Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 68
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33804123

RESUMO

BACKGROUND: Based on the holistic approach to prevention diabetic disease, the role of periodontal inflammation in type 2 diabetes mellitus (T2DM) is under intensive scrutiny. Data from clinical trials have shown benefit from a periodontal therapy in providing patients with type 2 diabetes improvement despite relatively disappointing long-terms response rates. The aim of this study was to investigate the short-term glycemic control level and systemic inflammatory status after periodontal therapy. METHODS: This was a randomized trial with a 6-months follow-up. Participants aged 56.4 ± 7.9 years with diagnosed type 2 diabetes and periodontitis were enrolled. Among the 187 type 2 diabetic patients, 93 were randomly assigned to receive non-surgical periodontal treatment immediately and 94 to receive the delayed treatment. Within and between groups comparison was done during the study period, and the differences between groups were assessed. RESULTS: The difference between HbA1c values at baseline (Mdn = 7.7) and 6 months after non-surgical periodontal treatment (Mdn = 7.2) was statistically significant, U = 3174.5, p = 0.012, r = 0.187. However, although technically a positive correlation, the relationship between the glycated hemoglobin value and periodontal variables was weak. The differences between both the groups over 6 months were not statistically considerable, failing to reach statistical significance. At 6 months the difference between groups about the C-reactive protein (CRP) levels was statistically significant, U=1839.5, p = 0, r = 0.472, with a lower concentration for the intervention group. Furthermore, the intervention group showed a statistically significant difference between baseline and 6 months evaluation (U = 2606.5, p = 0, r = 0.308). CONCLUSIONS: The periodontal intervention potentially may allow individuals with type 2 diabetes to improve glycemic control and CRP concentrations, and diabetes alters the periodontal status.


Assuntos
Periodontite Crônica , Diabetes Mellitus Tipo 2 , Periodontite , Glicemia , Diabetes Mellitus Tipo 2/terapia , Hemoglobina A Glicada/análise , Humanos , Pessoa de Meia-Idade , Periodontite/terapia
2.
Artigo em Inglês | MEDLINE | ID: mdl-33675216

RESUMO

OBJECTIVES: Prader-Willi syndrome (PWS) is a rare genetic syndrome characterized by hyperphagia and early development of morbid obesity. Cardiovascular disease (CVD) and metabolic syndrome (MetS) are major comorbidities in these patients leading to premature death. Inhibitory factor 1 (IF1) works as a regulatory protein, inhibiting the ATP hydrolase activity of mitochondrial ATP synthase and likely playing a role in lipid metabolism. We aimed to assay IF1 in adult patients with PWS evaluating any relationship with clinical, genetic and biochemical parameters. METHODS: We recruited 35 adult patients with genetically confirmed PWS. RESULTS: IF1 serum concentration displayed a normal distribution with an average value of 70.7 ± 22.6 pg/mL, a median value of 66.1 pg/mL. It was above the reference range only in one patient. All parameters were compared from both sides of IF1 median without displaying any significant differences. Patients with normal or low HDL-cholesterol did not present any difference as regards IF1 levels, which were not different between patients with and without MetS. Non-esterified fatty acids (NEFA) serum levels (r=0.623; p<0.001) showed a statistically significant correlation with IF1. Cholesterol and its fractions did not present any correlation with IF1. CONCLUSIONS: In this study we do not confirm that HDL-cholesterol and IF1 are correlated, but we show that in adult PWS patients, NEFA are correlated with serum IF1. This protein could play a role to some extent in determining the complex metabolic alterations in PWS patients.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33374694

RESUMO

The scientific community has definitely demonstrated the importance of the use of mouthwash in daily oral hygiene. In our pilot study, we tested the effectiveness of a novel mouth rinse containing sea salt, xylitol, and lysozyme. Streptococcus mutans (S. mutans) growth, and plaque index in adolescent patients aged 14-17 years, were observed. The bacterial load was investigated by in vitro microbiological analysis; the plaque index was assessed through the O'Leary's Plaque Control Record (PCR). The study has shown that the use of a sea salt-based mouthwash in daily oral hygiene reduces the bacterial levels of S. mutans (p < 0.01) linked to the combined action of xylitol and lysozyme, together with the action of sea salt. Our preliminary data confirm and improve the main results reported in the scientific literature on the importance of the use of xylitol, lysozyme, and sea salt in oral health.


Assuntos
Antissépticos Bucais/uso terapêutico , Higiene Bucal , Cloreto de Sódio/uso terapêutico , Xilitol/uso terapêutico , Adolescente , Placa Dentária/prevenção & controle , Humanos , Muramidase/uso terapêutico , Projetos Piloto , Streptococcus mutans
4.
Artigo em Inglês | MEDLINE | ID: mdl-33050132

RESUMO

BACKGROUND: Diabetes is known to be one of the major global epidemic diseases, significantly associated with mortality and morbidity worldwide, conferring a substantial burden to the health care system. The epidemiological transition of this chronic disease tends to worsen unless preventive health strategies are implemented. Appropriate screening devices and standardized methods are crucial to prevent this potentially inauspicious life condition. Currently, the glucometer is the conventional device employed for blood glucose level determination that outputs the blood glucose reading. Glucometer performed in the dental office may be an important device in screening diabetes, so it can be addressed during a periodontal examination. Because gingival blood is a useful source to detect the glucose level, the focus is placed on the opportunity that might provide valuable diagnostic information. This study aimed to compare gingival crevicular blood with finger-stick blood glucose measurements using a self-monitoring glucometer, to evaluate whether gingival crevicular blood could be an alternative to allow accurate chairside glucose testing. METHODS: A cross-sectional comparative study was performed among a 31-67-year-old population. Seventy participants with diagnosed type 2 diabetes and seventy healthy subjects, all with positive bleeding on probing, were enrolled. The gingival crevicular blood was collected using a glucometer to estimate the blood glucose level and compared with finger-stick blood glucose level. RESULTS: The mean capillary blood glucose and gingival crevicular blood levels from all samples were, respectively, 160.42 ± 31.31 mg/dL and 161.64 ± 31.56 mg/dL for diabetic participants and 93.51 ± 10.35 mg/dL and 94.47 ± 9.91 mg/dL for healthy patients. In both groups, the difference between gingival crevicular blood and capillary blood glucose levels was non-significant (P < 0.05). The highly significant correlation between capillary blood glucose and gingival crevicular blood (r = 0.9834 for diabetic patients and r = 0.8153 for healthy participants) in both the groups was found. CONCLUSIONS: Gingival crevicular blood test was demonstrated as a feasible and useful primary screening tool test for detecting diabetes and for glucose estimation in non-diabetic patients. Use of gingival crevicular blood for screening is an attractive way of identifying a reasonable option of finger-stick blood glucose measurement under the appropriate circumstances. Rapid assessment may precede diagnostic evaluation in diabetic as well as healthy patients with acute severe bleeding. In addition, gingival crevicular blood levels may be needed to monitor the diabetic output.

5.
Ital J Pediatr ; 46(1): 161, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115520

RESUMO

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is a rare genetic neurodevelopmental disorder caused by the defect in the 7-dehydrocholesterol reductase. This defect leads to the deficiency of cholesterol biosynthesis with accumulation of 7-dehydrocholesterol. Inhibitory factor 1 (IF1) is a well-known mitochondrial protein. Recently, it has been discovered in the human serum where it is reported to be involved in the HDL-cholesterol intake. Here we report the IF1 presence in the serum of two paediatric SLOS dizygotic twins treated with dietary cholesterol supplementation. CASE PRESENTATION: The patients showed a typical phenotype. They started dietary supplementation with cholesterol when 2 months old. The cholesterol intake was periodically titrated on the basis of weight increase and the twin 1 required a larger supplementation than the twin 2 during the follow-up. When 6.4-year-old, they underwent IF1 assay that was 7-fold increased in twin 2 compared to twin 1 (93.0 pg/ml vs 13.0 pg/ml, respectively). CONCLUSIONS: We report, for the first time, the presence of circulating IF1 in the serum of SLOS patients, showing different levels among them. Our findings confirm that IF1 could be a novel research target in cholesterol-related disorders and also in SLOS, and could contribute to the general debate on IF1 as a new modulator of cholesterol levels.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32751340

RESUMO

BACKGROUND: It is established that inflammation is involved in the pathogenesis of Type 2 Diabetes Mellitus (T2DM) by promoting insulin resistance and impaired beta cell function in the pancreas. Among the hypothesized independent risk factors implicated in the pathogenetic basis of disease, periodontal infection has been proposed to promote an amplification of the magnitude of the advanced glycation end product (AGE)-mediated upregulation of cytokine synthesis and secretion. These findings suggest an interrelationship between periodontal disease and type 2 diabetes, describing poor metabolic control in subjects with periodontitis as compared to nondiabetic subjects and more severe periodontitis in subjects with T2DM as compared to a healthy population, with a significant positive correlation between periodontal inflammatory parameters and glycated hemoglobin level. Results from clinical trials show that periodontal treatment is able to improve glycemic control in subjects with diabetes. Many therapeutic strategies have been developed to improve periodontal conditions in conjunction with conventional treatment, among which ozone (O3) is of specific concern. The principal aim of this trial was to compare the clinical effectiveness of an intensive periodontal intervention consisting of conventional periodontal treatment in conjunction with ozone gas therapy in reducing glycated hemoglobin level in type 2 diabetic patients and standard periodontal treatment. METHODS: This study was a 12-month unmasked randomized trial and included 100 patients aged 40-74 years older, with type 2 diabetes mellitus diagnosed. All the patients received conventional periodontal treatment, or periodontal treatment in conjunction with ozone gas therapy in a randomly assigned order (1:1). The primary outcome was a clinical measure of glycated hemoglobin level at 3, 6, 9 and 12 months from randomization. Secondary outcomes were changes in periodontal inflammatory parameters. RESULTS: At 12 months, the periodontal treatment in conjunction with ozone gas therapy did not show significant differences than standard therapy in decreasing glycated hemoglobin (HbA1C) level and the lack of significant differences in balance is evident. CONCLUSIONS: Although the change was not significant, periodontal treatment in conjunction with the gaseous ozone therapy tended to reduce the levels of glycated hemoglobin. The study shows a benefit with ozone therapy as compared to traditional periodontal treatment.


Assuntos
Diabetes Mellitus Tipo 2 , Hemoglobina A Glicada , Ozônio , Doenças Periodontais , Adulto , Idoso , Glicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Hemoglobina A Glicada/análise , Humanos , Pessoa de Meia-Idade , Ozônio/uso terapêutico , Doenças Periodontais/complicações , Doenças Periodontais/terapia
7.
Artigo em Inglês | MEDLINE | ID: mdl-32431669

RESUMO

The emergence of link between periodontal disease and diabetes has created conditions for analyzing new interdisciplinary approach making toward tackling oral health and systemic issues. As periodontal disease is a readily modifiable risk factor this association has potential clinical implications. The aim of this paper was systematically review the extant literature related to analytics data in order to identify the association between type 1 diabetes (T1DM) in childhood and adolescence with periodontal inflammation. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a database search between 2004 and 2019. A manual search of the literature was conducted as an additional phase of the search process, with the aim of identifying studies that were missed in the primary search. One hundred and thirty-nine records were screened and 10 fulfilled the inclusion criteria. Most studies were of moderate methodological quality. Outcomes included assessments of diabetes and periodontal status. In diabetic populations, compared to healthy subjects, interindividual differences in periodontal status are reflected in higher severity of periodontal inflammation. The most reported barriers to evidence uptake were the intrinsic limits of cross-sectional report data and relevant research, and lack of timely research output. Based on the evidence presented within the literature, the aforementioned biomarkers correlate with poor periodontal status in type 1 diabetic patients. Whilst the corpus of the evidence suggests that there may be an association between periodontal status and type 1 diabetes, study designs and methodological limitations hinder interpretation of the current research.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32316357

RESUMO

AIM: Diabetes and periodontal disease are both chronic pathological conditions linked by several underlying biological mechanisms, in which the inflammatory response plays a critical role, and their association has been largely recognized. Recently, attention has been given to diabetes as an important mediator of vascular endothelial growth factor (VEGF) overexpression in periodontal tissues, by virtue of its ability to affect microvasculature. This review aims to summarize the findings from studies that explored VEGF expression in diabetic patients with periodontitis, compared to periodontally healthy subjects. MATERIALS AND METHODS: A systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A PubMed search of select medical subject heading (MeSH) terms was carried out to identify all studies reporting findings about VEGF expression in periodontal tissues of diabetic patients up to May 2018. The inclusion criteria were studies on VEGF expression in periodontally diseased tissues of diabetic patients compared with nondiabetic subjects, with any method of analysis, and published in the English language. RESULTS: Eight articles met the inclusion criteria. Immunohistochemistry was used in six of the studies, reverse transcriptase polymerase chain reaction (real-time RT-PCR) aiming to quantify mRNA VEGF expression was used in one study, and ELISA analysis was used for one study. Compared with nondiabetic patients, a higher VEGF expression in gingival tissue and gingival crevicular fluid (GCF) samples in diabetic patients with periodontitis was reported. CONCLUSIONS: Overall, novel evidence for the VEGF expression within the periodontal tissue of diabetic patients paves the way for further studies on the role of this protein in neovascularization physiology and pathophysiology in microvasculature of the periodontium.


Assuntos
Diabetes Mellitus/patologia , Periodonto/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Estudos de Casos e Controles , Líquido do Sulco Gengival/metabolismo , Humanos , Periodontite/metabolismo
9.
Oncotarget ; 11(4): 480-487, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32064051

RESUMO

Osteoimmunology was coined about twenty years ago to identify a strict cross talk between bone niche and immune system both in physiological and pathological activities, including cancer. Several molecules are involved in the complex interaction between bone niche, immune and cancer cells. The Receptor Activator of NF-kB (RANK)/RANK Ligand (RANKL/Osteoprotegerin (OPG) pathway plays a crucial role in bone cells/cancer interactions with subsequently immune system control failure, bone destruction, inhibition of effect and metastasis outcome. The bidirectional cross talk between bone and immune system could became a potential target for anticancer drugs. Several studies evidenced a direct anticancer role with improved survival of bone-targeted therapies such as bisphosphonates and RANKL antagonist Denosumab. Conversely, initial data evidenced a possible anti-bone resorption effect of systemic anticancer drugs through and immunomodulation activity, i.e. new generation antiandrogens (Abiraterone) in prostate cancer. All data could open a future rationale of combined bone, immunologic and targeted therapies in cancer treatment.

10.
Molecules ; 25(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31906370

RESUMO

l-Carnitine is an amino acid derivative widely known for its involvement in the transport of long-chain fatty acids into the mitochondrial matrix, where fatty acid oxidation occurs. Moreover, l-Carnitine protects the cell from acyl-CoA accretion through the generation of acylcarnitines. Circulating carnitine is mainly supplied by animal-based food products and to a lesser extent by endogenous biosynthesis in the liver and kidney. Human muscle contains high amounts of carnitine but it depends on the uptake of this compound from the bloodstream, due to muscle inability to synthesize carnitine. Mitochondrial fatty acid oxidation represents an important energy source for muscle metabolism particularly during physical exercise. However, especially during high-intensity exercise, this process seems to be limited by the mitochondrial availability of free l-carnitine. Hence, fatty acid oxidation rapidly declines, increasing exercise intensity from moderate to high. Considering the important role of fatty acids in muscle bioenergetics, and the limiting effect of free carnitine in fatty acid oxidation during endurance exercise, l-carnitine supplementation has been hypothesized to improve exercise performance. So far, the question of the role of l-carnitine supplementation on muscle performance has not definitively been clarified. Differences in exercise intensity, training or conditioning of the subjects, amount of l-carnitine administered, route and timing of administration relative to the exercise led to different experimental results. In this review, we will describe the role of l-carnitine in muscle energetics and the main causes that led to conflicting data on the use of l-carnitine as a supplement.


Assuntos
Carnitina/análogos & derivados , Carnitina/metabolismo , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos/metabolismo , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Carnitina/administração & dosagem , Carnitina/biossíntese , Carnitina/química , Carnitina/farmacologia , Carnitina O-Palmitoiltransferase/metabolismo , Suplementos Nutricionais/efeitos adversos , Exercício Físico/fisiologia , Humanos , Metilaminas/metabolismo , Músculo Esquelético/efeitos dos fármacos , Oxirredução
11.
Antibiotics (Basel) ; 8(4)2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31739644

RESUMO

Sepsis is a life-threatening condition that accounts for numerous deaths worldwide, usually complications of common community infections (i.e., pneumonia, etc), or infections acquired during the hospital stay. Sepsis and septic shock, its most severe evolution, involve the whole organism, recruiting and producing a lot of molecules, mostly proteins. Proteins are dynamic entities, and a large number of techniques and studies have been devoted to elucidating the relationship between the conformations adopted by proteins and what is their function. Although molecular dynamics has a key role in understanding these relationships, the number of protein structures available in the databases is so high that it is currently possible to build data sets obtained from experimentally determined structures. Techniques for dimensionality reduction and clustering can be applied in exploratory data analysis in order to obtain information on the function of these molecules, and this may be very useful in immunology to better understand the structure-activity relationship of the numerous proteins involved in host defense, moreover in septic patients. The large number of degrees of freedom that characterize the biomolecules requires special techniques which are able to analyze this kind of data sets (with a small number of entries respect to the number of degrees of freedom). In this work we analyzed the ability of two different types of algorithms to provide information on the structures present in three data sets built using the experimental structures of allosteric proteins involved in sepsis. The results obtained by means of a principal component analysis algorithm and those obtained by a random projection algorithm are largely comparable, proving the effectiveness of random projection methods in structural bioinformatics. The usefulness of random projection in exploratory data analysis is discussed, including validation of the obtained clusters. We have chosen these proteins because of their involvement in sepsis and septic shock, aimed to highlight the potentiality of bioinformatics to point out new diagnostic and prognostic tools for the patients.

12.
Antibiotics (Basel) ; 8(4)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683838

RESUMO

Background: Malnutrition-inflammation complex syndrome (MICS) is a common and usually concurrent condition occurring in patients undergoing hemodialysis (HD), with a pathogenesis linked to biological and in situ environmental traditional risk factors. Periodontitis, one of the major types of infection-driven inflammation, often co-occurs in the in the hemodialysis population and correlates with markers of malnutrition and inflammation, such as albumin, creatinine, and C-reactive protein. Aim: The present study aimed to determine whether the periodontal inflammatory status parameters correlate with the albumin, creatinine, and C-reactive protein serum concentrations in HD patients, and investigate whether periodontal treatment improves these markers of nutritional and systemic inflammation. Materials and Methods: The serum creatinine, albumin, and C-reactive Protein (CRP) levels were measured at baseline and after non-surgical periodontal treatment, at 3 months and 6 months. Results: At 3 months, a significant correlation between plaque index and C-reactive protein (p = 0.012), bleeding on probing and C-reactive protein (p < 0.0019), and clinical attachment level and C-reactive protein (p = 0.022) was found. No significant correlation was found between clinical periodontal parameters and nutrition markers at each time. Conclusions: Our results confirmed the association between C-reactive protein serum concentration and periodontal inflammatory status, but further research is necessary to identify the contributing role of periodontitis on the onset and progression of MICS.

13.
Medicina (Kaunas) ; 55(12)2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31766556

RESUMO

The few therapeutic strategies for advance hepatocellular carcinoma (HCC) on poor knowledge of its biology. For several years, sorafenib, a tyrosine kinase inhibitors (TKI) inhibitor, has been the approved treatment option, to date, for advanced HCC patients. Its activity is the inhibition of the retrovirus-associated DNA sequences protein (RAS)/Rapidly Accelerated Fibrosarcoma protein (RAF)/mitogen-activated and extracellular-signal regulated kinase (MEK)/extracellular-signal regulated kinases (ERK) signaling pathway. However, the efficacy of sorafenib is limited by the development of drug resistance, and the major neuronal isoform of RAF, BRAF and MEK pathways play a critical and central role in HCC escape from TKIs activity. Advanced HCC patients with a BRAF mutation display a multifocal and/or more aggressive behavior with resistance to TKI. Moreover, also long non-coding RNA (lnc-RNA) have been studied in epigenetic studies for BRAF aggressiveness in HCC. So far, lnc-RNA of BRAF could be another mechanism of cancer proliferation and TKI escape in HCC and the inhibition could become a possible strategy treatment for HCC. Moreover, recent preclinical studies and clinical trials evidence that combined treatments, involving alternative pathways, have an important role of therapy for HCC and they could bypass resistance to the following TKIs: MEK, ERKs/ribosomal protein S6 kinase 2 (RSK2), and phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR). These initial data must be confirmed in clinical studies, which are currently ongoing. Translational research discoveries could create new strategies of targeted therapy combinations, including BRAF pathway, and they could eventually bring light in new treatment of HCC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Humanos
14.
Medicina (Kaunas) ; 55(10)2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31627433

RESUMO

Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib had been the standardcare for almost a decade until 2018 when the Food and Drug Administration approved an alternative first-line agent namely lenvatinib. Cabozantinib, regorafenib, and ramucirumab also displayed promising results in second line settings. FOLFOX4, however, results inan alternative first-line treatment for the Chineseclinical oncology guidelines. Moreover,nivolumab and pembrolizumab,two therapeutics against the Programmed death (PD)-ligand 1 (PD-L1)/PD1 axis have been recently approvedfor subsequent-line therapy. However, similar to other solid tumors, the response rate of single agent targeting PD-L1/PD1 axis is low. Therefore, a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors (ICIs), the addition of ICIs after resection or during loco-regional therapy, ICIs in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with a careful assessmentof new ICIs-based combinatory approaches.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma Hepatocelular/fisiopatologia , Humanos , Neoplasias Hepáticas/fisiopatologia , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico
15.
Medicina (Kaunas) ; 55(10)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640191

RESUMO

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Animais , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais/análise , Humanos , Compostos de Fenilureia/uso terapêutico , Prognóstico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Sorafenibe/efeitos adversos
16.
Int J Biochem Cell Biol ; 117: 105618, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31542428

RESUMO

Quercetin (Que), a widely distributed flavonoid in the human diet, exerts neuroprotective action because of its property to antagonize oxidative stress. Here, we investigated the effects of Que on lipid synthesis in C6 glioma cells. A rapid Que-induced inhibition of cholesterol and, to a lesser extent, of fatty acid synthesis from [1-14C]acetate was observed. The maximum decrease was detected at the level of palmitate, the end product of de novo fatty acid synthesis. The effect of Que on the enzyme activities of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS), the two enzymes of this pathway, was investigated directly in situ in permeabilized C6 cells. An inhibitory effect on ACC1 was observed after 4 h of 25 µM Que treatment, while FAS activity was not affected. A reduction of polar lipid biosynthesis was also detected. A remarkable decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) activity, regulatory enzyme of cholesterol synthesis, was evidenced. Expression studies demonstrated that Que acts at transcriptional level, by reducing the mRNA abundance and protein amount of ACC1 and HMGCR. Deepening the molecular mechanism, we found that Que decreased the expression of SREBP-1 and SREBP-2, transcriptional factors representing the main regulators of de novo fatty acid and cholesterol synthesis, respectively. Que also reduced the nuclear content of ChREBP, a glucose-induced transcription factor involved in the regulation of lipogenic genes. Our results represent the first evidence that a direct and rapid downregulatory effect of Que on cholesterol and de novo fatty acid synthesis is elicited in C6 cells.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Colesterol/metabolismo , Ácidos Graxos/metabolismo , Glioma/metabolismo , Quercetina/antagonistas & inibidores , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Humanos , Ratos
17.
Med Oncol ; 36(9): 80, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399784

RESUMO

The aim of our study is to investigate the efficacy of metronomic cyclophosphamide plus low dose of corticosteroids in advanced or metastatic castration-resistant prostate cancer (CRPC) before, between, and after standard chemotherapy, such as docetaxel and cabazitaxel, and new hormonal treatments, such as abiraterone and enzalutamide. A retrospective analysis was performed on 37 patients. Cyclophosphamide was given orally 50 mg per day together with low dose of corticosteroids, namely dexametasone orally 1 mg per day or prednisone 10 mg per day. Seventeen patients (51%) showed a PSA decline≥ 50%. Median progression-free survival (PFS) and overall survival (OS) were 11 and 28 months, respectively. Median PFS and OS in the subgroup of patients with a PSA decline ≥ 50% were 14 and 35 months, respectively. Treatment was very well tolerated. We suggest that oral metronomic cyclophosphamide plus low dose of oral dexamethasone or prednisone may be a good and safe therapeutic option not only in those CRPC patients unfit for standard treatments but also in those heavily pre-treated patients.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Ciclofosfamida/administração & dosagem , Glucocorticoides/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/uso terapêutico , Resultado do Tratamento
18.
Antibiotics (Basel) ; 8(3)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438651

RESUMO

Immune suppressed renal transplant patients are more prone to developing oral tissue alterations due to medications associated with a pleiotropic set of side effects involving the oral cavity. Drug-induced gingival overgrowth (DIGO) is the most commonly encountered side effect resulting from administration of calcineurin inhibitors such as cyclosporine-A (CsA), the standard first-line treatment for graft rejection prevention in transplant patients. Pathogenesis of gingival overgrowth (GO) is determined by the interrelation between medications and a pre-existing inflammatory periodontal condition, the main modifiable risk factor. Severity of gingival hyperplasia clinical manifestation is also related to calcium channel blocker association, frequently provided in addition to pharmacological therapy of transplant recipients. Specifically, nifedipine-induced enlargements have a higher prevalence rate compared to amlodipine-induced enlargements; 47.8% and 3.3% respectively. Available epidemiological data show a gender difference in prevalence, whereby males are generally more frequently affected than females. The impact of GO on the well-being of an individual is significant, often leading to complications related to masticatory function and phonation, a side effect that may necessitate switching to the tacrolimus drug that, under a similar regimen, is associated with a low incidence of gingival lesion. Early detection and management of GO is imperative to allow patients to continue life-prolonging therapy with minimal morbidity. The purpose of this study was threefold: firstly, to determine the prevalence and incidence of GO under the administration of CsA and Tacrolimus; secondly, to assess the correlation between periodontal status before and after periodontal therapy and medications on progression or recurrence of DIGO; and finally, to analyse the effect of immunosuppressant in association to the channel blocker agents on the onset and progression of gingival enlargement. We compared seventy-two renal transplant patients, including 33 patients who were receiving CsA, of which 25% were also receiving nifedipine and 9.72% also receiving amlodipine, and 39 patients who were receiving tacrolimus, of which 37.5% were also receiving nifedipine and 5.55% also receiving amlodipine, aged between 35 and 60 years. Medical and pharmacological data were recorded for all patients. Clinical periodontal examination, in order to establish the inflammatory status and degree of gingival enlargement, was performed at baseline (T0), 3 months (T1), 6 months (T2), and 9 months (T3). All patients were subjected to periodontal treatment. Statistically significant correlation between the reduction of the mean value of periodontal indices and degree of gingival hyperplasia at the three times was revealed. The prevalence of GO in patients taking cyclosporine was higher (33.3%) in comparison with those taking tacrolimus (14.7%). In accordance with previous studies, this trial highlighted the clinical significance of the pathological substrate on stimulating drug-induced gingival lesion, confirming the key role of periodontal inflammation in pathogenesis of gingival enlargement, but did not confirm the additional effect of calcium-channel blocker drugs in inducing gingival enlargement.

19.
IUBMB Life ; 71(7): 863-872, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30707786

RESUMO

Hepatic de novo lipogenesis (DNL), the process by which carbohydrates are converted into lipids, is strictly controlled by nutritional and hormonal status. 3,5-Diiodo-L-thyronine (T2), a product of the 3,5,3'-triiodo-L-thyronine (T3) peripheral metabolism, has been shown to mimic some T3 effects on lipid metabolism by a short-term mechanism independent of protein synthesis. Here, we report that T2, administered for 1 week to hypothyroid rats, increases total fatty acid synthesis from acetate in isolated hepatocytes. Studies carried out on liver subcellular fractions demonstrated that T2 not only increases the activity and the expression of acetyl-CoA carboxylase and fatty acid synthase but also of other proteins linked to DNL such as the mitochondrial citrate carrier and the cytosolic ATP citrate lyase. Parallelly, T2 stimulates the activities of enzymes supplying cytosolic NADPH needed for the reductive steps of DNL. With respect to both euthyroid and hypothyroid rats, T2 administration decreases the hepatic mRNA level of SREBP-1, a transcription factor which represents a master regulator of DNL. However, when compared to hypothyroid rats T2 significantly increases, without bringing to the euthyroid value, the content of both mature (nSREBP-1), and precursor (pSREBP-1) forms of the SREBP-1 protein as well as their ratio. Moreover, T2 administration strongly augmented the nuclear content of ChREBP, another crucial transcription factor involved in the regulation of lipogenic genes. Based on these results, we can conclude that in the liver of hypothyroid rats the transcriptional activation by T2 of DNL genes could depend, at least in part, on SREBP-1- and ChREBP-dependent mechanisms. © 2019 IUBMB Life, 2019.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Di-Iodotironinas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotireoidismo/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/patologia , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Ativação Transcricional
20.
Oxid Med Cell Longev ; 2018: 9086947, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29849923

RESUMO

Mitochondria are fundamental organelles producing energy and reactive oxygen species (ROS); their impaired functions play a key role in endothelial dysfunction. Hydroxytyrosol (HT), a well-known olive oil antioxidant, exerts health benefits against vascular diseases by improving endothelial function. However, the HT role in mitochondrial oxidative stress in endothelial dysfunction is not clear yet. To investigate the HT effects on mitochondrial ROS production in the inflamed endothelium, we used an in vitro model of endothelial dysfunction represented by cultured endothelial cells, challenged with phorbol myristate acetate (PMA), an inflammatory, prooxidant, and proangiogenic agent. We found that the pretreatment of endothelial cells with HT (1-30 µmol/L) suppressed inflammatory angiogenesis, a crucial aspect of endothelial dysfunction. The HT inhibitory effect is related to reduced mitochondrial superoxide production and lipid peroxidation and to increased superoxide dismutase activity. HT, in a concentration-dependent manner, improved endothelial mitochondrial function by reverting the PMA-induced reduction of mitochondrial membrane potential, ATP synthesis, and ATP5ß expression. In PMA-challenged endothelial cells, HT also promoted mitochondrial biogenesis through increased mitochondrial DNA content and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, nuclear respiratory factor-1, and mitochondrial transcription factor A. These results highlight that HT blunts endothelial dysfunction and pathological angiogenesis by ameliorating mitochondrial function, thus suggesting HT as a potential mitochondria-targeting antioxidant in the inflamed endothelium.


Assuntos
Mitocôndrias/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Linhagem Celular , Movimento Celular/efeitos dos fármacos , DNA Mitocondrial/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Molécula 1 de Adesão de Célula Vascular/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...