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1.
Int J Mol Sci ; 22(4)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671213

RESUMO

Palmitoylethanolamide (PEA), a fatty acid amide, has been widely investigated for its analgesic and anti-inflammatory properties. The ultra-micronized formulation of PEA (um-PEA), that has an enhanced rate of dissolution, is extensively used. Acetyl-l-carnitine (LAC), employed for the treatment of neuropathic pain in humans, is able to cause analgesia by up-regulating type-2 metabotropic glutamate (mGlu2) receptors. In the present study, we tested different associations of um-PEA, LAC and non-micronized PEA (non-m-PEA) in a rat model of carrageenan (CAR)-induced paw edema. Intraplantar injection of CAR into the hind paw of animals caused edema, thermal hyperalgesia, accumulation of infiltrating inflammatory cells and augmented myeloperoxidase (MPO) activity. All these parameters were decreased in a significantly manner by oral administration of a compound constituted by a mixture of um-PEA and LAC in relation 1:1 (5 mg/kg), but not with the association of single compounds administered one after the other. These findings showed the superior anti-inflammatory and anti-nociceptive action displayed by oral administration of um-PEA and LAC versus LAC plus, separate but consecutive, um-PEA in the rat paw CAR model of inflammatory pain.


Assuntos
Acetilcarnitina/uso terapêutico , Amidas/uso terapêutico , Etanolaminas/uso terapêutico , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Ácidos Palmíticos/uso terapêutico , Acetilcarnitina/farmacologia , Amidas/farmacologia , Animais , Carragenina , Contagem de Células , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Edema/complicações , Edema/tratamento farmacológico , Edema/patologia , Etanolaminas/farmacologia , Hiperalgesia/complicações , Hiperalgesia/tratamento farmacológico , Inflamação/complicações , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Dor/complicações , Dor/patologia , Ácidos Palmíticos/farmacologia , Peroxidase/metabolismo , Ratos Sprague-Dawley , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo
2.
Pain Res Manag ; 2020: 3938640, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32377286

RESUMO

Background: Palmitoylethanolamide (PEA) is emerging as a new therapeutic approach in pain and inflammatory conditions, and it has been evaluated in studies on various painful diseases. The aim of this open-label study was to evaluate the efficacy of ultramicronized PEA (umPEA) in the prophylactic treatment of migraine. Methods: The study included 70 patients with mean age of 10.3 ± 2.7 (24.5% M and 75.5% F). All patients had a diagnosis of migraine without aura (ICHD 3 criteria) and received umPEA (600 mg/day orally) for three months. We compared the attack frequency (AF) and attack intensity at baseline and after three months. Patients were asked to classify the intensity of the attack with a value ranging from 1 to 3, where 1 means mild attack, 2 moderate, and 3 severe attack. Results: Nine patients discontinued treatment before the target time of 12 weeks. After 3 months of treatment with umPEA, the headache frequency was reduced by >50% per month in 63.9% patients. The number of monthly attacks at T 1 decreased significantly compared with the baseline assessment (from 13.9 ± 7.5 SD of T 0 to 6.5 ± 5.9 SD of T 1; p < 0.001). The mean intensity of the attacks dropped from 1.67 ± 0.6 (T 0) to 1.16 ± 0.5 (T 1) (p < 0.001), and the percentage of patients with severe attacks decreased after treatment (from 8.2% to 1.6%; p < 0.05). The monthly assumptions of drugs for the attack reduced from 9.5 ± 4.4 to 4.9 ± 2.5 (p < 0.001). Only one patient developed mild side effects (nausea and floating). Conclusions: Our preliminary data show that umPEA administered for three month reduces pain intensity and the number of attacks per month in pediatric patients with migraine. Although the small number of patients and the lack of control group do not allow us to consider these initial results as definitely reliable, they encourage us to expand the sample.


Assuntos
Analgésicos/uso terapêutico , Etanolaminas/uso terapêutico , Transtornos de Enxaqueca/prevenção & controle , Ácidos Palmíticos/uso terapêutico , Amidas , Criança , Feminino , Humanos , Masculino , Projetos Piloto , Resultado do Tratamento
3.
Invest Ophthalmol Vis Sci ; 61(4): 15, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32298438

RESUMO

Purpose: Pathological neovascularization and fibrosis are common pathological changes of many retinal diseases, such as proliferative retinopathy (PR) and age-related macular degeneration (AMD). Treatment modalities for these pathological changes are limited. The purpose of the present study was to test the effects of palmitoylethanolamide (PEA), an endocannabinoid mimetic amide, on retinal neovascularization and fibrosis and to determine its molecular mechanism of action. Methods: A rat Müller cell line (rMC-1), a mouse model of oxygen-induced retinopathy (OIR), and the very-low-density lipoprotein receptor (VLDLR) knockout mouse model were used. PEA was intraperitoneally injected or orally administrated in animal models. Inflammation and profibrotic changes were evaluated by western blot analysis. Glial fibrillary acidic protein (GFAP) and peroxisome proliferator-activated receptor alpha (PPARα) were measured by RT-PCR and western blot analysis. Results: Profibrotic changes were present in OIR and Vldlr-/- retinas. PEA significantly alleviated inflammation and inhibited neovascularization in OIR and Vldlr-/- retinas and suppressed profibrotic changes in OIR and Vldlr-/- retinas. Moreover, PEA potently suppressed Müller gliosis in these retinas. In rMC-1 cells, PEA suppressed Müller gliosis, reduced inflammatory cytokines, and attenuated profibrotic changes. Further, both mRNA and protein levels of PPARα were elevated in the retina under PEA treatment, and the effects of PEA were abolished in Pparα-/- OIR mice. Conclusions: PEA reduced retinal neovascularization and fibrotic changes and suppressed Müller gliosis in experimental PR and neovascular AMD by activating PPARα. PEA may be a potential treatment for retinopathies with pathological neovascularization and fibrosis.


Assuntos
Agonistas de Receptores de Canabinoides/uso terapêutico , Etanolaminas/uso terapêutico , Gliose/tratamento farmacológico , PPAR alfa/metabolismo , Ácidos Palmíticos/uso terapêutico , Retina/patologia , Neovascularização Retiniana/tratamento farmacológico , Administração Oral , Amidas , Animais , Western Blotting , Linhagem Celular , Modelos Animais de Doenças , Células Ependimogliais/efeitos dos fármacos , Fibrose/tratamento farmacológico , Fibrose/metabolismo , Fibrose/patologia , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/metabolismo , Gliose/patologia , Marcação In Situ das Extremidades Cortadas , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxigênio/toxicidade , PPAR alfa/genética , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Receptores de LDL/genética , Retina/metabolismo , Neovascularização Retiniana/induzido quimicamente , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologia
4.
J Orthop Traumatol ; 21(1): 1, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31993783

RESUMO

BACKGROUND: The placebo effect can account for part of the improvement seen in patients undergoing any type of treatment, be it surgical or pharmacological. The objective of this study is to quantify the placebo effect in carpal tunnel syndrome treatment. MATERIALS AND METHODS: A double-blinded randomized trial was performed with 68 patients suffering from mild to moderate carpal tunnel syndrome, divided into two groups with no statistically significant differences regarding age, weight, or degree of nerve compression. The patients were evaluated clinically and electromyographically before and after 2 months of treatment with either palmitoylethanolamide (PEA) or placebo. RESULTS: The results, comparing the two groups, showed an improvement in both groups on a visual analogue scale (VAS) and Levine's questionnaire, which have been reported to show statistical differences in only a few items. In the placebo group, the mean age was 53.32 years (±13.43) and the BMI was 28.85 kg/m2 (±4.84). Before treatment, the average symptom severity score (SSS) on the Levine questionnaire was 2.57 (±0.74) and the functional status score (FSS) was 2.24 (±0.66). After treatment, these decreased to 2.11 (±0.81) and 1.96 (±0.77), being statistically nonsignificant for SSS (p = 0.0865) but significant for FSS (p = 0.0028). VAS showed a statistically nonsignificant decrease from 4.06 to 3.25 (p = 0.3407). After placebo treatment, SSS, FSS, and VAS improved by 0.46, 0.28, and 0.81 points or 17.89%, 12.5%, and 19.95%, respectively. CONCLUSIONS: These results show an improvement in the studied parameters by up to 20%, but when compared with those published in literature, these show great variability due to the wide variety of factors involved in the placebo effect. Several factors that affect the placebo effect are discussed, and the present work tries to quantify it in carpal tunnel syndrome. LEVEL OF EVIDENCE: Level 2 of evidence according to "The Oxford 2011 Level of Evidence."


Assuntos
Síndrome do Túnel Carpal/tratamento farmacológico , Etanolaminas/uso terapêutico , Ácidos Palmíticos/uso terapêutico , Adolescente , Adulto , Idoso , Amidas , Anti-Inflamatórios não Esteroides/uso terapêutico , Síndrome do Túnel Carpal/diagnóstico , Método Duplo-Cego , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Efeito Placebo , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
5.
Mol Neurobiol ; 57(2): 860-878, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31506900

RESUMO

Chronic relapsing experimental allergic encephalomyelitis (CR-EAE) exhibits neuropathological and immunological dysfunctions similar to those found in multiple sclerosis (MS) and has been used as an animal model of MS. Inflammatory infiltrates and oxidative stress have been linked to the development of both diseases. Ethanolamine plasmalogen derivates have been shown to be powerful antioxidants and immunomodulators. Therefore, the objective of this study was to analyse inflammatory infiltrates, the state of the oxidative defences and the possible protective effects of calcium, magnesium and phosphate ethanolamine (EAP) in the CR-EAE rat hippocampus. To this aim, we evaluated, by immunohistochemistry, T cell infiltrates, Iba-1+ (a marker of activated microglia) immunoreactivity and TUNEL (+) cells. We also measured the protein levels and activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GP) and glutathione reductase (GR). In addition, reduced (GSH) and oxidized (GSSG) glutathione levels, lipid peroxidation and cholesterol as well as desmosterol content were determined. We found an increase in T cell infiltrates and Iba1+ immunoreactivity, lipid peroxidation, SOD, GP and GR activities as well as enhanced cholesterol levels and a decrease in CAT activity, GSH and desmosterol levels in the first and second attack in the CR-EAE rat hippocampus. Pretreatment of CR-EAE rats with EAP led to a delay in the onset of the clinical signs of the disease as well as a decrease in inflammatory infiltrates and alterations of the antioxidant defences in the hippocampus. Altogether, the present results suggest a protective role of EAP in the CR-EAE rat hippocampus.


Assuntos
Encefalomielite Autoimune Experimental/imunologia , Etanolaminas/uso terapêutico , Hipocampo/patologia , Hipersensibilidade/imunologia , Linfócitos/patologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Animais , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Complexo CD3/metabolismo , Catalase/metabolismo , Doença Crônica , Encefalomielite Autoimune Experimental/enzimologia , Encefalomielite Autoimune Experimental/patologia , Etanolaminas/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Hipersensibilidade/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Endogâmicos Lew , Ratos Wistar , Recidiva , Esteróis/metabolismo , Superóxido Dismutase/metabolismo , Fatores de Tempo
6.
Ann Parasitol ; 66(4): 561-571, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33789028

RESUMO

The purpose of this study was to update efficacy data of Artesunate-Amodiaquine (AS+AQ) and Artemether-Lumefantrine (AL) used as first-line malaria treatment in Côte d'Ivoire since 2005. This was an open-label, randomized trial conducted in patients older than 6 months with uncomplicated P. falciparum malaria at six sentinel sites. The WHO 2009 protocol on surveillance of anti-malaria drug efficacy was used with primary outcomes as ACPR corrected by PCR at day 42. Secondary endpoints were parasite and fever clearance times and safety. From January to July 2016, 712 patients were included in the trial. 353 and 359 patients were randomly assigned respectively to the AS+AQ and AL arm. Day 42 PCR-adjusted ACPR in the per-protocol analysis was 99.4% and 98.8% in AS+AQ and AL arm respectively. Delayed parasite clearance was observed in six patients at Abidjan and Yamousssoukro sites. Both ACTs were well tolerated. Both ACTs remain efficacious for uncomplicated P. falciparum malaria treatment in Côte d'Ivoire. But regarding delayed parasite clearance observed in this study, a close monitoring and supervision for ACT resistance are essential for future malaria treatment and control strategies in Côte d'Ivoire.


Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Malária , Amodiaquina/uso terapêutico , Antimaláricos/uso terapêutico , Artemeter/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Costa do Marfim/epidemiologia , Combinação de Medicamentos , Etanolaminas/uso terapêutico , Fluorenos/uso terapêutico , Humanos , Lactente , Malária/tratamento farmacológico , Malária/epidemiologia , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Resultado do Tratamento
7.
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 , Dieta Saudável , Suplementos Nutricionais , Etanolaminas/uso terapêutico , Inflamação/prevenção & controle , Ácidos Palmíticos/uso terapêutico , Amidas , 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
8.
CNS Neurol Disord Drug Targets ; 18(6): 491-495, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31269891

RESUMO

BACKGROUND: Despite being widely prescribed, relatively few controlled trials have been conducted on the class of neurotrophic/antinociceptive nutraceuticals. While performing a search in the literature, we came across an old registration study on micronized palmitoylethanolamide in patients with low back pain - sciatica by Guida and colleagues. METHODS: We contacted the authors of the article and obtained all the original material, which allowed us to reanalyze the study. We assessed its clinical relevance by calculating the numbers needed to treat for pain (visual analog scale) and function (Roland-Morris Questionnaire). After excluding patients for whom the information available was insufficient, we assigned each patient to one of the five categories of increasing probability of neuropathic pain: pure lumbago, lumbago with projecting pain to surrounding regions (e.g. gluteus or groin), lumbago with projecting pain to the thigh or leg, pure sciatica and radiculopathy, and investigated any correlations (Spearman) between the improvement in pain and function with these five classes. RESULTS: Compared with placebo, palmitoylethanolamide 600 mg/die yielded a number needed to treat of 1.7 (95% confidence interval: 1.4-2) for pain, and 1.5 (95% confidence interval: 1.4-1.7) for function. The correlation between the five categories was highly significant for pain relief (P <0.0001), though not significant for reduced dysfunction. CONCLUSION: Palmitoylethanolamide was extremely effective on pain and function in a large cohort of patients with low back pain - sciatica. Although, the multiple mechanisms of action of palmitoylethanolamide are ideal for mixed pain conditions such as low back pain - sciatica, the correlation between pain relief and the likelihood of neuropathic pain suggests that this drug exerts a predominant action on the neuropathic pain component.


Assuntos
Etanolaminas/uso terapêutico , Dor Lombar/tratamento farmacológico , Neuralgia/tratamento farmacológico , Medição da Dor , Ácidos Palmíticos/uso terapêutico , Ciática/tratamento farmacológico , Adulto , Amidas , Estudos de Coortes , Feminino , Humanos , Dor Lombar/complicações , Masculino , Pessoa de Meia-Idade , Ciática/complicações , Inquéritos e Questionários
9.
CNS Neurol Disord Drug Targets ; 18(7): 530-554, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244434

RESUMO

BACKGROUND: Delirium is a disorder in awareness, attention and cognition. Pathophysiologically it is a response to stress. Postoperative delirium (POD) is a usual complication in aged patients following hip fracture surgery. Neuroinflammation is an important factor linked with the progress of POD. Though there are no efficient cures for delirium the endocannabinoid system may have a role in neuropsychiatric disorders. OBJECTIVE: Therefore, we examined the effects of co-ultramicronized PEALut (co-ultraPEALut) in the LPS murine model of delirium and in elderly hip fractured patients. METHODS: In the preclinical study, mice were injected intraperitoneally (i.p.) with Escherichia coli LPS (10 mg/kg). Co-ultraPEALut (1 mg/kg o.s.) was administered 1h before LPS injection or 1h and 6h after LPS injection or 1h before LPS injection and 1h and 6h after LPS. In the clinical study, the effects of Glialia® (co-ultramicronized 700 mg PEA + 70 mg luteolin) administration was evaluated in elderly hip fractured patients with an interventional, randomized, single-blind, monocentric study. RESULTS: Administration of co-ultraPEALut to LPS-challenged mice ameliorated cognitive dysfunctions and locomotor activity; moreover, it reduced inflammation and apoptosis, while stimulating antioxidant response and limiting the loss of neurotrophins. In the clinical study, the results obtained demonstrated that administration of Glialia® to these surgical patients prevented the onset of POD and attenuated symptom intensity and their duration. CONCLUSION: Therefore, the results obtained enhanced the idea that co-ultraPEALut may be a potential treatment to control cognitive impairment and the inflammatory and oxidative processes associated with delirium.


Assuntos
Delírio/tratamento farmacológico , Etanolaminas/farmacologia , Etanolaminas/uso terapêutico , Luteolina/farmacologia , Luteolina/uso terapêutico , Psicotrópicos/farmacologia , Psicotrópicos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Animais , Disfunção Cognitiva/tratamento farmacológico , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Feminino , Fraturas do Quadril , Humanos , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Método Simples-Cego , Resultado do Tratamento
10.
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 , Amidas , 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
11.
Neurourol Urodyn ; 38(5): 1229-1240, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30937955

RESUMO

AIMS: The cardiotoxic effects of antimuscarinics constitute a significant restriction in their application in elderly people. Overactive bladder syndrome pharmacotherapy using compounds with cardioprotective properties would seem an ideal solution. The main goal of the study was to assess the impacts of nebivolol (NEB) on the activity of BRL 37344 - ß3-adrenergic receptor (ß3AR) agonist, in the animal model of detrusor overactivity. As both these substances can impact on the cardiovascular system, their effect on the parameters of this system and diuresis was also examined. METHODS: Retinyl acetate (RA; 0.75%) solution was used to induce detrusor overactivity in female Wistar rats. BRL and/or NEB were administered intra-arterially during cystometry in a single dose (2.5 or 5, 0.05 or 0.1 mg/kg, respectively). In addition, a 24 hours measurement of heart rate, blood pressure, and urine production was carried out. RESULTS: NEB (0.05 mg/kg) and BRL (2.5 mg/kg) monotherapy proved to have no influence on the cystometric parameters of animals with RA-induced detrusor overactivity. NEB at 0.1 mg/kg resulted in a drop in the detrusor overactivity index, similarly to BRL at 5 mg/kg. Coadministration of NEB and BRL, both at ineffective doses, decreased the detrusor overactivity index and ameliorated the nonvoiding contractions. ß3AR stimulation proved to induce tachycardia and hypertension. NEB at 0.05 mg/kg proved to ameliorate detrusor overactivity and have preventive properties against adverse cardiovascular effects of the ß3AR agonist. CONCLUSIONS: The combined application of the ß3AR agonist and NEB may improve detrusor overactivity without affecting the heart rate, blood pressure, and urine production.


Assuntos
Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Etanolaminas/uso terapêutico , Nebivolol/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Animais , Pressão Arterial/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Diterpenos , Diurese/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Infusões Intra-Arteriais , Ratos , Ratos Wistar , Bexiga Urinária Hiperativa/prevenção & controle , Urodinâmica/efeitos dos fármacos , Vitamina A/análogos & derivados
12.
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 , Amidas , 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
13.
J Biomater Appl ; 33(10): 1434-1443, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30935278

RESUMO

Many studies have reported that silver has excellent antibacterial properties. However, silver ions can easily react with oxygen to form Ag2O, thus leading to a color change and a reduction in its anti-microbial characteristics. In this study, silver triethanolamine- (ST) loaded PVB/CO solution was prepared as a potential candidate liquid bandage. PVB/CO/ST retained high transparency after exposure to light for 12 months, which allowed convenient inspection of the wound bed without removal of the dressing. The PVB/CO/ST film exhibited favorable properties, such as speed of drying, excellent tensile strength and elongation characteristics and water vapor transmission rate (WVTR). It was comfortable and waterproof, and therefore effective at preventing bacterial invasion, providing effective biosafety. PVB/CO/ST solution-treated wounds exhibited accelerated healing and reduced inflammation in a nude mouse mode. Our data suggested that PVB/CO/ST solution could serve as a promising liquid bandage for treatment of minor trauma.


Assuntos
Antibacterianos/administração & dosagem , Bandagens , Etanolaminas/administração & dosagem , Polivinil/química , Prata/administração & dosagem , Animais , Antibacterianos/uso terapêutico , Materiais Biocompatíveis/química , Óleo de Rícino/química , Sistemas de Liberação de Medicamentos , Etanolaminas/uso terapêutico , Camundongos Nus , Prata/uso terapêutico , Vapor , Resistência à Tração , Cicatrização/efeitos dos fármacos
14.
Endocrine ; 66(2): 178-184, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30949911

RESUMO

PURPOSE: To evaluate the effect of oral alpha-lipoic acid (ALA) ± palmitoyl-ethanolamide (PEA) on neuropathic symptoms in patients with diabetic peripheral neuropathy (DPN) and to identify factors related to the efficacy of the treatment. METHODS: This is a retrospective observational pilot study evaluating 49 patients with diabetes and positive Neuropathy Symptoms Score (NSS). Clinical and biochemical variables, including NSS, were compared between untreated patients and patients treated with oral 600 mg/day ALA ± 600 mg/day PEA at baseline (first occurrence of NSS ≥ 3) and at least 2 months after baseline. Number of days between treatment initiation and symptoms' relief and related factors were also investigated. RESULTS: Thirty subjects were treated with ALA ± PEA and 19 subjects did not receive any specific treatment for neuropathy symptoms. Follow-up visits occurred after 98 ± 46 days. NSS significantly decreased in patients treated with ALA ± PEA (5.4 ± 1.3 at baseline vs. 1.7 ± 2.4 at follow-up, p < 0.001), but not in untreated patients (p = 0.164). Subjects treated with ALA ± PEA reported a mean time from treatment initiation to symptoms' relief of 18.4 ± 9.0 days. The number of days of treatment needed for symptoms' relief was inversely related to HDL-cholesterol levels (r = -0.503, p = 0.010) and to eGFR (r = -0.428, p = 0.033), whereas there was no significant relationship between time to symptoms' relief and age, HbA1c, lipid profile and the severity of symptoms at baseline. CONCLUSIONS: This study documents that oral administration of ALA ± PEA helps in controlling neuropathy symptoms in diabetes. Moreover, our data show that higher HDL-c levels and better renal function are associated to a faster therapeutic effect, suggesting them as biomarkers of response to therapy with ALA ± PEA.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Neuropatias Diabéticas/tratamento farmacológico , Etanolaminas/uso terapêutico , Ácidos Palmíticos/uso terapêutico , Ácido Tióctico/uso terapêutico , Triglicerídeos/sangue , Adulto , Idoso , Amidas , Biomarcadores/sangue , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
15.
Drug Metab Dispos ; 47(6): 567-573, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30952677

RESUMO

Rolapitant [(Varubi), 5S,8S)-8-[[(1R)-1-[3,5 bis(trifluoromethyl phenyl]ethoxy]methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one] is a high-affinity NK1 receptor antagonist that was approved in September 2015 as a treatment for nausea and vomiting caused by chemotherapy. In vivo rolapitant moderately inhibits CYP2D6 for at least 7 days after one 180 mg dose. Due to the long inhibition time, we investigated rolapitant as a possible mechanism-based inactivator of CYP2D6. Rolapitant docked in the active site of CYP2D6 and displayed type I binding to CYP2D6 with a K s value of 1.2 ± 0.4 µM. However, in NADPH-, time-, and concentration-dependent assays of CYP2D6 activity, no evidence for mechanism-based inactivation and no metabolites of rolapitant were observed. Stopped-flow binding studies yielded a kon /koff (K d) value of 6.2 µM. The IC50 value for rolapitant inhibition of CYP2D6 activity was 24 µM, suggesting that inhibition is not due to tight binding of rolapitant to CYP2D6. By Lineweaver-Burk analysis, rolapitant behaved as a mixed, reversible inhibitor. The K i values of 20 and 34 µM were determined by Dixon analysis, with bufuralol and dextromethorphan as reporter substrates, respectively, and drug-drug interaction modeling did not predict the reported in vivo inhibition. The interaction of rolapitant with CYP2D6 was also examined in 1 microsecond molecular dynamics simulations. Rolapitant adopted multiple low-energy binding conformations near the active site, but at distances not consistent with metabolism. Given these findings, we do not see evidence that rolapitant is a mechanism-based inactivator. Moreover, the reversible inhibition of CYP2D6 by rolapitant may not fully account for the moderate inhibition described in vivo.


Assuntos
Inibidores do Citocromo P-450 CYP2D6/uso terapêutico , Citocromo P-450 CYP2D6/metabolismo , Compostos de Espiro/uso terapêutico , Domínio Catalítico/fisiologia , Dextrometorfano/uso terapêutico , Interações Medicamentosas/fisiologia , Etanolaminas/uso terapêutico , Humanos
16.
CNS Neurol Disord Drug Targets ; 18(4): 326-333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30827269

RESUMO

BACKGROUND: Fibromyalgia syndrome is a chronic multifaceted disease characterized by widespread pain, muscle stiffness, fatigue, unrefreshing sleep and cognitive disorders. To date, no medication has been shown to significantly improve pain, associated symptoms and Quality of Life in fibromyalgic patients. METHODS: In this retrospective observational study, we analyzed data regarding 407 patients with diagnosis of fibromyalgia syndrome who between 2013 and 2016 have been prescribed orally ultramicronized palmitoylethanolamide tablets (Normast® Epitech Group SpA, Saccolongo, Italy) regardless of the concomitant pharmacological therapy (add-on treatment). RESULTS: Regarding efficacy, in the 359 analyzed patients, the change over time in Visual Analogue Scale pain score was statistically significant, ranging from 75.84 (±15.15) to 52.49 (±16.73) (p<0.001). Regarding quality of life, the change over time in Fibromyalgia Impact Questionnaire score was statistically significant, ranging from 68.4 (±14.1) to 49.1 (±19.6) (p<0.001). In the treated population, only 36 patients (13,7%) reported Adverse Events predominantly of gastrointestinal type (diarrhea, dyspepsia, bloating, constipation, vomiting). Globally, 151 patients (57,63%) left the treatment due to inefficacy. CONCLUSION: The results of ultramicronized palmitoylethanolamide treatment in this retrospective analysis represent an important step for the development of a new and well-tolerated therapy for fibromyalgia syndrome, mostly suitable for these patients who need long-term treatments. Further methodologically stronger studies will be necessary to validate our observation.


Assuntos
Etanolaminas/uso terapêutico , Fibromialgia/tratamento farmacológico , Ácidos Palmíticos/uso terapêutico , Adulto , Amidas , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
17.
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 , Amidas , 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
18.
J Am Acad Dermatol ; 81(2): 558-567, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30802561

RESUMO

Radiation dermatitis is a common sequela of radiation therapy; up to 95% of patients will develop moderate-to-severe skin reactions. No criterion standard currently exists for the treatment of acute radiation-induced skin toxicity. It is therefore imperative to develop a greater understanding of management options available to allow clinicians to make informed decisions when managing radiation oncology patients. This literature review discusses the topical agents that have been studied for the treatment of acute radiation dermatitis, reviews their mechanisms of action, and presents a treatment algorithm for clinicians managing patients experiencing radiation dermatitis.


Assuntos
Algoritmos , Fármacos Dermatológicos/uso terapêutico , Radiodermatite/tratamento farmacológico , Doença Aguda , Corticosteroides/uso terapêutico , Anti-Infecciosos Locais/uso terapêutico , Bandagens , Produtos Biológicos/uso terapêutico , Etanolaminas/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Preparações de Plantas/uso terapêutico , Radiodermatite/etiologia , Radioterapia/efeitos adversos , Sulfadiazina de Prata/uso terapêutico , Sucralfato/uso terapêutico , Vitaminas/uso terapêutico
19.
Biochem Biophys Res Commun ; 511(3): 504-509, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30803757

RESUMO

The anti-metastatic effects of cationic liposomes (CL) composed of 87 mol% dimyristoylphosphatidylcholine (DMPC), 8 mol% O,O'-ditetradecanoyl-N-(α-trimethylammonioacetyl) diethanolamine chloride (2C14ECl) and 5 mol% polyoxyethylene(21) dodecyl ether (C12(EO)21) was investigated for human pancreatic cancer (BxPC-3) cells. The inhibitory effect of CL on the migration of BxPC-3 cells was observed based on a wound scratch assay. CL suppressed pseudopodium formation of BxPC-3 cells. The anti-invasive effect of CL against BxPC-3 cells was observed via a Matrigel invasion assay. The anti-invasive effect of CL for BxPC-3 cells was found to occur through the inhibition of MMP2, MMP9, and MMP14. Overall, the results of this study revealed for the first time, the therapeutic effects and anti-metastasis activity of CL in xenograft mouse models for peritoneal metastasis of human pancreatic cancer.


Assuntos
Dimiristoilfosfatidilcolina/uso terapêutico , Etanolaminas/uso terapêutico , Etilaminas/uso terapêutico , Lipossomos/uso terapêutico , Invasividade Neoplásica/prevenção & controle , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Cátions/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica/patologia , Neoplasias Pancreáticas/patologia
20.
CNS Neurol Disord Drug Targets ; 18(3): 232-238, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30706796

RESUMO

BACKGROUND: The cannabinoid system may be involved in the humoral mechanisms at the neuromuscular junction. Ultramicronized-palmitoylethanolamide (µm-PEA) has recently been shown to reduce the desensitization of Acetylcholine (ACh)-evoked currents in denervated patients modifying the stability of ACh receptor (AChR) function. OBJECTIVE: To analyze the possible beneficial effects of µm-PEA in patients with myasthenia gravis (MG) on muscular fatigue and neurophysiological changes. METHOD: The duration of this open pilot study, which included an intra-individual control, was three weeks. Each patient was assigned to a 1-week treatment period with µm-PEA 600 mg twice a day. A neurophysiological examination based on repetitive nerve stimulation (RNS) of the masseteric and the axillary nerves was performed, and the quantitative MG (QMG) score was calculated in 22 MG patients every week in a three-week follow-up period. AChR antibody titer was investigated to analyze a possible immunomodulatory effect of PEA in MG patients. RESULTS: PEA had a significant effect on the QMG score (p=0.03418) and on RNS of the masseteric nerve (p=0.01763), thus indicating that PEA reduces the level of disability and decremental muscle response. Antibody titers did not change significantly after treatment. CONCLUSION: According to our observations, µm-PEA as an add-on therapy could improve muscular response to fatigue in MG. The possible modulation of AChR currents as a means of eliciting a direct effect from PEA on the conformation of ACh receptors should be investigated. The co-role of cytokines also warrants an analysis. Given the rapidity and reversibility of the response, we suppose that PEA acts directly on AChR, though further studies are needed to confirm this hypothesis.


Assuntos
Agonistas de Receptores de Canabinoides/uso terapêutico , Etanolaminas/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Ácidos Palmíticos/uso terapêutico , Amidas , Fadiga/tratamento farmacológico , Fadiga/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/fisiopatologia , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/fisiopatologia , Projetos Piloto , Resultado do Tratamento
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