Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 97
Filtrar
1.
Nurse Educ Today ; 70: 115-120, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30179783

RESUMO

BACKGROUND: Low academic success rates lead to fewer than the required number of nurses entering the national health systems, impacting on the supply of nurses and with negative consequences for global health care since low nurse-to-patient ratios are associated with an increase of patients' adverse outcomes. OBJECTIVES: This study was mainly aimed at documenting any of the academic outcomes' potential predictors among Nursing Degree Program (NDP) students' characteristics. DESIGN: A retrospective multi-cohort study was conducted. PARTICIPANTS AND SETTING: Ten cohorts of nursing students enrolled in a central Italy university were involved. METHODS: Qualitative and quantitative data on entry characteristics and academic outcomes were retrieved, observing retrospectively 10 cohorts of Italian nursing students for 13 academic years (2004-2017). Multiple regression analyses were conducted to assess if potential predictors reporting a p-value < 0.05 in univariate analyses were independently related to academic outcomes. RESULTS: A total of 2278 students were enrolled in this study. Multivariate analyses showed that 'female gender', 'having attended classical or scientific upper-secondary school', and 'having higher upper-secondary diploma grade' were associated both with the qualitative outcomes (graduation within the legal duration of NDP) and the quantitative ones (final degree exam grade). The weight of the 'admission-test score' in explaining the variance of academic performances was very low (ß = 0.03, 95% CI = 0.01 to 0.05) compared to the 'upper-secondary diploma grade' (ß = 0.14, 95% CI = 0.12 to 0.16). CONCLUSIONS: This evidence should lead to a reflection on the entry-selection methods for NDP, especially in those countries such as Italy, where these methods are essentially based on the entry-test, which in this study was shown to have a very low predictive power for academic outcomes.


Assuntos
Sucesso Acadêmico , Bacharelado em Enfermagem/tendências , Estudantes de Enfermagem/estatística & dados numéricos , Adulto , Feminino , Humanos , Itália , Masculino , Estudos Retrospectivos , Critérios de Admissão Escolar , Escolas de Enfermagem
2.
Eur J Paediatr Dent ; 19(1): 10-15, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29569447

RESUMO

AIM: The present study aimed to evaluate the association between caries and oral health status, age, salivary cortisol levels, and parental education in children with and without prior dental caries experience. MATERIALS AND METHODS: An observational case-control study was performed including 122 children aged between 3 and 6 years who were clinically examined for caries experience using the sum of decayed, missing, and filled teeth in the primary (dmft index) and permanent (DMFT index) dentition. Oral health status was also evaluated using the Simplified Oral Hygiene index (OHI-S). Parents filled a questionnaire to provide information on other variables. Salivary cortisol levels were estimated 1 h after routine dental brushing. RESULTS: We found that dental caries experience was associated with cortisol level, plaque, age, and high calculus levels. High cortisol levels and age are important risk factors for caries development with odds ratios of 3.05 (95% CI: 1.84-5.06) and 1.59 (95% CI: 1.09-2.58), respectively. Multivariate logistic analysis showed that cortisol level and age were independently associated with caries presence. Caries experience was not associated with education of parents, feeding-hygiene habits of child or birth events. CONCLUSION: The present findings support the hypothesis that caries is mainly correlated with high salivary cortisol levels. Dental caries experience in children was also positively associated with tartar, plaque, and age.


Assuntos
Cárie Dentária/metabolismo , Hidrocortisona/metabolismo , Saliva/química , Estudos de Casos e Controles , Criança , Pré-Escolar , Índice CPO , Cárie Dentária/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Higiene Bucal , Fatores de Risco , Inquéritos e Questionários
3.
Artigo em Inglês | MEDLINE | ID: mdl-28458716

RESUMO

BACKGROUND: Earthquakes can result in a range of psychopathology and in negative and positive consequences for survivors. OBJECTIVE: To examine the association between clinical aftereffects (anxiety and depressive symptoms) and post-traumatic growth (PTG) among young survivors of the 2009 L'Aquila earthquake, Italy. METHOD: 316 young earthquake survivors enrolled in the University of L'Aquila were evaluated two years after the natural disaster. Participants completed three main questionnaires, including Patient Health Questionnaire-9 items (PHQ-9), Self-Rating Anxiety Scale (SAS), and Posttraumatic Growth Inventory (PTGI). RESULTS: 59.6% of the student sample showed different levels of depression, whereas 13.3% reported anxiety symptoms. In both clinical dimensions (anxiety and depression), gender differences were found: female gender was confirmed risk factor for a clinical post-traumatic response. Personal PTG, demonstrated by 18% of the L'Aquila youths included in our sample, was predicted by moderate levels of depression (O.R. 2.7). In our model, gender, age, and anxiety did not show any predictive value. CONCLUSION: In a post-traumatic setting, the development of individual cognitive strategies is crucial, whereas after a natural disaster, paradoxically, a moderate depressive condition and the related distress could promote the drive to overcome the psychological consequences of the traumatic event.

4.
Artigo em Inglês | MEDLINE | ID: mdl-25893001

RESUMO

Aim of the study was the assessment of coping strategies, specifically substance use and post-traumatic growth (PTG), in 411 college students two years after 2009 L'Aquila earthquake. Post-Traumatic Growth Inventory (PTGI) was used to assess PTG and one question about substance use (alcohol, tobacco, cannabis) was asked to verify if students had modified their use in the post-earthquake compared with the pre-earthquake period. The 77.1% of college students were exposed to L'Aquila earthquake. The PTGI mean score was 35.23, underlining low positive coping strategies among student community. About substance abuse, the 43.8% of college students reported a marked increase in alcohol use, 7.8% in cannabis and the 15.8% reported an increase in nicotine use in the post-earthquake period. Despite these data, 12.5 % of the students reported a decrease in alcohol use after the earthquake and 17.3% of the sample reported a PTG, showing positive behaviors and attitudes after the traumatic experience of the natural disaster (increase of social relationships, appreciation of new future possibilities, and development of a new deep meaning of life). Inferential analysis shows a strong negative correlation between direct earthquake exposure and PTGI total score. In post-disaster settings, a systematic framework of case identification, triage, and mental health interventions, including the improvement of positive coping strategies, like the PTG, should be integrated into emergency medicine and trauma care responses.

6.
Indian J Med Res ; 140 Suppl: S91-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25673551

RESUMO

The human vaginal microbiota plays an important role in the maintenance of a woman's health, as well as of her partner's and newborns'. When this predominantly Lactobacillus community is disrupted, decreased in abundance and replaced by different anaerobes, bacterial vaginosis (BV) may occur. BV is associated with ascending infections and obstetrical complications, such as chorioamnionitis and preterm delivery, as well as with urinary tract infections and sexually transmitted infections. In BV the overgrowth of anaerobes produces noxious substances like polyamines and other compounds that trigger the release of pro-inflammatory cytokines interleukin (IL)-1 ß and IL-8. BV can profoundly affect, with different mechanisms, all the phases of a woman's life in relation to reproduction, before pregnancy, during fertilization, through and at the end of pregnancy. BV can directly affect fertility, since an ascending dissemination of the involved species may lead to tubal factor infertility. Moreover, the increased risk of acquiring sexually transmitted diseases contributes to damage to reproductive health. Exogenous strains of lactobacilli have been suggested as a means of re-establishing a normal healthy vaginal flora. Carefully selected probiotic strains can eliminate BV and also exert an antiviral effect, thus reducing viral load and preventing foetal and neonatal infection. The administration of beneficial microorganisms (probiotics) can aid recovery from infection and restore and maintain a healthy vaginal ecosystem, thus improving female health also in relation to reproductive health.


Assuntos
Infertilidade Feminina/microbiologia , Microbiota/efeitos dos fármacos , Probióticos/uso terapêutico , Saúde Reprodutiva/normas , Vagina/microbiologia , Vaginose Bacteriana/tratamento farmacológico , Feminino , Fertilização/fisiologia , Humanos , Microbiota/genética , Gravidez , Probióticos/farmacologia , Vaginose Bacteriana/complicações
7.
J Neurosurg Sci ; 56(3): 239-45, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22854592

RESUMO

AIM: Approximate survival for glioblastoma is less than 1 year. Age, histological features and performance status at presentation represent the three statistically independent factors affecting longevity. The purpose of the study was to assess the role of surgery and to analyze prognostic factors in our patients operated for glioblastoma. METHODS: We evaluated in 56 patients operated for glioblastoma their depressive and performance status in the preoperative and postoperative time. Moreover we analyzed the extent of surgery, the site and the size of lesions. RESULTS: Median overall survival was 17 months. An age of ≥60 years (P<0.03), a preoperative Karnofsky Performance Status KPS≤70 (P=0.04), a subtotal tumor resection (P<0.001), a tumor size >5 cm (P=0.01), and no postoperative adjuvant treatment (P=0.01) were associated with the worst prognosis. Before surgery we found the presence of depression in 10 patients with a significative reduction of mean Back Depression Inventory scores after tumor resection (P=0.03). Finally, a KPS≤70 was significantly associated with an increased incidence of depression in the postoperative time. CONCLUSION: Tumor size, total resection and affective disorders were identified as predictors of survival in our series of patients with glioblastoma in addition to age and KPS score. In our opinion an early diagnosis and the use of specific safeguards in the operating room contribute to have an extension of the tumor progression time and median survival.


Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Glioblastoma/mortalidade , Glioblastoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/psicologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/mortalidade , Feminino , Glioblastoma/psicologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/psicologia , Prognóstico , Qualidade de Vida/psicologia , Fatores de Risco , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricos
8.
Int J Immunopathol Pharmacol ; 25(1): 9-17, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22507312

RESUMO

On a planetary scale, Metabolic Syndrome (MetS)is the third cause of inability after malnutrition and nicotinism, even higher than water shortage and sedentariness. In the USA, the prevalence is estimated at over 25 percent of the population; in Italy, it involves approximately 25 percent of men and even 27 percent of women. These are very high figures, corresponding to approximately 14 million affected individuals. The prevalence is alarming and must not be underestimated, particularly in the dental field, where more than one patient out of four sitting in a dentist chair is affected. The etiology of periodontal disease has not yet been clarified, and recently the idea to consider it as a multifactor pathology has been developed. Cofactors such as the formation of free radicals of oxygen (ROS), oxidative stress, lipid peroxidation, and formation of glycation end-products (AGEs) probably play an important role in the onset of periodontal disease. The AGEs are compounds physiologically produced by the cells. However, they accumulate and cause pro-inflammatory conditions, when the cellular clearance fails, or in hyperglycemic and oxidative states. All these conditions can be clinically summarized as Metabolic Syndrome. The purpose of this literature review is to establish a relationship between two pathologies with very high prevalence: Metabolic Syndrome and Periodontal Disorder. The literature seems to have clarified that MetS involves a pro-oxidation status, which induces AGE formation. AGEs play a very important role in the course and severity of periodontal diseases.


Assuntos
Produtos Finais de Glicação Avançada/fisiologia , Síndrome Metabólica/complicações , Doenças Periodontais/etiologia , Feminino , Humanos , Masculino , Síndrome Metabólica/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/fisiologia
9.
J Cell Physiol ; 227(3): 939-51, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21503892

RESUMO

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults, with a median survival of ~12-18 months post-diagnosis. GBM usually recurs within 12 months post-resection, with poor prognosis. Thus, novel therapeutic strategies to target and kill GBM cells are urgently needed. The marked difference of tumour cells with respect to normal brain cells renders glioblastoma a good candidate for selective targeted therapies. Recent experimental strategies focus on over expressed cell surface receptors. Targeted toxins represent a new class of selective molecules composed by a potent protein toxin and a carrier ligand. Targeted toxins approaches against glioblastoma were under investigation in phase I and II clinical trials with several immunotoxins (IT)/ligand toxins such as IL4-Pseudomonas aeruginosa exotoxin A (IL4-PE, NBI-3001), tumour growth factor fused to PE38, a shorter PE variant, (TGF)alpha-TP-38, IL13-PE38, and a transferrin-C diphtheriae toxin mutant (Tf-CRM107). In this work, we studied the effects of the plant ribosome-inactivating saporin and of its chimera transferrin-saporin against two different GBM cell lines. The data obtained here indicate that cell proliferation is affected by the toxin treatments but that different mechanisms are used, directly linked to the presence of an active or inactive p53. A model is proposed for these alternative intracellular pathways.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Proteínas Inativadoras de Ribossomos Tipo 1/toxicidade , Transferrina/toxicidade , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Ensaios Clínicos como Assunto/métodos , Desenho de Fármacos , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Nanoconjugados/toxicidade , Proteínas Inativadoras de Ribossomos Tipo 1/genética , Saporinas , Transferrina/genética , Proteína Supressora de Tumor p53/metabolismo
10.
J Cell Biochem ; 113(2): 571-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21938743

RESUMO

Nucleolin is a multifunctional DNA and RNA binding protein involved in regulation of gene transcription, chromatin remodeling, RNA metabolism, and ribosomal RNA synthesis. Nucleolin seems to be over-expressed in highly proliferative cells and is involved in many aspect of gene expression: DNA recombination and replication, RNA transcription by RNA polymerase I and II, rRNA processing, mRNA stabilization, cytokinesis, and apoptosis. Although nucleolin is localized predominantly in the nucleolus, it has also been shown to be localized in a phosphorylated/glycolsilated form on the cell surface of different cells. Numerous articles dealing with surface nucleolin targeting for tumor therapy have been recently published. However, at present, no extensive informations are so far available for the presence of nucleolin in human gliomas. In the present work we investigated on the presence and localization of nucleolin in glioma on glioma specimens at different grade of malignancy and on primary glioma cell cultures derived by surgical resection, trying to correlate the presence of glycosilated membrane nucleolin with the malignancy grade. To this purpose an antibody produced by us against gp273 protein, demonstrated to recognized the glycosilated surface nucleolin, has been used. The results obtained demonstrate that surface nucleolin increase with the malignancy grade thus suggesting that it may constitute a histopathological marker for glioma grading and a possible tool for targeted therapy.


Assuntos
Astrocitoma/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Fosfoproteínas/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas de Ligação a RNA/metabolismo , Antígeno AC133 , Idoso , Antígenos CD/metabolismo , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Células Cultivadas , Proteína Glial Fibrilar Ácida/metabolismo , Glicoproteínas/metabolismo , Glicosilação , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Células-Tronco Neoplásicas/metabolismo , Peptídeos/metabolismo , Transporte Proteico , Fatores de Transcrição SOXB1/metabolismo , Nucleolina
11.
J Cell Biochem ; 112(12): 3891-901, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21866563

RESUMO

Glioblastoma multiforme (GBM) represents the most severe type of glioma, the most common brain tumor. Their malignancy shows a relationship with an increased proliferation and a poorly organized tumor vascularization, an event that leads to inadequate blood supply, hypoxic areas and at last to the formation of necrotic areas, a feature of glioblastoma. Hypoxic/necrotic tumors are more resistant to chemotherapy and radiation therapies, thus it is crucial to formulate new therapeutic approaches that can render these tumors more sensitive to the action of conventional therapies. It has been demonstrated that under hypoxia, gliomas accumulate lipid droplets and that this event is positively correlated with the degree of malignancy, glioblastoma being the most endowed with lipid droplets. We have previously demonstrated in ex vivo glioma specimens a grade-dependent lipid metabolism perturbation. Here we studied the lipid pathways and the presence of stemness markers in glioma primary cultures, obtained from surgical specimens of patients affected by glioma at different grade of malignancy, GBM primary cultures cultured under both hypoxic and normoxic conditions, as well as normal human astrocytes. The results obtained demonstrate that hypoxia plays a crucial role in regulating the expression of lipid metabolism peroxisomal enzymes, the lipid droplets accumulation as well as the transcription factor PPARα.


Assuntos
Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Metabolismo dos Lipídeos , PPAR gama/metabolismo , Peroxissomos/enzimologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioblastoma/patologia , Humanos
12.
Int J Immunopathol Pharmacol ; 24(2): 411-22, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21658315

RESUMO

In the present work the effects of a new low frequency, high intensity ultrasound technology on human adipose tissue ex vivo were studied. In particular, we investigated the effects of both external and surgical ultrasound-irradiation (10 min) by evaluating, other than sample weight loss and fat release, also histological architecture alteration as well apoptosis induction. The influence of saline buffer tissue-infiltration on the effects of ultrasound irradiation was also examined. The results suggest that, in our experimental conditions, both transcutaneous and surgical ultrasound exposure caused a significant weight loss and fat release. This effect was more relevant when the ultrasound intensity was set at 100 % (~2.5 W/cm², for external device; ~19-21 W/cm2, for surgical device) compared to 70 % (~1.8 W/cm² for external device; ~13-14 W/cm2 for surgical device). Of note, the effectiveness of ultrasound was much higher when the tissue samples were previously infiltrated with saline buffer, in accordance with the knowledge that ultrasonic waves in aqueous solution better propagate with a consequently more efficient cavitation process. Moreover, the overall effects of ultrasound irradiation did not appear immediately after treatment but persisted over time, being significantly more relevant at 18 h from the end of ultrasound irradiation. Evaluation of histological characteristics of ultrasound-irradiated samples showed a clear alteration of adipose tissue architecture as well a prominent destruction of collagen fibers which were dependent on ultrasound intensity and most relevant in saline buffer-infiltrated samples. The structural changes of collagen bundles present between the lobules of fat cells were confirmed through scanning electron microscopy (SEM) which clearly demonstrated how ultrasound exposure induced a drastic reduction in the compactness of the adipose connective tissue and an irregular arrangement of the fibers with a consequent alteration in the spatial architecture. The analysis of the composition of lipids in the fat released from adipose tissue after ultrasound treatment with surgical device showed, in agreement with the level of adipocyte damage, a significant increase mainly of triglycerides and cholesterol. Finally, ultrasound exposure had been shown to induce apoptosis as shown by the appearance DNA fragmentation. Accordingly, ultrasound treatment led to down-modulation of procaspase-9 expression and an increased level of caspase-3 active form.


Assuntos
Adipócitos/efeitos da radiação , Tecido Adiposo/efeitos da radiação , Terapia por Ultrassom , Adipócitos/metabolismo , Adipócitos/ultraestrutura , Tecido Adiposo/metabolismo , Tecido Adiposo/ultraestrutura , Adulto , Análise de Variância , Apoptose/efeitos da radiação , Caspase 3/metabolismo , Caspase 9/metabolismo , Colágeno/efeitos da radiação , Colágeno/ultraestrutura , Feminino , Humanos , Técnicas In Vitro , Lipólise/efeitos da radiação , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Pele/efeitos da radiação , Pele/ultraestrutura , Fatores de Tempo
13.
Int J Immunopathol Pharmacol ; 23(2): 481-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20646343

RESUMO

Recent studies introduced the novel concept of chemical lipolysis where phosphatidylcholine (PC), an active component of commercial preparations, plays a pivotal role. Other studies suggested that sodium deoxycholate (DOC), an excipient contained in medical preparations, could be the real active component performing an adipocytolytic action. We investigated the effects of PC and DOC on human primary adipocyte cultures and on human fresh adipose tissue. Human adipocytes isolated by Rodbell's method, were cultured onto type I collagen-coated glass coverslips, placed into 24-well tissue culture plates. Cells were incubated with or without DOC (5-7-9%), PC (5%) or DOC/PC mixture and observed under phase contrast microscope. After incubation, cells were stained with Oil Red-O and with acridine orange/ethidium bromide to observe necrotic cells with phase contrast microscope and fluorescent microscope, respectively. Histological specimens from adipose tissue biopsies were observed with phase contrast microscopy and with scanning electron microscopy. To investigate the lipid pattern variability in the different experimental conditions, culture medium obtained from the different treatments was subjected to lipid extraction and subsequently to thin layer chromatography (TLC). Microscopic observation of adipocytes showed that DOC treatment led to a detrimental morphological effect in a dose-dependent manner. PC treatment did not significantly affect adipocyte viability. On the contrary, results from experiments aimed to analyze the effects of PC/DOC combined treatment suggested a PC protective role against the DOC harmful effects on adipocytes. Results indicated that clinical effects, observed in local treatment with pharmaceutical preparation, could be due only to DOC, a detergent inducing nonspecific lysis of cell membranes following adipocyte necrosis. On the other hand, PC could likely be incorporated in the lipid bilayer, thus strongly reducing the disruptive DOC effects.


Assuntos
Adipócitos/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Ácido Desoxicólico/farmacologia , Fosfatidilcolinas/farmacologia , Adipócitos/citologia , Tecido Adiposo/ultraestrutura , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos
14.
Int J Immunopathol Pharmacol ; 23(1): 235-46, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20378009

RESUMO

Gliomas are histologically graded by cellularity, cytological atypia, necrosis, mitotic figures, and vascular proliferation, features associated with biologically aggressive behaviour. However, abundant evidence suggests the presence of unrecognized, clinically relevant subclasses of the diffuse gliomas, both in respect to their underlying molecular phenotype and their clinical response to therapy. It is well-known that patient prognosis and therapeutic decisions rely on accurate pathological grading. Recently, it was reported that human gliomas accumulate lipid droplets during progression, suggesting a lipid metabolism impairment. Considering the crucial role of peroxisomes in lipid metabolism, in the present work we studied the expression profiles of proteins either exclusively localized to peroxisomes, such as peroxin14 (PEX14), peroxisomal membrane protein 70Kda (PMP70), acyl-CoA oxidase, thiolase, or partially associated to peroxisomes such as Hydroxymethylglutaryl-CoA reductase (HMGCoA-red) and peroxisomal-related proteins, namely PPARalpha, in human glioma specimens at different grades of malignancy. Moreover, Nile red staining of lipid droplets, thin layer chromatography (TLC) and proton nuclear magnetic resonance spectroscopy (NMR) were carried out in order to correlate the biochemical results with the lipid content of tumor tissues. The results obtained indicate that correlating the malignancy grade with the expression of peroxisomal genes and proteins, may constitute a sensitive tool to highlight possible subtypes not recognized by the classical histological techniques.


Assuntos
Glioma/metabolismo , Metabolismo dos Lipídeos , Peroxissomos/química , Transportadores de Cassetes de Ligação de ATP/análise , Acil-CoA Oxidase/análise , Western Blotting , Glioma/química , Humanos , Imuno-Histoquímica , Espectroscopia de Ressonância Magnética , Proteínas de Membrana/análise , Reação em Cadeia da Polimerase , Proteínas Repressoras/análise
15.
Int J Immunopathol Pharmacol ; 21(3): 539-51, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18831921

RESUMO

Various molecular mechanisms have been suggested to be involved in dexamethasone induced thymocyte apoptosis. In this study we show that pharmacological inhibition of cytoplasmic PLA2 in mouse thymocytes for 18 h with arachidonyl trifluoromethyl ketone (AACOCF3) (10 microM) and palmitoyl trifluoromethyl ketone (PACOCF3) (10 microM) induced a drastic increase of thymocyte apoptosis comparable to that observed following Dex (10(-7) M) treatment, while inhibition of secretory PLA2 with p-bromophenacyl bromide (pBPB) (20 microM) did not. AACOCF3-induced thymocyte apoptosis, similarly to Dex-induced thymocyte apoptosis, was eliminated by cell pre-treatment with the PI-PLCbeta inhibitor, U73122, but not by the PC-PLC inhibitor D609. These observations were corroborated by the ability of AACOCF3, like Dex, to induce a rapid and transient increase in DAG generation. In addition, AACOCF3-induced apoptosis involved the activation of the acidic sphingomyelinase (aSMase) but not of the neutral sphingomyelinase (nSMase), as evaluated by measurements of enzyme activity in cell extracts following thymocyte exposure to AACOCF3 and by the ability of monensin to inhibit AACOCF3-induced thymocyte apoptosis. In addition, the AACOCF3 apoptotic effect resulted in an early increase of ceramide levels. AACOCF3-induced thymocyte apoptosis involved the activation of caspase 3, and cell pre-treatment with a caspase 3 inhibitor prevented AACOCF3-induced apoptosis. These observations suggest that cPLA2 inhibition may have a role in Dex-induced thymocyte apoptosis and highlight the importance of cPLA2 activity in thymocyte survival.


Assuntos
Apoptose/efeitos dos fármacos , Citoplasma/enzimologia , Dexametasona/farmacologia , Inibidores de Fosfolipase A2 , Linfócitos T/efeitos dos fármacos , Animais , Ácido Araquidônico/metabolismo , Ácidos Araquidônicos/farmacologia , Caspase 3/metabolismo , Ceramidas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C3H , Mifepristona/farmacologia , Fosfoinositídeo Fosfolipase C/metabolismo , Fosfolipases A2/fisiologia
16.
Biochim Biophys Acta ; 1778(12): 2749-56, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18762164

RESUMO

Phospholipid and non-phospholipid vesicles are extensively studied as drug delivery systems to modify pharmacokinetics of drugs and to improve their action in target cells. It is believed that the major barrier to efficient drug delivery is entrapment of drugs in the endosomal compartment, since this eventually leads to its degradation in lysosomes. For these reasons, the knowledge of internalization pathway plays a fundamental role in optimizing drug targeting. The aim of this work is to characterize pH-sensitive Tween 20 vesicles, their interaction with macrophage-like cells and their comparison with pH-sensitive liposomes. The effect of different amounts of cholesteryl hemissucinate on surfactant vesicle formation and pH-sensitivity was studied. To evaluate the initial mode of internalization in Raw 264.7 and the intracellular fate of neutral and pH-sensitive formulations, flow cytometry in presence and in absence of selected inhibitors and fluorescence microscopy in absence and presence of specific fluorescent endocytotic markers were used. The obtained results showed that the surfactant vesicle pH-sensitivity was about two or three fold higher than that obtained with pH-sensitive liposomes in the presence of serum in vitro. The uptake mechanism of surfactant vesicles, after incubation with macrophage-like cells, is comparable to that of liposomes (clathrin-mediated endocytosis).


Assuntos
Endocitose/fisiologia , Macrófagos/metabolismo , Fosfolipídeos/farmacocinética , Polissorbatos/farmacocinética , Tensoativos/farmacocinética , Animais , Transporte Biológico/efeitos dos fármacos , Fenômenos Biofísicos , Linhagem Celular , Vesículas Citoplasmáticas/química , Vesículas Citoplasmáticas/metabolismo , Endocitose/efeitos dos fármacos , Fluoresceínas/metabolismo , Corantes Fluorescentes/metabolismo , Concentração de Íons de Hidrogênio , Lipossomos/química , Lipossomos/metabolismo , Lipossomos/farmacocinética , Camundongos , Microscopia de Fluorescência , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Polissorbatos/metabolismo , Polissorbatos/farmacologia , Tensoativos/metabolismo , Tensoativos/farmacologia
17.
J Cell Physiol ; 217(1): 93-102, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18446822

RESUMO

Gliomas are the most commonly diagnosed malignant brain primary tumors. Prognosis of patients with high-grade gliomas is poor and scarcely affected by radiotherapy and chemotherapy. Several studies have reported antiproliferative and/or differentiating activities of some lipophylic molecules on glioblastoma cells. Some of these activities in cell signaling are mediated by a class of transcriptional factors referred to as peroxisome proliferator-activated receptors (PPARs). PPARgamma has been identified in transformed neural cells of human origin and it has been demonstrated that PPARgamma agonists decrease cell proliferation, stimulate apoptosis and induce morphological changes and expression of markers typical of a more differentiated phenotype in glioblastoma and astrocytoma cell lines. These findings arise from studies mainly performed on long-term cultured transformed cell lines. Such experimental models do not exactly reproduce the in vivo environment since long-term culture often results in the accumulation of further molecular alterations in the cells. To be as close as possible to the in vivo condition, in the present work we investigated the effects of PPARgamma natural and synthetic ligands on the biomolecular features of primary cultures of human glioblastoma cells derived from surgical specimens. We provide evidence that PPARgamma agonists may interfere with glioblastoma growth and malignancy and might be taken in account as novel antitumoral drugs.


Assuntos
Anilidas/farmacologia , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Ácidos Linoleicos Conjugados/farmacologia , PPAR gama/agonistas , Apoptose/efeitos dos fármacos , Western Blotting , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Imunofluorescência , Humanos , Neovascularização Patológica/metabolismo , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos
18.
Int J Immunopathol Pharmacol ; 21(1): 137-43, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18336739

RESUMO

Several studies have demonstrated that ceramides play an essential role in both the barrier and water-holding functions of healthy stratum corneum, suggesting that the dysfunction of the stratum corneum associated with ageing as well that observed in patients with several skin diseases could result from a ceramide deficiency. In a previous study our group reported a significant increase in skin ceramide levels in healthy subjects after treatment in vivo with a cream containing a preparation of Streptococcus thermophilus. The presence of high levels of neutral sphingomyelinase activity in this organism was responsible for the observed increase of stratum corneum ceramide levels, thus leading to an improvement in barrier function and maintenance of stratum corneum flexibility. The aim of the present work is to investigate the effects of the topical treatment of a Streptococcus thermophilus-containing cream on ceramide levels of stratum corneum of healthy elderly women. The ceramide levels, transepidermal water loss and capacitance were evaluated on stratum corneum sheets from the forearms of 20 healthy female subjects treated with a base cream or the same cream containing a sonicated preparation of the lactic acid bacterium Streptococcus thermophilus. A 2-week topical application of a sonicated Streptococcus thermophilus preparation led to significant and relevant increase of stratum corneum ceramide levels. Moreover, the hydration values of the treated forearm of each subject was significantly higher than control sites. These results suggest that the experimental cream was able to improve the lipid barrier and to increase a resistance against ageing-associated xerosis.


Assuntos
Ceramidas/análise , Envelhecimento da Pele/efeitos dos fármacos , Pele/química , Esfingomielina Fosfodiesterase/administração & dosagem , Streptococcus/enzimologia , Administração Tópica , Idoso , Feminino , Humanos
19.
Oral Dis ; 13(4): 376-85, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17577323

RESUMO

OBJECTIVES: To analyze the anti-inflammatory effects of Lactobacillus brevis extracts on periodontitis patients and to investigate the involved mechanisms in vitro on activated macrophages. METHODS: Eight healthy subjects and 21 patients with chronic periodontitis were enrolled to analyze the effect of L. brevis-containing lozenges on periodontitis-associated symptoms and signs. Before and after the treatment, the patients received a complete periodontal examination. Saliva samples, collected before and after treatment, were analyzed for metalloproteinase and nitric oxide synthase (NOS) activity, immunoglobulin-A (IgA), prostaglandin E(2) (PGE(2)) and gamma-interferon (IFN-gamma) levels. Arginine deiminase (AD) and NOS activities were determined through a radiometric assay. Metalloproteinases were assayed by zymogram and Western blotting, whereas IgA, PGE(2) and IFN-gamma were assayed by enzyme-linked imunosorbent assay tests. RESULTS: The treatment led to the total disappearance or amelioration of all analyzed clinical parameters in all patients. This was paralleled to a significant decrease of nitrite/nitrate, PGE(2), matrix metalloproteinase, and IFN-gamma levels in saliva samples. CONCLUSION: Our results suggest that the anti-inflammatory effects of L. brevis could be attributed to the presence of AD which prevented nitric oxide generation. Our findings give further insights into the knowledge of the molecular basis of periodontitis and have a potential clinical significance, giving the experimental ground for a new innovative, simple and efficacious therapeutical approach of periodontal disease.


Assuntos
Anti-Inflamatórios/uso terapêutico , Hidrolases/uso terapêutico , Levilactobacillus brevis/enzimologia , Periodontite/terapia , Adulto , Animais , Anti-Inflamatórios/administração & dosagem , Células Cultivadas , Dinoprostona/análise , Método Duplo-Cego , Feminino , Humanos , Hidrolases/administração & dosagem , Imunoglobulina A Secretora/análise , Interferon gama/análise , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Masculino , Metaloproteinases da Matriz/análise , Pessoa de Meia-Idade , Óxido Nítrico Sintase/análise , Índice Periodontal , Ratos , Ratos Wistar , Saliva/química
20.
J Cell Physiol ; 211(3): 837-47, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17390299

RESUMO

Neuroblastomas are pediatric tumors originating from immature neuroblasts in the developing peripheral nervous system. Differentiation therapies could help lowering the high mortality due to rapid tumor progression to advanced stages. Oleic acid has been demonstrated to promote neuronal differentiation in neuronal cultures. Herein we report on the effects of oleic acid and of a specific synthetic PPARbeta agonist on cell growth, expression of differentiation markers and on parameters responsible for the malignancy such as adhesion, migration, invasiveness, BDNF, and TrkB expression of SH-SY5Y neuroblastoma cells. The results obtained demonstrate that many, but not all, oleic acid effects are mediated by PPARbeta and support a role for PPARbeta in neuronal differentiation strongly pointing towards PPAR ligands as new therapeutic strategies against progression and recurrences of neuroblastoma.


Assuntos
Neuroblastoma/patologia , Ácido Oleico/farmacologia , PPAR beta/agonistas , Neoplasias do Sistema Nervoso Periférico/patologia , Tiazóis/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Neuritos/efeitos dos fármacos , PPAR beta/genética , PPAR beta/metabolismo , RNA Interferente Pequeno , Receptor trkB/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA