Effects of exogenous lactase administration on hydrogen breath excretion and intestinal symptoms in patients presenting lactose malabsorption and intolerance

To establish whether supplementation with a standard oral dose of Beta-Galactosidase affects hydrogen breath excretion in patients presenting with lactose malabsorption. METHODS: Ninety-six consecutive patients positive to H2 Lactose Breath Test were enrolled. Mean peak H2 levels, the time to reach the peak H2, the time to reach the cut-off value of 20 ppm, the cumulative breath H2 excretion, the areas under the curve, and a Visual Analogical 10-point Scale for symptoms were calculated. Genotyping of the C/T-13910 variant was carried out. RESULTS: Following the oral administration of Beta-Galactosidase, in 21.88% of the cases, H2 Lactose Breath Test became negative (Group A), while mean peak H2 levels (74.95 ppm versus 7.85), P < 0.0000, in 17.71% (Group B) were still positive, with the H2 level 20 ppm above the baseline, but the peak H2 levels were significantly lower than those observed at the baseline test (186.7 ppm versus 66.64), P < 0.0000, while in 60.41% (Group C) they were still positive with the peak H2 levels similar to those observed at the baseline test (94.43 versus 81.60 ppm). All 96 individuals tested presented the C/C-13910 genotype nonpersistence. CONCLUSIONS: The response to oral administration of Beta-Galactosidase in patients with symptoms of lactose malabsorption presents a significant variability

Anti-BVDV activity evaluation of naphthoimidazole derivatives compared with parental imidazoquinoline compounds.

Background: Pestivirus genus includes animal pathogens which are involved in economic impact for the livestock industry. Among others, Bovine Viral Diarrhoea Virus (BVDV) establish a persistent infection in cattle causing a long list of symptoms and a high mortality rate. In the last decades, we synthesised and reported a certain number of anti-BVDV compounds. Methods: In them, imidazoquinoline derivatives turned out as the most active. Their mechanism of actions has been deeply investigated, BVDV RNA-dependent RNA polymerase (RpRd) resulted as target and the way of binding was predicted in silico through three main H-bond interaction with the target. The prediction could be confirmed by target or ligand mutation. The first approach has already been performed and published confirming the in silico prediction. Results: Here, we present how the ligand chemical modification affects the anti-BVDV activity. The designed compounds were synthesised and tested against BVDV as in silico assay negative control. Conclusion: The antiviral results confirmed the predicted mechanism of action, as the newly synthesised compounds resulted not active in the in vitro BVDV infection inhibitio

Los procesos de gramaticalización de algunos conectores concesivos del castellano medieval

En aquest treball d'investigació es descriuen els trets principals dels processos de gramaticalització. Alhora, s'ha aplicat alguns dels postulats formulats en el marc de la Teoria de la gramaticalització a la formació d'alguns connectors concessius del castellà medieval: aunque, maguer (que) i comoquier (que). Per a l'anàlisi d'aquests fenòmens s'ha decidit recórrer a la Teoria dels prototips (en termes de Hilferty, 1993) i a la Teoria de la Rellevància (en termes de Blakemore, 2002): creiem que aquestes dues postures casen a la perfecció i ens han permès oferir una visió més global dels fetsEn el presente trabajo de investigación describimos los rasgos principales de los procesos de gramaticalización. Asimismo, aplicamos algunos de los postulados formulados en el marco de la Teoría de la gramaticalización a la formación de algunos conectores concesivos del castellano medieval: aunque, maguer (que) y comoquier (que). Para el análisis de estos fenómenos se ha decidido aplicar la Teoría de los prototipos (en términos de Hilferty, 1993) y la Teoría de la Relevancia (en términos de Blakemore, 2002): creemos que estas dos posturas casan a la perfección y nos han permitido ofrecer una visión más global de los hechos

Los procesos de gramaticalización de algunos conectores concesivos del castellano medieval

En aquest treball d'investigació es descriuen els trets principals dels processos de gramaticalització. Alhora, s'ha aplicat alguns dels postulats formulats en el marc de la Teoria de la gramaticalització a la formació d'alguns connectors concessius del castellà medieval: aunque, maguer (que) i comoquier (que). Per a l'anàlisi d'aquests fenòmens s'ha decidit recórrer a la Teoria dels prototips (en termes de Hilferty, 1993) i a la Teoria de la Rellevància (en termes de Blakemore, 2002): creiem que aquestes dues postures casen a la perfecció i ens han permès oferir una visió més global dels fetsEn el presente trabajo de investigación describimos los rasgos principales de los procesos de gramaticalización. Asimismo, aplicamos algunos de los postulados formulados en el marco de la Teoría de la gramaticalización a la formación de algunos conectores concesivos del castellano medieval: aunque, maguer (que) y comoquier (que). Para el análisis de estos fenómenos se ha decidido aplicar la Teoría de los prototipos (en términos de Hilferty, 1993) y la Teoría de la Relevancia (en términos de Blakemore, 2002): creemos que estas dos posturas casan a la perfección y nos han permitido ofrecer una visión más global de los hechos

Telocytes in minor salivary glands of primary Sjogren&#8217;s syndrome: association with the extent of inflammation and ectopic lymphoid neogenesis

It has been recently reported that telocytes, a stromal (interstitial) cell subset involved in the control of local tissue homeostasis, are hampered in the target organs of inflammatory/autoimmune disorders. Since no data concerning telocytes in minor salivary glands (MSGs) are currently available, aim of the study was to evaluate telocyte distribution in MSGs with normal architecture, non-specific chronic sialadenitis (NSCS) and primary Sjögren’s syndrome (pSS)-focal lymphocytic sialadenitis. Twelve patients with pSS and 16 sicca non-pSS subjects were enrolled in the study. MSGs were evaluated by haematoxylin and eosin staining and immunofluorescence for CD3/CD20 and CD21 to assess focus score, Tarpley biopsy score, T/B cell segregation and germinal center (GC)-like structures. Telocytes were identified by immunoperoxidase-based immunohistochemistry for CD34 and CD34/platelet-derived growth factor receptor α double immunofluorescence. Telocytes were numerous in the stromal compartment of normal MSGs, where their long cytoplasmic processes surrounded vessels and encircled both the excretory ducts and the secretory units. In NSCS, despite the presence of a certain degree of inflammation, telocytes were normally represented. Conversely, telocytes were markedly reduced in MSGs from pSS patients compared to normal and NSCS MSGs. Such a decrease was associated with both worsening of glandular inflammation and progression of ectopic lymphoid neogenesis, periductal telocytes being reduced in the presence of smaller inflammatory foci and completely absent in the presence of GC-like structures. Our findings suggest that a loss of MSG telocytes might have important pathophysiological implications in pSS. The specific pro-inflammatory cytokine milieu of pSS MSGs might be one of the causes of telocyte loss

A two-step immunomagnetic microbead-based method for the isolation of human primary skin telocytes/CD34+ stromal cells

Telocytes (TCs), commonly referred to as TCs/CD34+ stromal cells, are a peculiar type of interstitial cells with distinctive morphologic traits that are supposed to exert several biological functions, including tissue homeostasis regulation, cell-to-cell signaling, immune surveillance, and reparative/regenerative effects. At present, the majority of studies investigating these cells are mainly descriptive and focus only on their morphology, with a consequent paucity of functional data. To gain relevant insight into the possible functions of TCs, in vitro analyses are clearly required, but currently, the protocols for TC isolation are only at the early stages and not fully standardized. In the present in vitro study, we describe a novel methodology for the purification of human primary skin TCs through a two-step immunomagnetic microbead-based cell separation (i.e., negative selection for CD31 followed by positive selection for CD34) capable of discriminating these cells from other connective tissue-resident cells on the basis of their different immunophenotypic features. Our experiments clearly demonstrated that the proposed method allows a selective purification of cells exhibiting the peculiar TC morphology. Isolated TCs displayed very long cytoplasmic extensions with a moniliform silhouette (telopodes) and presented an immunophenotypic profile (CD31&minus;/CD34+/PDGFR&alpha;+/vimentin+) that unequivocally differentiates them from endothelial cells (CD31+/CD34+/PDGFR&alpha;&minus;/vimentin+) and fibroblasts (CD31&minus;/CD34&minus;/PDGFR&alpha;+/vimentin+). This novel methodology for the isolation of TCs lays the groundwork for further research aimed at elucidating their functional properties and possible translational applications, especially in the field of regenerative medicine

Genetic parameters of milk fatty acid profile in sheep: comparison between gas chromatographic measurements and Fourier-transform IR spectroscopy predictions.

Fatty acid (FA) composition is a key component of sheep milk nutritional quality. However, breeding for FA composition in dairy sheep is hampered by the logistic and phenotyping costs. This study was aimed at estimating genetic parameters for sheep milk FA and to test the feasibility of their routine measurement by using Fourier-transform IR (FTIR) spectroscopy. Milk FA composition of 989 Sarda ewes farmed in 48 flocks was measured by gas chromatography (FA GC ). Moreover, FTIR spectrum was collected for each sample, and it was used to predict FA composition (FA FTIR ) by partial least squares regression: 700 ewes were used for estimating model parameters, whereas the remaining 289 animals were used to validate the model. One hundred replicates were performed by randomly assigning animals to estimation and validation data set, respectively. Variance components for both measured and predicted traits were estimated with an animal model that included the fixed effects of parity, days in milking interval, lambing month, province, altitude of flock location, the random effects of flock-test-date and animal genetic additive. Genetic correlations among FA GC , and between corresponding FA GC and FA FTIR were estimated by bivariate analysis. Coefficients of determination between FA GC and FA FTIR ranged from moderate (about 0.50 for odd- and branched-chain FA) to high (about 0.90 for de novo FA) values. Low-to-moderate heritabilities were observed for individual FA (ranging from 0.01 to 0.47). The largest value was observed for GC measured C16:0. Low–to-moderate heritabilities were estimated for FA groups. In most of cases, heritabilites were slightly larger for FA GC than FA FTIR . Estimates of genetic correlations among FA GC showed a large variability in magnitude and sign. The genetic correlation between FA FTIR and FA GC was higher than 60% for all investigated traits. Results of the present study confirm the existence of genetic variability of the FA composition in sheep and suggest the feasibility of using FA FTIR as proxies for these traits in large scale breeding programs

Derivation of multivariate indices of milk composition, coagulation properties, and individual cheese yield in dairy sheep

Milk composition and its technological properties are traits of interest for the dairy sheep industry because almost all milk produced is processed into cheese. However, several variables define milk technological properties and a complex correlation pattern exists among them. In the present work, we measured milk composition, coagulation properties, and individual cheese yields in a sample of 991 Sarda breed ewes in 47 flocks. The work aimed to study the correlation pattern among measured variables and to obtain new synthetic indicators of milk composition and cheese-making properties. Multivariate factor analysis was carried out on individual measures of milk coagulation parameters; cheese yield; fat, protein, and lactose percentages; somatic cell score; casein percentage; NaCl content; pH; and freezing point. Four factors that were able to explain about 76% of the original variance were extracted. They were clearly interpretable: the first was associated with composition and cheese yield, the second with udder health status, the third with coagulation, and the fourth with curd characteristics. Factor scores were then analyzed by using a mixed linear model that included the fixed effect of parity, lambing month, and lactation stage, and the random effect of flock-test date. The patterns of factor scores along lactation stages were coherent with their technical meaning. A relevant effect of flock-test date was detected, especially on the 2 factors related to milk coagulation properties. Results of the present study suggest the existence of a simpler latent structure that regulates relationships between variables defining milk composition and coagulation properties in sheep. Heritability estimates for the 4 extracted factors were from low to moderate, suggesting potential use of these new variables as breeding goals

Effect of Appendectomy on ClinicalCourse of Diverticulosis

Diverticulitis is a common condition where inflammation seems to play a key role in all forms of the disease. Since diverticular disease, in some cases, exhibits clinical and histopathologic similarities with the idiopathic inflammatory bowel disease, could have in common, with these some environmental risk factors, as appendectomy, that could interfere with the natural history of diverticular disease. Since the prevalence and the role of appendectomy in patients with colonic diverticula has not been defined, the aim of this study was to evaluate the prevalence of appendectomy, both in uncomplicated diverticular disease and in patients with diverticulitis. Two hundred and seven consecutive patients with verified diagnosis of diverticular disease of the colon were enrolled. Diagnosis of diverticulitis was defined by means of clinical, colonoscopic, and computerised tomography criteria. Logistic regression was used to describe the relation between the dependent variable (diverticulitis) and several covariates: sex, age (60), BMI (26), and history of appendectomy (emergency or elective appendectomy). We included the first order interactions in the model to assess the effect of each variable for a particular degree of the others covariates. Statistical analysis was performed using SPSS software. Results: The first order interactions did not show a relevant effect (p>0.10) and therefore were excluded from the logistic model. Sex (p=0.88), BMI (p=0.80), elective appendectomy (p=0.17), age (p=0,11), do not affect significantly, either as an independent variable or as a confounder, the risk of development of diverticulitis, and therefore were also excluded from the model. According to the final model the risk of diverticulitis is 4,94 fold higher (95% confidence interval: 1.98 to 12.37) in patients with history of appendectomy with emergency operative treatment, compared with patients without appendectomy or history of elective resection (p<0.001. Conclusions: The risk of diverticulitis does not increase in patients with elective appendectomy, therefore only patients with emergency appendectomy have an increased risk of diverticuliti

Antiviral activity of benzotriazole based derivatives

Background: For the last thirty years, the benzotriazole scaffold has been the object of our group interest and we have already presented some results on the antiviral activity of our compounds. Objective: In this article, we conclude the exploration of N-(4-(R-2H-benzo[d][1,2,3]triazol-2-yl)phenyl)-4-R’-benzamides and 1-(4-(R-2H-benzo[d][1,2,3]triazol-2-yl)phenyl)-3-R’-ureas by synthesizing further modified derivatives, in order to have more elements for SARs evaluation. Methods: Here, we reported the synthesis and the antiviral screening results of 38 newly synthesized benzotriazole derivatives against a panel of DNA and RNA viruses. We also analyse SARs in comparing these compounds with previously published benzotriazole analogues, taking stock of the situation. Results: Among the newly presented derivatives, compounds 17 and 18 were the most active with EC50 6.9 and 5.5 µM, respectively against Coxsackievirus B5 (CV-B5) and 20.5 and 17.5 µM against Poliovirus (Sb-1). Conclusion: we can conclude that N-(4-(2H-benzo[d] [1-3] triazol-2-yl)phenyl-R-amide is a good chemical scaffold for the development of new antiviral molecules