Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) u...Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method.Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized.Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations.Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.展开更多
Renal fibrosis and inflammation are common pathological features of chronic kidney disease(CKD).Since currently available treatments can only delay the progression of CKD,the outcome of patients with CKD is still poor...Renal fibrosis and inflammation are common pathological features of chronic kidney disease(CKD).Since currently available treatments can only delay the progression of CKD,the outcome of patients with CKD is still poor.One therapeutic option for the prevention of CKD-related complications could be the use of mesenchymal stromal cells(MSCs),which have shown beneficial effects in tissue fibrosis and regeneration after damage.However,safety issues,such as cellular rejection and carcinogenicity,limit their clinical application.Among the bioactive factors secreted by MSCs,extracellular vesicles(EVs)have shown the same beneficial effect of MSCs,without any notable side effects.This heterogeneous population of membranous nano-sized particles can deliver genetic material and functional proteins to injured cells,prompting tissue regeneration.Here we describe the anti-fibrotic and antiinflammatory properties of MSC-derived EVs in CKD preclinical models and summarize the potential molecular mechanisms involved in the regulation of renal fibrosis and inflammation.展开更多
Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Holl...Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair.Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance.In this study,we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model.Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks.Nevertheless,the molecular assessment in the early regeneration phase(7,14,and 28 days)has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones.Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1,a growth factor that plays an important role in Schwann cell transdifferentiation.The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2,VEGF-A,BDNF,c-Jun,and ATF3.展开更多
Background: Two trials were performed to evaluate a partially defatted Hermetia illucens(HI) larvae meal as potential feed ingredient in rainbow trout(Oncorhynchus mykiss Walbaum) diets. In the first trial, 360 trout(...Background: Two trials were performed to evaluate a partially defatted Hermetia illucens(HI) larvae meal as potential feed ingredient in rainbow trout(Oncorhynchus mykiss Walbaum) diets. In the first trial, 360 trout(178.9 ± 9.8 g of mean initial body weight) were randomly divided into three experimental groups(4 tanks/treatment, 30 fish/tank). The fish were fed for 78 days with isonitrogenous, isolipidic and isoenergetic diets containing increasing levels of HI, on as fed basis: 0%(HI0, control diet), 25%(HI25) and 50%(HI50) of fish meal substitution, corresponding to dietary inclusion levels of 0, 20% and 40%. In the second trial, 36 trout(4 tanks/treatment, 3 fish/tank) were used to evaluate the in vivo apparent digestibility coefficients(ADC) of the same diets used in the first trial.Results: Survival, growth performance, condition factor, somatic indexes, and dorsal fillet physical quality parameters were not affected by diet. The highest dietary inclusion of HI larvae meal increased dry matter and ether extract contents of trout dorsal fillet. The use of HI larvae meal induced a decrease of valuable polyunsaturated fatty acids(PUFA) even if differences were only reported at the highest level of HI inclusion. The insect meal worsened the lipids health indexes of the same muscle. Dietary inclusion of insect meal did not alter the villus height of the fish. No differences were found among treatments in relation to ADC of ether extract and gross energy, while ADC of dry matter and crude protein were higher in HI25 if compared to HI50.Conclusions: The obtained results showed that a partially defatted HI larvae meal can be used as feed ingredient in trout diets up to 40% of inclusion level without impacting survival, growth performance, condition factor, somatic indexes, dorsal fillet physical quality parameters, and intestinal morphology of the fish. However, further investigations on specific feeding strategies and diet formulations are needed to limit the observed negative effects of the insect meal on the FA composition of dorsal muscle.展开更多
Laparoscopic resection for colon and rectal cancer is associated with quicker return of bowel function, reduced postoperative morbidity rates and shorter length of hospital stay compared to open surgery, with no diffe...Laparoscopic resection for colon and rectal cancer is associated with quicker return of bowel function, reduced postoperative morbidity rates and shorter length of hospital stay compared to open surgery, with no differences in long-term survival. Conversion to open surgery is reported in up to 30% of patients enrolled in randomized control trials comparing open and laparoscopic colorectal resection for cancer. In this review, reasons for conversion are anatomical-related factors, disease-related-factors and surgeon-related factors. Body mass index, local tumour extension and co-morbidities are independent predictors of conversion. The current evidence has shown that patients with converted resection for colon cancer have similar outcomes compared to patients undergoing a laparoscopic completed or open resection. The few studies that have assessed the outcomes after conversion of laparoscopic rectal resection reported significantly higher rates of complications and longer length of hospital stay in converted patients compared to laparoscopically treated patients. No definitive conclusions can be drawn when converted and open rectal resections are compared. Early and pre-emptive conversion appears to have more favourable outcomes than reactive conversion; however, further large studies are needed to better define the optimal timing of conversion. With regard to long-term oncologic outcome, overall and disease-free survival in the case of conversion in laparoscopic colorectal cancer surgery seems to be worse than those achieved in patients in whom resection was successfully completed by laparoscopy. Although a worse long-term oncologic outcome has been suggested, it remains difficult to draw a proper conclusion due to the heterogeneity of the long-term outcomes as well as the inclusion of both colon and rectal cancer patients in most of the studies. Therefore, we discuss the currently available evidence of the impact of conversion in laparoscopic resection for colon and rectal cancer on both short-term outcomes and long-term survival.展开更多
Angiogenesis is a dynamic,hypoxia-stimulated and growth factor-dependent process,and is currently referred to as the formation of new vessels from preexisting blood vessels.Experimental and clinical studies have unequ...Angiogenesis is a dynamic,hypoxia-stimulated and growth factor-dependent process,and is currently referred to as the formation of new vessels from preexisting blood vessels.Experimental and clinical studies have unequivocally reported that hepatic angiogenesis,irrespective of aetiology,occurs in conditions of chronic liver diseases(CLDs) characterized by perpetuation of cell injury and death,inflammatory response and progressive fibrogenesis.Angiogenesis and related changes in liver vascular architecture,that in turn concur to increase vascular resistance and portal hypertension and to decrease parenchymal perfusion,have been proposed to favour fibrogenic progression of the disease towards the end-point of cirrhosis.Moreover,hepatic angiogenesis has also been proposed to modulate the genesis of portal-systemic shunts and increase splanchnic blood flow,thus potentially affecting complications of cirrhosis.Hepatic angiogenesis is also crucial for the growth and progression of hepatocellular carcinoma.Recent literature has identified a number of cellular and molecular mechanisms governing the cross-talk between angiogenesis and fibrogenesis,with a specifi c emphasis on the crucial role of hypoxic conditions and hepatic stellate cells,particularly when activated to the myofibroblast-like pro-fibrogenic.Experimental anti-angiogenic therapy has been proven to be effective in limiting the progression of CLDs in animal models.From a clinical point of view,anti-angiogenic therapy is currently emerging as a new pharmacologic intervention in patients with advanced fibrosis and cirrhosis.展开更多
A large body of experimental and clinical data supports the notion that inflammation in acute pancreatitis has a crucial role in the pathogenesis of local and systemic damage and is a major determinant of clinical sev...A large body of experimental and clinical data supports the notion that inflammation in acute pancreatitis has a crucial role in the pathogenesis of local and systemic damage and is a major determinant of clinical severity.Thus,research has recently focused on molecules that can regulate the inflammatory processes,such as phosphoinositide 3-kinases(PI3Ks),a family of lipid and protein kinases involved in intracellular signal transduction.Studies using genetic ablation or pharmacologic inhibitors of different PI3 K isoforms,in particular the class I PI3Kδ and PI3Kγ,have contributed to a greater understanding of the roles of these kinases in the modulation of inflammatory and immune responses.Recent data suggest that PI3 Ks are also involved in the pathogenesis of acute pancreatitis.Activation of the PI3K signaling pathway,and in particular of the class IB PI3Kγ isoform,has a significant role in those events which are necessary for the initiation of acute pancreatic injury,namely calcium signaling alteration,trypsinogen activation,and nuclear factor-κB transcription.Moreover,PI3Kγ is instrumental in modulating acinar cell apoptosis,and regulating local neutrophil infiltration and systemic inflammatory responses during the course of experimental acute pancreatitis.The availability of PI3 K inhibitors selective for specific isoforms may provide new valuable therapeutic strategies to improve the clinical course of this disease.This article presents a brief summary of PI3 K structure and function,and highlights recent advances that implicate PI3 Ks in the pathogenesis of acute pancreatitis.展开更多
AIM: To report a case of severe idiopathic gastroparesis in complete absence of Kit-positive gastric interstitial cells of Cajal (ICC). METHODS: Gastric tissue from a patient with severe idiopathic gastroparesis unres...AIM: To report a case of severe idiopathic gastroparesis in complete absence of Kit-positive gastric interstitial cells of Cajal (ICC). METHODS: Gastric tissue from a patient with severe idiopathic gastroparesis unresponsive to medical treatment and requiring surgery was analyzed by conventional histology and immunohistochemistry. RESULTS: Gastric pacemaker cells expressing Kit receptor had completely disappeared while the local level of stem cell factor, the essential ligand for its development and maintenance, was increased. No signs of cell death were observed in the pacemaker region. CONCLUSION: These results are consistent with the hypothesis that a lack of Kit expression may lead to impaired functioning of ICC. Total gastrectomy proves to be curative.展开更多
The worldwide prevalence of hepatitis C virus(HCV)infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injec...The worldwide prevalence of hepatitis C virus(HCV)infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, motherto-child transmission(MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance(SVC) that usually occurs within 6 years of life. IL-28 B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.展开更多
Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes i...Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes increases expression and activity of matrix metalloproteinase-9,a proteolytic enzyme available in specific gelatinase granules,which contain several enzymes including lysozyme.Present work investigated active lysozyme release after phagocytosis of hemozoin and its dependence on production of tumor necrosis factor alpha. Methods:After phagocytosis of hemozoin,hemozoin-containing trophozoites or control meals(opsonized nonparasitized red blood cells and latex particles),monocyte supematants were monitored for 2 hours,in presence of blocking anti-human tumor necrosis factor alpha antibodies or recombinant human tumor necrosis factor alpha cytokine in selected experiments.Lysozyme release was evaluated by a specific spectrometric assay measuring lysozyme activity after coincubation of cell supematants with suspensions of Mycrococcus Lysodeikticus,while levels of soluble tumor necrosis factor alpha were analyzed by specific enzyme-linked immunodsorbent assay. Results:Levels of lysozyme activity and soluble tumor necrosis factor alpha protein were increased in hemozoin in-or trophozoites-laden monocytes supematants.Phagocytosis per se(control meals) also increased lysozyme release,but levels were significantly lower than those obtained after phagocytosis of hemozoin or trophozoites. Interestingly,all effects on lysozyme release observed after phagocytosis were abrogated by blocking anti-human tumor necrosis factor alpha antibodies,while they were mimicked by recombinant human tumor necrosis factor alpha cytokine.Conclusions:Present work shows that phagocytosis of hemozoin promotes monocyte degranulation and enhances active lysozyme release.The effect requires tumor necrosis factor alpha mediation.展开更多
Ultrahigh-pressure(UHP) metamorphic rocks are distinctive products of crustal deep subduction,and are mainly exposed in continental subduction-collision terranes. UHP slices of continental crust are usually involved...Ultrahigh-pressure(UHP) metamorphic rocks are distinctive products of crustal deep subduction,and are mainly exposed in continental subduction-collision terranes. UHP slices of continental crust are usually involved in multistage exhumation and partial melting, which has obvious influence on the rheological features of the rocks, and thus significantly affect the dynamic behavior of subducted slices. Moreover,partial melting of UHP rocks have significant influence on element mobility and related isotope behavior within continental subduction zones, which is in turn crucial to chemical differentiation of the continental crust and to crust-mantle interaction.Partial melting can occur before, during or after the peak metamorphism of UHP rocks. Post-peak decompression melting has been better constrained by remelting experiments; however, because of multiple stages of decompression, retrogression and deformation, evidence of former melts in UHP rocks is often erased. Field evidence is among the most reliable criteria to infer partial melting. Glass and nanogranitoid inclusions are generally considered conclusive petrographic evidence. The residual assemblages after melt extraction are also significant to indicate partial melting in some cases. Besides field and petrographic evidence, bulk-rock and zircon trace-element geochemical features are also effective tools for recognizing partial melting of UHP rocks. Phase equilibrium modeling is an important petrological tool that is becoming more and more popular in P-T estimation of the evolution of metamorphic rocks; by taking into account the activity model of silicate melt, it can predict when partial melting occurred if the P-T path of a given rock is provided.UHP silicate melt is commonly leucogranitic and peraluminous in composition with high SiO_2,low MgO, FeO, MnO, TiO_2 and CaO, and variable K_2 O and Na_2 O contents. Mineralogy of nanogranites found in UHP rocks mainly consists of plagioclase + K-feldspar + quartz, plagioclase being commonly albite-rich.Trace element pattern of the melt is characterized by significant enrichment of large ion lithophile elements(LILE), depletion of heavy rare earth elements(HREE) and high field strength elements(HFSE),indicating garnet and rutile stability in the residual assemblage. In eclogites, significant Mg-isotope fractionation occurs between garnet and phengite; therefore, Mg isotopes may become an effective indicator for partial melting of eclogites.展开更多
Berberine is used in traditional Chinese medicine for the treatment of congestive heart failure, hypertension, diabetes, and dyslipidaemia and has a good safety profile. We report a case of a 53-year-old sportsman ref...Berberine is used in traditional Chinese medicine for the treatment of congestive heart failure, hypertension, diabetes, and dyslipidaemia and has a good safety profile. We report a case of a 53-year-old sportsman referred to our hospital for the onset of fatigue and dyspnoea upon exertion after he started berberine to treat hypercholesterolaemia. An electrocardiogram showed sinus bradycardia (45 bpm), first-degree atrioventricular block, and competitive junctional rhythm. An ergometric stress test showed slightly reduced chronotropic competence and the presence of runs of competitive junctional rhythm, atrial tachycardia, and sinus pauses in the recovery. After 10 d of wash-out from berberine, the patient experienced a complete resolution of symptoms, and an ergometric stress test showed good chronotropic competence. An electrocardiogram Holtershowed a latent hypervagotonic state. This is the first case report that shows that berberine could present certain side effects in hypervagotonic people, even in the absence of a situation that could cause drug accumulation. Therefore, berberine's use should be carefully weighed in hypervagotonic people due to the drug's bradycardic and antiarrhythmic properties, which could became proarrhythmic, exposing patients to potential health risks.展开更多
AIM: To investigate the state of the art regarding Cartilage Autograft Implantation System(CAIS) or Particulated Juvenile Allograft Cartilage(PJAC).METHODS: The authors searched the English literature regarding CAIS a...AIM: To investigate the state of the art regarding Cartilage Autograft Implantation System(CAIS) or Particulated Juvenile Allograft Cartilage(PJAC).METHODS: The authors searched the English literature regarding CAIS and PJAC. The search strategy was:(particulated cartilage) OR autologous cartilage fragments. All basic science articles were included. Clinical articles with less than 10 patients treated and less than 6 mo of follow-up were excluded. With these criteria, a total of 17 articles were available for the present review. RESULTS: PJAC and CAIS are relatively novel techniques for cartilage repair. Good basic science evidence was described to support the concept. Although the preliminary clinical reports show encouraging results, clinical data are still limited, especially for CAIS. The indications for both techniques need to be precisely defined(age of the patients, size of the lesion, and involvement of the subchondral bone), together with other debated issues. CONCLUSION: In conclusion, the authors can state that encouraging preliminary results are available for both techniques. However, further studies are necessary to precisely determine the indications, surgical techniques, and long term outcomes for PJAC and CAIS.展开更多
Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemo...Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemozoin;lipid free hemozoin;and control latex particles),then tumor necrosis factor alpha was monitored in cell supernatants up to 48 hours through western blotting or specific enzyme-linked immunoadsorbent assay.In selected experiments,unfed monocytes were treated with different doses of 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid or 4-hydroxynonenal instead of phagocytosis.Results:Hemozoin-fed monocytes produced higher levels of tumor necrosis factor alpha than unstimulated and latex-fed cells, while lipid-free hemozoin did not reproduce these results.Additionally,hemozoin effects were mimicked dose-dependently by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid,but not by 4-hydroxynonenal.Conclusions:Present data suggest an essential role for lipids in hemozoindependent enhanced release of tumor necrosis factor alpha from monocytes,and 15(S,R)hydroxy -6,8,11,13-eicosatetraenoic acid could be one possible specific mediator.展开更多
Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal s...Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal stump of chronically transected nerves; moreover, Schwann cells undergo atrophy, losing their ability to sustain regeneration. In the present study, to provide a three-dimensional environment and trophic factors supporting Schwann cell activity and axon re-growth, we combined the use of an effective conduit(a chitosan tube) with a promising intraluminal structure(fresh longitudinal skeletal muscle fibers). This enriched conduit was used to repair a 10-mm rat median nerve gap after 3-month delay and functional and morphometrical analyses were performed 4 months after nerve reconstruction. Our data show that the enriched chitosan conduit is as effective as the hollow chitosan conduit in promoting nerve regeneration,and its efficacy is not statistically different from the autograft, considered the "gold standard" technique for nerve reconstruction. Since hollow tubes not always lead to good results after long defects(> 20 mm), we believe that the conduit enriched with fresh muscle fibers could be a promising strategy to repair longer gaps, as muscle fibers create a favorable three-dimensional environment and release trophic factors. All procedures were approved by the Bioethical Committee of the University of Torino and by the Italian Ministry of Health(approval number: 864/2016/PR) on September 14, 2016.展开更多
More than 2 billion people are at risk of malaria,which primarily affects poor populations in tropical and subtropical areas,including Southern Asia.As malaria incidence has been reduced strongly in some parts of ende...More than 2 billion people are at risk of malaria,which primarily affects poor populations in tropical and subtropical areas,including Southern Asia.As malaria incidence has been reduced strongly in some parts of endemic regions by combinations of interventions,including artemisinin-based therapies and insecticide-treated bed nets,a new goal has been established recently by charity foundations which support research on malaria:the worldwide eradication of the pathology.Doing away with control approaches which have been applied for the last 50 years and more focus on elimination objectives will deeply change priorities in the area of malaria treatment,chemoprevention,vector control,vaccine research and health system assessment.In this review,actual knowledge on pathogenesis and pharmacology is discussed,and new drugs, vaccines and insecticides are described.展开更多
It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein un...It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein unbound, and active ICS can cause systemic adverse effects. Therefore, a detailed investigation of drug-protein interaction could be of great interest to understand the pharmacokinetic behaviour of corticosteroids and for the design of new analogues with effective pharmacological properties. In the present work, the interaction between some corticosteroids and human serum albumin(HSA) has been studied by spectroscopic approaches. UV–Vis spectroscopy confirmed that all the investigated corticosteroids can bind to HSA forming a protein-drug complex. The intrinsic fluorescence of HSA was quenched by all the investigated drugs, which was rationalized in terms of a static quenching mechanism. The thermodynamic parameters determined by the Van't Hoff analysis of the binding constants(negative ΔH and ΔS values) clearly indicate thathydrogen bonds and van der Waals forces play a major role in the binding process between albumin and betamethasone, flunisolide and prednisolone, while hydrophobic forces may play a major role in stabilizing albumin-triamcinolone complexes.展开更多
Background:The possibility of assessing meat quality traits over the meat chain is strongly limited,especially in the context of selective breeding which requires a large number of phenotypes.The main objective of thi...Background:The possibility of assessing meat quality traits over the meat chain is strongly limited,especially in the context of selective breeding which requires a large number of phenotypes.The main objective of this study was to investigate the suitability of portable infrared spectrometers for phenotyping beef cattle aiming to genetically improving the quality of their meat.Meat quality traits(pH,color,water holding capacity,tenderness)were appraised on rib eye muscle samples of 1,327 Piemontese young bulls using traditional(i.e.,reference/gold standard)laboratory analyses;the same traits were also predicted from spectra acquired at the abattoir on the intact muscle surface of the same animals 1 d after slaughtering.Genetic parameters were estimated for both laboratory measures of meat quality traits and their spectra-based predictions.Results:The prediction performances of the calibration equations,assessed through external validation,were satisfactory for color traits(R^(2) from 0.52 to 0.80),low for pH and purge losses(R^(2) around 0.30),and very poor for cooking losses and tenderness(R^(2) below 0.20).Except for lightness and purge losses,the heritability estimates of most of the predicted traits were lower than those of the measured traits while the genetic correlations between measured and predicted traits were high(average value 0.81).Conclusions:Results showed that NIRS predictions of color traits,pH,and purge losses could be used as indicator traits for the indirect genetic selection of the reference quality phenotypes.Results for cooking losses were less effective,while the NIR predictions of tenderness were affected by a relatively high uncertainty of estimate.Overall,genetic selection of some meat quality traits,whose direct phenotyping is difficult,can benefit of the application of infrared spectrometers technology.展开更多
AIM: To determine the outcome of the management of iatrogenic gastrointestinal tract perforations treated by over-the-scope clip(OTSC) placement.METHODS: We retrospectively enrolled 20 patients(13 female and 7 male; m...AIM: To determine the outcome of the management of iatrogenic gastrointestinal tract perforations treated by over-the-scope clip(OTSC) placement.METHODS: We retrospectively enrolled 20 patients(13 female and 7 male; mean age: 70.6 ± 9.8 years) in eight high-volume tertiary referral centers with upper or lower iatrogenic gastrointestinal tract perforation treated by OTSC placement. Gastrointestinal tract perforation could be with oval-shape or with round-shape. Ovalshape perforations were closed by OTSC only by suction and the round-shape by the "twin-grasper" plus suction. RESULTS: Main perforation diameter was 10.1 ± 4.3 mm(range 3-18 mm). The technical success rate was 100%(20/20 patients) and the clinical success rate was 90%(18/20 patients). Two patients(10%) who did not have complete sealing of the defect underwent surgery. Based upon our observations we propose two types of perforation: Round-shape "type-1 perforation" and oval-shape "type-2 perforation". Eight(40%) out of the 20 patients had a type-1 perforation and 12 patients a type-2(60%). CONCLUSION: OTSC placement should be attempted after perforation occurring during diagnostic or therapeutic endoscopy. A failed closure attempt does not impair subsequent surgical treatment.展开更多
AIM: To investigate the prevalence of undernutrition, risk of malnutrition and obesity in the Italian gastroenterological population. METHODS: The Italian Hospital Gastroenterology Association conducted an observation...AIM: To investigate the prevalence of undernutrition, risk of malnutrition and obesity in the Italian gastroenterological population. METHODS: The Italian Hospital Gastroenterology Association conducted an observational, cross-sectional multicenter study. Weight, weight loss, and body mass index were evaluated. Undernutrition was defined as unintentional weight loss > 10% in the last threesix months. Values of Malnutrition Universal Screening Tool(MUST) > 2, NRS-2002 > 3, and Mini Nutritional Assessment(MNA) from 17 to 25 identified risk of malnutrition in outpatients, inpatients and elderly patients, respectively. A body mass index ≥ 30 indicated obesity. Gastrointestinal pathologies were categorized into acute, chronic and neoplastic diseases. RESULTS: A total of 513 patients participated in the study. The prevalence of undernutrition was 4.6% in outpatients and 19.6% in inpatients. Moreover, undernutrition was present in 4.3% of the gastrointestinal patients with chronic disease, 11.0% of those with acute disease, and 17.6% of those with cancer. The risk of malnutrition increased progressively and significantly in chronic, acute and neoplastic gastrointestinal diseases in inpatients and the elderly population. Logistical regression analysis confirmed that cancer was a risk factor for undernutrition(OR = 2.7; 95%CI: 1.2-6.44, P = 0.02). Obesity and overweight were more frequent in outpatients. CONCLUSION: More than 63% of outpatients and 80% of inpatients in gastroenterological centers suffered from significant changes in body composition and required specific nutritional competence and treatment.展开更多
文摘Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method.Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized.Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations.Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.
文摘Renal fibrosis and inflammation are common pathological features of chronic kidney disease(CKD).Since currently available treatments can only delay the progression of CKD,the outcome of patients with CKD is still poor.One therapeutic option for the prevention of CKD-related complications could be the use of mesenchymal stromal cells(MSCs),which have shown beneficial effects in tissue fibrosis and regeneration after damage.However,safety issues,such as cellular rejection and carcinogenicity,limit their clinical application.Among the bioactive factors secreted by MSCs,extracellular vesicles(EVs)have shown the same beneficial effect of MSCs,without any notable side effects.This heterogeneous population of membranous nano-sized particles can deliver genetic material and functional proteins to injured cells,prompting tissue regeneration.Here we describe the anti-fibrotic and antiinflammatory properties of MSC-derived EVs in CKD preclinical models and summarize the potential molecular mechanisms involved in the regulation of renal fibrosis and inflammation.
基金funded by the Spanish “Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministerio de Economía y Competitividad (Instituto de Salud Carlos Ⅲ),grants Nos. FIS PI14-1343, FIS PI17-0393, and FIS PI20-0318 co-financed by the “Fondo Europeo de Desarrollo Regional ERDF-FEDER European Union”grant No. P18-RT-5059 by “Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020),Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, España”grant No. A-CTS-498-UGR18 by “Programa Operativo FEDER Andalucía 2014–2020, Universidad de Granada, Junta de Andalucía, España”, co-funded by ERDF-FEDER, the European Union (all to VC)
文摘Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair.Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance.In this study,we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model.Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks.Nevertheless,the molecular assessment in the early regeneration phase(7,14,and 28 days)has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones.Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1,a growth factor that plays an important role in Schwann cell transdifferentiation.The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2,VEGF-A,BDNF,c-Jun,and ATF3.
基金Financial support for this work was provided by the University of Turin(ex 60%)grant(Es.fin.2015–2016)
文摘Background: Two trials were performed to evaluate a partially defatted Hermetia illucens(HI) larvae meal as potential feed ingredient in rainbow trout(Oncorhynchus mykiss Walbaum) diets. In the first trial, 360 trout(178.9 ± 9.8 g of mean initial body weight) were randomly divided into three experimental groups(4 tanks/treatment, 30 fish/tank). The fish were fed for 78 days with isonitrogenous, isolipidic and isoenergetic diets containing increasing levels of HI, on as fed basis: 0%(HI0, control diet), 25%(HI25) and 50%(HI50) of fish meal substitution, corresponding to dietary inclusion levels of 0, 20% and 40%. In the second trial, 36 trout(4 tanks/treatment, 3 fish/tank) were used to evaluate the in vivo apparent digestibility coefficients(ADC) of the same diets used in the first trial.Results: Survival, growth performance, condition factor, somatic indexes, and dorsal fillet physical quality parameters were not affected by diet. The highest dietary inclusion of HI larvae meal increased dry matter and ether extract contents of trout dorsal fillet. The use of HI larvae meal induced a decrease of valuable polyunsaturated fatty acids(PUFA) even if differences were only reported at the highest level of HI inclusion. The insect meal worsened the lipids health indexes of the same muscle. Dietary inclusion of insect meal did not alter the villus height of the fish. No differences were found among treatments in relation to ADC of ether extract and gross energy, while ADC of dry matter and crude protein were higher in HI25 if compared to HI50.Conclusions: The obtained results showed that a partially defatted HI larvae meal can be used as feed ingredient in trout diets up to 40% of inclusion level without impacting survival, growth performance, condition factor, somatic indexes, dorsal fillet physical quality parameters, and intestinal morphology of the fish. However, further investigations on specific feeding strategies and diet formulations are needed to limit the observed negative effects of the insect meal on the FA composition of dorsal muscle.
文摘Laparoscopic resection for colon and rectal cancer is associated with quicker return of bowel function, reduced postoperative morbidity rates and shorter length of hospital stay compared to open surgery, with no differences in long-term survival. Conversion to open surgery is reported in up to 30% of patients enrolled in randomized control trials comparing open and laparoscopic colorectal resection for cancer. In this review, reasons for conversion are anatomical-related factors, disease-related-factors and surgeon-related factors. Body mass index, local tumour extension and co-morbidities are independent predictors of conversion. The current evidence has shown that patients with converted resection for colon cancer have similar outcomes compared to patients undergoing a laparoscopic completed or open resection. The few studies that have assessed the outcomes after conversion of laparoscopic rectal resection reported significantly higher rates of complications and longer length of hospital stay in converted patients compared to laparoscopically treated patients. No definitive conclusions can be drawn when converted and open rectal resections are compared. Early and pre-emptive conversion appears to have more favourable outcomes than reactive conversion; however, further large studies are needed to better define the optimal timing of conversion. With regard to long-term oncologic outcome, overall and disease-free survival in the case of conversion in laparoscopic colorectal cancer surgery seems to be worse than those achieved in patients in whom resection was successfully completed by laparoscopy. Although a worse long-term oncologic outcome has been suggested, it remains difficult to draw a proper conclusion due to the heterogeneity of the long-term outcomes as well as the inclusion of both colon and rectal cancer patients in most of the studies. Therefore, we discuss the currently available evidence of the impact of conversion in laparoscopic resection for colon and rectal cancer on both short-term outcomes and long-term survival.
文摘Angiogenesis is a dynamic,hypoxia-stimulated and growth factor-dependent process,and is currently referred to as the formation of new vessels from preexisting blood vessels.Experimental and clinical studies have unequivocally reported that hepatic angiogenesis,irrespective of aetiology,occurs in conditions of chronic liver diseases(CLDs) characterized by perpetuation of cell injury and death,inflammatory response and progressive fibrogenesis.Angiogenesis and related changes in liver vascular architecture,that in turn concur to increase vascular resistance and portal hypertension and to decrease parenchymal perfusion,have been proposed to favour fibrogenic progression of the disease towards the end-point of cirrhosis.Moreover,hepatic angiogenesis has also been proposed to modulate the genesis of portal-systemic shunts and increase splanchnic blood flow,thus potentially affecting complications of cirrhosis.Hepatic angiogenesis is also crucial for the growth and progression of hepatocellular carcinoma.Recent literature has identified a number of cellular and molecular mechanisms governing the cross-talk between angiogenesis and fibrogenesis,with a specifi c emphasis on the crucial role of hypoxic conditions and hepatic stellate cells,particularly when activated to the myofibroblast-like pro-fibrogenic.Experimental anti-angiogenic therapy has been proven to be effective in limiting the progression of CLDs in animal models.From a clinical point of view,anti-angiogenic therapy is currently emerging as a new pharmacologic intervention in patients with advanced fibrosis and cirrhosis.
基金Supported by Ministero dell’Universitàe della Ricerca Scientifica e Tecnologica(MURST,ex-60%to GM and EL)
文摘A large body of experimental and clinical data supports the notion that inflammation in acute pancreatitis has a crucial role in the pathogenesis of local and systemic damage and is a major determinant of clinical severity.Thus,research has recently focused on molecules that can regulate the inflammatory processes,such as phosphoinositide 3-kinases(PI3Ks),a family of lipid and protein kinases involved in intracellular signal transduction.Studies using genetic ablation or pharmacologic inhibitors of different PI3 K isoforms,in particular the class I PI3Kδ and PI3Kγ,have contributed to a greater understanding of the roles of these kinases in the modulation of inflammatory and immune responses.Recent data suggest that PI3 Ks are also involved in the pathogenesis of acute pancreatitis.Activation of the PI3K signaling pathway,and in particular of the class IB PI3Kγ isoform,has a significant role in those events which are necessary for the initiation of acute pancreatic injury,namely calcium signaling alteration,trypsinogen activation,and nuclear factor-κB transcription.Moreover,PI3Kγ is instrumental in modulating acinar cell apoptosis,and regulating local neutrophil infiltration and systemic inflammatory responses during the course of experimental acute pancreatitis.The availability of PI3 K inhibitors selective for specific isoforms may provide new valuable therapeutic strategies to improve the clinical course of this disease.This article presents a brief summary of PI3 K structure and function,and highlights recent advances that implicate PI3 Ks in the pathogenesis of acute pancreatitis.
基金Supported by a grant from MIUR (Roma,Italy) to G Emanuelli and partly by a grant from Regione Piemonte to G Bellone
文摘AIM: To report a case of severe idiopathic gastroparesis in complete absence of Kit-positive gastric interstitial cells of Cajal (ICC). METHODS: Gastric tissue from a patient with severe idiopathic gastroparesis unresponsive to medical treatment and requiring surgery was analyzed by conventional histology and immunohistochemistry. RESULTS: Gastric pacemaker cells expressing Kit receptor had completely disappeared while the local level of stem cell factor, the essential ligand for its development and maintenance, was increased. No signs of cell death were observed in the pacemaker region. CONCLUSION: These results are consistent with the hypothesis that a lack of Kit expression may lead to impaired functioning of ICC. Total gastrectomy proves to be curative.
文摘The worldwide prevalence of hepatitis C virus(HCV)infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, motherto-child transmission(MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance(SVC) that usually occurs within 6 years of life. IL-28 B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.
基金supported in the context of the Italian Malaria Network by grants from Compagnia di San Paolo-IMIthe University of Torino Intramural FundsRegione Piemonte,Ricerca Sanitaria Finalizzata 2007 to PA
文摘Objective:Avidly phagocytosed hemozoin(malarial pigment) alters several functions of human monocytes and stimulates generation of several cytokines.Recently,we showed that phagocytosis of hemozoin by human monocytes increases expression and activity of matrix metalloproteinase-9,a proteolytic enzyme available in specific gelatinase granules,which contain several enzymes including lysozyme.Present work investigated active lysozyme release after phagocytosis of hemozoin and its dependence on production of tumor necrosis factor alpha. Methods:After phagocytosis of hemozoin,hemozoin-containing trophozoites or control meals(opsonized nonparasitized red blood cells and latex particles),monocyte supematants were monitored for 2 hours,in presence of blocking anti-human tumor necrosis factor alpha antibodies or recombinant human tumor necrosis factor alpha cytokine in selected experiments.Lysozyme release was evaluated by a specific spectrometric assay measuring lysozyme activity after coincubation of cell supematants with suspensions of Mycrococcus Lysodeikticus,while levels of soluble tumor necrosis factor alpha were analyzed by specific enzyme-linked immunodsorbent assay. Results:Levels of lysozyme activity and soluble tumor necrosis factor alpha protein were increased in hemozoin in-or trophozoites-laden monocytes supematants.Phagocytosis per se(control meals) also increased lysozyme release,but levels were significantly lower than those obtained after phagocytosis of hemozoin or trophozoites. Interestingly,all effects on lysozyme release observed after phagocytosis were abrogated by blocking anti-human tumor necrosis factor alpha antibodies,while they were mimicked by recombinant human tumor necrosis factor alpha cytokine.Conclusions:Present work shows that phagocytosis of hemozoin promotes monocyte degranulation and enhances active lysozyme release.The effect requires tumor necrosis factor alpha mediation.
基金financially supported by the National Basic Research Program of China (Grant No. 2015CB856104)the National Natural Science Foundation of China (Grant No. 41273036)
文摘Ultrahigh-pressure(UHP) metamorphic rocks are distinctive products of crustal deep subduction,and are mainly exposed in continental subduction-collision terranes. UHP slices of continental crust are usually involved in multistage exhumation and partial melting, which has obvious influence on the rheological features of the rocks, and thus significantly affect the dynamic behavior of subducted slices. Moreover,partial melting of UHP rocks have significant influence on element mobility and related isotope behavior within continental subduction zones, which is in turn crucial to chemical differentiation of the continental crust and to crust-mantle interaction.Partial melting can occur before, during or after the peak metamorphism of UHP rocks. Post-peak decompression melting has been better constrained by remelting experiments; however, because of multiple stages of decompression, retrogression and deformation, evidence of former melts in UHP rocks is often erased. Field evidence is among the most reliable criteria to infer partial melting. Glass and nanogranitoid inclusions are generally considered conclusive petrographic evidence. The residual assemblages after melt extraction are also significant to indicate partial melting in some cases. Besides field and petrographic evidence, bulk-rock and zircon trace-element geochemical features are also effective tools for recognizing partial melting of UHP rocks. Phase equilibrium modeling is an important petrological tool that is becoming more and more popular in P-T estimation of the evolution of metamorphic rocks; by taking into account the activity model of silicate melt, it can predict when partial melting occurred if the P-T path of a given rock is provided.UHP silicate melt is commonly leucogranitic and peraluminous in composition with high SiO_2,low MgO, FeO, MnO, TiO_2 and CaO, and variable K_2 O and Na_2 O contents. Mineralogy of nanogranites found in UHP rocks mainly consists of plagioclase + K-feldspar + quartz, plagioclase being commonly albite-rich.Trace element pattern of the melt is characterized by significant enrichment of large ion lithophile elements(LILE), depletion of heavy rare earth elements(HREE) and high field strength elements(HFSE),indicating garnet and rutile stability in the residual assemblage. In eclogites, significant Mg-isotope fractionation occurs between garnet and phengite; therefore, Mg isotopes may become an effective indicator for partial melting of eclogites.
文摘Berberine is used in traditional Chinese medicine for the treatment of congestive heart failure, hypertension, diabetes, and dyslipidaemia and has a good safety profile. We report a case of a 53-year-old sportsman referred to our hospital for the onset of fatigue and dyspnoea upon exertion after he started berberine to treat hypercholesterolaemia. An electrocardiogram showed sinus bradycardia (45 bpm), first-degree atrioventricular block, and competitive junctional rhythm. An ergometric stress test showed slightly reduced chronotropic competence and the presence of runs of competitive junctional rhythm, atrial tachycardia, and sinus pauses in the recovery. After 10 d of wash-out from berberine, the patient experienced a complete resolution of symptoms, and an ergometric stress test showed good chronotropic competence. An electrocardiogram Holtershowed a latent hypervagotonic state. This is the first case report that shows that berberine could present certain side effects in hypervagotonic people, even in the absence of a situation that could cause drug accumulation. Therefore, berberine's use should be carefully weighed in hypervagotonic people due to the drug's bradycardic and antiarrhythmic properties, which could became proarrhythmic, exposing patients to potential health risks.
文摘AIM: To investigate the state of the art regarding Cartilage Autograft Implantation System(CAIS) or Particulated Juvenile Allograft Cartilage(PJAC).METHODS: The authors searched the English literature regarding CAIS and PJAC. The search strategy was:(particulated cartilage) OR autologous cartilage fragments. All basic science articles were included. Clinical articles with less than 10 patients treated and less than 6 mo of follow-up were excluded. With these criteria, a total of 17 articles were available for the present review. RESULTS: PJAC and CAIS are relatively novel techniques for cartilage repair. Good basic science evidence was described to support the concept. Although the preliminary clinical reports show encouraging results, clinical data are still limited, especially for CAIS. The indications for both techniques need to be precisely defined(age of the patients, size of the lesion, and involvement of the subchondral bone), together with other debated issues. CONCLUSION: In conclusion, the authors can state that encouraging preliminary results are available for both techniques. However, further studies are necessary to precisely determine the indications, surgical techniques, and long term outcomes for PJAC and CAIS.
基金supported in the context of the Italian Malaria Network by grants from Compagnia di San Paolo-IMI and from Regione Piemonte,Ricerca Sanitaria Finalizzata 2008bis to PA
文摘Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemozoin;lipid free hemozoin;and control latex particles),then tumor necrosis factor alpha was monitored in cell supernatants up to 48 hours through western blotting or specific enzyme-linked immunoadsorbent assay.In selected experiments,unfed monocytes were treated with different doses of 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid or 4-hydroxynonenal instead of phagocytosis.Results:Hemozoin-fed monocytes produced higher levels of tumor necrosis factor alpha than unstimulated and latex-fed cells, while lipid-free hemozoin did not reproduce these results.Additionally,hemozoin effects were mimicked dose-dependently by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid,but not by 4-hydroxynonenal.Conclusions:Present data suggest an essential role for lipids in hemozoindependent enhanced release of tumor necrosis factor alpha from monocytes,and 15(S,R)hydroxy -6,8,11,13-eicosatetraenoic acid could be one possible specific mediator.
基金supported by the European Community’s Seventh Framework Programme(FP7-HEALTH-2011),No.278612(to SG)by Compagnia di San Paolo,No.D86D15000100005InTheCure project(to SR)
文摘Nerve regeneration after delayed nerve repair is often unsuccessful. Indeed, the expression of genes associated with regeneration, including neurotrophic and gliotrophic factors, is drastically reduced in the distal stump of chronically transected nerves; moreover, Schwann cells undergo atrophy, losing their ability to sustain regeneration. In the present study, to provide a three-dimensional environment and trophic factors supporting Schwann cell activity and axon re-growth, we combined the use of an effective conduit(a chitosan tube) with a promising intraluminal structure(fresh longitudinal skeletal muscle fibers). This enriched conduit was used to repair a 10-mm rat median nerve gap after 3-month delay and functional and morphometrical analyses were performed 4 months after nerve reconstruction. Our data show that the enriched chitosan conduit is as effective as the hollow chitosan conduit in promoting nerve regeneration,and its efficacy is not statistically different from the autograft, considered the "gold standard" technique for nerve reconstruction. Since hollow tubes not always lead to good results after long defects(> 20 mm), we believe that the conduit enriched with fresh muscle fibers could be a promising strategy to repair longer gaps, as muscle fibers create a favorable three-dimensional environment and release trophic factors. All procedures were approved by the Bioethical Committee of the University of Torino and by the Italian Ministry of Health(approval number: 864/2016/PR) on September 14, 2016.
基金supported by the Compagnia di San Paolo-IMI grants to MP in the context of the Italian Malaria Network
文摘More than 2 billion people are at risk of malaria,which primarily affects poor populations in tropical and subtropical areas,including Southern Asia.As malaria incidence has been reduced strongly in some parts of endemic regions by combinations of interventions,including artemisinin-based therapies and insecticide-treated bed nets,a new goal has been established recently by charity foundations which support research on malaria:the worldwide eradication of the pathology.Doing away with control approaches which have been applied for the last 50 years and more focus on elimination objectives will deeply change priorities in the area of malaria treatment,chemoprevention,vector control,vaccine research and health system assessment.In this review,actual knowledge on pathogenesis and pharmacology is discussed,and new drugs, vaccines and insecticides are described.
基金supported by a grant from the University of Torino(Ricerca Locale ex-60%,Bando 2015)
文摘It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein unbound, and active ICS can cause systemic adverse effects. Therefore, a detailed investigation of drug-protein interaction could be of great interest to understand the pharmacokinetic behaviour of corticosteroids and for the design of new analogues with effective pharmacological properties. In the present work, the interaction between some corticosteroids and human serum albumin(HSA) has been studied by spectroscopic approaches. UV–Vis spectroscopy confirmed that all the investigated corticosteroids can bind to HSA forming a protein-drug complex. The intrinsic fluorescence of HSA was quenched by all the investigated drugs, which was rationalized in terms of a static quenching mechanism. The thermodynamic parameters determined by the Van't Hoff analysis of the binding constants(negative ΔH and ΔS values) clearly indicate thathydrogen bonds and van der Waals forces play a major role in the binding process between albumin and betamethasone, flunisolide and prednisolone, while hydrophobic forces may play a major role in stabilizing albumin-triamcinolone complexes.
基金This research was funded by FONDAZIONE CASSA DI RISPARMIO DI CUNEO and is part of the project“QUALIPIEM-Innovative tools for the selection of meat quality in the Piemontese breed”,project number 2014/0249 coordinator Andrea Albera.
文摘Background:The possibility of assessing meat quality traits over the meat chain is strongly limited,especially in the context of selective breeding which requires a large number of phenotypes.The main objective of this study was to investigate the suitability of portable infrared spectrometers for phenotyping beef cattle aiming to genetically improving the quality of their meat.Meat quality traits(pH,color,water holding capacity,tenderness)were appraised on rib eye muscle samples of 1,327 Piemontese young bulls using traditional(i.e.,reference/gold standard)laboratory analyses;the same traits were also predicted from spectra acquired at the abattoir on the intact muscle surface of the same animals 1 d after slaughtering.Genetic parameters were estimated for both laboratory measures of meat quality traits and their spectra-based predictions.Results:The prediction performances of the calibration equations,assessed through external validation,were satisfactory for color traits(R^(2) from 0.52 to 0.80),low for pH and purge losses(R^(2) around 0.30),and very poor for cooking losses and tenderness(R^(2) below 0.20).Except for lightness and purge losses,the heritability estimates of most of the predicted traits were lower than those of the measured traits while the genetic correlations between measured and predicted traits were high(average value 0.81).Conclusions:Results showed that NIRS predictions of color traits,pH,and purge losses could be used as indicator traits for the indirect genetic selection of the reference quality phenotypes.Results for cooking losses were less effective,while the NIR predictions of tenderness were affected by a relatively high uncertainty of estimate.Overall,genetic selection of some meat quality traits,whose direct phenotyping is difficult,can benefit of the application of infrared spectrometers technology.
文摘AIM: To determine the outcome of the management of iatrogenic gastrointestinal tract perforations treated by over-the-scope clip(OTSC) placement.METHODS: We retrospectively enrolled 20 patients(13 female and 7 male; mean age: 70.6 ± 9.8 years) in eight high-volume tertiary referral centers with upper or lower iatrogenic gastrointestinal tract perforation treated by OTSC placement. Gastrointestinal tract perforation could be with oval-shape or with round-shape. Ovalshape perforations were closed by OTSC only by suction and the round-shape by the "twin-grasper" plus suction. RESULTS: Main perforation diameter was 10.1 ± 4.3 mm(range 3-18 mm). The technical success rate was 100%(20/20 patients) and the clinical success rate was 90%(18/20 patients). Two patients(10%) who did not have complete sealing of the defect underwent surgery. Based upon our observations we propose two types of perforation: Round-shape "type-1 perforation" and oval-shape "type-2 perforation". Eight(40%) out of the 20 patients had a type-1 perforation and 12 patients a type-2(60%). CONCLUSION: OTSC placement should be attempted after perforation occurring during diagnostic or therapeutic endoscopy. A failed closure attempt does not impair subsequent surgical treatment.
文摘AIM: To investigate the prevalence of undernutrition, risk of malnutrition and obesity in the Italian gastroenterological population. METHODS: The Italian Hospital Gastroenterology Association conducted an observational, cross-sectional multicenter study. Weight, weight loss, and body mass index were evaluated. Undernutrition was defined as unintentional weight loss > 10% in the last threesix months. Values of Malnutrition Universal Screening Tool(MUST) > 2, NRS-2002 > 3, and Mini Nutritional Assessment(MNA) from 17 to 25 identified risk of malnutrition in outpatients, inpatients and elderly patients, respectively. A body mass index ≥ 30 indicated obesity. Gastrointestinal pathologies were categorized into acute, chronic and neoplastic diseases. RESULTS: A total of 513 patients participated in the study. The prevalence of undernutrition was 4.6% in outpatients and 19.6% in inpatients. Moreover, undernutrition was present in 4.3% of the gastrointestinal patients with chronic disease, 11.0% of those with acute disease, and 17.6% of those with cancer. The risk of malnutrition increased progressively and significantly in chronic, acute and neoplastic gastrointestinal diseases in inpatients and the elderly population. Logistical regression analysis confirmed that cancer was a risk factor for undernutrition(OR = 2.7; 95%CI: 1.2-6.44, P = 0.02). Obesity and overweight were more frequent in outpatients. CONCLUSION: More than 63% of outpatients and 80% of inpatients in gastroenterological centers suffered from significant changes in body composition and required specific nutritional competence and treatment.