Exposures to silica and inducers of xenobiotic metabolism in the rat lung

CYP1A1 metabolizes polycyclic aromatic hydrocarbons (PAHs), such as those in cigarettes, to reactive intermediates which interact with DNA and lead to cancer. Silica is a lung carcinogen. Epidemiology studies of silica and lung cancer are not all positive. A possible explanation for these inconsistencies may be that silica is a modifier of PAH metabolism and, thus, cigarette smoke carcinogenesis. We hypothesize that crystalline silica exposure alters CYP1A1 expression, thereby modifying lung cancer risk. Rats exposed to both crystalline silica and the model PAH, beta-naphthoflavone (NF), a CYP1A1 inducer have significantly decreased CYP1A1 enzymatic activity and CYP1A1 protein expression. In the proximal alveolar region of NF-exposed rats, silica exposure increases markers of alveolar type II cells but decreases proportional CYP1A1 expression in type II cells as detected by immunofluorescence. Our experiments support the hypothesis that silica is a negative modifier of CYP1A1 induction by PAH

The effect of expectation on facilitation of colour/form conjunction tasks by TMS over area V5

In an earlier paper, we reported task-specific impairments and improvements caused by applying TMS over cortical visual area V5 [Proceedings of the Royal Society of London B 265 (1998) 537]. The phenomenon is further investigated in the present study using two of the previous tasks: a motion/form conjunction in which TMS impaired performance and a colour/form conjunction in which performance was enhanced with TMS. In the earlier experiment, subjects were presented with blocks of trials of one task type perhaps allowing some of the observed effects to arise from knowing the type of stimulus to be discriminated. When blocks of trials consisted of randomly mixed moving/form and colour/form conjunction tasks, TMS over V5 still impaired target-present responses for the moving/form conjunction, but the facilitation seen for colour/form conjunction target-present responses disappeared. We suggest that the competitive inhibition postulated between visual movement areas and colour areas in the brain, in our previous paper, are subject to expectation or knowledge of forthcoming stimulus type

Chronic kidney disease: Which role for xanthine oxidoreductase activity and products?

The present review explores the role of xanthine oxidoreductase (XOR) in the development and progression of chronic kidney disease (CKD). Human XOR is a multi-level regulated enzyme, which has many physiological functions, but that is also implicated in several pathological processes. The main XOR activities are the purine catabolism, which generates uric acid, and the regulation of cell redox state and cell signaling, through the production of reactive oxygen species. XOR dysregulation may lead to hyperuricemia and oxidative stress, which could have a pathogenic role in the initial phases of CKD, by promoting cell injury, hypertension, chronic inflammation and metabolic derangements. Hypertension is common in CKD patients and many mechanisms inducing it (upregulation of renin-angiotensin-aldosterone system, endothelial dysfunction and atherosclerosis) may be influenced by XOR products. High XOR activity and hyperuricemia are also risk factors for obesity, insulin resistance, type 2 diabetes and metabolic syndrome that are frequent CKD causes. Moreover, CKD is common in patients with gout, which is characterized by hyperuricemia, and in patients with cardiovascular diseases, which are associated with hypertension, endothelial dysfunction and atherosclerosis. Although hyperuricemia is undoubtedly related to CKD, controversial findings have been hitherto reported in patients treated with urate-lowering therapies

Ricin: An ancient story for a timeless plant toxin

The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, anti-bacterial, laxative, abortifacient, for wounds, ulcers, and many other indications. Many cases of human intoxication occurred accidentally or voluntarily with the ingestion of castor seeds or derivatives. Ricinus toxicity depends on several molecules, among them the most important is ricin, a protein belonging to the family of ribosome-inactivating proteins. Ricin is the most studied of this category of proteins and it is also known to the general public, having been used for several biocrimes. This manuscript intends to give the reader an overview of ricin, focusing on the historical path to the current knowledge on this protein. The main steps of ricin research are here reported, with particular regard to its enzymatic activity, structure, and cytotoxicity. Moreover, we discuss ricin toxicity for animals and humans, as well as the relation between bioterrorism and ricin and its impact on environmental toxicity. Ricin has also been used to develop immunotoxins for the elimination of unwanted cells, mainly cancer cells; some of these immunoconjugates gave promising results in clinical trials but also showed critical limitation

Effect of maize, rumen-protected fat and whey permeate on energy utilisation and milk fat composition in lactating goats

The efficiency of utilisation of diets with different proportions of energy sources (starch, fat, lactose) was studied with three pairs of lactating Saanen goats; the animals were fed, in a Latin square design, 3 silage-based diets containing (on DM basis) the following energy sources: 32% maize meal (diet M); 4.7% rumen-protected fat (Megalac®) and 23.5% maize meal (diet F); 9.8% milk whey permeate powder and 22.3% maize meal (diet W). During each of the three experimental periods, 8 days of total collection balance trials were conducted during which goats were allocated for 72 h (three 24 h cycles) in open circuit respiration chambers to determine methane and heat production and, hence, the energy balance. Diet F, in comparison with diets M and W, significantly increased the milk fat content (4.13 vs 3.11 and 3.14%, P<0.001) and the 4%-FCM yield (3367 vs 2927 and 3055 g/d, P<0.01 and P<0.05, respectively), while no relevant changes were observed for milk protein content and yield. Energy digestibility was equal in diets F and W. Megalac® did not decrease fibre digestibility. The partition of the gross energy intake (EI) differed significantly between diets: diet M had lower DE (72.4 vs 74.3 and 74.3%; P<0.01) and ME (62.1 vs 64.7 and 63.5%; P<0.05) in comparison with diets F and W, respectively. Energy lost as methane was not significantly decreased by the inclusion of rumen- protected fat in the diet, although a trend for a reduction of methanogenesis was observed. Heat production deter- mined by treatment F was lower in comparison with the other treatments. This difference was almost significant (P=0.056) when expressed as a percentage of the ME. Milk energy output increased significantly (+12%, P<0.001) by including fat in the diet, as compared with treatments M and W: 21.4 vs 19.1 and 19.0% of the EI. The net ener- gy content of the protected fat was 27.94 MJ NEl/kg DM (+340% vs maize meal); its kl value resulted 0.77. The corresponding values for whey permeate were 7.76 MJ NEl/kg DM (-5% vs maize meal) and 0.50, respectively. Summarizing, the efficiency of energy utilization in diet M was significantly lower in comparison with the other two diets in terms of digestibility and metabolisability, while its NEl content was similar to that of diet W. On the other hand, diet F had a significantly higher ME (P<0.01) and NEl (P<0.05) as compared to the other two diets. Diet F greatly influenced the fatty acid composition of the milk fat with less short (-30%) and medium (-33%) chain fatty acids and more (+18%) long chain fatty acids. In conclusion, whey permeate and even more Megalac® can be suc- cessfully used as feed ingredients in the diet of highly productive lactating goats, but the economical convenience of their utilisation must be evaluated based on the market values of feedstuffs

The compensatory dynamic of inter-hemispheric interactions in visuospatial attention revealed using rTMS and fMRI

A balance of mutual tonic inhibition between bi-hemispheric posterior parietal cortices is believed to play an important role in bilateral visual attention. However, experimental support for this notion has been mainly drawn from clinical models of unilateral damage. We have previously shown that low-frequency repetitive TMS (rTMS) over the intraparietal sulcus (IPS) generates a contralateral attentional deficit in bilateral visual tracking. Here, we used functional magnetic resonance imaging (fMRI) to study whether rTMS temporarily disrupts the inter-hemispheric balance between bilateral IPS in visual attention. Following application of 1 Hz rTMS over the left IPS, subjects performed a bilateral visual tracking task while their brain activity was recorded using fMRI. Behaviorally, tracking accuracy was reduced immediately following rTMS. Areas ventro-lateral to left IPS, including inferior parietal lobule (IPL), lateral IPS (LIPS), and middle occipital gyrus (MoG), showed decreased activity following rTMS, while dorsomedial areas, such as Superior Parietal Lobule (SPL), Superior occipital gyrus (SoG), and lingual gyrus, as well as middle temporal areas (MT+), showed higher activity. The brain activity of the homologues of these regions in the un-stimulated, right hemisphere was reversed. Interestingly, the evolution of network-wide activation related to attentional behavior following rTMS showed that activation of most occipital synergists adaptively compensated for contralateral and ipsilateral decrement after rTMS, while activation of parietal synergists, and SoG remained competing. This pattern of ipsilateral and contralateral activations empirically supports the hypothesized loss of inter-hemispheric balance that underlies clinical manifestation of visual attentional extinction

Bollettino Sismico Italiano 2011

Questo lavoro illustra lo stato della Rete Sismica Nazionale Italiana (RSNI) e le principali caratteristiche della sismicità in Italia nell’anno 2011. In tale anno, tramite i dati raccolti dalla RSNI, sono stati localizzati 16499 eventi registrati da 359 stazioni appartenenti sia all’INGV, sia ad altre reti locali e regionali connesse in tempo reale al Centro Nazionale Terremoti (CNT) di Roma. La magnitudo minima di completezza del Bollettino Sismico Italiano (BSI) è ML 1.5. La magnitudo massima è stata registrata per un evento localizzato nella pianura padano veneta (ML 4.8). Nella sismicità italiana del 2011 sono state individuate 46 sequenze sismiche rilevanti; tra esse riveste particolare interesse la sequenza nel Montefeltro: iniziata a fine maggio e durata diversi mesi, essa comprende due eventi di magnitudo ML 4.0. La sequenza del Pollino, iniziata nel 2009 e proseguita a più riprese fino al 25 ottobre 2012 con un evento di magnitudo MW 5.2, presenta a inizio 2011 un aumento della sismicità che è culminato con l’evento maggiore di quell’anno (ML 3.6). L’analisi del BSI ha inoltre permesso di individuare una nuova area caratterizzata da eventi di origine antropica (esplosioni in cava) che si aggiunge alle 16 già rilevate negli anni precedenti. In questo lavoro vengono analizzati anche i segnali prodotti da frane di crollo, molto diffuse nel nostro paese lungo gli archi montani alpini e appenninici

Bollettino Sismico Italiano 2009

Questo lavoro illustra lo stato della Rete Sismica Nazionale Italiana e descrive la sismicità italiana nell’anno 2009. Vengono evidenziate le principali sequenze sismiche occorse durante l’anno, con particolare riguardo alla sequenza sismica dell’aquilano-reatino. Nel 2009 la Rete Sismica Nazionale dell’INGV ha registrato circa 26000 terremoti avvenuti sul territorio nazionale e nelle aree limitrofe, che sono stati analizzati e localizzati dal gruppo di analisti sismologi che si occupano della redazione del Bollettino Sismico Italiano (BSI). La magnitudo minima di completezza Mc del BSI 2009, ovvero la soglia di magnitudo minima media calcolata su tutto il territorio nazionale, è risultata pari a ML 1.6 (il dato del BSI 2008 si attestava sul valore di ML 2.1). Il numero di stazioni sismiche attive (Rete Nazionale e reti locali) nel corso del 2009 è stato di 305 (279 nel 2008). Viene fornita infine una stima del numero e della magnitudo di eventi di origine antropica (esplosioni) presenti nel BSI 2009. This paper describes the status of the Italian National Seismic Network and the Italian seismicity in year 2009. We outline the main seismic sequences that occurred during the year, with particular emphasis on the L’Aquila-Rieti seismic period. The INGV National Seismic Network recorded about 26000 earthquakes in Italy and neighboring areas during 2009, which were analyzed and localized by the seismology group of analysts involved in the publication of the Italian Seismic Bulletin (BSI). The minimum magnitude of completeness Mc of the BSI 2009 is ML 1.6 (ML 2.1 in the BSI 2008). The number of active seismic stations during 2009 was 305 (279 in 2008). We provide an estimate of the number and magnitude of anthropic events (quarry-blasts) included in the BSI 2009

Bollettino Sismico Italiano 2010

This paper describes the status of the Italian National Seismic Network and the main feautures of the Italian seismicity in 2010. In that year the network counted 313 velocimeters and 107 accelerometers. More than 14500 earthquakes were located in Italy and surrounding areas and seas, with an average minimum magnitude of completeness MC = 1.6. Most of that seismicity appears in cluster (a spatio-temporal concentration of seismic events): in 2010 more than 70% of the located Italian earthquakes belongs to about 430 cluster. We selected all the cluster with at least 20 events of any magnitudes, and all the cluster with at least 10 events and at least one event of magnitude 2.5 or greater, and cluster with at least two events and one of magnitude 3.5 or greater, ending up with a list of 48 significant cluster. The Italian Seismic Bulletin contains also seismic events originated by anthropic activities (quarry explosions). Through the analysis of the last 7 years of data from the bulletin, we pinpointed 16 areas with extended extractive activities. Nevertheless the presence of quarries in Italy is so widespread that our list can be considered by no means complete. Extraction areas frequently coincide with regions affected by high seismicity rate. Records due to explosion quakes can show distinguishing characteristics (compressive first onset and a low frequency secondary phase). However, these markers are not present in all the artificial events, and are not sufficient to exclude the totality of the explosions from the bulletin. Nowadays the BSI incorporates, together with true tectonic earthquakes, a significant portion of low magnitude events due to explosions, evaluated about 5% in 2010