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1.
Nutrients ; 11(9)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514292

RESUMO

The use of a complete nutritional approach seems increasingly promising to combat chronic inflammation. The choice of healthy sources of carbohydrates, fats, and proteins, associated with regular physical activity and avoidance of smoking is essential to fight the war against chronic diseases. At the base of the analgesic, anti-inflammatory, or antioxidant action of the diets, there are numerous molecules, among which some of a lipidic nature very active in the inflammatory pathway. One class of molecules found in diets with anti-inflammatory actions are ALIAmides. Among all, one is particularly known for its ability to counteract the inflammatory cascade, the Palmitoylethanolamide (PEA). PEA is a molecular that is present in nature, in numerous foods, and is endogenously produced by our body, which acts as a balancer of inflammatory processes, also known as endocannabionoid-like. PEA is often used in the treatment of both acute and chronic inflammatory pathologies, either alone or in association with other molecules with properties, such as antioxidants or analgesics. This review aims to illustrate an overview of the different diets that are involved in the process of opposition to the inflammatory cascade, focusing on capacity of PEA and new formulations in synergy with other molecules.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Suplementos Nutricionais , Etanolaminas/uso terapêutico , Inflamação/prevenção & controle , Ácidos Palmíticos/uso terapêutico , Animais , Anti-Inflamatórios/efeitos adversos , Antioxidantes/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Sinergismo Farmacológico , Etanolaminas/efeitos adversos , Etanolaminas/metabolismo , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Ácidos Palmíticos/efeitos adversos , Ácidos Palmíticos/metabolismo , Transdução de Sinais
2.
Am J Hosp Palliat Care ; 36(12): 1134-1154, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31113223

RESUMO

Palmitoylethanolamide (PEA) is a nutraceutical endocannabinoid that was retrospectively discovered in egg yolks. Feeding poor children with known streptococcal infections prevented rheumatic fever. Subsequently, it was found to alter the course of influenza. Unfortunately, there is little known about its pharmacokinetics. Palmitoylethanolamide targets nonclassical cannabinoid receptors rather than CB1 and CB2 receptors. Palmitoylethanolamide will only indirectly activate classical cannabinoid receptors by an entourage effect. There are a significant number of prospective and randomized trials demonstrating the pain-relieving effects of PEA. There is lesser evidence of benefit in patients with nonpain symptoms related to depression, Parkinson disease, strokes, and autism. There are no reported drug-drug interactions and very few reported adverse effects from PEA. Further research is needed to define the palliative benefits to PEA.


Assuntos
Etanolaminas/uso terapêutico , Ácidos Palmíticos/uso terapêutico , Animais , Etanolaminas/farmacologia , Humanos , Transtornos Mentais/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Dor/tratamento farmacológico , Ácidos Palmíticos/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico
3.
Medicina (Kaunas) ; 55(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939862

RESUMO

Asthma is a common allergic pathology of the respiratory tract that requires the study of mechanisms underlying it, due to severe forms of the disease, which are refractory to therapy. The review is devoted to the search for molecular targets of fatty acid ethanolamides in asthma, in particular palmitoylethanolamide (PEA), which has been successfully used in the treatment of chronic inflammatory and neurodegenerative diseases, in the pathogenesis of which the nervous and immune systems are involved. Recently, the potentially important role of neuro-immune interactions in the development of allergic reactions has been established. Many of the clinical symptoms accompanying allergic airway inflammation are the result of the activation of neurons in the airways, so the attention of researchers is currently focused on neuro-immune interactions, which can play an important role in asthma pathophysiology. A growing number of scientific works confirm that the key molecule in the implementation of these inter-systemic interactions is nerve growth factor (NGF). In addition to its classic role in nervous system physiology, NGF is considered as an important factor associated with the pathogenesis of allergic diseases, particularly asthma, by regulating of mast cell differentiation. In this regard, NGF can be one of the targets of PEA in asthma therapy. PEA has a biological effect on the nervous system, and affects the activation and the degranulation of mast cells.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Asma/tratamento farmacológico , Asma/metabolismo , Etanolaminas/uso terapêutico , Terapia de Alvo Molecular , Fator de Crescimento Neural/metabolismo , Ácidos Palmíticos/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Asma/imunologia , Eosinófilos/metabolismo , Etanolaminas/metabolismo , Ácidos Graxos/metabolismo , Humanos , Hipersensibilidade/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Mastócitos/metabolismo , Camundongos , Neurônios/metabolismo , Ácidos Palmíticos/metabolismo
4.
Inflammopharmacology ; 27(3): 475-485, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30927159

RESUMO

BACKGROUND: The aim of the study was to assess the safety, tolerability and efficacy of palmitoylethanolamide (PEA) when dosed at 300 mg and 600 mg per day on symptoms of knee osteoarthritis. METHODS: This was a single site, comparative, double-blind placebo controlled study in adults with mild to moderate knee osteoarthritis with 111 participants randomized to receive 300 mg PEA, 600 mg PEA or placebo each day, in divided doses b.i.d, for 8 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The secondary outcomes were the Numerical Rating Scales (NRS) for pain, the Depression Anxiety Stress Scale (DASS), the Perceived Stress Scale (PSS), the Pittsburg Sleep Quality Index (PSQI), the Short Form Health Survey (SF-36), the use of rescue pain medication and clinical safety assessment. RESULTS: There was a significant reduction in the total WOMAC score in the 300 mg PEA (p = 0.0372) and the 600 mg PEA (p = 0.0012) groups, the WOMAC pain score (300 mg PEA, p = 0.0074; 600 mg PEA, p = < 0.001), the WOMAC stiffness score (PEA 300 mg, p < 0.0490; 600 mg PEA, p = 0.001) and in the WOMAC function score in the 600 mg PEA group (p = 0.033) compared to placebo. The NRS pain evaluations for "worst pain" and "least pain" were significantly reduced in the 300 mg PEA group (p < 0.001, p = 0.005) and the 600 mg PEA group (p < 0.001, p < 0.001) compared to placebo. There was a significant reduction in anxiety (DASS) in both active treatment groups (300 mg PEA, p = 0.042; 600 mg PEA group (p = 0.043) compared to placebo. There were no changes in the clinical markers and the product was well tolerated. CONCLUSIONS: The study demonstrated that palmitoylethanolamide may be a novel treatment for attenuating pain and reducing other associated symptoms of knee osteoarthritis. Further studies on the pharmacological basis of this anti-inflammatory effect are now required.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Etanolaminas/efeitos adversos , Etanolaminas/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Ácidos Palmíticos/efeitos adversos , Ácidos Palmíticos/uso terapêutico , Adulto , Idoso , Transtorno Depressivo Maior/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Dor/tratamento farmacológico , Dor/fisiopatologia , Medição da Dor/métodos , Qualidade de Vida , Resultado do Tratamento
5.
J Pharmacol Exp Ther ; 369(1): 163-172, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30635472

RESUMO

N-Palmitoylethanolamide (PEA), an endocannabinoid-like molecule, participates in controlling behaviors associated with mental disorders as an endogenous neuroprotective factor. On the basis of accumulating evidence and our previous data, we tested the hypothesis that the antidepressant-like effects of PEA observed during chronic unpredictable mild stress (CUMS) are mediated by possible targets in the peroxisome proliferator-activated receptor alpha (PPARα) pathway. In this study, rats were subjected to 35 days of CUMS and treated with drugs such as PEA (2.5, 5.0, or 10 mg/kg, by mouth), fluoxetine (10 mg/kg, by mouth), or the combination of PEA and MK886 (1-[(4-chlorophenyl) methyl]-3-[(1,1-dimethylethyl) thio]-α,α-dimethyl-5-(1-methylethyl)-1H-indole-2-propanoic acid). After behavioral tests, the animals were sacrificed and their hippocampi were dissected for subsequent studies. PEA normalized weight gain, sucrose preferences, locomotor activity in an open-field test, and levels of the PPARα mRNA and protein in the hippocampus, and it reduced serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels in rats subjected to CUMS. PEA reversed the abnormal levels of several oxidative stress biomarkers and increased the concentrations of two neurotrophic factors in the hippocampus of CUMS-induced rats. In addition, PEA alleviated the decrease in hippocampal weight. However, the aforementioned effects of PEA were completely or partially abolished by MK886, a selective PPARα antagonist. On the basis of these findings, the PPARα pathway in the hippocampus is a possible target of the antidepressant effects of PEA, and the maintenance of a stable hypothalamic-pituitary-adrenal axis, the antioxidant defenses, and normalization of neurotrophic factor levels in the hippocampus are involved in this process.


Assuntos
Antidepressivos/farmacologia , Etanolaminas/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , PPAR alfa/metabolismo , Ácidos Palmíticos/farmacologia , Hormônio Adrenocorticotrópico/sangue , Animais , Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corticosterona/sangue , Etanolaminas/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Glutationa/metabolismo , Hipocampo/patologia , Masculino , Malondialdeído/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ácidos Palmíticos/uso terapêutico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/sangue , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia , Superóxido Dismutase/metabolismo
6.
PLoS One ; 14(1): e0208730, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30653511

RESUMO

The disruption of coordinated control between the brain, spinal cord and peripheral nervous system caused by spinal cord injury (SCI) leads to several secondary pathological conditions, including lower urinary tract dysfunction. In fact, urinary tract dysfunction associated with SCI is urinary dysfunction could be a consequence of a lack of neuroregeneration of supraspinal pathways that control bladder function. The object of the current research was to explore the effects of adelmidrol + sodium hyaluronate, on bladder damage generated after SCI in mice. Spinal cord was exposed via laminectomy, and SCI was induced by extradural compression at T6 to T7 level, by an aneurysm clip with a closing force of 24 g. Mice were treated intravesically with adelmidrol + sodium hyaluronate daily for 48 h and 7 days after SCI. Adelmidrol + sodium hyaluronate reduced significantly mast cell degranulation and down-regulated the nuclear factor-κB pathway in the bladder after SCI both at 48 h and 7days. Moreover, adelmidrol + sodium hyaluronate reduced nerve growth factor expression, suggesting an association between neurotrophins and bladder pressure. At 7 days after SCI, the bladder was characterized by a marked bacterial infection and proteinuria; surprisingly, adelmidrol + sodium hyaluronate reduced significantly both parameters. These data show the protective roles of adelmidrol + sodium hyaluronate on bladder following SCI, highlighting a potential therapeutic target for the reduction of bladder changes.


Assuntos
Ácidos Dicarboxílicos/uso terapêutico , Ácido Hialurônico/uso terapêutico , Ácidos Palmíticos/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/fisiopatologia , Bexiga Urinária/efeitos dos fármacos , Animais , Western Blotting , Imunofluorescência , Masculino , Camundongos , Fator de Crescimento Neural/metabolismo , Traumatismos da Medula Espinal/metabolismo , Bexiga Urinária/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
7.
Clin Oral Investig ; 23(6): 2743-2750, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30361792

RESUMO

OBJECTIVES: This preliminary randomized double-blind controlled trial was performed to test the efficacy of ultramicronized palmitoylethanolamide treatment in the burning mouth syndrome. MATERIALS AND METHODS: Patients with referred burning mouth intensity greater than 4, according to the Numeric Rating Scale, were included in the study according to established inclusion and exclusion criteria. Patients were randomized into two groups and received either placebo or ultramicronized palmitoylethanolamide 600 mg twice daily for 60 days. Patients were assessed at baseline, 30 and 60 days after treatment start, and 4 months after treatment discontinuation. In order to evaluate the change in the burning mouth sensation over time, the generalized linear mixed model was employed. RESULTS: A total of 35 patients were considered eligible, among which 6 withdrew prior to the end of treatment. A statistically significant reduction of burning mouth sensation (p < 0.0132) was registered at the end of the active treatment in the ultramicronized palmitoylethanolamide group compared to the placebo one. Any side effect related to the active treatment was neither observed nor reported both by patients and by physicians. CONCLUSIONS: The significant decrease of burning sensation in the ultramicronized palmitoylethanolamide group compared to the placebo group suggests to consider this naturally occurring molecule as a viable therapy in the management of burning mouth syndrome. CLINICAL RELEVANCE: The use of an effective compound to manage the burning mouth syndrome, devoid of adverse effects for the patient and that does not interfere with other pharmacological therapies, could find wide employability from clinicians.


Assuntos
Síndrome da Ardência Bucal/tratamento farmacológico , Etanolaminas/uso terapêutico , Ácidos Palmíticos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
Front Immunol ; 9: 2671, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30505308

RESUMO

Easy-to-achieve interventions to promote healthy longevity are desired to diminish the incidence and severity of infections, as well as associated disability upon recovery. The dietary supplement palmitoylethanolamide (PEA) exerts anti-inflammatory and neuroprotective properties. Here, we investigated the effect of prophylactic PEA on the early immune response, clinical course, and survival of old mice after intracerebral E. coli K1 infection. Nineteen-month-old wild type mice were treated intraperitoneally with two doses of either 0.1 mg PEA/kg in 250 µl vehicle solution (n = 19) or with 250 µl vehicle solution only as controls (n = 19), 12 h and 30 min prior to intracerebral E. coli K1 infection. The intraperitoneal route was chosen to reduce distress in mice and to ensure exact dosing. Survival time, bacterial loads in cerebellum, blood, spleen, liver, and microglia counts and activation scores in the brain were evaluated. We measured the levels of IL-1ß, IL-6, MIP-1α, and CXCL1 in cerebellum and spleen, as well as of bioactive lipids in serum in PEA- and vehicle-treated animals 24 h after infection. In the absence of antibiotic therapy, the median survival time of PEA-pre-treated infected mice was prolonged by 18 h compared to mice of the vehicle-pre-treated infected group (P = 0.031). PEA prophylaxis delayed the onset of clinical symptoms (P = 0.037). This protective effect was associated with lower bacterial loads in the spleen, liver, and blood compared to those of vehicle-injected animals (P ≤ 0.037). PEA-pre-treated animals showed diminished levels of pro-inflammatory cytokines and chemokines in spleen 24 h after infection, as well as reduced serum concentrations of arachidonic acid and of one of its metabolites, 20-hydroxyeicosatetraenoic acid. In the brain, prophylactic PEA tended to reduce bacterial titers and attenuated microglial activation in aged infected animals (P = 0.042). Our findings suggest that prophylactic PEA can counteract infection associated detrimental responses in old animals. Accordingly, PEA treatment slowed the onset of infection symptoms and prolonged the survival of old infected mice. In a clinical setting, prophylactic administration of PEA might extend the potential therapeutic window where antibiotic therapy can be initiated to rescue elderly patients.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Escherichia coli/metabolismo , Etanolaminas/uso terapêutico , Inflamação/dietoterapia , Meningite devida a Escherichia coli/dietoterapia , Meningite devida a Escherichia coli/prevenção & controle , Ácidos Palmíticos/uso terapêutico , Envelhecimento/imunologia , Animais , Cerebelo/microbiologia , Citocinas/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Estimativa de Kaplan-Meier , Meningite devida a Escherichia coli/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Baço/microbiologia , Estatísticas não Paramétricas , Taxa de Sobrevida
9.
Minerva Med ; 109(5): 358-362, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30338679

RESUMO

BACKGROUND: Painful distal symmetric polyneuropathy (pDSPN) is one of the most common and invalidating complications of diabetes mellitus, both of type 1 and type 2. Mechanisms responsible for the occurrence of the pDSPN are multifactorial and involve metabolic pathways regulating inflammation, microvessel circulation, axonal degeneration and so on. Several therapeutic approaches have been proposed to treat pain and each of them showed positive effects associated to drug-related side effects. METHODS: Twenty-five consecutive patients with diagnosis of diabetes mellitus and pDSPN and tried to manage pain with a dietary supplement composed of a mixture of natural extracts (ß-caryophyllene, myrrh, carnosic acid) and PEA. This is a nutraceutical with potential multiple effects on metabolic, pain and vascular compartments, a profile considered useful in pDSPN. Patients were enrolled and polyneuropathy evaluated by means of nerve conduction study. Pain was assessed using VAS score scale and MNSI. Each patient was evaluated at T0 (time of enrollment) and at T1 (after 16 weeks of treatment). RESULTS: Supplement administration was well tolerated and induced unexpectedly significant amelioration of polyneuropathy with increase amplitude and reduction of pain. No side effects were reported. CONCLUSIONS: This fixed combination could well be considered as a potential nutraceutical option to manage pDSPN in diabetic patients.


Assuntos
Neuropatias Diabéticas/dietoterapia , Suplementos Nutricionais , /administração & dosagem , Adulto , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/fisiopatologia , Etanolaminas/administração & dosagem , Etanolaminas/uso terapêutico , Feminino , Humanos , Masculino , Medição da Dor , Ácidos Palmíticos/administração & dosagem , Ácidos Palmíticos/uso terapêutico , Sesquiterpenos/administração & dosagem , Sesquiterpenos/uso terapêutico , Índice de Gravidade de Doença , Nervo Sural/fisiopatologia , Terpenos/administração & dosagem , Terpenos/uso terapêutico , Resultado do Tratamento , Adulto Jovem
10.
J Bioenerg Biomembr ; 50(5): 391-401, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30187271

RESUMO

The paper examines membranotropic Ca2+-dependent effects of ω-hydroxypalmitic acid (HPA), a product of ω-oxidation of fatty acids, on the isolated rat liver mitochondria and artificial membrane systems (liposomes). It was established that in the presence of Ca2+, HPA induced aggregation of liver mitochondria, which was accompanied by the release of cytochrome c from the organelles. It was further demonstrated that the addition of Ca2+ to HPA-containing liposomes induced their aggregation and/or fusion. Ca2+ also caused the release of the fluorescent dye sulforhodamine B from liposomes, indicating their permeabilization. HPA was shown to induce a high-amplitude swelling of Ca2+-loaded mitochondria, to decrease their membrane potential, to induce the release of Ca2+ from the organelles and to result in the oxidation of the mitochondrial NAD(P)H pool. Those effects of HPA were not blocked by the MPT pore inhibitor CsA, but were suppressed by the mitochondrial calcium uniporter inhibitor ruthenium red. The effects of HPA were also observed when Ca2+ was replaced with Sr2+ (but not with Ba2+ or Mg2+). A supposition is made that HPA can induce a Ca2+-dependent aggregation of mitochondria, as well as Ca2+dependent CsA-insensitive permeabilization of the inner mitochondrial membrane - with the subsequent lysis of the organelles.


Assuntos
Lipossomos/metabolismo , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias/metabolismo , Ácidos Palmíticos/uso terapêutico , Animais , Ácidos Palmíticos/farmacologia , Permeabilidade , Ratos
11.
Inflamm Res ; 67(10): 891-901, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30121836

RESUMO

OBJECTIVE AND DESIGN: Temporomandibular disorder (TMD) is a common painful condition in the temporomandibular joint (TMJ). Joint inflammation is believed to be a chief cause of pain in patients with TMD, through the release of pro-inflammatory cytokines that induce peripheral sensitization of nerve terminals followed by microglial stimulation. MATERIALS AND SUBJECT: TMJ was induced in rats with the injection of complete Freund's adjuvant (CFA) emulsion into the left TMJ capsule. TREATMENT: The present study would assess the effects of micronized palmitoylethanolamide (m-PEA) on glial activation and trigeminal hypersensitivity. METHODS: Ten mg/kg m-PEA or corresponding vehicle was administered 1 h after CFA and mechanical allodynia and edema were evaluated at 24 and 72 h after CFA injection. RESULTS: CFA-injected animals showed TMJ edema and ipsilateral mechanical allodynia accompanied by a robust growth in GFAP protein-positive satellite glial cells and activation of resident macrophages in the TG. Moreover, m-PEA administration significantly reduced the degree of TMJ damage and pain, macrophage activation in TG and up-regulation of Iba1. CONCLUSIONS: The results confirm that m-PEA could represent a novel approach for monitoring pain during trigeminal nerve sensitization.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Artralgia/tratamento farmacológico , Etanolaminas/uso terapêutico , Hiperalgesia/tratamento farmacológico , Neuroglia/efeitos dos fármacos , Ácidos Palmíticos/uso terapêutico , Articulação Temporomandibular , Animais , Artralgia/induzido quimicamente , Artralgia/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Adjuvante de Freund , Proteína Glial Fibrilar Ácida/metabolismo , Hiperalgesia/induzido quimicamente , Hiperalgesia/metabolismo , Masculino , Neuroglia/metabolismo , Ratos Sprague-Dawley
13.
Clin Dermatol ; 36(3): 399-419, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29908582

RESUMO

The plant and mushroom kingdoms have species used for intoxication, inebriation, or recreation. Some of these species are toxic. Given that many of these plants or substances are illegal and have histories of abuse, much of the research regarding therapeutic application is based on basic science, animal studies, and traditional use. This review examines Cannabis, Euphorbia, Ricinus, Podophyllum, Veratrum, mushrooms, and nightshades, along with resveratrol and cocaine as they relate to dermatology.


Assuntos
Agaricales , Cannabis , Fitoterapia , Preparações de Plantas/uso terapêutico , Dermatopatias/tratamento farmacológico , Pele/patologia , Solanum , Animais , Canabinoides/uso terapêutico , Dermatologia , Dermatomicoses/tratamento farmacológico , Dronabinol/uso terapêutico , Etanolaminas/uso terapêutico , Euphorbia , Fibrose , Humanos , Inflamação/tratamento farmacológico , Ácidos Palmíticos/uso terapêutico , Preparações de Plantas/farmacologia , Podophyllum peltatum , Resveratrol , Ricinus , Envelhecimento da Pele/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/prevenção & controle , Estilbenos/uso terapêutico , Veratrum
15.
J Psychiatr Res ; 103: 104-111, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29807317

RESUMO

Inflammation as well as glutamate excitotoxicity have been proposed to participate in the propagation of autism. Palmitoylethanolamide (PEA) is an endocannabinoid proven to prevent glutamatergic toxicity and inhibit inflammatory responses simultaneously. The present randomized, parallel group, double-blind placebo-controlled trial is the first study depicted to probe the efficacy of co-treatment with risperidone and PEA over 10 weeks in children with autism. Seventy children (aged 4-12 years) with autism and moderate to severe symptoms of irritability were randomly assigned to two treatment regimens. The study outcomes were measured using the Aberrant Behavior Checklist-Community Edition (ABC-C). At trial endpoint (week 10), combination of PEA and risperidone had superior efficacy in ameliorating the ABC-irritability and hyperactivity/noncompliance symptoms (Cohen's d, 95% confidence interval (CI) = 0.94, 0.41 to 1.46, p = 0.001) compared with a risperidone plus placebo regimen. Interestingly, effect of combination treatment on hyperactivity symptoms was also observed at trial midpoint (week 5) but with a smaller effect size (d = 0.53, p = 0.04) than that at the endpoint (d = 0.94, p = 0.001). Meanwhile, there was a trend toward significance for superior effect of risperidone plus PEA over risperidone plus placebo on inappropriate speech at trial endpoint (d = 0.51, p = 0.051). No significant differences existed between the two treatment groups for the other two ABC-C subscales (lethargy/social withdrawal and stereotypic behavior). The findings suggest that PEA may augment therapeutic effects of risperidone on autism-related irritability and hyperactivity. Future studies are warranted to investigate whether PEA can serve as a stand-alone treatment for autism.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Transtorno Autístico/tratamento farmacológico , Etanolaminas/uso terapêutico , Ácidos Palmíticos/uso terapêutico , Resultado do Tratamento , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Risperidona/uso terapêutico , Antagonistas da Serotonina/uso terapêutico , Estatísticas não Paramétricas
16.
Mol Neurobiol ; 55(11): 8455-8472, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29552727

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease characterized by degeneration of dopaminergic neurons. Aging is a major risk factor for idiopathic PD. Several prior studies examined the neuroprotective effects of palmitoylethanolamide (PEA), alone or combined with antioxidants, in a model of PD induced by the dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here, we analyzed the pretreatment effect of micronized PEA (PEAm) on neuroinflammation and neuronal cell death in the MPTP model. Male CD mice (21 months of age) were pre-treated for 60 days with PEAm. After this time, they received four intraperitoneal injections of MPTP over a 24-h period and were killed 7 days later. On the 8th day, brains were processed. Pretreatment with PEAm ameliorated behavioral deficits and the reductions in expression of tyrosine hydroxylase and dopamine transporter, while blunting the upregulation of α-synuclein and ß3-tubulin in the substantia nigra after MPTP induction. Moreover, PEAm reduced proinflammatory cytokine expression and showed a pro-neurogenic effect in hippocampus. These findings propose this strategy as a valid approach to prevent neurodegenerative diseases associated with old age.


Assuntos
Envelhecimento/patologia , Etanolaminas/uso terapêutico , Ácidos Palmíticos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/prevenção & controle , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Comportamento Animal/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/metabolismo , Membrana Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Giro Denteado/efeitos dos fármacos , Giro Denteado/metabolismo , Giro Denteado/patologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Etanolaminas/administração & dosagem , Etanolaminas/farmacologia , Proteína Glial Fibrilar Ácida/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos , Proteínas dos Microfilamentos/metabolismo , Ácidos Palmíticos/administração & dosagem , Ácidos Palmíticos/farmacologia , Doença de Parkinson/patologia , Fenótipo , Agregados Proteicos , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia , Tubulina (Proteína)/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Regulação para Cima/efeitos dos fármacos , alfa-Sinucleína/metabolismo
17.
J Neuroinflammation ; 15(1): 94, 2018 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-29573741

RESUMO

BACKGROUND: Diarrhea is a severe complication in HIV-1-infected patients with Trans-activator of transcription (HIV-1 Tat) protein being recognized as a major underlying cause. Beside its direct enterotoxic effects, Tat protein has been recently shown to affect enteric glial cell (EGC) activity. EGCs regulate intestinal inflammatory responses by secreting pro-inflammatory molecules; nonetheless, they might also release immune-regulatory factors, as palmytoilethanolamide (PEA), which exerts anti-inflammatory effects by activating PPARα receptors. We aimed at clarifying whether EGCs are involved in HIV-1 Tat-induced diarrhea and if PEA exerts antidiarrheal activity. METHODS: Diarrhea was induced by intracolonic administration of HIV-1 Tat protein in rats at day 1. PEA alone or in the presence of peroxisome proliferator-activated receptor (PPAR) antagonists was given intraperitoneally from day 2 to day 7. S100B, iNOS, NF-kappaB, TLR4 and GFAP expression were evaluated in submucosal plexi, while S100B and NO levels were measured in EGC submucosal plexi lysates, respectively. To verify whether PEA effects were PPARα-mediated, PPARα-/- mice were also used. After 7 days from diarrhea induction, endogenous PEA levels were measured in submucosal plexi homogenates deriving from rats and PPARα-/- mice. RESULTS: HIV-1 Tat protein induced rapid onset diarrhea alongside with a significant activation of EGCs. Tat administration significantly increased all hallmarks of neuroinflammation by triggering TLR4 and NF-kappaB activation and S100B and iNOS expression. Endogenous PEA levels were increased following HIV-1 Tat exposure in both wildtype and knockout animals. In PPARα-/- mice, PEA displayed no effects. In wildtype rats, PEA, via PPARα-dependent mechanism, resulted in a significant antidiarrheal activity in parallel with marked reduction of EGC-sustained neuroinflammation. CONCLUSIONS: EGCs mediate HIV-1 Tat-induced diarrhea by sustaining the intestinal neuroinflammatory response. These effects are regulated by PEA through a selective PPARα-dependent mechanism. PEA might be considered as an adjuvant therapy in HIV-1-induced diarrhea.


Assuntos
Antivirais/uso terapêutico , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Etanolaminas/uso terapêutico , Neuroglia/efeitos dos fármacos , Ácidos Palmíticos/uso terapêutico , Produtos do Gene tat do Vírus da Imunodeficiência Humana/toxicidade , Anestésicos Locais/uso terapêutico , Animais , Modelos Animais de Doenças , Etanolaminas/metabolismo , Trato Gastrointestinal/patologia , Trato Gastrointestinal/virologia , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Lidocaína/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , PPAR alfa/deficiência , PPAR alfa/genética , Ácidos Palmíticos/metabolismo , Ratos , Ratos Wistar , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo
18.
J Affect Disord ; 232: 127-133, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29486338

RESUMO

BACKGROUND: Experimental studies provide evidence for antidepressant effects of Palmitoylethanolamide (PEA) in animal models of depression. We aimed to evaluate the efficacy and tolerability of PEA add-on therapy in treatment of patients with major depressive disorder (MDD). METHODS: In a randomized double-blind, and placebo-controlled study, 58 patients with MDD (DSM-5) and Hamilton Depression Rating Scale (HAM-D) score ≥ 19 were randomized to receive either 600 mg twice daily Palmitoylethanolamide or placebo in addition to citalopram for six weeks. Patients were assessed using the HAM-D scale at baseline and weeks 2, 4, and 6. RESULTS: Fifty-four individuals completed the trial. At week 2, patients in the PEA group demonstrated significantly greater reduction in HAM-D scores compared to the placebo group (8.30 ± 2.41 vs. 5.81 ± 3.57, P = .004). The PEA group also demonstrated significantly greater improvement in depressive symptoms [F (3, 156) = 3.35, P = .021] compared to the placebo group throughout the trial period. The patients in the PEA group experienced more response rate (≥ 50% reduction in the HAM-D score) than the placebo group (100% vs. 74% respectively, P = .01) at the end of the trial. Baseline parameters and frequency of side effects were not significantly different between the two groups. LIMITATIONS: The population size in this study was small and the follow-up period was relatively short. CONCLUSIONS: Palmitoylethanolamide adjunctive therapy to citalopram can effectively improve symptoms of patients (predominantly male gender) with major depressive disorder. PEA showed rapid-onset antidepressant effects which need further investigation.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antidepressivos/uso terapêutico , Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Etanolaminas/uso terapêutico , Ácidos Palmíticos/uso terapêutico , Adulto , Quimioterapia Adjuvante , Transtorno Depressivo Maior/fisiopatologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Resultado do Tratamento
19.
J Clin Pharmacol ; 58(6): 733-739, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29364513

RESUMO

Palmitoyl ethanol amide (PEA) is an endogenous substance that plays a role in neuropathic pain. In this article, we evaluated both the safety and the efficacy of ultramicronized PEA (um-PEA) in the treatment of low back pain related to nonsurgical lumbar radiculopathy. In this prospective single-blind study, patients with low back pain related to nonsurgical lumbar radiculopathy received the fixed combination acetaminophen/codeine (500 mg + 30 mg/d) for 7 days, and then it was stopped and changed to um-PEA (1200 mg/d) for 30 days. Patients without an improvement in pain or disability started a second cycle of treatment with um-PEA (600 mg/d in tablets) for 30 days and then acetaminophen/codeine for 30 days. A total of 155 patients were included in the analysis. After the first cycle of treatment we recorded an improvement of pain in all patients with mild pain (visual analog scale score from 3-4 to 1) and in 75% of the patients with moderate pain (visual analog scale score from 5-6 to 2). After the second cycle, we recorded an improvement of pain and disability in all patients with moderate pain (P < .01), but in 26% of patients with severe pain we did not record any improvement in disability (P > .05). In conclusion we evaluated the role of um-PEA in patients with lumbar radiculopathy with a long-term follow-up (24 months) and put in evidence the effectiveness and the safety of this formulation in patients with mild and moderate pain.


Assuntos
Etanolaminas/uso terapêutico , Neuralgia/tratamento farmacológico , Ácidos Palmíticos/uso terapêutico , Radiculopatia/tratamento farmacológico , Acetaminofen/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Codeína/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego
20.
J Ocul Pharmacol Ther ; 33(9): 670-677, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29045169

RESUMO

PURPOSE: Chronic use of topical hypotensive therapies in glaucoma patients leads to chronic inflammation of the ocular surface, which decreases the success rate of long-term glaucoma management. The aim of this study is to evaluate the effect of topical palmitoylethanolamide (PEA) (Defluxa©), a well-known anti-inflammatory and analgesic agent, in suppressing the ocular surface inflammation associated with the use of hypotensive eye drops. METHODS: In a pilot clinical trial, we enrolled 15 glaucomatous patients who received topical PEA (Defluxa) in addition to the current antiglaucoma drugs, while 15 glaucomatous patients did not receive any additional treatment. At 3 different time points (day 0, 15, and 30), signs of ocular surface involvement, adverse events, visual acuity, and intraocular pressure were assessed. RESULTS: Topical PEA (Defluxa) was effective in increasing the Schirmer test (P < 0.05) and the tear film breakup time (T-BUT) (P < 0.0001), and improving the conjunctival hyperemia (P < 0.0001) by day 30, compared to baseline. Compared to control, by day 15, the conjunctival hyperemia score was significantly decreased in the PEA (Defluxa) group (P < 0.01), while the T-BUT and the Schirmer Test achieved a significant improvement by day 30 (P < 0.05; P < 0.01). DISCUSSION: Our data suggests that topical PEA (Defluxa) is a safe, effective, and generally well-tolerated treatment to prevent or suppress ocular surface inflammation attributable to chronic glaucoma treatment.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Doenças da Túnica Conjuntiva/tratamento farmacológico , Etanolaminas/uso terapêutico , Glaucoma/tratamento farmacológico , Hiperemia/tratamento farmacológico , Ácidos Palmíticos/uso terapêutico , Administração Oftálmica , Idoso , Analgésicos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Doenças da Túnica Conjuntiva/induzido quimicamente , Doenças da Túnica Conjuntiva/metabolismo , Etanolaminas/administração & dosagem , Feminino , Humanos , Hiperemia/induzido quimicamente , Hiperemia/metabolismo , Pressão Intraocular/efeitos dos fármacos , Masculino , Soluções Oftálmicas , Ácidos Palmíticos/administração & dosagem , Estudos Prospectivos , Método Simples-Cego , Lágrimas/metabolismo , Acuidade Visual/efeitos dos fármacos
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