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1.
Life Sci ; 250: 117585, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32243928

RESUMO

AIMS: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been associated with risk factors for metabolic syndrome (MetS). Our objective was to evaluate the effect of nicotinamide (NAM) on the activities, expression and protein content of cholinesterases in a MetS model. MAIN METHODS: MetS was induced in male rats administrating 40% fructose to the drinking water for 16 weeks. Additionally, from 5th week onward, the carbohydrate solution was replaced by NAM, at several concentrations for 5 h each morning for the next 12 weeks. In the 15th week, the glucose tolerance test was conducted, and blood pressure was measured. After the treatment period had concluded, the biochemical profile; oxidant stress; proinflammatory markers; and the activity, quantity and expression of cholinesterases were evaluated, and molecular docking analysis was performed. KEY FINDINGS: The MetS group showed anthropometric, hemodynamic and biochemical alterations and increased cholinesterase activity, inflammation and stress markers. In the liver, cholinesterase activity and mRNA, free fatty acid, tumor necrosis factor-alpha (TNF-α), and thiobarbituric acid-reactive substance (TBARS) levels were increased, while reduced glutathione (GSH) levels were decreased. NAM partially or totally decreased risk factors for MetS, markers of stress and inflammation, and the activity (serum and liver) and expression (liver) of cholinesterases. Molecular docking analysis showed that NAM has a greater affinity for cholinesterases than acetylcholine (ACh), suggesting NAM as an inhibitor of cholinesterases. SIGNIFICANCE: Supplementation with 40% fructose induced MetS, which increased the activity and expression of cholinesterases, oxidative stress and the inflammation. NAM attenuated these MetS-induced alterations and changes in cholinesterases.


Assuntos
Inflamação/metabolismo , Síndrome Metabólica/tratamento farmacológico , Niacinamida/uso terapêutico , Estresse Oxidativo , Receptores Colinérgicos/metabolismo , Acetilcolinesterase/metabolismo , Animais , Antropometria , Anti-Inflamatórios/uso terapêutico , Arildialquilfosfatase/metabolismo , Butirilcolinesterase/metabolismo , Colinesterases/metabolismo , Frutose , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Hemodinâmica , Humanos , Peroxidação de Lipídeos , Fígado/enzimologia , Masculino , Síndrome Metabólica/induzido quimicamente , Simulação de Acoplamento Molecular , Ratos , Ratos Sprague-Dawley
2.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(3. Vyp. 2): 49-53, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32307430

RESUMO

AIM: To evaluate the efficacy of including cytoflavin in rehabilitation measures in the early recovery period of patients with ischemic stroke. MATERIAL AND METHODS: Results of rehabilitation measures of 100 patients (50 women and 50 men, aged 18 to 85 years) in the early recovery period of ischemic stroke were analyzed. Psychological testing included NIHSS, MMSE, Rankin scale, Rivermead mobility index, exercise tolerance test. Depending on the rehabilitation scheme, patients were divided into the main group (n=50), who received a verticalization course and cytoflavin (intravenously, drip 20.0 ml in 250.0 ml 5% glucose for 14 days). The control group (n=50) included patients who received standard treatment. RESULTS AND CONCLUSION: Inclusion of cytoflavin in the rehabilitation scheme for patients with ischemic stroke increased the effectiveness of treatment, which was manifested by a decrease in the severity of neurological disorders assessed with NIHSS by 17.6% in the main group versus 10.8% in the control group (p<0.05) and recovery of cognitive functions assessed with MMSE by 5.8% versus 1.6%, respectively (p<0.05). In addition, there was a positive dynamics in the restoration of blood pressure (by 37.1% in the main group versus 30.6% in the control group (p<0.05)).


Assuntos
Isquemia Encefálica/terapia , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Cognição/efeitos dos fármacos , Combinação de Medicamentos , Feminino , Mononucleotídeo de Flavina/administração & dosagem , Mononucleotídeo de Flavina/farmacologia , Mononucleotídeo de Flavina/uso terapêutico , Humanos , Inosina Difosfato/administração & dosagem , Inosina Difosfato/farmacologia , Inosina Difosfato/uso terapêutico , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Acidente Vascular Cerebral/metabolismo , Succinatos/administração & dosagem , Succinatos/farmacologia , Succinatos/uso terapêutico , Resultado do Tratamento , Adulto Jovem
3.
Chem Biol Interact ; 324: 109093, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32298659

RESUMO

Polycystic Ovary Syndrome (PCOS), as a common endocrine disorder is accompanied by hyperandrogenism, insulin resistance, ovulation problems, and infertility. Various types of off-label drugs like metformin have been used for the management of targeted problems caused by PCOS such as insulin resistance and hyperandrogenism. Nicotinamide (NAM) acts as a substrate of visfatin and Nicotinamide N-Methyltransferase (NNMT) leading to the generation of Nicotinamide Adenine Dinucleotide (NAD) and N1-Methylnicotinamide (MNAM), respectively. MNAM is known as an anti-inflammatory, anti-thrombosis, and anti-diabetic agent. In this study, the effects of NAM and MNAM on metabolic and endocrine abnormalities were evaluated in the adipose and ovarian tissues of a letrozole-induced rat model of PCOS. Our results showed that MNAM and NAM reversed abnormal estrous cycle and reduced the serum testosterone levels and CYP17A1 gene expression. Furthermore, all therapeutic factors improved HOMA-IR after treatment and NAM significantly increased the expression of GLUT4 and decreased the gene expression of visfatin. Also, MNAM diminished the gene expression of visfatin and resistin. It is noteworthy that all the therapeutic factors successfully activated the AMPK. In summary, this study is the first study reported beneficial effects of NAM and MNAM on the treatment of PCOS. Additionally, the alleviative effects of our therapeutic factors may be partially mediated by the AMPK-dependent manner due to the contribution of the AMPK in the expression of CYP17A1, visfatin, resistin, and GLUT4. Although more studies are required to unravel the exact mode of actions of MNAM and NAM in the PCOS, the findings of the current study shed light on an urgent need for discovering novel therapeutic pharmaceuticals regarding the treatment of PCOS.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Citocinas/genética , Citocinas/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hiperandrogenismo/tratamento farmacológico , Hormônio Luteinizante/metabolismo , Metformina/uso terapêutico , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Ratos Wistar , Resistina/genética , Resistina/metabolismo , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Testosterona/metabolismo
4.
Drugs Today (Barc) ; 56(2): 151-163, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32163530

RESUMO

Janus kinase (JAK) inhibitors are novel small molecules with a mechanism of action in multiple signaling pathways that allows their application in a broad spectrum of autoimmune and autoinflammatory diseases. As far as the field of dermatology is concerned, chronic plaque psoriasis is currently one of the most studied indications regarding the potential use of JAK inhibitors. The purpose of this review is to provide a summarized overview of the existing information on the efficacy and safety of JAK inhibitors in plaque psoriasis, with a focus on tofacitinib, ruxolitinib, baricitinib, peficitinib and filgotinib. Although the published data on the therapeutic benefit of these agents in the therapy of this chronic condition are promising, further prospective studies and real-life data are necessary in order to sufficiently evaluate their role as an adequate treatment option for psoriatic patients.


Assuntos
Inibidores de Janus Quinases/uso terapêutico , Psoríase/tratamento farmacológico , Adamantano/análogos & derivados , Adamantano/uso terapêutico , Azetidinas/uso terapêutico , Humanos , Janus Quinases , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Piperidinas/uso terapêutico , Estudos Prospectivos , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Triazóis/uso terapêutico
5.
Photochem Photobiol Sci ; 19(2): 171-179, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-31942903

RESUMO

Nicotinamide (NAM), an amide form of vitamin B3, replenishes cellular energy after ultraviolet radiation (UVR) exposure, thereby enhancing DNA repair and reducing UVR's immunosuppressive effects. NAM reduces actinic keratoses and new keratinocyte cancers in high risk individuals, but its effects on melanoma are unknown. Melanomas arising on NAM or placebo within the ONTRAC skin cancer chemoprevention trial (Oral Nicotinamide To Reduce Actinic Cancer) were examined by immunohistochemistry. The effects of NAM (50 µM, 5 mM and 20 mM) on the viability, proliferation and invasiveness of four human melanoma cell lines and on the viability and proliferation of two human melanocyte lines, with and without UV irradiation were also investigated. 50 µM NAM did not affect viability, proliferation or invasion of melanoma or melanocyte cell lines, whereas concentrations too high to be achievable in vivo reduced viability and proliferation. Nicotinamide did not enhance melanoma viability, proliferation or invasiveness in vitro, providing additional confidence in its safety for use in clinical trials in high risk patients. Peritumoral and tumour infiltrating CD4+ and CD8+ lymphocytes were significantly increased in melanomas arising on NAM compared to those arising on placebo. Given the chemopreventive activity of nicotinamide against keratinocyte cancers, its DNA repair enhancing effects in melanocytes and now its potential enhancement of tumour-infiltrating lymphocytes and lack of adverse effects on melanoma cell growth and proliferation, clinical trials of nicotinamide for melanoma chemoprevention are now indicated.


Assuntos
Melanoma/patologia , Niacinamida/farmacologia , Neoplasias Cutâneas/patologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Melanoma/tratamento farmacológico , Melanoma/prevenção & controle , Niacinamida/química , Niacinamida/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Raios Ultravioleta
6.
Gynecol Oncol ; 156(2): 301-307, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31870556

RESUMO

OBJECTIVE: To compare the combination of a MEK inhibitor (pimasertib) and a PI3K inhibitor (SAR245409) to pimasertib alone in recurrent unresectable borderline/low malignant potential (LMP) or low-grade serous ovarian carcinoma (LGSOC), determining whether combination is superior. METHODS: Patients with previously treated, recurrent LMP or LGSOC with measurable disease received either combination of pimasertib (60 mg daily) + SAR245409 (SAR) (70 mg daily) or pimasertib alone (60 mg BID) until progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR) by RECIST 1.1, determining whether combination was superior to pimasertib alone. Secondary endpoints included progression free survival (PFS), disease control, and adverse events. RESULTS: Sixty-five patients were randomized between September 2012 and December 2014. ORR was 9.4% (80% CI, 3.5 to 19.7) in the combination arm and 12.1% (80% CI, 5.4 to 22.8) in the pimasertib alone arm. Median PFS was 7.23 months (80% CI, 5.06 to -) and 9.99 (80% CI, 7.39 to 10.35) for pimasertib alone and pimasertib + SAR, respectively. Six-month PFS was 63.5% (80% CI, 47.2% to 75.9%) and 70.8% (80% CI, 56.9% to 80.9%). Eighteen (56.3%) patients in the combination arm and 19 (57.6%) patients in the pimasertib alone arm discontinued the trial. The study was terminated early because of low ORR and high rate of discontinuation. CONCLUSIONS: Response to pimasertib alone (ORR 12%) suggests that MEK inhibition could be used as an alternative treatment method to cytotoxic chemotherapy in this population. The MEK inhibitor alone was as effective as the combination, although the trial was limited by small numbers. Additional studies investigating the role of single agent or combination MEK and PI3K inhibition are warranted to further evaluate the utility of these treatments and describe a standard of care for LGSOC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Niacinamida/análogos & derivados , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/enzimologia , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , MAP Quinase Quinase 1/antagonistas & inibidores , MAP Quinase Quinase 1/metabolismo , MAP Quinase Quinase 2/antagonistas & inibidores , MAP Quinase Quinase 2/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/enzimologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Niacinamida/administração & dosagem , Niacinamida/uso terapêutico , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Quinoxalinas/administração & dosagem , Sulfonamidas/administração & dosagem , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Adulto Jovem
7.
Artigo em Russo | MEDLINE | ID: mdl-31851169

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Сytoflavin in the treatment of cognitive and emotional disorders in patients with tension headache. MATERIAL AND METHODS: Fifty patients with tension headache, aged from 18 to 50 years, were studied. The following methods and tests were used: neurological examination, NPRS, STAI, CFQ, RAVLT, TOVA, electroencephalography (routine and spectral analysis). The patients were treated with Сytoflavin. RESULTS: After the treatment, clinical improvement was observed in 62.0% of the patients. A significant decrease in trait anxiety and inattention, as well as an improvement of memory performance were observed. A comparative analysis of neurophysiological results before and after the treatment showed a decrease in the manifestations of dysfunction of nonspecific regulation of the brain. CONCLUSION: The results of this study demonstrate the efficacy of Cytoflavin in the treatment of tension headache and associated emotional and cognitive impairments.


Assuntos
Mononucleotídeo de Flavina , Inosina Difosfato , Transtornos do Humor , Niacinamida , Succinatos , Cefaleia do Tipo Tensional , Adolescente , Adulto , Ansiedade , Cognição , Combinação de Medicamentos , Mononucleotídeo de Flavina/uso terapêutico , Humanos , Inosina Difosfato/uso terapêutico , Pessoa de Meia-Idade , Transtornos do Humor/complicações , Transtornos do Humor/tratamento farmacológico , Niacinamida/uso terapêutico , Succinatos/uso terapêutico , Cefaleia do Tipo Tensional/complicações , Cefaleia do Tipo Tensional/tratamento farmacológico , Adulto Jovem
8.
Int Immunopharmacol ; 77: 105918, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31639616

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease that affects cognition and behavior. The neuroinflammatory response in the brain is an important pathological characteristic in AD. In this study, we investigated the neuroprotective effects of 1-Methylnicotinamide (MNA), known as the main metabolite of nicotinamide, on reducing lipopolysaccharide (LPS)-induced cognitive deficits via targeting neuroinflammation and neuronal apoptosis. We found that the mice treated with LPS exhibited cognitive deficits in the novel object recognition, Morris water maze and Y-maze avoidance tests. However, intragastric administration of MNA (100 or 200 mg/kg) for 3 weeks significantly attenuated LPS-induced cognitive deficits in mice. Importantly, MNA treatment suppressed the protein expression of nuclear factor-kappa B p65 (NF-κB p65), pro-inflammatory cytokines (TNF-α, IL-6) and decreased the activation of microglia and astrocytes in the hippocampus and frontal cortex of LPS-induced mice. In addition, MNA treatment suppressed neuronal apoptosis by reducing the number of TUNEL-positive cells, caspase-3 activation and increasing the level of Bcl-2/Bax ratio in the hippocampus and frontal cortex. These findings indicate that MNA could be a potential neuroprotective drug in neurodegenerative diseases such as AD.


Assuntos
Anti-Inflamatórios/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Niacinamida/análogos & derivados , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/imunologia , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Interleucina-6/imunologia , Lipopolissacarídeos , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/imunologia , Camundongos Endogâmicos ICR , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Fator de Transcrição RelA/imunologia , Fator de Necrose Tumoral alfa/imunologia
9.
Artigo em Russo | MEDLINE | ID: mdl-31626218

RESUMO

AIM: To analyze the efficacy of cytoflavin in the complex treatment of sleep disorders in asthenic syndrome. MATERIAL AND METHODS: One hundred patients with sleep disorders and asthenic syndrome of various etiology and severity were studied. The patients were divided into three groups depending on the type of therapy: the first group received intravenous infusions of cytoflavin for 10 days; the second group, in addition to cytoflavin, received per os melatonin (3 mg or 5 mg) at bedtime; the third group in addition to cytoflavin received per os zopiclone (7.5 mg) at bedtime. RESULTS: On the 14th day of the study, a decrease in severity or complete relief of asthenia manifestations (according to the SHAS scale) and, accordingly, improvement or normalization of sleep in 97% of patients was found. At the same time, during polysomnographic study, the data obtained are characteristic for improving the quality of sleep phases mainly in the first and second groups of patients and, to a lesser extent, in the third group. CONCLUSION: Cytoflavin effectively suppresses the main manifestations of asthenic syndrome, including sleep disorders.


Assuntos
Antioxidantes , Astenia , Mononucleotídeo de Flavina , Inosina Difosfato , Melatonina , Niacinamida , Transtornos do Sono-Vigília , Succinatos , Administração Oral , Antioxidantes/uso terapêutico , Astenia/tratamento farmacológico , Combinação de Medicamentos , Mononucleotídeo de Flavina/uso terapêutico , Humanos , Inosina Difosfato/uso terapêutico , Melatonina/uso terapêutico , Niacinamida/uso terapêutico , Transtornos do Sono-Vigília/tratamento farmacológico , Succinatos/uso terapêutico , Síndrome , Resultado do Tratamento
10.
Adv Gerontol ; 32(3): 439-444, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31512432

RESUMO

The article presents the results of a study of the effectiveness of the addition of a standard course of conservative therapy to 104 patients of the older age group with coxarthrosis deforming the drug «Cytoflavin¼ and cognitive-behavioral therapy courses. It was found that such scheme increases the effectiveness of therapeutic interventions, which manifests itself as the improvement of the mental and physical components of quality of life by reducing pain and increasing the functionality of some of the affected hip. At the heart of positive clinical effect is a decrease in processes of inflammation and reduction of tension of regulatory processes in the organism.


Assuntos
Terapia Cognitivo-Comportamental , Mononucleotídeo de Flavina , Inosina Difosfato , Niacinamida , Osteoartrite do Quadril , Succinatos , Idoso , Combinação de Medicamentos , Mononucleotídeo de Flavina/farmacologia , Mononucleotídeo de Flavina/uso terapêutico , Humanos , Inosina Difosfato/farmacologia , Inosina Difosfato/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Quadril/terapia , Qualidade de Vida , Succinatos/farmacologia , Succinatos/uso terapêutico
11.
Life Sci ; 235: 116843, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31494172

RESUMO

Polycystic ovary syndrome (PCOS) is a multifactorial disease, which is resulted from the three common features, hyperandrogenism (HA), ovulatory dysfunction (OD), and polycystic ovarian morphology (PCOM). The environmental inducers (like diet, lifestyle, chemicals, drugs, and ageing) and cardiometabolic risk factors (such as insulin resistance, metabolic syndrome, and obesity) are involved in pathogenesis of PCOS. The growing body of evidence has been shown that there exist endothelial cell dysfunction (ECD) in women with PCOS independent of age, weight and metabolic abnormalities. It has been shown that a broad spectrum of cardiovascular risk markers are involved in ECD- induced cardiovascular disease. It is well described that there are no worldwide treatments for PCOS and all of pharmacological treatments are off -label without any approval. MNAM is one of potential therapeutic factor, which produced by nicotinamide N-methyltransferase (NNMT) via consumption of S-adenosyl methionine (SAM) and nicotinamide. Only one study has shown higher expression of its producer enzyme, NNMT, in the cumulus cells of women with PCOS. Therefore, we reviewed beneficial effects of MNAM on modulation of cardiometabolic risk factors, which are associated to PCOS and try to describe possible mode of action of MNAM in the regulation of these markers.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Niacinamida/análogos & derivados , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Sintomas Prodrômicos , Biomarcadores/sangue , Feminino , Humanos , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Fatores de Risco
12.
Int J Mol Sci ; 20(17)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461911

RESUMO

The purpose of this study is to investigate whether nicotinamide riboside (NR) can improve inflammation and cognitive function in diabetic mice. ICR male mice were fed for 14 weeks with either high-fat chow diet (HF, 60% kcal fat) or standard chow diet (CON, 10% kcal fat). HF, streptozotocin, and nicotinamide were used to induce hyperglycemia. NR or vehicle was delivered via stomach gavage for six weeks. Oral glucose tolerance test, Y-maze test, and nest construction test were conducted before and after the NR treatment period. NR treatment induced down-regulation of NLRP3, ASC, and caspase-1. NR reduced IL-1 expression significantly by 50% in whole brains of hyperglycemic mice. Other inflammatory markers including TNF-α and IL-6 were also attenuated by NR. Brain expression of amyloid-ß precursor protein and presenilin 1 were reduced by NR. In addition, NR induced significant reduction of amyloid-ß in whole brains of diabetic mice. NR treatment restored hyperglycemia-induced increases in brain karyopyknosis to the levels of controls. Nest construction test showed that NR improved hippocampus functions. Spatial recognition memory and locomotor activity were also improved by NR supplementation. These findings suggest that NR may be useful for treating cognitive impairment by inhibiting amyloidogenesis and neuroinflammation.


Assuntos
Anti-Inflamatórios/uso terapêutico , Encéfalo/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Niacinamida/análogos & derivados , Animais , Anti-Inflamatórios/farmacologia , Encéfalo/metabolismo , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Cognição , Disfunção Cognitiva/etiologia , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos ICR , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo
13.
Future Oncol ; 15(22): 2657-2666, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31339065

RESUMO

Tyrosine kinase inhibitors still play a very important role in the treatment of metastatic renal cell carcinoma despite a continuously changing scenario, in which immunotherapy and several combination-based approaches are also available. In this light, patient-reported outcomes and health-related quality of life are important factors in the selection of the best first-line treatment. This Review focuses on the existing evidence on patient-reported outcomes and health-related quality of life with several tyrosine kinase inhibitors (pazopanib, sunitinib, cabozantinib and tivozanib) used as first-line treatment for metastatic renal cell carcinoma.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma de Células Renais/patologia , Humanos , Indóis/uso terapêutico , Neoplasias Renais/patologia , Metástase Neoplásica , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Pirimidinas/uso terapêutico , Qualidade de Vida , Quinolinas/uso terapêutico , Sorafenibe/uso terapêutico , Sulfonamidas/uso terapêutico , Sunitinibe/uso terapêutico , Resultado do Tratamento
14.
Adv Gerontol ; 32(1-2): 128-132, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31228378

RESUMO

To study the effectiveness of the inclusion of Cytoflavin in the management of postoperative delirium treating in elderly patients. Analyzed the results of treatment of 89 elderly patients (65-74 years) who, according to similar emergency indications, underwent surgery and postoperatively showed signs of delirium (according to the DDS scale ≥8 points). Depending on the treatment regimen, the patients were divided into three groups: in the first (n=32) group, bromodihydrochlorophenylbenzodiazepine was administered intravenously (1-5 min) in a dose of 1 mg in the 1st group (n=32) to the group (patients of the 2nd group (n=28) with the same purpose and at the same time cytoflavin was injected: 10 ml of the drug in dilution per 200 ml of 10% glucose solution intravenously at a rate of 140 drops (7 ml) per minute. Patients of 3rd group (n=29) were injected with ethylmethylhydroxypyridine succinate intravenous (within 5-7 min) at a dose of 200 mg. The condition was assessed using the SOFA, DDS and RASS scales. The inclusion of drugs with antioxidant/membrane-protective action (Cytoflavin and ethylmethylhydroxypyridine succinate) in the treatment regimen of postoperative delirium in the elderly increases the effectiveness of treatment, which is manifested in more rapid relief of the condition. When comparing the efficacy of Cytoflavin and ethylmethylhydroxypyridine succinate, it was noted that in a number of indicators (restoration of spontaneous breathing, improvement after the first dose and complete relief of signs of delirium) both drugs showed comparable results, however, when assessing the depth of sedation (on the RASS scale), Cytoflavin was more effective (p=0,001).The obtained results of the effectiveness of cytoflavin in combination with good patient tolerance allows us to recommend the inclusion of the drug in the treatment regimens of this pathology.


Assuntos
Antioxidantes , Delírio , Complicações Pós-Operatórias , Idoso , Antioxidantes/uso terapêutico , Delírio/tratamento farmacológico , Combinação de Medicamentos , Mononucleotídeo de Flavina/uso terapêutico , Humanos , Inosina Difosfato/uso terapêutico , Niacinamida/uso terapêutico , Piridinas/uso terapêutico , Succinatos/uso terapêutico
15.
Biomed Res Int ; 2019: 9068314, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31143777

RESUMO

Background: Malar melasma has a chronic and recurrent character that may be related to epigenetic changes. Objective: To recognize the expression and DNA methylation of DNA methyltransferases (DNMTs) in malar melasma and perilesional skin, as well as the changes in DNMTs after their treatment with sunscreen in combination with 4% niacinamide, 0.05% retinoic acid, or placebo. Methods: Thirty female patients were clinically evaluated for the expression of DNMT1 and DNMT3b using real-time PCR and immunofluorescence. These initial results were compared to results after eight weeks of treatment with sunscreen in combination with niacinamide, retinoic acid, or placebo. Results: The relative expression of DNMT1 was significantly elevated in melasma compared with unaffected skin in all subjects, indicating DNA hypermethylation. After treatment, it was decreased in all groups: niacinamide (7 versus 1; p<0.01), retinoic acid (7 versus 2; p<0.05), and placebo (7 versus 3; p<0.05), which correlates with clinical improvement. DNMT3b was not overexpressed in lesional skin but reduced in all groups. Conclusions: We found DNA hypermethylation in melasma lesions. Environmental factors such as solar radiation may induce cellular changes that trigger hyperpigmentation through the activation of pathways regulated by epigenetic modifications. However, limiting or decreasing DNA methylation through sunscreen, niacinamide, and retinoic acid treatments that provide photoprotection and genetic transcription can counteract this.


Assuntos
Metilases de Modificação do DNA/metabolismo , Melanose/tratamento farmacológico , Melanose/enzimologia , Niacinamida/uso terapêutico , Protetores Solares/uso terapêutico , Tretinoína/uso terapêutico , 5-Metilcitosina/metabolismo , Adulto , Metilação de DNA , Metilases de Modificação do DNA/genética , Epiderme/efeitos dos fármacos , Epiderme/patologia , Feminino , Fluorescência , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Placebos , Protetores Solares/farmacologia
16.
Ann Dermatol Venereol ; 146 Suppl 2: IIS31-IIS35, 2019 May.
Artigo em Francês | MEDLINE | ID: mdl-31133228

RESUMO

Transplant recipients are at high risk of developing actinic keratosis (AK) and skin cancer. For this reason, initiating treatment at an early stage is crucial. Topical and systemic therapeutic options for AK have widely been described in studies of immunocompetent patients. However, little is known about AK management in organ transplant recipients (OTR). Photodynamic therapy (PDT), along with imiquimod, topical NSAIDs and topical 5-fluorouracil have been used on ORT patients in small non randomized studies. Although these studies seem to suggest that PDT offers best results, solid evidence is lacking. Nicotinamide and oral retinoids have also been described as reasonably effective preventive treatments in ORT patients. Management of immunosuppressive drugs is also considered as a key point for reducing the number of AK in ORT patients; an early switch for m-tor inhibitors has been shown to be protective while azathioprine, ciclosporin and tacrolimus have been shown to heighten the risk of developing AKs and skin cancer in this population. © 2019 Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Kératoses actiniques : comprendre et traiter réalisé avec le soutien institutionnel de Galderma International.


Assuntos
Ceratose Actínica/terapia , Transplantados , Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/uso terapêutico , Crioterapia , Fármacos Dermatológicos/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Imiquimode/uso terapêutico , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Terapia a Laser , Niacinamida/uso terapêutico , Fototerapia
17.
J Drugs Dermatol ; 18(5): 454-459, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31141852

RESUMO

Background: Stubborn dyschromia such as melasma and post-inflammatory hyperpigmentation (PIH) are leading causes for cosmetic consultation. Topical treatment is challenging, using a range of modalities, to stop, hinder, and/or prevent steps in the pigment production process. Tranexamic acid (TXA), a potent plasmin inhibitor, is proposed to control pigmentation by inhibiting the release of inflammatory mediators involved in triggering melanogenesis. TXA has been recently introduced as a topical therapy aimed at reducing pigmentation in melasma. Methods: In a 12-week clinical study, a novel, topical facial serum containing 3% TXA, 1% kojic acid, and 5% niacinamide was evaluated for its effectiveness in treating melasma, PIH, and hyperpigmentation in Brazilian female subjects with Fitzpatrick skin types I-IV. Efficacy evaluations were performed at pre-treatment baseline, weeks 2, 4, 8, and 12, and included expert clinical grading, bio-instrumental measurements, and self-assessment questionnaires. Cutaneous tolerability was also evaluated by assessing subjective and objective irritation of the treatment area. Results: A significant improvement in the appearance of PIH, hyperpigmentation, melasma, skin texture, and skin tone homogeneity was observed beginning at week 2 and continued through week 12. Melanin index, as measured by Mexameter®, demonstrated a significant decrease by week 12 as compared to both pre-treatment baseline and control. Conclusions: The findings suggest that the test product is an effective and well-tolerated treatment option for addressing hyperpigmentary conditions, including melasma. Additional in vitro data suggests that TXA may act by mediating the inhibition of PGE2-stimulated human epidermal melanocytes. J Drugs Dermatol. 2019;18(5):454-459.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Dermatoses Faciais/tratamento farmacológico , Hiperpigmentação/tratamento farmacológico , Administração Cutânea , Adulto , Fármacos Dermatológicos/administração & dosagem , Dermatoses Faciais/patologia , Feminino , Humanos , Hiperpigmentação/patologia , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/uso terapêutico , Pironas/administração & dosagem , Pironas/uso terapêutico , Inquéritos e Questionários , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/uso terapêutico , Resultado do Tratamento
18.
J Drugs Dermatol ; 18(5): 477-479, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31141858

RESUMO

Here, we present a case of arsenic-induced Bowen's disease treated with a regimen consisting of topical 5-fluouracil and oral nicotinamide. The use of this therapy modality resulted in near complete resolution of all of the patient's lesions except for those on her palms, soles, and scalp. Excellent wound care and treatment adherence were major factors contributing to the success of this treatment option. Our results ultimately provide an alternative approach to treating multiple arsenical keratoses in patients who are limited to a drug plan involving 5-FU and oral nicotinamide and who are able to be rigorously compliant with application of medication and wound care. J Drugs Dermatol. 2019;18(5):477-479.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Arsênico/efeitos adversos , Doença de Bowen/diagnóstico , Fluoruracila/uso terapêutico , Neoplasias Cutâneas/diagnóstico , Poluentes da Água/efeitos adversos , Administração Cutânea , Administração Oral , Antimetabólitos Antineoplásicos/administração & dosagem , Doença de Bowen/induzido quimicamente , Doença de Bowen/tratamento farmacológico , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Fluoruracila/administração & dosagem , Humanos , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/uso terapêutico , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Abastecimento de Água
19.
Expert Rev Clin Pharmacol ; 12(6): 547-554, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059310

RESUMO

Introduction: Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease characterized by synovitis as well as symmetric and destructive arthropathy. Although several disease modified antirheumatic-drugs (DMARDs) have widely used in clinical practice, certain patients are nonresponsive to or cannot take such medications due to adverse reactions. It is evident that Janus kinase (JAK) inhibitors have the potential to provide a significant breakthrough in the treatment of RA. These potent, orally administered, JAK inhibitors simplify the treatment options for patients. Areas covered: We discuss the pharmacodynamics, pharmacokinetics, efficacy, and safety of peficitinib for the treatment of RA. Expert opinion: Peficitinib is a novel JAK3 inhibitor potently inhibiting JAK3 enzymatic activity and JAK1/3-mediated cell proliferation. Its selectivity for JAK family kinases is similar to that of tofacitinib, but slightly less potent for JAK2. It is currently being evaluated by the FDA to treat adult patients with moderately to severely active RA who show inadequate response to or are intolerant of methotrexate. It can be used either as monotherapy or combination therapy with methotrexate, or other DMARDs. However, we think that more cautious consideration and measurement for adverse events are needed, after considering the safety results of ongoing clinical studies of peficitinib.


Assuntos
Adamantano/análogos & derivados , Artrite Reumatoide/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Niacinamida/análogos & derivados , Adamantano/efeitos adversos , Adamantano/farmacologia , Adamantano/uso terapêutico , Adulto , Antirreumáticos/efeitos adversos , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/enzimologia , Proliferação de Células/efeitos dos fármacos , Humanos , Janus Quinase 3/antagonistas & inibidores , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/farmacologia , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Niacinamida/efeitos adversos , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Pirróis/farmacologia , Pirróis/uso terapêutico
20.
Drugs ; 79(8): 887-891, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31093950

RESUMO

Peficitinib [Smyraf® (Astellas Pharma)] is a Janus kinase (JAK)1, JAK2, JAK3 and tyrosine kinase (Tyk)2 (pan-JAK) inhibitor recently approved in Japan for the treatment of rheumatoid arthritis. Inhibition of JAK suppresses the activation of cytokine signalling pathways involved in inflammation and joint destruction in rheumatoid arthritis. Peficitinib has been shown to significantly improve ACR20 and other measures of disease severity and to reduce the mean modified total Sharp score change from baseline in clinical trials. This article summarizes the milestones in the development of peficitinib leading to this first approval as a treatment for rheumatoid arthritis in patients who have an inadequate response to conventional therapies.


Assuntos
Adamantano/análogos & derivados , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Niacinamida/análogos & derivados , Inibidores de Proteínas Quinases/uso terapêutico , Adamantano/farmacologia , Adamantano/uso terapêutico , Antirreumáticos/farmacologia , Aprovação de Drogas , Humanos , Janus Quinases/antagonistas & inibidores , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores
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