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a b s t r a c tBackground: Hepatitis C virus (HCV) infection has certain characteristics that enable it to play an important role in atherosclerosis. Some studies report its association with an increased risk of carotid artery plaque. Objectives: The aim of this study was to evaluate the presence of HCV genomic sequences and replicative intermediates in plaque tissues. Study Design: A cohort of consecutive, prospectively recruited patients with HCV infection and chronic ischemic heart disease from the Cardiology, Vascular Surgery and Hepatology Units of a University Hospital in Florence, Italy, were studied. Results: Positive-strand HCV RNA was detected in seven carotid plaque tissues from anti-HCV-positive patients and was not detected in the nine carotid plaque tissues obtained from anti-HCV-negative patients. In three patients, HCV RNA was found in carotid plaque and not in serum. HCV replicative intermediates were detected in three plaque samples. Direct sequencing of HCV RNA from the plaque and serum showed HCV genotypes 2 (five cases) and 1 (two cases). Conclusions: The novel finding of HCV RNA sequences in plaque tissue strongly suggests an active local infection. This in turn makes it conceivable that the virus may exert local action in carotid atherosclerosis.

Recent studies indicate that mesenchymal stem cells (MSC) exhibit a degree of immune privilege due to their ability to suppress T cell mediated responses causing tissue rejection; however, the impact of allogeneic MSC in the setting of organ transplantation has been poorly investigated so far. The aim of our study was to evaluate the eVect of intravenous donor MSC infusion for clinical tolerance induction in allogeneic skin graft transplantations in rats. MSC were isolated from Wistar rats and administered in Sprague-Dawley rats receiving Wistar skin graft with or without cyclosporine A (CsA). Graft biopsies were performed at day 10 post transplantation in all experimental groups for histological and gene expression studies. Intravenous infusion with donor MSC in CsA-treated transplanted rats resulted in prolongation of skin allograft survival compared to control animals. Unexpectedly, donor MSC infusion in immunocompetent rats resulted in a faster rejection as compared to control group. Cytokine expression analysis at the site of skin graft showed that CsA treatment signiWcantly decreased pro-inXammatory cytokines IFN-and IL-2 and reduced TNF-gene expression; however, the level of TNF-is high in MSC-treated and not immunosuppressed rats. Results of our study in a rat tissue transplantation model demonstrated a possible immunogenic role for donor (allogeneic) MSC, conWrming the need of adequate preclinical experimentation before clinical use.

The aim of this review is to focus the attention on the nutrition ecology of the heavy metals and on the major criticisms related to the heavy metals content in animal feeds, manure, soil and animal-origin products. Heavy metals are metallic elements that have a high density that have progressively accumulated in the food chain with negative effects for human health. Some metals are essential (Fe, I, Co, Zn, Cu, Mn, Mo, Se) to maintain various physiological functions and are usually added as nutritional additives in animal feed. Other metals (As, Cd, F, Pb, Hg) have no established biological functions and are considered as contaminants/ undesirable substances. The European Union adopted several measures in order to control their presence in the environment, as a result of human activities such as: farming, industry or food processing and storage contamination. The control of the animal input could be an effective strategy to reduce human health risks related to the consumption of animal-origin products and the environmental pollution by manure. Different management of raw materials and feed, animal species as well as different legal limits can influence the spread of heavy metals. To set up effective strategies against heavy metals the complex interrelationships in rural processes, the widely variability of farming practices, the soil and climatic conditions must be considered. Innovative and sustainable approaches have discussed for the heavy metal nutrition ecology to control the environmental pollution from livestockrelated activities.

Objective. Postnatal angiogenesis relies on a proper response of endothelial cells to angiogenic stimuli. In systemic sclerosis (SSc), endothelial cells are unresponsive to angiogenic factors. Since circumstantial and experimental evidence points to tissue kallikreins as powerful effectors of the angiogenic response, we undertook this study to investigate the kallikrein pattern of normal and SSc endothelial cells in order to identify differences that can account for defective angiogenesis.Methods. Expression of 14 tissue kallikreins was studied by a microarray approach, by reverse transcription-polymerase chain reaction, and by Western blotting in endothelial cells isolated from the skin of clinically healthy subjects and SSc patients. Cell proliferation was quantified by direct cell counting. Invasion and capillary morphogenesis were evaluated in a Boyden chamber and in culture flasks layered with Matrigel. Cyclic nucleotide production was measured by enzyme immunoassay. MAP kinase and ERK activation were measured by Western blotting.Results. Endothelial cells from SSc patients showed poor expression of kallikreins 9, 11, and 12 compared with endothelial cells from normal subjects. Antibodies against the relevant kallikreins on normal endothelial cells revealed that while kallikreins 9, 11, and 12 induced cell growth, only kallikrein 12 regulated invasion and capillary morphogenesis. Buffering of kallikrein 12 with antibodies resulted in the acquisition of an SSc-like pattern by normal cells in in vitro angiogenesis. Reduction of cAMP and cGMP production and of ERK phosphorylation upon administration of antikallikrein antibodies revealed that the activity of kallikreins 9, 11, and 12 was mediated by kinins.Conclusion. Reduction of tissue kallikreins 9, 11, and 12 may be relevant to reduced angiogenesis in SSc patients.

The goal of this study was to examine the prevalence, assessment and management of pediatric pain in a public teaching hospital. The study sample consisted of 121 inpatients (70 infants, 36 children, and 15 adolescents), their families, 40 physicians, and 43 nurses. All participants were interviewed except infants and children who could not communicate due to their clinical status. The interview included open-ended questions concerning the inpatients' pain symptoms during the 24 h preceding data collection, as well as pain assessment and pharmacological/non-pharmacological management of pain. The data were obtained from 100% of the eligible inpatients. Thirty-four children/adolescents (28%) answered the questionnaire and for the other 72% (unable to communicate), the family/health professional caregivers reported pain. Among these 34 persons, 20 children/adolescents reported pain, 68% of whom reported that they received pharmacological intervention for pain relief. Eighty-two family caregivers were available on the day of data collection. Of these, 40 family caregivers (49%) had observed their child's pain response. In addition, 74% reported that the inpatients received pharmacological management. Physicians reported that only 38% of the inpatients exhibited pain signs, which were predominantly acute pain detected during clinical procedures. They reported that 66% of patients received pharmacological intervention. The nurses reported pain signs in 50% of the inpatients, which were detected during clinical procedures. The nurses reported that pain was managed in 78% of inpatients by using pharmacological and/or non-pharmacological interventions. The findings provide evidence of the high prevalence of pain in pediatric inpatients and the under-recognition of pain by health professionals.

The aim of this study was to investigate the effects of tributyrin supplementation on the production traits, the main metabolic parameters and gut microbiota in weaned piglets. One hundred and twenty crossbred piglets (Large White × Landrace) were randomly divided into two experimental groups (six pens each; 10 piglets per pen): the control group (CTRL), that received a basal diet, and the tributyrin group (TRIB) that received the basal diet supplemented with 0.2% tributyrin. The experimental period lasted 40 days. Production traits were measured at days 14, 28 and 40. A subset composed of 48 animals (n = 4 for each pen; n = 24 per group) was considered for the evaluation of serum metabolic parameters and hair cortisol by enzyme-linked immunosorbent assay (ELISA), and faecal microbiota by real-time polymerase chain reaction (PCR). Our results showed that the treatment significantly increased body weight (BW) at day 28 and day 40 (p = 0.0279 and p = 0.0006, respectively) and average daily gain (ADG) from day 28 to day 40 (p = 0.046). Gain to feed ratio (G:F) was significantly higher throughout the experimental period (p = 0.049). Even if the serum parameters were in the physiological range, albumin, albumin/globulin (A/G) ratio, glucose and high-density lipoproteins (HDL) fraction were significantly higher in the TRIB group. On the contrary, tributyrin significantly decreased the urea blood concentration (p = 0.0026), which was correlated with lean gain and feed efficiency. Moreover, serum insulin concentration, which has a regulatory effect on protein and lipid metabolism, was significantly higher in the TRIB group (p = 0.0187). In conclusion, this study demonstrated that tributyrin can be considered as a valid feed additive for weaned piglets.

Increased expression of hemoglobin chain genes as well as of genes involved in erythrocyte mechanical stability were observed in the AAA RNA pools. The association between low levels of LRP5 gene expression and increased levels of Lp(a) in AAA patients suggests a potential role of LRP5 in Lp(a) catabolism. Our data underline the power of microarrays in identifying further molecular perturbations associated with AAA.