinery. Similarly, presynaptic muscarinic signalling plays a fundamental modulatory function in this synapse. However, whether or not these signalling pathways are compromised in ageing neuromuscular system has not yet been analysed. The present study analyses, through Western blotting, the differences in expression and activation of the main key proteins of the BDNF/NT-4 and muscarinic pathways related to neurotransmission in young versus ageing Extensor digitorum longus (EDL) rat muscles. The main results show an imbalance in several sections of these pathways: (i) a change in the stoichiometry of BDNF/NT-4, (ii) an imbalance of Tropomyosin-related kinase B receptor (TrkB)-FL/TrkB-T1 and neurotrophic receptor p 75 (p75NTR), (iii) no changes in the cytosol/membrane distribution of phosphorylated downstream protein kinase C (PKC)ßI and PKCε, (iv) a reduction in the M2-subtype muscarinic receptor and P/Q-subtype voltage-gated calcium channel, (v) an imbalance of phosphorylated mammalian uncoordinated-18-1 (Munc18-1) (S313) and synaptosomal-associated protein 25 (SNAP-25) (S187), and (vi) normal levels of molecules related to the management of acetylcholine (Ach). Based on this descriptive analysis, we hypothesise that these pathways can be adjusted to ensure neurotransmission rather than undergoing negative alterations caused by ageing. However, further studies are needed to assess this hypothetical suggestion. Our results contribute to the understanding of some previously described neuromuscular functional age-related impairments. Strategies to promote these signalling pathways could improve the neuromuscular physiology and quality of life of older people.

Evidence of viral dissemination and seasonality in a Mediterranean river catchment: Implications for water pollution management.

Conventional wastewater treatment does not completely remove and/or inactive viruses; consequently, viruses excreted by the population can be detected in the environment. This study was undertaken to investigate the distribution and seasonality of human viruses and faecal indicator bacteria (FIB) in a river catchment located in a typical Mediterranean climate region and to discuss future trends in relation to climate change. Sample matrices included river water, untreated and treated wastewater from a wastewater treatment plant within the catchment area, and seawater from potentially impacted bathing water. Five viruses were analysed in the study. Human adenovirus (HAdV) and JC polyomavirus (JCPyV) were analysed as indicators of human faecal contamination of human pathogens; both were reported in urban wastewater (mean values of 10(6) and 10(5) GC/L, respectively), river water (10(3) and 10(2) GC/L) and seawater (10(2) and 10(1) GC/L). Human Merkel Cell polyomavirus (MCPyV), which is associated with Merkel Cell carcinoma, was detected in 75% of the raw wastewater samples (31/37) and quantified by a newly developed quantitative polymerase chain reaction (qPCR) assay with mean concentrations of 10(4) GC/L. This virus is related to skin cancer in susceptible individuals and was found in 29% and 18% of river water and seawater samples, respectively. Seasonality was only observed for norovirus genogroup II (NoV GGII), which was more abundant in cold months with levels up to 10(4) GC/L in river water. Human hepatitis E virus (HEV) was detected in 13.5% of the wastewater samples when analysed by nested PCR (nPCR). Secondary biological treatment (i.e., activated sludge) and tertiary sewage disinfection including chlorination, flocculation and UV radiation removed between 2.22 and 4.52 log10 of the viral concentrations. Climate projections for the Mediterranean climate areas and the selected river catchment estimate general warming and changes in precipitation distribution. Persistent decreases in precipitation during summer can lead to a higher presence of human viruses because river and sea water present the highest viral concentrations during warmer months. In a global context, wastewater management will be the key to preventing environmental dispersion of human faecal pathogens in future climate change scenarios.

Estudio inmunohistoquímico de moléculas de adhesión en placentas de niños de bajo peso al nacer en el Hospital Universidad del Norte, Barranquilla (Colombia) / Immunohistochemical studies of adhesion molecules in placentas from low birth infants at Hospital Universidad of the Norte, Barranquilla (Colombia)

Objetivo: Observar la expresión de moléculas de adhesión VCAM-1, ICAM-1 en placentas de niños de bajo peso al nacer. Se estudiaron 21 placentas de pacientes atendidas en el Hospital Universidad del Norte en el periodo de mayo a diciembre de 2006. Materiales y métodos: Se realizó estudio macroscópico de las placentas: forma, peso, diámetro grosor, consistencia, color, olor. Para estudios microscópicos se realizaron 5 cortes de la placa corial, uno del rollo de membrana y otro del cordón umbilical. Los cortes fueron fijados en formol al 10 %, incluidos en parafina, coloreados con hematoxilia - eosina para estudios morfológicos. Para estudios inmunohistoquímicos se usaron anticuerpos mono-clonales Nova Castra para ICAM-1, VCAM-1, macrófagos. Resultados: Dieciocho placentas de forma redonda, 3 ovaladas; el peso varió entre 240 -400 gramos; 3 presentaron infarto en los cotiledones. En la micro 18 presentaron necrosis hialina de la media, hiperplasia de la intima, macrófagos xantomatosos, infiltrado linfoci-tario en tres. En la inmunohistoquímica se observó expresión de ICAM-1, VCAM-1, en la basal de las vellosidades coriales, en la basal de los vasos sanguíneos y macrófagos en el estroma conjuntivo Conclusiones: En dieciocho de los casos los cambios fueron compatibles con preeclampsia, tres con proceso virales. La expresión de moléculas de adhesión y macrófago en la inmunohistoquímica nos sugiere que estas moléculas son fundamentales en los proceso fisiopatológicos de la placenta.

Objective: To observe the expression of adhesion molecules VCAM -1, ICAM -1 in placentas of infants with low birthweight 21 placentas of patients treated at the University Hospital North in the period from May to December were studied 2006. Materials and methods: Macroscopic study of the placentas was performed; shape, weight, diameter, thickness, consistency, color, and odor: For five cuts microscopic studies chorionic plate, one membrane roll and another cord were performed. The sections were fixed in 10 % formalin, embedded in paraffin, stained with hematoxylin-eosin for morphological studies. For immunohistochemical studies monoclonal antibodies were used castra nova for ICAM1, VCAM1, macrophages. Results: 18 placentas round, three oval, the various weight between 240-400 grams, 3 had infarction in the cotyledons. In the micro 18 presented hyaline medial necrosis, hyperplasia of the intima, xanthomatous macrophages, lymphocytic infiltrate in three . In the immunohistochemical expression of ICAM-1, VCAM-1 was observed in the basal of chorionic villi in the basal blood vessel and macrophages in stroma. Conclusions: cases changes are compatible with pre -eclampsia, three viral process. The expression of adhesion molecules and macrophage in immunohistochemistry suggests that these molecules are critical in the pathophysiological process of the placenta.