169,914 research outputs found
Study of synthetic peptides derived from PKI55, a PKC modulator, in stimulated human neutrophils.
No full textFor-Met-Leu-Phe-OH (fMLP) and its derivative methyl ester, fMLP-OMe, represent highly potent chemoattractants for neutrophils. The interaction of fMLP with its receptor (FPR) activates multiple second messengers and involves specific kinases such as protein kinase C (PKC) and mitogen activated protein kinases (MAPKs). We reported a strong relationship between specific PKC isoforms and human neutrophils function activated by formylpeptides [1]. Recently, we have identified the PKI55 protein that acts as a specific modulator of PKC [2]. We tested peptides derived from both C-terminal and N-terminal sequence of PKI55, with the objective to identify the portion of the protein maintaining the biochemical effect to inhibit PKC. Enzyme activity in vitro assay, using recombinant PKC isoforms, showed that the peptides G16, G8 and G5 (Tab.1), inhibited the specific PKC isozymes. These same peptides were used to evaluate in human neutrophils their ability to affect chemotaxis, superoxide and lysozyme release. Neutrophils were purified from peripheral blood of health donors, preincubated with peptides at concentration from 0,1μM, to 25μM and then activated with fMLP-OMe. Our data demonstrate that the peptides reduced chemotaxis, while superoxide generation and lysozyme release were never modified. Previously we demonstrated that chemotactic movement of neutrophils was mediated by activation of PKC β1 [3]. Since we suggest that the selected peptides act as PKC inhibitors, to confirm our hypothesis western blotting analysis were performed on neutrophils stimulated with fMLP-OMe in presence or absence of G16, G8 and G5 and PKC β1 levels were studied. The results confirmed the significant reduction of PKC β1 levels in presence of G16, G8 and G5 peptides in comparison with control samples. The peculiar inhibiting properties of the peptides render them a promising pharmacological tool to control the over-expression of PKC isoforms.
[1] Selvatici R., Falzarano S., Mollica A. and Spisani S. (2006) Eur J. Pharmacol 18:1-11
[2] Selvatici R., Melloni E., Ferrati m., Piubello C., Marincola F.C. And Gandini (2003) E. J. Mol Evol, 57:131-139. [3] Spisani S., Falzarano S., Traniello S., Nalli M. and Selvatici R. (2005) FEBS J. 272:883-91
Effects of some antineoplastic drugs (vincristine, doxorubicin and epirubicin) on human platelet aggregation
No full textEffects of tetanus toxin, Salmonella typhimurium porin, and bacterial lipopolysaccharide on platelet aggregation
No full textDuchenne muscular dystrophy: From diagnosis to therapy
No full textDuchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disorder due to mutations in the dystrophin gene. It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein that causes degeneration of skeletal and cardiac muscle. The molecular diagnostic of DMD involves a deletions/duplications analysis performed by quantitative technique such as microarray-based comparative genomic hybridization (array-CGH), Multiple Ligation Probe Assay MLPA. Since traditional methods for detection of point mutations and other sequence variants require high cost and are time consuming, especially for a large gene like dystrophin, the use of next-generation sequencing (NGS) has become a useful tool available for clinical diagnosis. The dystrophin gene is large and finely regulated in terms of tissue expression, and RNA processing and editing includes a variety of fine tuned processes. At present, there are no effective treatments and the steroids are the only fully approved drugs used in DMD therapy able to slow disease progression. In the last years, an increasing variety of strategies have been studied as a possible therapeutic approach aimed to restore dystrophin production and to preserve muscle mass, ameliorating the DMD phenotype. RNA is the most studied target for the development of clinical strategies and Antisense Oligonucleotides (AONs) are the most used molecules for RNA modulation. The identification of delivery system to enhance the efficacy and to reduce the toxicity of AON is the main purpose in this area and nanomaterials are a very promising model as DNA/RNA molecules vectors. Dystrophinopathies therefore represent a pivotal field of investigation, which has opened novel avenues in molecular biology, medical genetics and novel therapeutic options
Synthetic formyl tripeptide chemoattractants: a C-alpha,C-alpha-dialkylated, amphiphilic glycyl residue at position 1
No full textThe two diastereomeric tripeptides f-(S)-HmMet-Leu-Phe-OMe and f-(R)-HmMet-Leu-Phe-OMe, analogues of the prototypical chemoattractant f-Met-Leu-Phe-OH, were synthesized in solution by classical methods and fully characterized. A conformational study was performed in solution by 1H-NMR. Concomitantly, the two peptides were tested for their ability to induce chemotaxis, superoxide anion production and lysozyme secretion from human neutrophils. The conformational and biological data are discussed with regard to the proposed model of the chemotactic receptor on neutrophils
C. C. Canta: Prefazione
No full textIl saggio, che costituisce la prefazione al testo curato da R. Memoli e A. Falzarano sottolinea gli aspetti sulla transizione al futuro che sono presenti nei vari saggi presenti nel libro. Il futuro è un diritto di ogni essere umano e la preoccupazione per il futuro ha sempre costituito una priorità nella vita delle persone, anzi, pensare il futuro è essenziale per la crescita armonica della personalità (Erikson 1969). Il/la sociologo/a non può perciò disinteressarsi del futuro della società (Bell, Mau 1971) in cui vive e accettare che il sistema sociale e le istituzioni rimangano statiche e immobili ma operare per proporre alternative in una società che è in continuo mutamento (Mannheim 1972).
Viviamo in un tempo di grandi cambiamenti, se non di veri e propri sconvolgimenti, che hanno messo in crisi i modelli sociali e comportamentali di appena poco tempo fa: le crisi climatiche e ambientali; l’inasprirsi di conflitti e guerre in varie parti del mondo e, in particolare, nel vicino Mare Nostrum; la paura di virus sconosciuti e di inedite pandemie ancor più letali di quelle già sperimentate; il ruolo delle neuroscienze nella crisi globale, l’impatto dell’“Intelligenza Artificiale (IA)” nel processo di cambiamento; la necessità di una giustizia sociale rispettosa della dignità della persona; la perdita dei legami sociali e l’acuirsi della frammentazione sociale; l’assenza di un fondamento nel soggetto; la perdita di autostima e di fiducia nelle proprie capacità in particolare tra i più giovani. Tali cambiamenti, che oggi sono velocissimi, generano il diffondersi di una insicurezza soggettiva e collettiva che soffoca alla radice la speranza.
Eppure di fronte a questi problemi enormi non si può rimanere inerti, lasciare che il pessimismo e il panico soffochino la persona e abbiano il sopravvento sulla sua libertà: “Pensare il futuro” è l’unico modo per reagire, come è accaduto nel corso del novecento. Parafasando Aurelio Peccei oggi guardare al futuro è l’unico modo per compiere una rivoluzione.
Poiché la costruzione del futuro è strettamente legata anche ad un impegno etico, è importante individuare «le chiavi storiche che manovrano le leve del cambiamento sociale; i cambiamenti nella più vasta struttura sociale» (Bell 1973: 7).The essay, which constitutes the preface to the text edited by R. Memoli and A. Falzarano, underlines the aspects on the transition to the future that are present in the various essays in the book. The future is a right of every human being and concern for the future has always been a priority in people's lives; indeed, thinking about the future is essential for the harmonious growth of the personality (Erikson 1969). The sociologist cannot therefore be disinterested in the future of the society in which he lives (Bell, Mau 1971) and accept that the social system and institutions remain static and immobile but work to propose alternatives in a society that is constantly changing ( Mannheim 1972).
We live in a time of great changes, if not real upheavals, which have put the social and behavioral models of just a short time ago into crisis: the climate and environmental crises; the worsening of conflicts and wars in various parts of the world and, in particular, in the nearby Mare Nostrum; the fear of unknown viruses and unprecedented pandemics even more lethal than those already experienced; the role of neuroscience in the global crisis, the impact of "Artificial Intelligence (AI)" in the process of change; the need for social justice that respects the dignity of the person; the loss of social ties and the worsening of social fragmentation; the absence of a foundation in the subject; the loss of self-esteem and confidence in one's abilities, particularly among younger people. These changes, which are very fast today, generate the spread of a subjective and collective insecurity which suffocates hope at its roots.
Yet in the face of these enormous problems one cannot remain inert, let pessimism and panic suffocate the person and take over his freedom: "Thinking about the future" is the only way to react, as has happened during the twentieth century. Paraphasing Aurelio Peccei, today looking to the future is the only way to carry out a revolution.
Since the construction of the future is also closely linked to an ethical commitment, it is important to identify «the historical keys that operate the levers of social change; changes in the larger social structure” (Bell 1973: 7)
Structural characterization of promoter sequences of the gene coding human PKI55 protein, a protein kinase C inhibitor
No full textThe PKI55 protein was identified in our laboratory as specific protein kinase C inhibitor. We previously demonstrated that PKI55 is poorly translated in vivo and acts promoting PKC degradation and establishing a feedback loop of inhibition. However, our understanding of mechanisms by which the expression of PKI55 is regulated, is limited. In the present work we investigated the mRNA expression of PKI55 in human tissues by Northern blotting and RT- PCR, demonstrating that it is highly expressed in brain tissue. Moreover, since the computational analysis of the gene promoter region showed two sites (Box 1 and Box 2) similar to consensus sequences for AP1 and GAGA-factors, we investigated their ability to bind to these proteins. Electrophoretic Mobility Shift Assays showed that GAGA-factors preferentially interacted with Box 2, while AP-1 elements linked preferentially Box 1 sequence. We suggest that the interaction of these transcription factors with Box 1 and Box 2 could regulate the transcription of the PKI55 gene and, consequently, the expression of PKC
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Structure–activity relationship of for-l-Met l-Leu-l-Phe-OMe analogues in human neutrophils
No full textNeutrophils constitute the first line of defence against bacterial invasion. They migrate to infected tissues along a concentration gradient of chemoattractant molecules, the most important of which is for-Met-Leu-Phe-OH (fMLP). Different responses arise from formylpeptides binding to different isoforms of the specific receptor. The aim of the studies reported herein was to clarify (i) the role of fMLP-OMe amide bonds in receptor-ligand cross-linking, (ii) the nature of the group occupying the N- and C-terminal positions, (iii) the features peculiar to the Met, Leu, and Phe receptor pockets, and (iv) the features which determine the specific neutrophil response
Mitomycin C in highly myopic eyes - Author reply
No full textOphthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
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