Publications by authors named "Alessandra Acquaviva"

12 Publications

  • Page 1 of 1

Metabolomic Profile and Antioxidant/Anti-Inflammatory Effects of Industrial Hemp Water Extract in Fibroblasts, Keratinocytes and Isolated Mouse Skin Specimens.

Antioxidants (Basel) 2021 Jan 1;10(1). Epub 2021 Jan 1.

Department of Pharmacy, Università Degli Studi "Gabriele d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.

Industrial hemp is a multiuse crop whose phytocomplex includes terpenophenolics and flavonoids. In the present study, the phenolic and terpenophenolic compounds were assayed in the water extract of the hemp variety Futura 75. Protective effects were also investigated in human fibroblast and keratinocytes and isolate mouse skin specimens, which were exposed to hydrogen peroxide and/or to the extract (1-500 µg/mL). The results of phytochemical analysis suggested the cannabidiol, cannabidiolic acid and rutin as the prominent phytocompounds. In the in vitro system represented by human keratinocytes and fibroblasts, the hemp extract was found to be able to protect cells from cytotoxicity and apoptosis induced by oxidative stress. Moreover, modulatory effects on IL-6, a key mediator in skin proliferation, were found. In isolated rat skin, the extract reduced hydrogen peroxide-induced l-dopa turnover, prostaglandin-E2 production and the ratio kynurenine/tryptpophan, thus corroborating anti-inflammatory/antioxidant effects. The in silico docking studies also highlighted the putative interactions between cannabidiol, cannabidiolic acid and rutin with tyrosinase and indoleamine-2,3-dioxygenase, involved in l-dopa turnover and tryptophan conversion in kynurenine, respectively. In conclusion, the present findings showed the efficacy of hemp water extract as a skin protective agent. This could be partly related to the extract content in cannabidiol, cannabidiolic acid and rutin.
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http://dx.doi.org/10.3390/antiox10010044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823476PMC
January 2021

Anti-Inflammatory and Neuromodulatory Effects Induced by Water Extract: Results from In Silico, In Vitro and Ex Vivo Studies.

Molecules 2020 Dec 23;26(1). Epub 2020 Dec 23.

Department of Pharmacy, Università degli Studi "Gabriele d'Annunzio", via dei Vestini 31, 66100 Chieti, Italy.

(feverfew) has traditionally been employed as a phytotherapeutic remedy in the treatment of migraine. In this study, a commercial water extract was investigated to explore its anti-inflammatory and neuromodulatory effects. Isolated mouse cortexes were exposed to a K 60 mM Krebs-Ringer buffer and treated with water extract. The prostaglandin E (PGE) level, brain-derived neurotrophic factor (BDNF), interleukin-10 (IL-10), and IL-1β gene expression were evaluated in the cortex. The effects on dopamine (DA) release and dopamine transporter (DAT) gene expression were assayed in hypothalamic HypoE22 cells. A bioinformatics analysis was conducted to further investigate the mechanism of action. The extract was effective in reducing cortex PGE release and IL-1β gene expression. In the same experimental system, IL-10 and BDNF gene expressions increased, and in HypoE22 cells, the extract decreased the extracellular dopamine level and increased the DAT gene expression due to the direct interaction of parthenolide with the DAT. Overall, the present findings highlight the efficacy of water extract in controlling the inflammatory pathways that occur during cortical-spreading depression. Additionally, the inhibition of the hypothalamic DA release observed in this study further supports the role of dopaminergic pathways as key targets for novel pharmacological approaches in the management of migraine attacks.
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http://dx.doi.org/10.3390/molecules26010022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793142PMC
December 2020

Characterization of Competitive ELISA and Formulated Alhydrogel Competitive ELISA (FAcE) for Direct Quantification of Active Ingredients in GMMA-Based Vaccines.

Methods Protoc 2020 Aug 31;3(3). Epub 2020 Aug 31.

GSK Vaccines Institute for Global Health s.r.l (GVGH), 53100 Siena, Italy.

Generalized modules for membrane antigens (GMMA) represent a technology particularly attractive for designing affordable vaccines against Gram-negative bacteria. We explored such technology for the development of O-antigen-based vaccines against and nontyphoidal . Adsorption of GMMA on Alhydrogel was required for abrogation of pyrogenicity in rabbits, and GMMA on Alhydrogel was well tolerated and immunogenic in humans. Quantification of key antigens in formulated vaccines was fundamental for release and to check stability overtime. Traditionally, the direct quantification of antigens adsorbed on aluminum salts has been challenging, and the quantification of each active ingredient in multicomponent formulated vaccines has been even more complicated. To directly quantify each active ingredient and unbound drug substances in formulated vaccines, we developed the Formulated Alhydrogel competitive ELISA (FAcE) and the competitive ELISA method, respectively. The methods were both fully characterized, assessing specificity, repeatability, intermediate precision, and accuracy, for OAg quantification, both in a single component or multicomponent GMMA formulation also containing GMMA. The developed immunological methods allowed us to fully characterize GMMA drug products, supporting their preclinical and clinical development. The same methods, already extended to GMMA from nontyphoidal and , could be potentially extended to any antigen formulated on Alhydrogel.
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http://dx.doi.org/10.3390/mps3030062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563494PMC
August 2020

Protective effect of Group B Streptococcus type-III polysaccharide conjugates against maternal colonization, ascending infection and neonatal transmission in rodent models.

Sci Rep 2018 02 7;8(1):2593. Epub 2018 Feb 7.

GSK, Siena, Italy.

Group B Streptococcus (GBS) is a normal inhabitant of recto-vaginal mucosae in up to 30% of healthy women. Colonization is a major risk factor for perinatal infection which can lead to severe complications such as stillbirth and neonatal invasive disease. Intra-partum antibiotic prophylaxis in colonized women is a safe and cost-effective preventive measure against early-onset disease in the first days of life, but has no effect on late-onset manifestations or on early maternal infection. Maternal immunization with capsular polysaccharide-based vaccines shows promise for the prevention of both early-onset and late-onset neonatal infections, although ability to prevent maternal colonization and ascending infection has been less studied. Here we investigated the effect of a GBS glycoconjugate vaccine since the very early stage of maternal GBS acquisition to neonatal outcome by rodent models of vaginal colonization and ascending infection. Immunization of female mice and rats with a type III glycoconjugate reduced vaginal colonization, infection of chorioamniotic/ placental membranes and bacterial transmission to fetuses and pups. Type III specific antibodies were detected in the blood and vagina of vaccinated mothers and their offspring. The obtained data support a potential preventive effect of GBS glycoconjugate vaccines during the different stages of pregnancy.
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http://dx.doi.org/10.1038/s41598-018-20609-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803199PMC
February 2018

Preliminary Results of a Simplified Breast MRI Protocol to Characterize Breast Lesions: Comparison with a Full Diagnostic Protocol and a Review of the Current Literature.

Acad Radiol 2017 11 1;24(11):1387-1394. Epub 2017 Jun 1.

Department of Advanced Biomedical Sciences, University "Federico II," Via Pansini 5, Naples 80123, Italy. Electronic address:

Rationale And Objectives: This study aimed to investigate whether a simplified breast magnetic resonance imaging (MRI) protocol consisting of a localizer, one precontrast sequence, and three time-point postcontrast sequences (at 28 seconds, 84 seconds and 252 seconds after the contrast agent administration) is suitable for the characterization of breast lesions as compared to a full diagnostic protocol (FDP). This study also aimed to review the current literature concerning abbreviated breast MRI protocols and offer an alternative protocol.

Materials And Methods: Breast magnetic resonance (MR) examinations with detected breast lesions of 98 patients were retrospectively evaluated. Two expert radiologists in consensus reviewed the simplified breast protocol (SBP) first and only thereafter the regular FDP, recording a diagnosis for each detected lesion for both protocols. Receiver operating characteristic curve analysis was performed to determine the diagnostic performance of the SBP compared to the standard FDP. A revision of the previously reported abbreviated breast magnetic resonance protocols was also carried out.

Results: A total of 180 lesions were identified; of these, 110 (61%) were malignant and 70 (39%) were benign. Of the 110 malignant lesions, 86 (78%) were invasive ductal carcinoma, 18 (16%) were invasive lobular carcinoma, and 6 (6%) were ductal carcinoma in situ. Areas under the curve for the receiver operating characteristic curves for the SBP vs the FDP were equivalent (0.98 vs 0.99, respectively; P = 0.76). The SBP could be performed in approximately 6 minutes and 58 seconds, compared to 14 minutes and 48 seconds for the FDP.

Conclusions: An SBP protocol including a late postcontrast time point is accurate for the characterization of breast lesions and was comparable to the standard FDP protocol, allowing a potential reduction of the total acquisition and interpretation times.
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http://dx.doi.org/10.1016/j.acra.2017.04.011DOI Listing
November 2017

Atypical Presentation of Ewing's Sarcoma with a Single Left Orbital Metastasis.

Pol J Radiol 2015 25;80:483-5. Epub 2015 Oct 25.

Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy.

Background: We present an uncommon case of Ewing's sarcoma in a 16-year-old boy.

Case Report: This case can be considered unique because of the atypical presentation, normal laboratory tests and absence of the typical symptoms such as pain, masses or swelling, fatigue or weight loss, breathing problems linked to lung metastases or pathologic fractures. The only event that brought the patient to our attention was the sudden onset of left proptosis.

Conclusions: The final histopathology together with CT and PET-CT findings led to the diagnosis of a multi-metastatic Ewing's sarcoma involving the orbit, skeleton, bone marrow and lymph nodes.
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http://dx.doi.org/10.12659/PJR.894507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625620PMC
November 2015

Poly Implant Prothèse (PIP) incidence of rupture: a retrospective MR analysis in 64 patients.

Quant Imaging Med Surg 2014 Dec;4(6):462-8

1 Department of Radiology, University "Federico II", Napoli, Italy ; 2 Department of Radiology, Ospedale S.M.delle Grazie, Pozzuoli, Napoli, Italy ; 3 Department of General, Geriatric, Oncologic Surgery and Advanced Technologies, Napoli, Italy.

Aim Of The Study: The purpose of this retrospective study was to describe the magnetic resonance imaging (MRI) features of Poly Implant Prothèse (PIP) hydrogel implants in a group of 64 patients and to assess the incidence of rupture, compared to other clinical trials.

Material And Methods: In this double-center study, we retrospectively reviewed the data sets of 64 consecutive patients (mean age, 43±9 years, age range, 27-65 years), who underwent breast MRI examinations, between January 2008 and October 2013, with suspected implant rupture on the basis of clinical assessment or after conventional imaging examination (either mammography or ultrasound). All patients had undergone breast operation with bilateral textured cohesive gel PIP implant insertion for aesthetic reasons. The mean time after operation was 8 years (range, 6-14 years). No patients reported history of direct trauma to their implants.

Results: At the time of clinical examination, 41 patients were asymptomatic, 16 complained of breast tenderness and 7 had clinical evidence of rupture. Normal findings were observed in 15 patients. In 26 patients there were signs of mild collapse, with associated not significant peri-capsular fluid collections and no evidence of implant rupture; in 23 patients there was suggestion of implant rupture, according to breast MRI leading to an indication for surgery. In particular, 14 patients showed intra-capsular rupture, with associated evidence of the linguine sign in all cases; the keyhole sign and the droplet signs were observed in 6 cases. In 9 patients there was evidence of extra-capsular rupture, with presence of axillary collections (siliconomas) in 7 cases and peri-prosthetic and mediastinal cavity siliconomas, in 5 cases.

Conclusions: The results of this double center retrospective study, confirm the higher incidence (36%) of prosthesis rupture observed with the PIP implants, compared to other breast implants.
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http://dx.doi.org/10.3978/j.issn.2223-4292.2014.08.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256241PMC
December 2014

Markers of inflammation and oxidative stress studied in adjuvant-induced arthritis in the rat on systemic and local level affected by pinosylvin and methotrexate and their combination.

Autoimmunity 2015 Feb 21;48(1):46-56. Epub 2014 Jul 21.

Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences , Bratislava , Slovak Republic .

Oxidative stress (OS) is important in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and its experimental model--adjuvant arthritis (AA). Antioxidants are scarcely studied in autoimmunity, and future analyses are needed to assess its effects in ameliorating these diseases. Although there are studies about antioxidants effects on the course of RA, their role in combination therapy has not yet been studied in detail, especially on extra-articular manifestations of AA. During the 28-d administration of pinosylvin (PIN) in monotherapy and in combination with methotrexate (MTX) to AA rats, we evaluated the impact of the treatment on selected parameters. The experiment included: healthy controls, untreated AA, AA administered 50 mg/kg b.w. of PIN daily p.o., AA administered 0.4 mg/kg b.w. of MTX twice weekly p.o. and AA treated with a combination of PIN+MTX. AA was monitored using: hind paw volume, C-reactive protein, monocyte chemotactic protein-1 (MCP-1), thiobarbituric acid reactive substances (TBARS) and F2-isoprostanes in plasma, γ-glutamyltransferase activity in spleen, activity of lipoxygenase (LOX) in lung, heme oxygenase-1 (HO-1) and nuclear factor kappa B (NF-κB) in liver and lung. PIN monotherapy significantly improved the activation of NF-κB in liver and lung, HO-1 expression and activity of LOX in the lung, MCP-1 levels in plasma (on 14th d) and plasmatic levels of F2-isoprostanes. An important contribution of PIN to MTX effect was the reduction of OS (an increase of HO-1 expression in lung and reduction of plasmatic TBARS) and decrease of LOX activity in the lung.
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http://dx.doi.org/10.3109/08916934.2014.939268DOI Listing
February 2015

N-feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis.

Fundam Clin Pharmacol 2014 Dec 2;28(6):616-26. Epub 2014 Oct 2.

Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dubravska cesta 9, SK-841 04, Bratislava, Slovak Republic.

Many of disease-modifying anti-rheumatic drugs often have side effects at high doses and/or during long-term administration. Increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis (RA). The aim of the study was to examine the effect of N-feruloylserotonin (N-f-5HT) and methotrexate (MTX) in monotherapy and in combination therapy on disease progression and inflammation in arthritic rats. Adjuvant arthritis was induced by intradermal injection of Mycobacterium butyricum in incomplete Freund's adjuvant in Lewis rats. The experiment included healthy animals, arthritic animals without any drug administration, arthritic animals with administration of N-f-5HT in the oral daily dose of 15 mg/kg b.w., arthritic animals with administration of MTX in the oral dose of 0.3 mg/kg b.w. twice a week and arthritic animals treated with the combination of N-f-5HT and MTX. N-f-5HT in monotherapy reduced only activation of NF-κB and did not have any significant effect on other parameters monitored. Low-dose treatment of MTX decreased the level of IL-1β and MCP-1 on day 14 and activation of NF-κB in liver without significant effect on other parameters. N-f-5HT and MTX combination showed both the anti-arthritic (hind paw volume and arthritic score) and anti-inflammatory effect (plasmatic levels of IL-1β, IL-17, MCP-1, CRP, and activation of NF-κB in liver). In combination with MTX, N-f-5HT markedly potentiated the therapeutic effect of MTX low dose, which resulted in significant improvement of all parameters measured. The findings showed that the combination therapy simultaneously decreased multiple markers of inflammation, a result crucial for future therapy of RA.
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http://dx.doi.org/10.1111/fcp.12085DOI Listing
December 2014

Downregulation of NOX4 expression by roflumilast N-oxide reduces markers of fibrosis in lung fibroblasts.

Mediators Inflamm 2013 21;2013:745984. Epub 2013 Aug 21.

Department of Dermatology, Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital, 40 Blossom Street, Boston, MA 02114, USA.

The phosphodiesterase 4 inhibitor roflumilast prevents bleomycin- (BLM-) induced lung fibrosis in animal models. However, its mechanism of action remains unknown. We investigated whether roflumilast N-oxide (RNO), the active metabolite of roflumilast, can modulate in vitro the oxidative effects of BLM on human lung fibroblasts (HLF). In addition, since BLM increases the production of F₂-isoprostanes that have per se fibrogenic activity, the effect of RNO on oxidative stress and fibrogenesis induced by the F₂-isoprostane 8-epi-PGF₂α was investigated. HLF were preincubated either with the vehicle or with RNO and exposed to either BLM or 8-epi-PGF₂α. Proliferation and collagen synthesis were assessed as [(3)H]-thymidine and [(3)H]-proline incorporation. Reactive oxygen species (ROS) and F₂-isoprostanes were measured. NADPH oxidase 4 (NOX4) protein and mRNA were also evaluated. BLM increased both cell proliferation and collagen synthesis and enhanced ROS and F₂-isoprostane production. These effects were significantly prevented by RNO. Also, RNO significantly reduced the increase in both NOX4 mRNA and protein, induced by BLM. Finally, 8-epi-PGF₂α   per se stimulated HLF proliferation, collagen synthesis, and NOX4 expression and ROS generation, and RNO prevented these effects. Thus, the antifibrotic effect of RNO observed in vivo may be related to its ability to mitigate ROS generation via downregulation of NOX4.
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http://dx.doi.org/10.1155/2013/745984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763264PMC
February 2014

Signaling pathways involved in isoprostane-mediated fibrogenic effects in rat hepatic stellate cells.

Free Radic Biol Med 2013 Dec 20;65:201-207. Epub 2013 Jun 20.

Department of Molecular and Developmental Medicine, University of Siena, I-53100 Siena, Italy. Electronic address:

Despite evidence supporting a potential role for F2-isoprostanes (F2-IsoP's) in liver fibrosis, their signaling mechanisms are poorly understood. We have previously provided evidence that F2-IsoP's stimulate hepatic stellate cell (HSC) proliferation and collagen hyperproduction by activation of a modified form of isoprostane receptor homologous to the classic thromboxane receptor (TP). In this paper, we examined which signal transduction pathways are set into motion by F2-IsoP's to exert their fibrogenic effects. HSCs were isolated from rat liver, cultured to their activated myofibroblast-like phenotype, and then treated with the isoprostane 15-F2t-isoprostane (15-F2t-IsoP). Inositol trisphosphate (IP3) and adenosine 3',5'-cyclic monophosphate (cAMP) levels were determined using commercial kits. Mitogen-activated protein kinase (MAPK) and cyclin D1 expression was assessed by Western blotting. Cell proliferation and collagen synthesis were determined by measuring [(3)H]thymidine and [(3)H]proline incorporation, respectively. 15-F2t-IsoP elicited an activation of extracellular-signal-regulated kinase (ERK), p38 MAPK, and c-Jun NH2-terminal kinase (JNK), which are known to be also regulated by G-protein-coupled receptors. Preincubation with specific ERK (PD98059), p38 (SB203580), or JNK (SP600125) inhibitors prevented 15-F2t-IsoP-induced cell proliferation and collagen synthesis. 15-F2t-IsoP decreased cAMP levels within 30 min, suggesting binding to the TPβ isoform and activation of Giα protein. Also, 15-F2t-IsoP increased IP3 levels within a few minutes, suggesting that the Gq protein pathway is also involved. In conclusion, the fibrogenic effects of F2-IsoP's in HSCs are mediated by downstream activation of MAPKs, through TP binding that couples via both Gqα and Giα proteins. Targeting TP receptor, or its downstream pathways, may contribute to preventing oxidative damage in liver fibrosis.
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http://dx.doi.org/10.1016/j.freeradbiomed.2013.06.023DOI Listing
December 2013

NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells.

Toxicol Appl Pharmacol 2013 Feb 16;267(1):30-40. Epub 2012 Dec 16.

Department of Molecular and Developmental Medicine, University of Siena, Italy.

During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 μg/mL O(3) per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1(NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H(2)O(2)) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozonated serum in the endothelium, and have a practical importance as an expedient approach to the treatment of patients with both effective orthodox drugs and ozonated autohemotherapy, targeted to the restoration of redox homeostasis.
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http://dx.doi.org/10.1016/j.taap.2012.12.001DOI Listing
February 2013