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81.
Dario Sorrentino Marco Marino Themistocles Dassopoulos Dimitra Zarifi Tiziana Del Bianco 《PloS one》2015,10(12)
Objective
In patients with postoperative recurrence of Crohn’s disease endoscopic and clinical remission can be maintained for up to 1 year with low infliximab doses (3 mg/Kg). However, in theory low-dose infliximab treated patients could develop subtherapeutic trough levels, infiximab antibodies, and might loose response to therapy. To verify this hypothesis infliximab pharmacokinetics and clinical/endoscopic response were checked in a group of patients treated in the long term with low infliximab doses.Design
Infliximab antibodies, infliximab levels, highly-sensitive CRP and fecal calprotectin were measured during the 8-week interval in 5 consecutive patients in clinical (Crohn’s Disease Activity Index < 150) and endoscopic (Rutgeerts scores 0–1) remission after one year of therapy with infliximab 3 mg/Kg. For comparison with reported standards, infliximab pharmacokinetics and inflammatory parameters were also tested in 6 Crohn’s disease patients who did not undergo surgery and who were in clinical remission while on infliximab 5 mg/Kg. Patients on low infliximab dose also underwent colonoscopy after 18 additional months of therapy.Results
Highly sensitive CRP and fecal calprotectin increased in all patients during the 8-week interval. Infliximab trough levels were lower in patients treated with the low dose compared to controls (mean±SE: 2.0±0.3 vs 4.75±0.83 μg/mL respectively p<0.05). Infliximab antibodies were present in two of the subjects treated with low infliximab dose and in none of the controls. However, in low dose-treated patients after 18 additional months of therapy endoscopy continued to show mucosal remission and none of them developed clinical recurrence or side effects.Conclusions
Patients treated with low infliximab doses had lower trough levels compared to patients treated with 5 mg/Kg and some developed antibodies to infliximab. However, low infliximab doses sustained clinical and endoscopic remission for a total of 30 months of treatment. 相似文献82.
Parkinson's disease is the most common neurodegenerative movement disorder, affecting about 6 million people worldwide with a slow progression of the symptoms. Its prevalence is expected to double in the most populated areas within the next two decades, according to increasing aged population. Consequently, Parkinson's disease is a socio-economic trouble and a major challenge for the public health system. Parkinson's disease treatment is merely symptomatic, as clinical symptoms appear when about 70% of the involved neurons are lost and potential disease-modifying/neuroprotective therapies would have no effect. In turn, the availability of an objective measure that allows early diagnosis would strongly impact on the costs that biotech- and pharma-companies will sustain in order to develop disease-modifying therapies. The establishment of suitable models to investigate the mechanisms of Parkinson's disease progression and, on the other hand, the discovery and validation of selective and specific molecular biomarkers for early and differential diagnosis are indeed two important goals for a better management of the disease. In this review, we focus on cellular and animal models of Parkinson's disease by describing their advantages and limitations as useful tools to identify pathogenetic pathways that deserve further exploitation. In parallel, we discuss how proteomics may provide a potent tool to observe altered pathways in models or altered biomarkers in patients with an unbiased, hypothesis-free approach. 相似文献
83.
Barbara Manconi Tiziana Cabras Alberto Vitali Chiara Fanali Antonella Fiorita Rosanna Inzitari Massimo Castagnola Irene Messana Maria Teresa Sanna 《Protein expression and purification》2010,69(2):219-225
This work reports the successful recombinant expression of human statherin in Escherichia coli, its purification and in vitro phosphorylation. Human statherin is a 43-residue peptide, secreted by parotid and submandibular glands and phosphorylated on serine 2 and 3. The codon-optimized statherin gene was synthesized and cloned into commercial pTYB11 plasmid to allow expression of statherin as a fusion protein with intein containing a chitin-binding domain. The plasmid was transformed into E. coli strains and cultured in Luria–Bertani medium, which gave productivity of soluble statherin fusion protein of up to 47 mg per liter of cell culture, while 112 mg of fusion protein were in the form of inclusion bodies. No significant refolded target protein was obtained from inclusion bodies. The amount of r-h-statherin purified by RP–HPLC corresponded to 0.6 mg per liter of cell culture. Attenuated total reflection-Fourier transform infrared spectroscopy experiments performed on human statherin isolated from saliva and r-h-statherin assessed the correct folding of the recombinant peptide. Recombinant statherin was transformed into the diphosphorylated biologically active form by in vitro phosphorylation using the Golgi-enriched fraction of pig parotid gland containing the Golgi-casein kinase. 相似文献
84.
Larussa T Suraci E Leone I Nazionale I Abenavoli L Galasso O Amorosi A Imeneo M Luzza F 《Helicobacter》2010,15(5):449-459
Background: Selective cyclooxygenase‐2 (COX‐2) inhibitors and proton pump inhibitors may exert immune‐mediated effects in human gastric mucosa. T‐cell immune response plays a role in Helicobacter pylori‐induced pathogenesis. This study evaluated effects of celecoxib and lansoprazole on T‐helper (Th) 1 and Th2 immune response in human gastric mucosa. Methods: Dyspeptic patients with or without osteoarticular pain were given one of the following 4‐week therapies: celecoxib 200 mg, celecoxib 200 mg plus lansoprazole 30 mg, and lansoprazole 30 mg daily. Expression of COX‐2, T‐bet, and pSTAT6 and production of prostaglandin E2 (PGE2), interferon (IFN)‐γ, and interleukin (IL)‐4 were determined in gastric biopsies before and after therapy. Histology was evaluated. Results: Cyclooxygenase‐2 expression and PGE2 production was higher, and Th1 signaling pathway was predominant in H. pylori‐infected vs. uninfected patients. T‐bet expression and IFN‐γ production increased, while STAT6 activation and IL‐4 production decreased following therapy with celecoxib and celecoxib plus lansoprazole, respectively. Th1 and Th2 signaling pathways down‐regulated after therapy with lansoprazole, and this was associated with an improvement of gastritis. Effect of therapy was not affected by H. pylori status. Conclusion: Celecoxib and lansoprazole modulate Th1/Th2 immune response in human gastric mucosa. The use of these drugs may interfere with long‐term course of gastritis. 相似文献
85.
Gian Andrea Blengini Tiziana Di Carlo 《The International Journal of Life Cycle Assessment》2010,15(7):652-665
Background, aim and scope
A low-energy family house recently built in Northern Italy was selected by Regione Piemonte as an outstanding example of resource efficient building. An economic incentive was awarded to cover the extra costs of the thermal insulation, windows and equipment in order to decrease the yearly winter heat requirement from the legal standard of 109 to 10 kW h/m2, while existing buildings in the study area typically require 200 kW h/m2. As the building was claimed to be sustainable on the basis of its outstanding energy-saving performance, an ex post life cycle assessment (LCA) was set up to understand whether, and to what extent, the positive judgement could be confirmed in a life cycle perspective. 相似文献86.
Valentina Alessandria Paola Dolci Kalliopi Rantsiou Daniele Pattono Alessandra Dalmasso Tiziana Civera Luca Cocolin 《World journal of microbiology & biotechnology》2010,26(12):2211-2221
The present study aimed to evaluate the dominant microbial community naturally present in the Planalto de Bolona cheese, produced in the Cape Verde Islands. Samples of milk, curd and cheese from two different producers were examined through
culture-dependent and independent-methods. Traditional plating and genetic identification of lactic acid bacteria (LAB) and
yeast isolates were carried out. Moreover, DNA and RNA extracted directly from samples were subjected to Polymerase Chain
Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE). Concerning the LAB population, a total of 278 isolates were identified:
Lactococcus lactis subsp. lactis and Enterococcus faecium represented the most isolated species. Regarding yeasts, the analysis of isolates throughout the manufacturing period showed
a consistent presence of the genus Candida. Divergences in species detection between culture-dependent and culture-independent methods were observed, as well as between
DNA and RNA analysis. PCR-DGGE underlined high heterogeneity among bacterial species while yeast microbiota was dominated
by Aureobasidium pullulans at DNA level. The obtained results represent a first approach in the understanding of the Planalto de Bolona cheese microbial ecology and consequently may constitute a first step towards the full comprehension of the microbiota of
this artisanal cheese produced in unusual environmental conditions in the Cape Verde Islands. 相似文献
87.
Mitochondrial dysfunctions have been observed in subjects treated with antiretroviral nucleoside analogues, such as stavudine, as they can interfere with the activity of DNA polymerase gamma. Recently, stavudine-induced mitochondrial toxicity was associated to POLG mutations R964C and E1143G. A yeast model system useful to evaluate the association between D4T toxicity and mutations in MIP1, the yeast ortholog of POLG, was constructed and validated as a tool for pharmacogenetics research. We showed that mutant Mip1pR964C and possibly Mip1pE1143G are more sensitive to stavudine, and that stavudine has the potential to cause mitochondrial toxicity in heterozygous subjects harboring recessive mutations. 相似文献
88.
Domenico De Rasmo Giuseppe Palmisano Salvatore Scacco Zuzana Technikova-Dobrova Damiano Panelli Tiziana Cocco Anna Maria Sardanelli Antonio Gnoni Loris Micelli Antonio Trani Aldo Di Luccia Sergio Papa 《Mitochondrion》2010,10(5):464-471
The NDUFS4 subunit of complex I of the mammalian respiratory chain has a fully conserved carboxy-terminus with a canonical RVSTK phosphorylation site. Immunochemical analysis with specific antibodies shows that the serine in this site of the protein is natively present in complex I in both the phosphorylated and non-phosphorylated state. Two-dimensional IEF/SDS–PAGE electrophoresis, 32P labelling and immunodetection show that “in vitro” PKA phosphorylates the serine in the C-terminus of the NDUFS4 subunit in isolated bovine complex I. 32P labelling and TLC phosphoaminoacid mapping show that PKA phosphorylates serine and threonine residues in the purified heterologous human NDUFS4 protein. 相似文献
89.
Tiziana Greggi Konstantinos Martikos Emanuela Pipitone Francesco Lolli Francesco Vommaro Elena Maredi Stefano Cervellati Mario Di Silvestre 《Scoliosis》2010,5(1):1-11
Background
The reported incidence of scoliosis in arthrogryposis varies from 30% to 67% and, in most cases, the curves progress rapidly and become stiff from early age. The authors report six cases of scoliosis in arthrogryposis to assess the role of surgical treatment.Methods
Six cases (3 males, 3 females; mean age at surgery 13.2 years) with arthrogryposis multiplex congenita associated with the characteristic amyoplasia were reviewed: they were operated on for scoliosis at the authors' Spine Surgery Department between 1987 and 2008. Surgery was performed using the Harrington-Luque instrumentation (2 cases), the Luque system (1), a hybrid segmental technique with hooks and screws (1) and spinal anchoring with pedicle screws (2).Results
The patients were clinically and radiologically reviewed at a mean follow-up of 4.2 years, ± 2.7 (range, 1 to 9 years). Three minor postoperative complications were encountered; a long-term pulmonary complication was seen in one case after reintervention and was successfully resolved after 10 days. Surgery was successful in the other 5 cases, where solid arthrodesis was achieved and no significant curve progression was observed at follow-up.Conclusions
The experience acquired with the present case series leads the authors to assert that prompt action should be taken when treating such aggressive forms of scoliosis. In case of mild spinal deformities in arthrogryposis, brace treatment should be attempted, the evolution of the curves being unpredictable; however, when the curve exceeds 40° and presents with marked hyperkyphosis, hyperlordosis or pelvic obliquity, surgery should not be delayed. 相似文献90.
Tiziana Gigliobianco Bernard Lakaye Pierre Wins Benaïssa El Moualij Willy Zorzi Lucien Bettendorff 《BMC microbiology》2010,10(1):148