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

Steady-state visual evoked potentials and phase synchronization in migraine

We investigate phase synchronization in EEG recordings from migraine patients. We use the analytic signal technique, based on the Hilbert transform, and find that migraine brains are characterized by enhanced alpha band phase synchronization in presence of visual stimuli. Our findings show that migraine patients have an overactive regulatory mechanism that renders them more sensitive to external stimuli.Comment: 4 page

Advancing the Provision of Pain Education and Learning (APPEAL) study

Objectives Unrelieved pain is a substantial public health concern necessitating improvements in medical education. The Advancing the Provision of Pain Education and Learning (APPEAL) study aimed to determine current levels and methods of undergraduate pain medicine education in Europe. Design and methods Using a cross-sectional design, publicly available curriculum information was sought from all medical schools in 15 representative European countries in 2012–2013. Descriptive analyses were performed on: the provision of pain teaching in dedicated pain modules, other modules or within the broader curriculum; whether pain teaching was compulsory or elective; the number of hours/credits spent teaching pain; pain topics; and teaching and assessment methods. Results Curriculum elements were publicly available from 242 of 249 identified schools (97%). In 55% (133/242) of schools, pain was taught only within compulsory non-pain-specific modules. The next most common approaches were for pain teaching to be provided wholly or in part via a dedicated pain module (74/242; 31%) or via a vertical or integrated approach to teaching through the broader curriculum, rather than within any specific module (17/242; 7%). The curricula of 17/242 schools (7%) showed no evidence of any pain teaching. Dedicated pain modules were most common in France (27/31 schools; 87%). Excluding France, only 22% (47/211 schools) provided a dedicated pain module and in only 9% (18/211) was this compulsory. Overall, the median number of hours spent teaching pain was 12.0 (range 4–56.0 h; IQR: 12.0) for compulsory dedicated pain modules and 9.0 (range 1.0–60.0 h; IQR: 10.5) for other compulsory (non-pain specific) modules. Pain medicine was principally taught in classrooms and assessed by conventional examinations. There was substantial international variation throughout. Conclusions Documented pain teaching in many European medical schools falls far short of what might be expected given the prevalence and public health burden of pain

Effect of Different Percentage of Camelina sativa Cake in Laying Hens Diet: Performance, Welfare, and Eggshell Quality

Although camelina [Camelina sativa (L.) Crantz] is a good source of protein, antioxidants, and polyunsaturated fatty acids, its antinutritional compounds limit its use in animal feeding. The aim of this study was to verify the effect of feeding laying hens with up to 20% of camelina cake from a breeding line containing a low level of glucosinolates on performance, welfare, and eggshell quality. Two hundred and forty Hy-Line\uae hens from 18 to 51 weeks of age were divided into three treatments: control (C), camelina cake 10% (CAM10), and camelina cake 20% (CAM20). Egg number was recorded daily, while egg weight, feed consumption, and mortality were recorded weekly. At 24 and 43 weeks of hen age, shell resistance to fracture was measured. Our results demonstrate no detrimental effects for CAM10 and CAM20 diets on feed intake, growth performance, and welfare. No difference in egg production was detected among the diets. The significant (p &lt; 0.05) interaction of diet and age factors suggest that the addition of camelina cake, up to 20%, likely protects the eggshell of older hens. Our findings confirm that camelina cake might be an alternative and sustainable protein source for hens

Multi-dimensional assessment and scoring system for dairy farms

The aim of the study is to develop a scoring system for dairy farms in order to give specific information about the product and production process of milk. The scoring system, based on a multi-dimensional approach, was developed on the basis of data collected in 29 Italian dairy farms and included different aspects. For the evaluation of animal welfare, a selection of indicators set up in the European ProjectVR assessment protocol for cattle 2009 was used. Environmental sustainability of milk production was assessed by a cradle-to-farm-gate Life Cycle Assessment. Laboratory analyses were carried out on bulk tank milk to evaluate microbiological, nutritional and nutraceutical quality. Nineteen variables were selected and retained to define six quality aspects: animal welfare, environmental and economic sustainability of farms, microbiological, nutritional and nutraceutical quality of milk. Each farm was visited twice; each visit received, for each variable, a score between 1 and 3 based on the frequency distribution of that variable in the farm sample. The relation among farm characteristics and quality aspects showed the importance to maximise dairy efficiency to improve environmental and economic sustainability of the farms and the inclusion of hay in dairy cows\u2019 ration to enhance the nutraceutical and nutritional quality of milk. The proposed multi-dimensional scoring system is a practical tool: for the farmer, to support decisions for improving the quality of the product and the productive process; for the dairy company, as a value-added opportunity; for the consumer, who receives detailed information about nutritional characteristics and production system of dairy products