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1.
Healthcare (Basel) ; 9(11)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34828601

RESUMO

Background: An estimated 75% of women will have one episode of vulvovaginal candidiasis (VCC) during their lifetime, and 40-50% of these will experience further episodes. The high incidence of vulvovaginal candidiasis, combined with the problems of azole resistance and toxicity, highlights the necessity for new strategies for the treatment of this condition. In this context, natural compounds represent promising alternatives. Methods: We enrolled, between January 2020 and April 2021, forty women affected by uncomplicated vulvovaginal candidiasis. Women were divided into two groups. In the first group, we treated 20 women with clotrimazole daily administration for six days. In the second group, 20 women were treated with clotrimazole associated with Unilen® Microbio+, a new product containing Saccharomyces cerevisiae, melatonin, and GLA-14. Women underwent a check at days 15, 30, and 90. A clinical and cultural examination were performed to establish the effect of the treatments on vaginal flora. Results: In the group treated with Unilen® Microbio+, clinical and microbiological cure at 15 and 30 days was observed in 18 women (90%), compared with 16 women (80%) in the group treated only with clotrimazole. The efficacy of the association between clotrimazole and Unilen® Microbio+ in these uncomplicated forms was therefore not inferior to the azole treatment alone. Only four women (20%) in the Unilen® Microbio+ group presented symptomatic recurrences within the 3 months, compared with eight women (40%) in the clotrimazole-only group. Microscopic wet mount analysis at 1 and 3 months demonstrated a significant increase in lactobacillus count and a reduction in the polymorphonucleate cells in the Unilen® Microbio+ group. Conclusions: Unilen® Microbio+ supplementation was demonstrated to cure uncomplicated vulvovaginal candidiasis with clotrimazole, reducing recurrence and improving vaginal flora better than clotrimazole treatment alone.

2.
Pediatr Res ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654276

RESUMO

BACKGROUND: Propranolol (antagonist of ß1-/ß2-AR but minimally active against ß3-AR) is currently the first-line treatment for infantile hemangiomas (IH). Its efficacy is attributed to the blockade of ß2-AR. However, its success rate is ~60%. Considering the growing interest in the angiogenic role of ß3-ARs, we evaluated a possible relationship between ß3-AR expression and response to propranolol. METHODS: Fifteen samples of surgical biopsies were collected from patients with IH. Three were taken precociously from infants and then successfully treated with propranolol (responder group). Twelve were taken later, from residual lesions noncompletely responsive to propranolol (nonresponder group). A morphometrical analysis of the percentage of ß1-, ß2-, and ß3-ARs positively stained area was compared between the two groups. RESULTS: While no difference was found in both ß1- and ß2-AR expression level, a statistically significant increase of ß3-AR positively stained area was observed in the nonresponder group. CONCLUSIONS: Although the number of biopsies is insufficient to draw definitive conclusions, and the different ß-AR pattern may be theoretically explained by the different timing of samplings, this study suggests a possible correlation between ß3-AR expression and the reduced responsiveness to propranolol treatment. This study could pave the way for new therapeutic perspectives to manage IH. IMPACT: Propranolol (unselective antagonist of ß1 and ß2-ARs) is currently the first-line treatment for IHs, with a success rate of ~60%. Its effectiveness has been attributed to its ability to block ß2-ARs. However, ß3-ARs (on which propranolol is minimally active) were significantly more expressed in hemangioma biopsies taken from patients nonresponsive to propranolol. This study suggests a possible role of ß3-ARs in hemangioma pathogenesis and a possible new therapeutic target.

3.
Oncol Rep ; 45(2): 776-785, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33416143

RESUMO

Liver cancer (LC) is an aggressive disease with a markedly poor prognosis. Therapeutic options are limited, and, until recently the only FDA­approved agent for first­line treatment of patients with LC was the multi­kinase inhibitor sorafenib, which exhibits limited activity and an increased overall survival (OS) of only 3 months over placebo. Therefore, the development of alternative therapeutic molecules for the treatment of LC is an urgent medical need. Antibody­drug conjugates (ADCs) are an emerging class of novel anticancer agents, which have been developed recently for the treatment of malignant conditions, including LC, and are being studied in preclinical and clinical settings. Our group has recently generated an ADC [EV20/monomethyl auristatin F (MMAF)] by coupling the HER3 targeting antibody (EV20) to MMAF via a non­cleavable maleimidocaproyl linker. This ADC was revealed to possess potent therapeutic activity in melanoma and breast carcinoma. In the present study, using western blot and flow cytometric analysis, it was reported that HER­3 receptor was highly expressed in LC and activated by its ligand NRG­1ß in a panel of LC cell lines, thus indicating that this receptor may serve as a suitable target for ADC therapy. A novel ADC [EV20­sss­valine­citrulline (vc)/MMAF] was generated, in which the cytotoxic payload MMAF was site­specifically coupled to an engineered variant of EV20 via a vc cleavable linker. Cytotoxicity assays were performed to investigate in vitro antitumor activity of EV20­sss­vc/MMAF and it was compared to EV20/MMAF, which revealed only modest activity in LC.EV20­sss­vc/MMAF exhibited a significant cell killing activity in several LC cell lines. Additionally, in vivo xenograft experiments revealed that EV20­sss­vc/MMAF inhibited growth of LC tumors. The present data indicated that EV20­sss­vc/MMAF is a worthy candidate for the treatment of HER­3 positive LC.


Assuntos
Imunoconjugados/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Oligopeptídeos/farmacologia , Receptor ErbB-3/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Imunoconjugados/uso terapêutico , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Oligopeptídeos/uso terapêutico , Receptor ErbB-3/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Cancers (Basel) ; 12(10)2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33076448

RESUMO

Neuroblastoma is the most common extra-cranial solid tumor in infants and children, which accounts for approximately 15% of all cancer-related deaths in the pediatric population. New therapeutic modalities are urgently needed. Antibody-Drug Conjugates (ADC)s-based therapy has been proposed as potential strategy to treat this pediatric malignancy. LGALS3BP is a highly glycosylated protein involved in tumor growth and progression. Studies have shown that LGALS3BP is enriched in extracellular vesicles (EV)s derived by most neuroblastoma cells, where it plays a critical role in preparing a favorable tumor microenvironment (TME) through direct cross talk between cancer and stroma cells. Here, we describe the development of a non-internalizing LGALS3BP ADC, named 1959-sss/DM3, which selectively targets LGALS3BP expressing neuroblastoma. 1959-sss/DM3 mediated potent therapeutic activity in different types of neuroblastoma models. Notably, we found that treatments were well tolerated at efficacious doses that were fully curative. These results offer preclinical proof-of-concept for an ADC targeting exosomal LGALS3BP approach for neuroblastomas.

5.
Int J Mol Sci ; 21(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32752132

RESUMO

In recent years, antibody-drug conjugates (ADCs) have become promising antitumor agents to be used as one of the tools in personalized cancer medicine. ADCs are comprised of a drug with cytotoxic activity cross-linked to a monoclonal antibody, targeting antigens expressed at higher levels on tumor cells than on normal cells. By providing a selective targeting mechanism for cytotoxic drugs, ADCs improve the therapeutic index in clinical practice. In this review, the chemistry of ADC linker conjugation together with strategies adopted to improve antibody tolerability (by reducing antigenicity) are examined, with particular attention to ADCs approved by the regulatory agencies (the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA)) for treating cancer patients. Recent developments in engineering Immunoglobulin (Ig) genes and antibody humanization have greatly reduced some of the problems of the first generation of ADCs, beset by problems, such as random coupling of the payload and immunogenicity of the antibody. ADC development and clinical use is a fast, evolving area, and will likely prove an important modality for the treatment of cancer in the near future.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Imunoconjugados/uso terapêutico , Neoplasias/tratamento farmacológico , Anticorpos Monoclonais/imunologia , Antineoplásicos/imunologia , Humanos , Imunoconjugados/imunologia , Neoplasias/imunologia , Neoplasias/patologia
6.
Nucl Med Commun ; 40(10): 1060-1065, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31365492

RESUMO

OBJECTIVES: To identify the clinical relevance of incidentally detected lesions (IDLs) in the gastrointestinal tract (GIT) with 18F-FDG PET/CT and to assess the potential benefit of using semiquantitative PET measures to discern malignant from benign lesions. METHODS: Forty-one patients who underwent F-FDG PET/CT scans during the oncologic follow-up, revealing abnormal incidental 18F-FDG accumulations in the GIT were included in this retrospective analysis. Incidental PET/CT findings were correlated with endoscopic and histological findings. Semiquantitative PET values (SUVmax, SUVmean, SULpeak, and TLG) were evaluated by using a new graph-based method. Two sample t-test analysis has been performed to evaluate the differences of PET parameters between precancerous or cancerous lesions and inflammatory disease. RESULTS: Nine of the 41 patients had an IDL of the GIT on F-FDG PET/CT (detection rate 22%). Endoscopic examination and biopsy have confirmed the presence of precancerous or cancerous lesions as follow: colonic adenoma with high-grade dysplasia (N = 2), colonic adenoma with low-grade dysplasia (N =3), colonic metastatic lesion from primary breast cancer (N =1), gastric carcinoma (N=3). Precancerous or cancerous lesions showed a higher SUVmax, SUVmean, SULpeak, and TLG with a mean value of 10.6 (range, 5.3- 16.7), 6.2 (range, 2.1-10.6), 5.2 (2.7-11), and 66.6 (range, 7.4-164), than patients with inflammatory and endoscopically negative lesions. Two sample t-test analysis showed that SUVmean (P = 0.03), SULpeak (P = 0.05) were statistically different between the two subgroups. CONCLUSION: The use of new semiquantitative PET parameters may increase the diagnostic yield of FDG PET in the case of abnormal incidental F-FDG accumulations.


Assuntos
Endoscopia Gastrointestinal , Fluordesoxiglucose F18 , Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/patologia , Processamento de Imagem Assistida por Computador , Achados Incidentais , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Feminino , Neoplasias Gastrointestinais/metabolismo , Glicólise , Humanos , Masculino , Estudos Retrospectivos , Carga Tumoral
7.
J Control Release ; 294: 176-184, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30553852

RESUMO

Galectin-3-binding protein (Gal-3BP) has been identified as a cancer and metastasis-associated, secreted protein that is expressed by the large majority of cancers. The present study describes a special type of non-internalizing antibody-drug-conjugates that specifically target Gal-3BP. Here, we show that the humanized 1959 antibody, which specifically recognizes secreted Gal-3BP, selectively localized around tumor but not normal cells. A site specific disulfide linkage with thiol-maytansinoids to unpaired cysteine residues of 1959, resulting in a drug-antibody ratio of 2, yielded an ADC product, which cured A375m melanoma bearing mice. ADC products based on the non-internalizing 1959 antibody may be useful for the treatment of several human malignancies, as the cognate antigen is abundantly expressed and secreted by several cancers, while being present at low levels in most normal adult tissues.


Assuntos
Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/imunologia , Imunoconjugados/uso terapêutico , Neoplasias/terapia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Imunoconjugados/farmacocinética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Coelhos
8.
Nucl Med Commun ; 39(8): 741-746, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29782393

RESUMO

AIM: The aim of this retrospective multicentre study was to evaluate the clinical and prognostic effect of fluorine-18-fluorodeoxyglucose (F-FDG)-PET/computed tomography (CT) in the restaging process of pancreatic cancer (PC). MATERIALS AND METHODS: Data from patients treated for primary PC, who underwent F-FDG-PET/CT for suspicious of disease progression, were collected. Accuracy was assessed employing conventional diagnostic procedures, multidisciplinary team case notes, further F-FDG-PET/CT scans and/or follow-up. Receiver operating characteristic curve and likelihood ratio (LR+/-) analyses were used for completion of accuracy definition. Progression-free survival (PFS) and overall survival were assessed by using Kaplan-Meier method. The Cox proportional hazards model was used to identify predictors of outcome. RESULTS: Fifty-two patients (33 males and 19 females, with mean age of 59 years and range: 42-78 years) with PC were finally included in our study. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of F-FDG-PET were 85, 84, 90, 76, and 84%, respectively. Area under the curve was 0.84 (95% confidence intervals: 0.72-0.96; P<0.05). LR+ and LR- were 5.3 and 0.17, respectively. F-FDG-PET/CT revealed new metastatic foci in 5/52 patients (10%) and excluded suspicious lesions in 11/52 (21%). Analysis of PFS revealed F-FDG-PET/CT positivity to be associated with a worse cumulative survival rate over a 6 and 12-month period in comparison with F-FDG-PET/CT negativity (6-month PFS 95 vs. 67%, P<0.05; 12-month PFS 81 vs. 29%, P<0.05). A negative F-FDG-PET/CT result was associated with a significantly longer overall survival than a positive one (70 vs. 26% after 2 years, P<0.05). In addition, a positive F-FDG-PET/CT scan result and an maximum standardized uptake value (SUVmax) value more than 6 were significantly associated with an increased risk of disease progression (PET positivity hazard ratio=3.9, P=0.01; SUVmax>6 h=4.2, P=0.02) and death (PET positivity hazard ratio=3.5, P=0.02; SUVmax>6 h=3.7, P=0.01). CONCLUSION: F-FDG-PET/CT showed high diagnostic accuracy for restaging process of PC, proving also its potential value in predicting clinical outcome after primary treatment.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
9.
J Tissue Eng Regen Med ; 11(9): 2462-2470, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-29737636

RESUMO

The use of nanoscale materials in the design of scaffolds for CNS tissue is increasing, due to their ability to promote cell adhesion, to mimic an extracellular matrix microenvironment and to interact with neuronal membranes. In this framework, one of the major challenges when using undifferentiated neural cells is how to control the differentiation process. Here we report the characterization of a scaffold based on the self-assembled nanotubes of a mutant of the protein peroxiredoxin (from Schistosoma mansoni or Bos taurus), which allows the growth and differentiation of a model neuronal cell line (SHSY5Y). The results obtained demonstrate that SHSY5Y cells grow without any sign of toxicity and develop a neuronal phenotype, as shown by the expression of neuronal differentiation markers, without the use of any differentiation supplement, even in the presence of serum. The prodifferentiation effect is demonstrated to be dependent on the formation of the protein nanotube, since a wild-type (WT) form of the peroxiredoxin from Schistosoma mansoni does not induce any differentiation. The protein scaffold was also able to induce the spread of glioblastoma cancer stem cells growing in neurospheres and allowing the acquisition of a neuron-like morphology, as well as of immature rat cortical neurons. This protein used here as coating agent may be suggested for the development of scaffolds for tissue regeneration or anti-tumour devices. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Diferenciação Celular , Células-Tronco Neoplásicas/patologia , Neurônios/citologia , Peroxirredoxinas/química , Animais , Bovinos , Contagem de Células , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Células-Tronco Neoplásicas/ultraestrutura , Neuroblastoma/patologia , Neuroblastoma/ultraestrutura , Peroxirredoxinas/ultraestrutura , Ratos Sprague-Dawley , Schistosoma mansoni/metabolismo , Esferoides Celulares/patologia
10.
Eur J Nucl Med Mol Imaging ; 44(2): 224-233, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27565154

RESUMO

AIM: A small number of studies evaluated the detection rate of lesions from bladder carcinoma (BC) of 18 F-FDG PET/CT in the restaging process. However, the prognostic role of FDG PET/CT still remains unclear. The aim of the present study was to evaluate the accuracy, the effect upon treatment decision, and the prognostic value of FDG PET/CT in patients with suspected recurrent BC. MATERIALS AND METHODS: Forty-one patients affected by BC underwent FDG PET/CT for restaging purpose. The diagnostic accuracy of visually interpreted FDG PET/CT was assessed compared to histology (n = 8), other diagnostic imaging modalities (contrast-enhanced CT in 38/41 patients and MRI in 15/41) and clinical follow-up (n = 41). Semiquantitative PET values (SUVmax, SUVmean, SUL, MTV, TLG) were calculated using a graph-based method. Progression-free survival (PFS) and overall survival (OS) were assessed by using Kaplan-Meier curves. The risk of progression (hazard ratio, HR) was computed by Cox regression analysis by considering all the available variables. RESULTS: PET was considered positive in 21 of 41 patients. Of these, recurrent BC was confirmed in 20 (95 %). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET/CT were 87 %, 94 %, 95 %, 85 %, 90 %. AUC was 0.9 (95 %IC 0.8-1). Bayesian positive and negative likelihood ratios were 14.5 and 0.13, respectively. FDG PET/CT findings modified the therapeutic approach in 16 patients (modified therapy in 10 PET-positive patients, watch-and-wait in six PET-negative patients). PFS was significantly longer in patients with negative scan vs. those with pathological findings (85 % vs. 24 %, p < 0.05; HR = 12.4; p = 0.001). Moreover, an unremarkable study was associated with a longer OS (88 % vs. 47 % after 2 years and 87 % vs. 25 % after 3 years, respectively, p < 0.05). Standardized uptake value (SUV)max > 6 and total lesion glycolysis (TLG) > 8.5 were recognized as the most accurate thresholds to predict PFS (2-year PFS 62 % for SUVmax < 6 vs. 15 % for SUVmax > 6, p = 0.018; 2-year PFS 66 % for TLG < 8.5 vs. 18 % for TLG > 8.5, p = 0.09). CONCLUSION: A very good diagnostic performance for FDG PET/CT was confirmed in patients with suspected recurrent BC. FDG PET/CT allowed for a change in treatment decision in about 40 % of cases and showed an important prognostic value in assessing PFS and OS.


Assuntos
Fluordesoxiglucose F18 , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Itália/epidemiologia , Masculino , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prevalência , Prognóstico , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia
11.
J Cell Physiol ; 232(5): 1069-1078, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27474828

RESUMO

There is still a considerable debate concerning whether uric acid is neuroprotective or neurotoxic agent. To clarify this topic, we tested the effects of uric acid on neuronal cells biology by using differentiated SHSY5Y neuroblastoma cells incubated with amyloid ß to reproduce an in vitro model of Alzheimer's disease. The incubation of cells with uric acid at the dose of 40 µM or higher significantly reduced cell viability and potentiated the proapoptotic effect of amyloid ß. Finally, uric acid enhanced the generation of 4-hydroxynonenal and the expression of PPARß/δ promoted by amyloid ß, indicating a prooxidant effects. In conclusion, uric acid could exert a detrimental influence on neuronal biology being this influence further potentiated by the concomitant exposure to neurotoxic stimuli. This effect is evident for uric acid concentrations close to those achievable in cerebrospinal fluid in presence of mild hyperuricemia thus suggesting a potential role of uric acid in pathophysiology of cognitive dysfunction. These effects are influenced by the concentrations of uric acid and by the presence of favoring conditions that commonly occur in neurodegenerative disorders and well as in the aging brain, including increased oxidative stress and exposure to amyloid ß. J. Cell. Physiol. 232: 1069-1078, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Amiloide/metabolismo , Disfunção Cognitiva/patologia , Demência/patologia , Modelos Biológicos , Ácido Úrico/farmacologia , Aldeídos/metabolismo , Western Blotting , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proteínas do Citoesqueleto/metabolismo , Humanos , Espaço Intracelular/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR beta/metabolismo , Transdução de Sinais/efeitos dos fármacos
12.
Glob Chang Biol ; 21(8): 2844-60, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25891785

RESUMO

Future human well-being under climate change depends on the ongoing delivery of food, fibre and wood from the land-based primary sector. The ability to deliver these provisioning services depends on soil-based ecosystem services (e.g. carbon, nutrient and water cycling and storage), yet we lack an in-depth understanding of the likely response of soil-based ecosystem services to climate change. We review the current knowledge on this topic for temperate ecosystems, focusing on mechanisms that are likely to underpin differences in climate change responses between four primary sector systems: cropping, intensive grazing, extensive grazing and plantation forestry. We then illustrate how our findings can be applied to assess service delivery under climate change in a specific region, using New Zealand as an example system. Differences in the climate change responses of carbon and nutrient-related services between systems will largely be driven by whether they are reliant on externally added or internally cycled nutrients, the extent to which plant communities could influence responses, and variation in vulnerability to erosion. The ability of soils to regulate water under climate change will mostly be driven by changes in rainfall, but can be influenced by different primary sector systems' vulnerability to soil water repellency and differences in evapotranspiration rates. These changes in regulating services resulted in different potentials for increased biomass production across systems, with intensively managed systems being the most likely to benefit from climate change. Quantitative prediction of net effects of climate change on soil ecosystem services remains a challenge, in part due to knowledge gaps, but also due to the complex interactions between different aspects of climate change. Despite this challenge, it is critical to gain the information required to make such predictions as robust as possible given the fundamental role of soils in supporting human well-being.


Assuntos
Mudança Climática , Solo , Ecossistema , Nova Zelândia
13.
J Cell Physiol ; 230(4): 813-20, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25287669

RESUMO

Ketoprofen L-lysine salt (KLS), a NSAID, is widely used for its analgesic efficacy and tolerability. L-lysine salification was reported to increase the solubility and the gastric absorption and tolerance of ketoprofen. Since the management of NSAIDs gastrotoxicity still represents a major limitation in prolonged therapies, mainly when gastric lesions are present, this study investigated the gastro-protective activity of L-lysine by using a well-established model of gastric mucosa injury, the ethanol-gastric injury model. Several evidences show that the damaging action of ethanol could be attributed to the increase of ROS, which plays a key role in the increase of lipid peroxidation products, including malonyldialdehyde and 4-hydroxy-2-nonenal. With the aim to unravel the mechanism of L-lysine gastroprotection, cellular MDA levels and 4-HNE protein adducts as markers of lipid peroxidation and a panel of key endogenous gastro-protective proteins were assayed. The data obtained indicate a gastroprotective effect of L-lysine on gastric mucosa integrity.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Etanol/farmacologia , Mucosa Gástrica/metabolismo , Cetoprofeno/análogos & derivados , Lisina/análogos & derivados , Células Cultivadas , Humanos , Cetoprofeno/metabolismo , Cetoprofeno/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Lisina/metabolismo , Lisina/farmacologia , Óxido Nítrico/metabolismo
14.
J Cell Biochem ; 114(10): 2209-20, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23554028

RESUMO

The molecular mechanisms linking Aß to the onset of neurotoxicity are still largely unknown, but several lines of evidence point to reactive oxygen species, which are produced even under the effect of nanomolar concentrations of soluble Aß-oligomers. The consequent oxidative stress is considered as the mediator of a cascade of degenerative events in many neurological disorders. Epidemiological studies indicate that dietary habits and antioxidants from diet can influence the incidence of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In the recent years, a number of reviews have reported on neuroprotective effects of polyphenols in cell and animal models. However, the majority of these studies have focused only on the anti-oxidant properties of these compounds and less on the mechanism/s of action at cellular level. In this work we investigated the effect of cocoa polyphenolic extract on a human AD in vitro model. The results obtained, other than confirming the anti-oxidant properties of cocoa, demonstrate that cocoa polyphenols triggers neuroprotection by activating BDNF survival pathway, both on Aß plaque treated cells and on Aß oligomers treated cells, resulting in the counteraction of neurite dystrophy. On the light of the results obtained the use of cocoa powder as preventive agent for neurodegeneration is further supported.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/prevenção & controle , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cacau/química , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Citoesqueleto/metabolismo , Imunofluorescência , Humanos , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/farmacologia , Polifenóis/química , Transdução de Sinais/efeitos dos fármacos
15.
J Cell Biochem ; 114(3): 708-15, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23060010

RESUMO

Peroxiredoxins are ubiquitous proteins that recently attracted major interests in view of the strict correlation observed in several cell lines and/or tissues between different levels of their expression and the increased capacity of cells to survive in different pathophysiological conditions. They are recently considered as the most important enzymes regulating the concentration of hydroperoxides inside the cells. Most of neurodisorders such as Parkinson, Huntington, Alzheimer's diseases, and ischemic injury are characterized by conditions of oxidative stress inside cells. In these pathophysiological conditions, a strict correlation between cell survival and Prx expression has been found. In CNS all the Prx isoforms are present though with different expression pattern depending on cell phenotype. Interestingly, neurons treated with amyloid beta peptide (Aß), showed an overexpression of PrxI. In this study, the neuroprotective effect of PrxI after Aß exposure and the underlying mechanisms by which PrxI expression counteracts cell death was investigated in a well established human AD in vitro model. Taking advantage on cells transfected by a construct where human PrxI is fused with a Green fluorescent protein (GFP) at the C-terminus, we report some events at the basis of cell survival after Aß injury, suggesting possible new signal cascades dealing with the antiapoptotic effect of PrxI. The results obtained indicated a protective role for PrxI in counteracting Aß injury by increasing cell viability, preserving neurites, and decreasing cell death.


Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Proteínas de Homeodomínio/metabolismo , Fármacos Neuroprotetores/metabolismo , Peptídeos beta-Amiloides/farmacologia , Apoptose , Linhagem Celular , Sobrevivência Celular , Proteínas de Fluorescência Verde , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Humanos , Estresse Oxidativo , Fragmentos de Peptídeos/metabolismo , Isoformas de Proteínas/biossíntese
16.
Acta Biomater ; 8(6): 2056-67, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22343002

RESUMO

Oxidative stress has been found to be associated with the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, Lou Gehrig's, etc. In the recent years, cerium oxide nanoparticles (CNPs) have been studied as potent antioxidant agents able to exert neuroprotective effects. This work reports polyethylene glycol (PEG)-coated and antibody-conjugated CNPs for the selective delivering to Aß aggregates, and the protective effect against oxidative stress/Aß-mediated neurodegeneration. In this study PEG-coated and anti-Aß antibody-conjugated antioxidant nanoparticles (Aß-CNPs-PEG) were developed, and their effects on neuronal survival and brain-derived neurotrophic factor (BDNF) signaling pathway were examined. Aß-CNPs-PEG specifically targets the Aß aggregates, and concomitant rescue of neuronal survival better than Aß-CNPs, by modulating the BDNF signaling pathway. This proof of concept work may allow in the future, once validated in vivo, for the selective delivery of CNPs only to affected brain areas.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Sobrevivência Celular , Cério/química , Nanopartículas , Neurônios/citologia , Polietilenoglicóis/química , Western Blotting , Linhagem Celular Tumoral , Imunofluorescência , Humanos , Imunoprecipitação
17.
Ecol Appl ; 21(3): 695-703, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21639037

RESUMO

Complex molecules are presumed to be preferentially stabilized as soil organic carbon (SOC) based on the generally accepted concept that the chemical composition of litter is a major factor in its rate of decomposition. Hence, a direct link between litter quality and SOC quantity has been assumed, accepted, and ultimately incorporated in SOC models. Here, however, we present data from an incubation and field experiment that refutes the influence of litter quality on the quantity of stabilized SOC. Three different qualities of litter (Tithonia diversifolia, Calliandra calothyrsus, and Zea mays stover; 4 Mg C x ha(-1) yr(-1)) with and without the addition of mineral N fertilizer (0 or 120 kg N x ha(-1)season(-1) were added to a red clay Humic Nitisol in a 3-yr field trial and a 1.5-yr incubation experiment. The litters differed in their concentrations of N, lignin, and polyphenols with the ratio of (lignin + polyphenols): N ranging from 3.5 to 9.8 for the field trial and from 2.3 to 4.0 for the incubation experiment in the order of T. diversifolia < C. calothyrsus < or = Z. mays. Litter quality did not affect the amount of SOC stabilized after three annual additions in the field trial. Even within the most sensitive soil aggregate fractions, SOC contents and C:N ratios did not differ with litter quality, indicating that litter quality did not influence the mechanisms by which SOC was stabilized. While increasing litter quality displayed faster decomposition and incorporation of C into soil aggregates after 0.25 yr in the incubation study, all litters resulted in equivalent amounts of C stabilized in the soil after 1.5 yr, further corroborating the results of the field trial. The addition of N fertilizer did not affect SOC stabilization in either the field or the incubation trial. Thus, we conclude that, while litter quality controls shorter-term dynamics of C decomposition and accumulation in the soil, longer-term SOC patterns cannot be predicted based on initial litter quality effects. Hence, the formation and stabilization of SOC is more controlled by the quantity of litter input and its interaction with the soil matrix than by litter quality.


Assuntos
Asteraceae/química , Carbono/química , Fabaceae/química , Solo/química , Zea mays/química , Folhas de Planta/química , Fatores de Tempo
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