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1.
J Med Ethics ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38889950

RESUMO

The development of vaccines against SARS-CoV-2 (COVID-19) presented a unique set of challenges. There was a global need for safe, effective vaccines against a new virus. In response to the development of vaccines for COVID-19 (some of which used novel technologies), there was a proliferation of no-fault compensation schemes (NFCS) for COVID-19 vaccine injuries. We identified 28 national vaccine injury NFCS operating in December 2019. Just 2 years later, over 130 countries had some NFCS coverage for COVID-19 vaccines. This rapid expansion was primarily driven by the creation of three multinational schemes. The COVID-19 Vaccines Global Access (COVAX) scheme covers vaccines given under the COVAX framework in 92 low and middle-income countries across the globe. The African Vaccines Acquisition Trust (AVAT) scheme covers vaccines administered under the AVAT framework in 36 African and Caribbean countries. The UNICEF scheme covers vaccines administered by UNICEF in 18 Asian countries.Because of the sudden expansion of no-fault compensation for vaccine injury, especially in developing economies, more research on the foundations, procedures and outcomes of NFCS is needed. In this article, we examine how these NFCS meet the needs of individual claimants and society more widely. To do so, we first review the rationales offered to support the creation of vaccine injury NFCS. We then argue that, in order to achieve their function as compensation mechanisms, NFCS should be accessible and offer substantive and procedural justice to claimants. Finally, we focus on transparency and accountability as necessary requirements to allow scrutiny over existing NFCS and their wider impacts.

2.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38731995

RESUMO

The gut-brain axis is a bidirectional relationship between the microbiota and the brain; genes related to the brain and gut synaptic formation are similar. Research on the causal effects of gut microbiota on human behavior, brain development, and function, as well as the underlying molecular processes, has emerged in recent decades. Probiotics have been shown in several trials to help reduce anxiety and depressive symptoms. Because of this, probiotic combinations have been tested in in vitro models to see whether they might modulate the gut and alleviate depression and anxiety. Therefore, we sought to determine whether a novel formulation might affect the pathways controlling anxiety and depression states and alter gut barrier activities in a 3D model without having harmful side effects. Our findings indicate that B. bifidum novaBBF7 10 mg/mL, B. longum novaBLG2 5 mg/mL, and L. paracasei TJB8 10 mg/mL may influence the intestinal barrier and enhance the synthesis of short-chain fatty acids. Additionally, the probiotics studied did not cause neuronal damage and, in combination, exert a protective effect against the condition of anxiety and depression triggered by L-Glutamate. All these findings show that probiotics can affect gut function to alter the pathways underlying anxiety and depression.


Assuntos
Ansiedade , Depressão , Microbioma Gastrointestinal , Probióticos , Ansiedade/terapia , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Eixo Encéfalo-Intestino , Suplementos Nutricionais
3.
Int J Mol Sci ; 25(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38397054

RESUMO

BACKGROUND: Peripheral neuropathy is caused by a malfunction in the axons and myelin sheaths of peripheral nerves and motor and sensory neurons. In this context, nonpharmacological treatments with antioxidant potential have attracted much attention due to the issues that some conventional pharmaceutical therapy can generate. Most of these treatments contain lipoic acid, but issues have emerged regarding its use. Considering this, the present study evaluated the beneficial effects of nutraceuticals based on Gastrodiae elata dry extract 10:1 or lipoic acid in combination with other substances (such as citicholine, B vitamins, and acetyl L-carnitine). METHOD: To assess the combination's absorption and biodistribution and exclude cytotoxicity, its bioavailability was first examined in a 3D intestinal barrier model that replicated oral ingestion. Subsequently, a 3D model of nerve tissue was constructed to investigate the impacts of the new combination on the significant pathways dysregulated in peripheral neuropathy. RESULTS: Our findings show that the novel combination outperformed in initial pain relief response and in recovering the mechanism of nerve healing following Schwann cell injury by successfully crossing the gut barrier and reaching the target site. CONCLUSION: This article describes a potential alternative nutraceutical approach supporting the effectiveness of combinations with Gastrodiae elata extract in decreasing neuropathy and regulating pain pathways.


Assuntos
Medicamentos de Ervas Chinesas , Neuralgia , Ácido Tióctico , Humanos , Ácido Tióctico/farmacologia , Ácido Tióctico/uso terapêutico , Distribuição Tecidual , Neuralgia/tratamento farmacológico , Suplementos Nutricionais
4.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38732008

RESUMO

Neuropathy affects 7-10% of the general population and is caused by a lesion or disease of the somatosensory system. The limitations of current therapies highlight the necessity of a new innovative approach to treating neuropathic pain (NP) based on the close correlation between oxidative stress, inflammatory process, and antioxidant action. The advantageous outcomes of a novel combination composed of Hop extract, Propolis, Ginkgo Biloba, Vitamin B, and palmitoylethanolamide (PEA) used as a treatment was evaluated in this study. To assess the absorption and biodistribution of the combination, its bioavailability was first examined in a 3D intestinal barrier model that replicated intestinal absorption. Further, a 3D nerve tissue model was developed to study the biological impacts of the combination during the essential pathways involved in NP. Our findings show that the combination could cross the intestinal barrier and reach the peripheral nervous system, where it modulates the oxidative stress, inflammation levels, and myelination mechanism (increased NRG, MPZ, ERB, and p75 levels) under Schwann cells damaging. This study proves the effectiveness of Ginkgo Biloba, Propolis, Hop extract, Vitamin B, and PEA in avoiding nerve damage and suggests a potential alternative nutraceutical treatment for NP and neuropathies.


Assuntos
Amidas , Suplementos Nutricionais , Etanolaminas , Neuralgia , Ácidos Palmíticos , Plantas Medicinais , Etanolaminas/farmacologia , Ácidos Palmíticos/farmacologia , Ácidos Palmíticos/administração & dosagem , Animais , Neuralgia/tratamento farmacológico , Amidas/farmacologia , Amidas/química , Plantas Medicinais/química , Polifenóis/farmacologia , Polifenóis/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ratos , Masculino , Antioxidantes/farmacologia , Ginkgo biloba/química , Humanos
5.
Int J Mol Sci ; 25(4)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38396866

RESUMO

Vitamin D3 (VitD3) plays a crucial role in various cellular functions through its receptor interaction. The biological activity of Vitamin D3 can vary based on its solubility and stability. Thus, the challenge lies in maximizing its biological effects through its complexation within cyclodextrin (ßNS-CDI 1:4) nanosponges (NS) (defined as VitD3NS). Therefore, its activity has been evaluated on two different gut-brain axes (healthy gut/degenerative brain and inflammatory bowel syndrome gut/degenerative brain axis). At the gut level, VitD3-NS mitigated liposaccharide-induced damage (100 ng/mL; for 48 h), restoring viability, integrity, and activity of tight junctions and reducing ROS production, lipid peroxidation, and cytokines levels. Following intestinal transit, VitD3-NS improved the neurodegenerative condition in the healthy axis and the IBS model, suggesting the ability of VitD3-NS to preserve efficacy and beneficial effects even in IBS conditions. In conclusion, this study demonstrates the ability of this novel form of VitD3, named VitD3-NS, to act on the gut-brain axis in healthy and damaged conditions, emphasizing enhanced biological activity through VitD3 complexation, as such complexation increases the beneficial effect of vitamin D3 in both the gut and brain by about 50%.


Assuntos
Colecalciferol , Síndrome do Intestino Irritável , Humanos , Colecalciferol/farmacologia , Colecalciferol/uso terapêutico , Síndrome do Intestino Irritável/tratamento farmacológico , Eixo Encéfalo-Intestino , Citocinas , Encéfalo , Vitamina D/farmacologia , Vitamina D/uso terapêutico
6.
Int J Mol Sci ; 24(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36982577

RESUMO

Neuropathic pain is a typical patient disorder resulting from damage and dysfunction of the peripheral neuraxis. Injury to peripheral nerves in the upper extremities can result in a lifelong reduction in quality of life and a devastating loss of sensory and motor function. Since some standard pharmaceutical therapies can cause dependence or intolerance, nonpharmacological treatments have gained great interest in recent years. In this context, the beneficial effects of a new combination of palmitoylethanolamide and Equisetum arvense L. are evaluated in the present study. The bioavailability of the combination was initially analyzed in a 3D intestinal barrier simulating oral intake to analyze its absorption/biodistribution and exclude cytotoxicity. In a further step, a 3D nerve tissue model was performed to study the biological effects of the combination during the key mechanisms leading to peripheral neuropathy. Our results demonstrate that the combination successfully crossed the intestinal barrier and reached the target site, modulating the nerve recovery mechanism after Schwann cell injury and offering the initial response of relieving pain. This work supported the efficacy of palmitoylethanolamide and Equisetum arvense L. in reducing neuropathy and modifying the major pain mechanisms, outlining a possible alternative nutraceutical approach.


Assuntos
Equisetum , Neuralgia , Humanos , Qualidade de Vida , Distribuição Tecidual , Neuralgia/tratamento farmacológico
7.
Int J Mol Sci ; 24(15)2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37569657

RESUMO

Despite the identification of several innovative targets for avoiding cognitive decline, there has yet to be a widely accepted approach that deals with minimising the deterioration of cognitive function. In this light, recent studies suggest that regulating the gut-brain axis with probiotics is a potential therapeutic strategy to support brain health. For this reason, in vitro models were used to examine the efficacy of different probiotic combinations to enhance intestinal homeostasis and positively affect the brain. Therefore, the new formulation has been evaluated for its capacity to modify intestinal barrier functions in a 3D in vitro model without any adverse effects and directly impact the mechanisms underlying cognitive function in a gut-brain axis model. According to our findings, B. bifidum novaBBF7 10 mg/mL, B. longum novaBLG2 5 mg/mL and L. paracasei TJB8 10 mg/mL may successfully modify the intestinal barrier and improve SCFA production. Successively, the probiotics studied caused no harm at the neuronal level, as demonstrated by iNOS, mitochondrial potential, and cell viability tests, confirming their safety features and enhancing antioxidant mechanisms and antineuroinflammation activity. Additionally, the damage caused by oxidative stress was also healed, and critical pathways that result in cognitive impairment were changed by synergetic action, supporting the hypothesis that brain ageing and neurodegeneration are slowed down. All these findings demonstrate the ability of probiotics to affect cognitive processes and their ability to sustain the mechanisms underlying cognitive function by acting on intestinal function.


Assuntos
Bifidobacterium bifidum , Bifidobacterium longum , Lacticaseibacillus paracasei , Probióticos , Bifidobacterium bifidum/fisiologia , Eixo Encéfalo-Intestino , Probióticos/farmacologia , Probióticos/uso terapêutico , Estresse Oxidativo
8.
Int J Mol Sci ; 24(6)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36982396

RESUMO

Vitamin D plays an important role in numerous cellular functions due to the ability to bind the Vitamin D receptor (VDR), which is present in different tissues. Several human diseases depend on low vitamin D3 (human isoform) serum level, and supplementation is necessary. However, vitamin D3 has poor bioavailability, and several strategies are tested to increase its absorption. In this work, the complexation of vitamin D3 in Cyclodextrin-based nanosponge (CD-NS, in particular, ßNS-CDI 1:4) was carried out to study the possible enhancement of bioactivity. The ßNS-CDI 1:4 was synthesized by mechanochemistry, and the complex was confirmed using FTIR-ATR and TGA. TGA demonstrated higher thermostability of the complexed form. Subsequently, in vitro experiments were performed to evaluate the biological activity of Vitamin D3 complexed in the nanosponges on intestinal cells and assess its bioavailability without cytotoxic effect. The Vitamin D3 complexes enhance cellular activity at the intestinal level and improve its bioavailability. In conclusion, this study demonstrates for the first time the ability of CD-NS complexes to improve the chemical and biological function of Vitamin D3.


Assuntos
Antineoplásicos , Ciclodextrinas , Nanoestruturas , Humanos , Ciclodextrinas/farmacologia , Ciclodextrinas/química , Vitamina D/farmacologia , Nanoestruturas/química , Colecalciferol/farmacologia , Receptores de Calcitriol
9.
Int J Mol Sci ; 24(4)2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36835105

RESUMO

Nasal sprays are medical devices useful for preventing infection and the subsequent spread of airborne pathogens. The effectiveness of these devices depends on the activity of chosen compounds which can create a physical barrier against viral uptake as well as incorporate different substances with antiviral activity. Among antiviral compounds, UA, a dibenzofuran derived from lichens, has the mechanical ability to modify its structure by creating a branch capable of forming a protective barrier. The mechanical ability of UA to protect cells from virus infection was investigated by analyzing the branching capacity of UA, and then the protection mechanism in an in vitro model was also studied. As expected, UA at 37 °C was able to create a barrier confirming its ramification property. At the same time, UA was able to block the infection of Vero E6 and HNEpC cells by interfering with a biological interaction between cells and viruses as revealed also by the UA quantification. Therefore, UA can block virus activity through a mechanical barrier effect without altering the physiological nasal homeostasis. The findings of this research could be of great relevance in view of the growing alarm regarding the spread of airborne viral diseases.


Assuntos
Antivirais , Antivirais/farmacologia , Sobrevivência Celular
10.
Aging Clin Exp Res ; 34(11): 2659-2674, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35920994

RESUMO

BACKGROUND: To date, the mitochondrial function has been related to several pathways involved in the cellular aging process. Dietary supplements might have reciprocal and multilevel interactions with mitochondria network; however, no systematic review assessed the role of different nutraceuticals in mitochondria modification of healthy older adults. AIM: To assess the effects of different dietary supplements on mitochondria modifications in older adults. METHODS: On February 22, 2022, PubMed, Scopus, Web of Science, and Cochrane were systematically searched from inception for randomized controlled trials (RCTs). According to PICO model, we considered healthy older adults as participants, nutraceutical treatment as intervention, any treatment as comparator, mitochondrial modifications as outcome. Jadad scale was used for the quality assessment. RESULTS: Altogether, 8489 records were identified and screened until 6 studies were included. A total of 201 healthy older adults were included in the systematic review (mean age ranged from 67.0 ± 1.0 years to 76.0 ± 5.6 years). The dietary supplements assessed were sodium nitrite, N-3 polyunsaturated fatty acids, hydrogen-rich water, nicotinamide riboside, urolithin A, and whey protein powder. Positive effects were reported in terms of mitochondrial oxidative and antioxidant capacity, volume, bioenergetic capacity, and mitochondrial transcriptome based on the nutritional supplements. The quality assessment underlined that all the studies included were of good quality. DISCUSSION: Although dietary supplements might provide positive effects on mitochondria modifications, few studies are currently available in this field. CONCLUSION: Further studies are needed to better elucidate the reciprocal and multilevel interactions between nutraceuticals, mitochondria, and environmental stressors in healthy older adults.


Assuntos
Ácidos Graxos Ômega-3 , Envelhecimento Saudável , Humanos , Idoso , Ensaios Clínicos Controlados Aleatórios como Assunto , Suplementos Nutricionais , Mitocôndrias
11.
Int J Mol Sci ; 23(7)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35409162

RESUMO

BACKGROUND: Hypercholesterolemia is a major cause of cardiovascular disease and statins, the HMGCoA inhibitors, are the most prescribed drugs. Statins reduce the production of hepatic cholesterol, leading to greater expression of the LDL receptor and greater absorption of circulating LDL, reducing peripheral LDL levels. Unfortunately, statins are believed to induce myopathy and other severe diseases. To overcome this problem, safe nutraceuticals with the same activity as statins could hold great promise in the prevention and treatment of hypercholesterolemia. In this study, the anti-cholesterol efficacy of a new nutraceutical, called Esterol10®, was evaluated. METHODS: HepG2 cells were used to study the biological mechanisms exerted by Esterol10® analyzing different processes involved in cholesterol metabolism, also comparing data with Atorvastatin. RESULTS: Our results indicate that Esterol10® leads to a reduction in total hepatocyte cholesterol and an improvement in the biosynthesis of free cholesterol and bile acids. Furthermore, the anti-cholesterol activity of Esterol10® was also confirmed by the modulation of the LDL receptor and by the accumulation of lipids, as well as by the main intracellular pathways involved in the metabolism of cholesterol. CONCLUSIONS: Esterol10® is safe and effective with anti-cholesterol activity, potentially providing an alternative therapy to those based on statins for hypercholesterolemia disease.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Colesterol/farmacologia , LDL-Colesterol/farmacologia , Homeostase , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Receptores de LDL
12.
Int J Mol Sci ; 23(15)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35897688

RESUMO

BACKGROUND: In recent decades, hyaluronic acid (HA) has attracted great attention as a new treatment option for osteoarthritis. Classical therapies are not able to stop the cartilage degeneration process nor do they favor tissue repair. Nowadays, it is accepted that high molecular weight HA can reduce inflammation by promoting tissue regeneration; therefore, the aim of this study was to verify the efficacy of a new high molecular weight HA of plant origin (called GreenIuronic®) in maintaining joint homeostasis and preventing the harmful processes of osteoarthritis. METHODS: The bioavailability of GreenIuronic® was investigated in a 3D intestinal barrier model that mimics human oral intake while excluding damage to the intestinal barrier. Furthermore, the chemical significance and biological properties of GreenIuronic® were investigated in conditions that simulate osteoarthritis. RESULTS: Our data demonstrated that GreenIuronic® crosses the intestinal barrier without side effects as it has a chemical-biological profile, which could be responsible for many specific chondrocyte functions. Furthermore, in the osteoarthritis model, GreenIuronic® can modulate the molecular mechanism responsible for preventing and restoring the degradation of cartilage. CONCLUSION: According to our results, this new form of HA appears to be well absorbed and distributed to chondrocytes, preserving their biological activities. Therefore, the oral administration of GreenIuronic® in humans can be considered a valid strategy to obtain beneficial therapeutic effects during osteoarthritis.


Assuntos
Cartilagem Articular , Osteoartrite , Cartilagem/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Humanos , Ácido Hialurônico , Inflamação/tratamento farmacológico , Osteoartrite/metabolismo
13.
J Vasc Res ; 55(1): 47-60, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29301117

RESUMO

This work demonstrates the cooperative effect of Q10, vitamin D3, and L-arginine on both cardiac and endothelial cells. The effects of Q10, L-arginine, and vitamin D3 alone or combined on cell viability, nitric oxide, and reactive oxygen species productions in endothelial and cardiac cells were studied. Moreover, the involvement of PI3K/Akt and ERK/MAPK pathways leading to eNOS activation as well as the involvement of vitamin D receptor were also investigated. The same agents were tested in an animal model to verify vasodilation, nitric oxide, and reactive oxygen species production. The data obtained in this work demonstrate for the first time the beneficial and cooperative effect of stimulation with Q10, L-arginine, and vitamin D3. Indeed, in cardiac and endothelial cells, Q10, L-arginine, and vitamin D3 combined were able to induce a nitric oxide production higher than the that induced by the 3 substances alone. The effects on vasodilation induced by cooperative stimulation have been confirmed in an in vivo model as well. The use of a combination of Q10, L-arginine, and vitamin D to counteract increased free radical production could be a potential method to reduce myocardial injury or the effects of aging on the heart.


Assuntos
Antioxidantes/farmacologia , Aorta Abdominal/efeitos dos fármacos , Arginina/farmacologia , Colecalciferol/farmacologia , Células Endoteliais/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Ubiquinona/análogos & derivados , Vasodilatadores/farmacologia , Animais , Aorta Abdominal/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Endoteliais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Masculino , Miócitos Cardíacos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Artéria Pulmonar/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sus scrofa , Fatores de Tempo , Ubiquinona/farmacologia , Vasodilatação/efeitos dos fármacos
14.
Cells Tissues Organs ; 203(4): 215-230, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27883993

RESUMO

The physiological effects of acetylcholine on keratinocytes depend on the presence of nicotinic and muscarinic receptors. The role of nonneuronal acetylcholine in keratinocytes could have important clinical implications for patients with various skin disorders such as nonhealing wounds. In order to evaluate the efficacy of highly diluted acetylcholine solutions obtained by sequential kinetic activation, we aimed to investigate the effects of these solutions on normal human keratinocytes. Two different concentrations (10 fg/mL and 1 pg/mL) and formulations (kinetically activated and nonkinetically activated) of acetylcholine were used to verify keratinocyte viability, proliferation, and migration and the intracellular pathways involved using MTT, crystal violet, wound healing, and Western blot compared to 147 ng/mL acetylcholine. The activated formulations (1 pg/mL and 10 fg/mL) revealed a significant capacity to increase migration, cell viability, and cell proliferation compared to 147 ng/mL acetylcholine, and these effects were more evident after a single administration. Sequential kinetic activation resulted in a statistically significant decrease in reactive oxygen species production accompanied by an increase in mitochondrial membrane potential and a decrease in oxygen consumption compared to 147 ng/mL acetylcholine. The M1 muscarinic receptor was involved in these effects. Finally, the involvement of ERK/mitogen-activated protein kinases (MAPK) and KI67 confirmed the effectiveness of the single treatment on cell proliferation. The intracellular pathways of calcium were investigated as well. Our results indicate for the first time that highly diluted and kinetically activated acetylcholine seems to play an active role in an in vitro model of wound healing. Moreover, the administration of acetylcholine within the physiological range may not only be effective but is also likely to be safe.


Assuntos
Acetilcolina/farmacologia , Queratinócitos/metabolismo , Sistema Colinérgico não Neuronal/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Receptores Muscarínicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Soluções
15.
BMC Gastroenterol ; 16(1): 127, 2016 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-27717330

RESUMO

BACKGROUND: Gastric diseases are a worldwide problem in modern society, as reported in the USA, in the range of 0.5-2 episodes/year/person and an incidence of 5-100 episodes/1000/week according to seasons and age. There is convincing evidence that oxidative stress is involved in the pathogenesis of acute gastric injury. Acid secreted from gastric parietal cells determines mucosal injuries which in turn cause inflammation and oxidative stress. Consequent inflammation produces free radicals by mitochondria thus causing lipid peroxidation, oxidative and acidic stress, which can lead to cell apoptosis. Vitamin D3, the active form of vitamin D, may counteract intracellular cell death and improve epithelial regeneration. METHODS: This study was planned to assess whether vitamin D3 is a protective factor against acid injury and oxidative stress in gastric epithelial cells. Primary epithelial cells and GTL-16 cells have been used to test the effects of Grisù® alone or in combination with vitamin D3 during oxidative stress or high acid exposition measuring cell viability, ROS production, cellular adhesion time along with apoptotic, autophagic and survival pathways. The combined effect of Grisù® and vitamin D3 was found more effective in counteracting the negative consequences of oxidative stress and acidity conditions than some other gastroprotective agents, such as Maalox® or Gaviscon®. RESULTS: In case of oxidative stress or acidity condition the stimulation with Grisù® alone caused an improvement of cell viability and a reduction of ROS production on epithelial gastric cells. In addition, the adhesion time of the cells was improved. All these effects were increased by the presence of vitamin D3. Similar data were also observed in primary gastric epithelial cells confirming the results obtained in GTL-16 cells. CONCLUSIONS: These results suggest that Grisù® in combination with vitamin D3 may exert a gastroprotective effect to maintain or restore the integrity of gastric epithelium through an antioxidant pathway, inhibiting apoptosis and activating survival kinases. Moreover, the combination of Grisù® and vitamin D3 improves cell viability and decreases ROS production compared to other gastroprotective agents combined with vitamin D3. All these data were validated using primary cells isolated from gastric tissue.


Assuntos
Alginatos/farmacologia , Colecalciferol/farmacologia , Células Epiteliais/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Vitaminas/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quimioterapia Combinada , Fármacos Gastrointestinais/farmacologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo
16.
Pediatr Allergy Immunol ; 26(2): 139-44, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25640609

RESUMO

BACKGROUND: The prevalence of allergy to kiwifruit is increasing in Europe since the last two decades. Different proteins have been identified as kiwifruit allergens; even though with geographic differences, Act d 1, a cysteine protease protein of 30 kDa, and Act d 2, a thaumatin-like protein of 24 kDa, are normally considered the most important. The aim of this study was (i) to identify at molecular level the sensitization pattern in a group of well-characterized patients allergic to kiwifruit and (ii) to assess the role of technological treatments on kiwifruit allergenic potential. METHODS: The differences in the pattern of antigenicity between fresh and processed kiwifruit were evaluated by both immunoelectrophoretic techniques and clinical tests. RESULTS: In the group of patients included in this study, three proteins were identified as major allergens in fresh kiwifruit, as the specific sensitization was present in ≥50% of the subjects. These proteins corresponded to actinidin (Act d 1), pectin methyl aldolase (Act d 6), and thaumatin-like protein (Act d 2). Kiwellin (Act d 5) and proteins of Bet v 1 family (Act d 8/act d 11) were also recognized as minor allergens. Immunoreactivity was totally eliminated by industrial treatments used for the production of kiwifruit strained derivative. CONCLUSIONS: In this group of allergic children, the technological treatments used in the production of kiwifruit strained product reduced drastically the allergenic potential of kiwifruit.


Assuntos
Actinidia/imunologia , Alérgenos/imunologia , Manipulação de Alimentos , Hipersensibilidade Alimentar/imunologia , Frutas/imunologia , Adolescente , Antígenos de Plantas/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Imunoeletroforese , Masculino , Testes Cutâneos
17.
Int J Gynecol Cancer ; 25(3): 389-98, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25594146

RESUMO

OBJECTIVE: Recent evidence strongly suggests that the fallopian tube is a site of origin of ovarian cancer. Although histological data show iron deposition in the fallopian tubes, its role remains unclear. To establish whether catalytic iron has a possible role in ovarian carcinogenesis, we isolated human fimbrial secretory epithelial cells (FSECs). METHODS: Fimbrial secretory epithelial cells, isolated from women undergoing isteroannessiectomy, were treated with different doses of catalytic iron (0.05-100 mM) to study cell viability; NO production; p53, Ras, ERK/MAPK, PI3K/Akt, Ki67, and c-Myc protein expressions through Western blot analysis; and immunocytochemistry or immunofluorescence. RESULTS: In FSECs treated with catalytic iron for up to 6 days, we observed an increase in cell viability, NO production, and p53, pan-Ras, ERK/MAPK, PI3K/Akt, Ki67, and c-Myc activations (P < 0.05) in a dose-dependent and time-dependent manner. These same results were also observed in FSECs maintained for respectively 2 and 4 weeks in the absence of catalytic iron after 6 days of stimulation. CONCLUSIONS: Our model aimed at studying the main nongenetic risk factor for ovarian cancer, providing an alternative interpretation for the role of menstruation in increasing risk of this pathology. This in vitro model mimics several features of the precursor lesions and opens new scenarios for further investigations regarding the correlation between damages produced by repeated retrograde menstruation carcinogenic stimuli.


Assuntos
Células Epiteliais/efeitos dos fármacos , Ferro/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Neoplásica/induzido quimicamente , Células Cultivadas , Relação Dose-Resposta a Droga , Células Epiteliais/química , Células Epiteliais/patologia , MAP Quinases Reguladas por Sinal Extracelular/análise , Tubas Uterinas/citologia , Feminino , Humanos , Ferro/administração & dosagem , Antígeno Ki-67/análise , Modelos Biológicos , Óxido Nítrico/biossíntese , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/análise , Proteínas Proto-Oncogênicas c-akt/análise , Proteínas Proto-Oncogênicas c-myc/análise , Proteína Supressora de Tumor p53/análise , Proteínas ras/análise
18.
Molecules ; 20(7): 13144-64, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26197307

RESUMO

Proteinaceous products are widely used as fining agents during winemaking to remove unwanted insoluble particles and undissolved microscopic particles (colloidal material) from the must or wine to improve stability. Some of them (egg white, caseinates, and fish gelatine) have allergenic potential and the presence of their residues in the final product could represent a risk for allergic individuals. Moreover, lysozyme (an egg allergen) is included among wine additives to control the fermentation processes and avoid spoiling during winemaking. The aim of this paper is to review the experimental/clinical data on the use of allergenic products in enology and the measurement of relative risk for sensitized subjects. In addition, methods developed specifically for the quantification of allergenic residues in must and wine are described.


Assuntos
Alérgenos , Análise de Alimentos , Inocuidade dos Alimentos , Muramidase , Vinho/análise , Alérgenos/análise , Alérgenos/química , Humanos , Muramidase/efeitos adversos , Muramidase/análise , Muramidase/química
19.
Molecules ; 20(5): 9344-57, 2015 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-26007187

RESUMO

Chlorhexidine (CHX), one of the most effective drugs administered for periodontal treatment, presents collateral effects including toxicity when used for prolonged periods; here, we have evaluated the bactericidal potency and the cytocompatibility of Juniperus excelsa M. Bieb essential oil (EO) in comparison with 0.05% CHX. The EO was extracted from berries by hydrodistillation and components identified by gas chromatography and mass spectrometry. Bacterial inhibition halo analysis, quantitative cell viability 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenyl amino) carbonyl]-2H-tetrazolium hydroxide assay (XTT), and colony forming unit (CFU) count were evaluated against the two biofilm formers Aggregatibacter actinomycetemcomitans and Streptococcus mutans. Finally, cytocompatibility was assessed with human primary gingival fibroblasts (HGF) and mucosal keratinocytes (HK). The resulting EO was mainly composed of monoterpene hydrocarbons and oxygenated monoterpenes. An inhibition halo test demonstrated that both bacteria were sensitive to the EO; XTT analysis and CFU counts confirmed that 10-fold-diluted EO determined a statistically significant (p < 0.05) reduction in bacteria count and viability towards both biofilm and planktonic forms in a comparable manner to those obtained with CHX. Moreover, EO displayed higher cytocompatibility than CHX (p < 0.05). In conclusion, EO exhibited bactericidal activity similar to CHX, but a superior cytocompatibility, making it a promising antiseptic alternative to CHX.


Assuntos
Aggregatibacter actinomycetemcomitans/efeitos dos fármacos , Óleos Voláteis/farmacologia , Doenças Periodontais/tratamento farmacológico , Óleos de Plantas/farmacologia , Streptococcus mutans/efeitos dos fármacos , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Clorexidina/efeitos adversos , Clorexidina/farmacologia , Cárie Dentária/tratamento farmacológico , Cárie Dentária/prevenção & controle , Farmacorresistência Bacteriana , Fibroblastos/efeitos dos fármacos , Gengiva/citologia , Gengiva/efeitos dos fármacos , Juniperus/metabolismo , Queratinócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Monoterpenos/efeitos adversos , Monoterpenos/farmacologia , Mucosa/citologia , Mucosa/efeitos dos fármacos , Óleos Voláteis/efeitos adversos , Saúde Bucal , Óleos de Plantas/efeitos adversos
20.
Eur J Nutr ; 53(5): 1177-86, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24240659

RESUMO

PURPOSE: Celiac disease (CD) is an autoimmune enteropathy, triggered by dietary gluten. The only treatment is a strict gluten-free diet. Oats are included in the list of gluten-free ingredients by European Regulation, but the safety of oats in CD is still a matter of debate. The present study examined the capability of different oat cultivars of activating the gliadin-induced transglutaminase-2 (TG2)-dependent events in some in vitro models of CD. In addition, we compared this capability with the electrophoresis pattern of peptic-tryptic digests of the proteins of the oat cultivars. METHODS: K562(S) cells agglutination, transepithelial electrical resistance of T84-cell monolayers, intracellular levels of TG2 and phosphorylated form of protein 42-44 in T84 cells were the early gliadin-dependent events studied. RESULTS: The results showed that the Nave oat cultivar elicited these events, whereas Irina and Potenza varieties did not. The ability of a cultivar to activate the above-described events was associated with the electrophoretic pattern of oat proteins and their reactivity to anti-gliadin antibodies. CONCLUSION: We found significant differences among oat cultivars in eliciting the TG2-mediated events of CD inflammation. Therefore, the safety of an oat cultivar in CD might be screened in vitro by means of biochemical and biological assays, before starting a clinical trial to definitely assess its safety.


Assuntos
Avena/efeitos adversos , Avena/classificação , Doença Celíaca/imunologia , Gliadina/química , Avena/química , Linhagem Celular Tumoral , Criança , Dieta Livre de Glúten , Duodeno/patologia , Eletroforese em Gel de Poliacrilamida , Feminino , Proteínas de Ligação ao GTP/imunologia , Proteínas de Ligação ao GTP/metabolismo , Humanos , Células K562 , Masculino , Fosforilação , Proteína 2 Glutamina gama-Glutamiltransferase , Transglutaminases/imunologia , Transglutaminases/metabolismo
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