RESUMO
BACKGROUND: There has been an increasing interest in gender differences both in the pathogenesis and treatment of acne vulgaris (acne). However, while acne prevalence among adolescents is comparable across sexes, acne is much more common in adult women than in adult men which has been largely ignored. Acne is likely less common in adult men because of the declining rate of sebum secretion observed with increasing age, and yet it can be more severe than in adult women. In addition, adherence to topical medications is especially poor in adult men where tactile and sensory perceptions are low. The first lotion formulation of tazarotene was developed using polymeric emulsion technology to provide an important alternative option to treat these acne patients, especially those who may be sensitive to the irritant effects of other tazarotene formulations. OBJECTIVE: To evaluate the efficacy and safety of a new tazarotene 0.045% lotion formulation based on polymeric emulsion technology in treating adult male subjects with moderate or severe acne, in comparison with adolescent males treated with the same tazarotene 0.045% lotion. METHODS: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies in moderate-or-severe acne. Subjects (aged 10 and older, N=1614) were randomized (1:1) to receive tazarotene 0.045% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and clear or almost clear). Quality of Life was assessed using the validated Acne-QoL scale. Safety, adverse events (AEs) were evaluated throughout; cutaneous tolerability (using a 4-point scale where 0=none and 3=severe) at each study visit. RESULTS: A total of 268 male subjects (85≥18 years old and 183<18 years old) were treated with tazarotene 0.045% lotion once-daily for 12 weeks. At week 12, percent reductions in inflammatory and noninflammatory lesions with tazarotene 0.045% lotion were 62.3% and 59.5% in the adult male population, compared with 49.4% (P=0.001) and 49.5% (P=0.016) in the adolescent male population. Treatment success was achieved by 33.0% of adult male subjects treated with tazarotene 0.045% lotion, compared with 21.6% in the adolescent male population (P=0.059). Quality of life (as assessed by Acne-QoL domain scores) was better in adolescent males at baseline. Improvements in QoL domain scores were similar to those seen in the overall study population, with greater absolute change in domain scores in the adult males. Improvement in acne symptom scores was significantly greater in adult males (P=0.029). Tazarotene 0.045% lotion was well-tolerated. The number of subjects reporting any AE in the adult male population was 11 (13.6%) compared with 39 (21.4%) in the adolescent male population. There was only one (1.2%) treatment-related AE (application site pain) reported in the adult males compared with 11 (6.0%) in the adolescent males, where the most common treatment-related AEs were application site pain (3.3%), dryness (1.1%), and erythema (1.1%). Mean scores for hyper- and hypopigmentation were very low at baseline in both groups with no appreciable change with treatment. CONCLUSIONS: Tazarotene 0.045% lotion provides greater efficacy and better tolerability in adult males (above 18 years old) than the adolescent male population with moderate-to-severe acne patients. J Drugs Dermatol. 2020;19(1):78-85. doi:10.36849/JDD.2020.3979
Assuntos
Acne Vulgar/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Ácidos Nicotínicos/administração & dosagem , Acne Vulgar/patologia , Administração Cutânea , Adolescente , Adulto , Fatores Etários , Criança , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Humanos , Masculino , Ácidos Nicotínicos/efeitos adversos , Qualidade de Vida , Índice de Gravidade de Doença , Creme para a Pele , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Narrow-band UVB (NB-UVB) has been shown to be one of the most effective treatment modalities for psoriasis. Tazarotene, a known effective anti-psoriatic modality, when combined with NB-UVB may enhance the therapeutic success. OBJECTIVE: To study clinical efficacy and safety of combination of NB-UVB with topical tazarotene 0.05% gel in psoriasis. METHOD: Thirty patients with plaque psoriasis having symmetrical lesions were enrolled for 12 weeks. All patients were instructed to apply tazarotene gel on target plaque on left side of body once daily. In addition, the whole body was irradiated with NB-UVB twice weekly. Efficacy was assessed by target plaque scoring and number of treatment sessions for clearance. RESULT: Our study resulted in 3 key findings: Firstly, therapeutic efficacy of NB-UVB was enhanced by addition of tazarotene. This enhanced efficacy was more apparent in decreasing scaling and thickness as compared to decrease in erythema. Secondly, combination therapy showed faster clearance of target plaques, with reduction in mean number of treatment sessions. Thirdly, mean cumulative NB-UVB dose needed to achieve clearance of target plaques was significantly reduced with combination therapy. STUDY LIMITATIONS: The study was not randomized or controlled, but an open-label trial. The study period was relatively short, i.e., 12 weeks, without any follow-up period. CONCLUSION: Tazarotene gel significantly enhances the therapeutic efficacy of NB-UVB irradiation with faster clearance and without serious side effects.
Assuntos
Fármacos Dermatológicos/administração & dosagem , Ácidos Nicotínicos/administração & dosagem , Psoríase/radioterapia , Terapia Ultravioleta/métodos , Adolescente , Adulto , Terapia Combinada/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psoríase/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Abstract: BACKGROUND: Narrow-band UVB (NB-UVB) has been shown to be one of the most effective treatment modalities for psoriasis. Tazarotene, a known effective anti-psoriatic modality, when combined with NB-UVB may enhance the therapeutic success. OBJECTIVE: To study clinical efficacy and safety of combination of NB-UVB with topical tazarotene 0.05% gel in psoriasis. METHOD: Thirty patients with plaque psoriasis having symmetrical lesions were enrolled for 12 weeks. All patients were instructed to apply tazarotene gel on target plaque on left side of body once daily. In addition, the whole body was irradiated with NB-UVB twice weekly. Efficacy was assessed by target plaque scoring and number of treatment sessions for clearance. RESULT: Our study resulted in 3 key findings: Firstly, therapeutic efficacy of NB-UVB was enhanced by addition of tazarotene. This enhanced efficacy was more apparent in decreasing scaling and thickness as compared to decrease in erythema. Secondly, combination therapy showed faster clearance of target plaques, with reduction in mean number of treatment sessions. Thirdly, mean cumulative NB-UVB dose needed to achieve clearance of target plaques was significantly reduced with combination therapy. STUDY LIMITATIONS: The study was not randomized or controlled, but an open-label trial. The study period was relatively short, i.e., 12 weeks, without any follow-up period. CONCLUSION: Tazarotene gel significantly enhances the therapeutic efficacy of NB-UVB irradiation with faster clearance and without serious side effects.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Psoríase/radioterapia , Terapia Ultravioleta/métodos , Seguimentos , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Fatores de Tempo , Estudos Prospectivos , Resultado do Tratamento , Terapia Combinada/métodos , Ácidos Nicotínicos/administração & dosagemRESUMO
Steady-fiber granule (SFG) is a functional food mixture that is composed of four major ingredients, resistant maltodextrin, white kidney bean (Phaseolus vulgaris) extract, mulberry leaf (Morus alba L.) extract, and niacin-bound chromium complex. This study focused on determining the safety of SFG. Genotoxicity and 28-day oral toxicity were evaluated. SFG did not induce mutagenicity in the bacterial reverse mutation assay using five Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) in the presence or absence of metabolic activation (S9 system). SFG also did not induce clastogenic effects in Chinese hamster ovary cells with or without S9 treatment. Similarly, SFG did not induce genotoxicity in a micronucleus test conducted with mice. A dose-dependent 28-day oral toxicity assessment of SFG for rats revealed no significant effects on mortality, body weight, selected organ weights, and behavior. Evaluations of hematology, clinical biochemistry, and histopathology showed no adverse effects in rats treated with SFG. These results suggest that SFG has no significant mutagenic or toxic properties, and the no observed adverse effect level of SFG was defined as at least 5000 mg/kg/day orally for 28 days for male and female rats.
Assuntos
Alimento Funcional/efeitos adversos , Morus/efeitos adversos , Ácidos Nicotínicos/efeitos adversos , Compostos Organometálicos/efeitos adversos , Phaseolus/efeitos adversos , Extratos Vegetais/efeitos adversos , Folhas de Planta/efeitos adversos , Polissacarídeos/efeitos adversos , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Células CHO , Cricetulus , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Testes de Mutagenicidade/métodos , Mutação/efeitos dos fármacos , Niacina/efeitos adversos , Ácidos Nicotínicos/administração & dosagem , Compostos Organometálicos/administração & dosagem , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Ratos , Ratos WistarRESUMO
Previous data demonstrate that bexarotene (Bex), retinoid X receptor (RXR) agonist, reduces soluble and insoluble amyloid-ß (Aß) in Alzheimer disease (AD)-transgenic mice either by increasing the levels of mouse apolipoprotein E (apoE) or increasing ABCA1/ABCG1-induced apoE lipoprotein association/lipidation. However, although the mechanism of action of RXR agonists remains unclear, a major concern for their use is human (h)-APOE4, the greatest AD genetic risk factor. If APOE4 imparts a toxic gain-of-function, then increasing apoE4 may increase soluble Aß, likely the proximal AD neurotoxin. If the APOE4 loss-of-function is lipidation of apoE4, then induction of ABCA1/ABCG1 may be beneficial. In novel EFAD-Tg mice (overexpressing h-Aß42 with h-APOE), levels of soluble Aß (Aß42 and oligomeric Aß) are highest in E4FAD hippocampus (HP) > E3FAD-HP > E4FAD cortex (CX) > E3FAD-CX, whereas levels of lipoprotein-associated/lipidated apoE have the opposite pattern (6 months). In E4FAD-HP, short-term RXR agonist treatment (Bex or LG100268; 5.75-6 months) increased ABCA1, apoE4 lipoprotein-association/lipidation, and apoE4/Aß complex, decreased soluble Aß, and increased PSD95. In addition, hydrogel delivery, which mimics low sustained release, was equally effective as gavage for Bex and LG100268. RXR agonists induced no beneficial effects in the E4FAD-HP in a prevention protocol (5-6 months) and actually increased soluble Aß levels in E3FAD-CX and E4FAD-CX with the short-term protocol, possibly the result of systemic hepatomegaly. Thus, RXR agonists address the loss-of-function associated with APOE4 and exacerbated by Aß pathology, i.e. low levels of apoE4 lipoprotein association/lipidation. Further studies are vital to address whether RXR agonists are an APOE4-specific AD therapeutic and the systemic side effects that limit translational application.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Apolipoproteínas E/genética , Ácidos Nicotínicos/administração & dosagem , Fragmentos de Peptídeos/metabolismo , Receptores X de Retinoides/agonistas , Tetra-Hidronaftalenos/administração & dosagem , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Administração Oral , Doença de Alzheimer/tratamento farmacológico , Animais , Bexaroteno , Proteína 4 Homóloga a Disks-Large , Avaliação Pré-Clínica de Medicamentos , Genótipo , Guanilato Quinases/metabolismo , Humanos , Lipoproteínas/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Ácidos Nicotínicos/efeitos adversos , Ácidos Nicotínicos/farmacocinética , Tamanho do Órgão/efeitos dos fármacos , Receptores X de Retinoides/metabolismo , Solubilidade , Tetra-Hidronaftalenos/efeitos adversos , Tetra-Hidronaftalenos/farmacocinéticaAssuntos
Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Medição de Risco , Resinas de Troca Aniônica/administração & dosagem , Doenças Cardiovasculares/sangue , Complicações do Diabetes , Dieta , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Fíbricos/administração & dosagem , Taxa de Filtração Glomerular , Humanos , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Ácidos Nicotínicos/administração & dosagem , Guias de Prática Clínica como Assunto , Prevenção Primária , Insuficiência Renal Crônica/complicações , Prevenção SecundáriaRESUMO
OBJECTIVE: To investigate the effect of chromium nicotinate supplementation on insulin sensitivity, glycemic control, and lipid profile in subjects with type 2 diabetes. MATERIALS AND METHODS: In a double-blind clinical trial, 56 overweight individuals with type 2 diabetes were randomized into 3 groups: placebo (NC0), 50 µg (NC50), and 200 µg (NC200) of chromium as chromium nicotinate. Chromium status, sensitivity to insulin, glycemic control, and lipid profile were assessed at the beginning of the study and 45 days and 90 days after. RESULTS: In the beginning, most subjects showed low concentrations of serum chromium (71.88%), regular levels of urinary chromium (80.65%), and insulin resistance (73.80%). The serum chromium concentrations did not differ among the groups over time (p = 0.2549). The changes in serum chromium and urine concentrations did not relate to changes in fasting glucose (p > 0.05). At 90 days of intervention, there was no significant difference between groups in fasting glucose, glycosylated hemoglobin, homeostasis model assessment insulin resistance (HOMA-IR), total cholesterol, and low-density lipoprotein (LDL); there was increase in homeostasis model assessment ß-cell function (HOMA-ß; p = 0.0349) and high-density lipoprotein (HDL; p = 0.0425) in the NC0 group and a reduction of triglycerides in the NC0 (p = 0.0177) and NC50 (p = 0.0336) groups. CONCLUSION: Supplementation at 50 and 200 µg of chromium as chromium nicotinate did not promote glycemic control, increase insulin sensitivity, or change the lipid profile of subjects with diabetes.
Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Resistência à Insulina , Ácidos Nicotínicos/administração & dosagem , Compostos Organometálicos/administração & dosagem , Adulto , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cromo/sangue , Cromo/urina , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Feminino , Hemoglobinas Glicadas/metabolismo , Homeostase , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: A low-fat, fiber-rich diet is the first step in the management for hypercholesterolemic children. Glucomannan (GM) is a natural fiber that has been demonstrated to lower total and LDL-cholesterol. The use of high-dose chromium-polynicotinate (CP) and policosanol (PC) has also shown cholesterol-lowering benefits. We aimed at investigating the effects of low-dose CP or PC and their GM combination in hypercholesterolemic children. METHODS: A double-blind trial was conducted in 120 children (60 M, 60 F, 9 ± 4 years, median 9.6 years, range: 3-16 years) randomly assigned to 5 neutraceutical and 1 placebo (only resistant starch) 8-week treatment groups. Fasting blood glucose (FBG), total cholesterol (CholT), triglycerides (TG), HDL and LDL cholesterol were considered. RESULTS: GM combination of low-dose CP or PC reduced CholT and LDL without changing HDL, TG and FBG. The highest post-treatment changes were seen after GM combination with CP (CholT 85 ± 3% and LDL 85 ± 5%, of pretreatment) which was significantly (p < 0.01) less than with low-dose CP or PC and starch. When GM was associated with starch, there was no lipid lowering effect, which was an unexpected finding as compared to previous data with GM and no starch. No adverse effects were reported. CONCLUSION: This is the first report to show the cholesterol-lowering efficacy of GM combined treatment with low-dose CP or PC. Further studies are needed to investigate the best combinations and doses of nutraceutics to be added to the standard GM treatment. The potential negative association of GM and nutraceutics with starch is clearly shown.
Assuntos
Inibidores da Colinesterase/administração & dosagem , Álcoois Graxos/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Mananas/administração & dosagem , Ácidos Nicotínicos/administração & dosagem , Adolescente , Aterosclerose/sangue , Aterosclerose/tratamento farmacológico , Glicemia/metabolismo , Catárticos/administração & dosagem , Criança , Pré-Escolar , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Jejum , Feminino , Humanos , Hipercolesterolemia/sangue , Masculino , Triglicerídeos/metabolismoRESUMO
Chromium(III) is long regarded as essential trace element but the biochemical function and even basic transport ways in the body are still unclear. For a more rational discussion on beneficial as well as toxic effects of Cr(III), we re-investigated the bioavailability of the most important oral Cr supplements by using radiolabeled compounds and whole-body-counting in rats and in the first time also in humans. The apparent absorption of (51)Cr(III) from Cr-picolinate, Cr-nicotinate, Cr-phenylalaninate, Cr-proprionate, or Cr-chloride was generally low (0.04-0.24 %) in rats with slightly higher values for Cr-chloride and -phenylalaninate. Taking a fast urine excretion into account, the true absorption of (51)Cr was clearly higher for CrPic(3) (0.99 %), probably indicating a different uptake mechanism of this rather stable organic Cr complex. The bioavailability of CrPic(3) and Cr(D: -Phen)(3), the leading compounds in actual investigations, was analysed also in human volunteer by intraindividual comparison. The apparent absorption (=Cr bioavailability) of (51)Cr from both compounds was substantially higher in humans (0.8-1 %) than in rats. Again, most of freshly absorbed CrPic(3) was excreted into the urine resulting in the same low whole-body retention after 7 days for both compounds. In summary, the bioavailability of Cr from pharmaceutical Cr compound is lower than hitherto assumed. Importantly, humans absorb Cr(III) clearly better than rats. The absorption mechanism of CrPic(3) seems to be different from ionic Cr(III) but, as only the same low amount of Cr is retained from this compound, it is also not more bioavailable than other Cr compounds.
Assuntos
Cromo/farmacocinética , Compostos Organometálicos/farmacocinética , Administração Oral , Idoso , Animais , Disponibilidade Biológica , Cromo/administração & dosagem , Radioisótopos de Cromo/administração & dosagem , Radioisótopos de Cromo/farmacocinética , Suplementos Nutricionais , Feminino , Humanos , Injeções Intraperitoneais , Injeções Intravenosas , Absorção Intestinal , Pessoa de Meia-Idade , Ácidos Nicotínicos/administração & dosagem , Ácidos Nicotínicos/farmacocinética , Compostos Organometálicos/administração & dosagem , Fenilalanina/administração & dosagem , Fenilalanina/análogos & derivados , Fenilalanina/farmacocinética , Ácidos Picolínicos/administração & dosagem , Ácidos Picolínicos/farmacocinética , Ratos , Ratos WistarRESUMO
This study was conducted to determine the effects of dietary supplementation with Cr nicotinate and Cr chloride and their optimum inclusion rate on performance, carcass traits, meat oxidative stability, serum metabolites, hematological parameters, and liver chromium concentration in heat-stressed broilers. A total number of 420, 1-day-old male broiler chicks were randomly assigned to seven treatments with four replicates of 15 chicks. The dietary treatments consisted of the basal diet supplemented with 0 (control), 500, 1,000, and 1,500 µg/kg Cr in the form of Cr nicotinate and Cr chloride. Chicks were raised for 6 weeks in heat stress condition (33 ± 2°C). Supplements of organic and inorganic Cr particularly at 1,500 µg/kg incorporation increased feed consumption (P < 0.05) and body mass gain of broilers (P < 0.01). Cr supplementation increased carcass yield and decreased abdominal fat (P < 0.01). Supplementation of 1,500 µg/kg Cr nicotinate (P < 0.05) enhanced liver Cr concentration. Storage time increased lipid oxidation of meat (P < 0.01). Cr decreased lipid oxidation of breast and thigh muscles over 2 (P < 0.01) or 6 (P < 0.05) days of storage time. Birds fed 1,500 µg/kg Cr nicotinate, had lower concentration of serum glucose and triglyceride at 21 days (P < 0.05). Hematological parameters tested at 21 and 42 days, were not influenced. The results suggested that dietary Cr supplementation regardless of its source have a positive effect on productive, and carcass traits, also enhances oxidative stability of refrigerated meat in broilers reared under heat stress conditions.
Assuntos
Peso Corporal/efeitos dos fármacos , Cloretos/farmacologia , Compostos de Cromo/farmacologia , Carne/análise , Ácidos Nicotínicos/farmacologia , Compostos Organometálicos/farmacologia , Animais , Animais Recém-Nascidos , Contagem de Células Sanguíneas , Glicemia/metabolismo , Galinhas , Cloretos/administração & dosagem , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Compostos de Cromo/administração & dosagem , Suplementos Nutricionais , Hematócrito , Hemoglobinas/metabolismo , Temperatura Alta , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ácidos Nicotínicos/administração & dosagem , Compostos Organometálicos/administração & dosagem , Oxirredução/efeitos dos fármacos , Proteínas/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Fatores de Tempo , Triglicerídeos/sangueRESUMO
(1) Plaque psoriasis is the most common form of psoriasis in children. Topical agents should be tried first, especially well-tolerated products such as emollients. Topical corticosteroids are sometimes useful during exacerbations but, given adverse effects, they should only be used for short periods; (2) UVB phototherapy is an option for extensive psoriasis refractory to local treatments, but it carries a long-term risk of skin cancer. Immunosuppressants have not been well assessed in this setting, but methotrexate has been better evaluated than the others.
Assuntos
Emolientes/uso terapêutico , Imunossupressores/uso terapêutico , Psoríase/tratamento farmacológico , Esteroides/uso terapêutico , Acitretina/administração & dosagem , Acitretina/efeitos adversos , Acitretina/uso terapêutico , Administração Tópica , Antralina/administração & dosagem , Antralina/efeitos adversos , Antralina/uso terapêutico , Calcitriol/administração & dosagem , Calcitriol/efeitos adversos , Calcitriol/análogos & derivados , Calcitriol/uso terapêutico , Criança , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Emolientes/administração & dosagem , Emolientes/efeitos adversos , Etanercepte , Humanos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/efeitos adversos , Imunoglobulina G/uso terapêutico , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Ácidos Nicotínicos/administração & dosagem , Ácidos Nicotínicos/efeitos adversos , Ácidos Nicotínicos/uso terapêutico , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Extratos Vegetais/uso terapêutico , Psoríase/terapia , Receptores do Fator de Necrose Tumoral/administração & dosagem , Receptores do Fator de Necrose Tumoral/uso terapêutico , Salicilatos/administração & dosagem , Salicilatos/efeitos adversos , Salicilatos/uso terapêutico , Esteroides/administração & dosagem , Esteroides/efeitos adversos , Alcatrões/efeitos adversos , Alcatrões/uso terapêutico , Resultado do Tratamento , Terapia UltravioletaRESUMO
Psoriasis is a chronic inflammatory disease causing important physical and psychological morbidity. Topical treatments are the first choice therapeutic alternatives for mild and moderate psoriasis. We review the different topical treatment options for this common skin disease.
Assuntos
Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Administração Cutânea , Antralina/administração & dosagem , Calcitriol/administração & dosagem , Calcitriol/análogos & derivados , Esquema de Medicação , Quimioterapia Combinada , Emolientes/administração & dosagem , Humanos , Ceratolíticos/administração & dosagem , Ácidos Nicotínicos/administração & dosagem , Pomadas/administração & dosagem , Terapia PUVA/métodos , Qualidade de Vida , Tacrolimo/administração & dosagem , Tacrolimo/análogos & derivados , Resultado do Tratamento , Vitaminas/administração & dosagemRESUMO
BACKGROUND: Tazarotene (Tazorac, Avage, Allergan, Inc., Irvine, CA, USA) is a synthetic retinoic acid receptor- betagamma topical retinoid approved for the treatment of plaque psoriasis and acne vulgaris. OBJECTIVES: To review a decade of experience using tazarotene as a monotherapy or as combination therapy for approved and other indications: acne, psoriasis, photoaging, basal cell carcinomas and various keratinization disorders. METHODS: We reviewed the published literature available on PubMed for safety and efficacy of topical tazarotene gel or cream preparations. RESULTS/CONCLUSIONS: Tazarotene, in both gel and cream formulations, has been used both as monotherapy and as an adjuvant therapy. For psoriasis it has been combined with steroids, calcipotriene and phototherapy, and for acne, with antibiotics. Tazarotene has been shown to upregulate the tumor suppressor, tazarotene induced gene 3, which is overexpressed in psoriasis and skin cancer. Adverse effects are limited to mild to moderate local irritation and erythema as seen with the 'retinization period' of other topical retinoid therapies. Daily application of tazarotene is effective with sustained benefits and limited local side effects.
Assuntos
Acne Vulgar/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Ácidos Nicotínicos/uso terapêutico , Psoríase/tratamento farmacológico , Acne Vulgar/fisiopatologia , Administração Cutânea , Animais , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Humanos , Ácidos Nicotínicos/administração & dosagem , Ácidos Nicotínicos/efeitos adversos , Psoríase/fisiopatologia , Receptores do Ácido Retinoico/efeitos dos fármacos , Receptores do Ácido Retinoico/genética , Envelhecimento da Pele/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
This study tested the hypothesis that 3-acetyl-7-oxo-dehydroepiandrosterone alone (7-Keto) and in combination with calcium citrate, green tea extract, ascorbic acid, chromium nicotinate and cholecalciferol (HUM5007) will increase the resting metabolic rate (RMR) of overweight subjects maintained on a calorie-restricted diet. In this randomized, double-blind, placebo-controlled, crossover trial, overweight adults on a calorie-restricted diet were randomized to three 7-day treatment periods with 7-Keto, HUM5007 or placebo. Resting metabolic rate was measured by indirect calorimetry at the beginning and end of each treatment period with a 7-day washout between testing periods. Of 45 subjects enrolled, 40 completed the study (30 women, 10 men; mean age, 38.5 years; mean mass index, 32.0 kg/m(2)). During the placebo treatment, RMR decreased by 3.9% (75+/-111 kcal/day; mean+/-S.D.); however, RMR increased significantly by 1.4% (21+/-115 kcal/day) and 3.4% (59+/-118 kcal/day) during the 7-Keto and HUM5007 treatment periods, respectively (each compared to placebo, P=.001). No significant differences were found between the treatment periods with respect to compliance or adverse events. In this study, the administration of HUM5007 or 7-Keto reversed the decrease in RMR normally associated with dieting. HUM5007 and 7-Keto increased RMR above basal levels and may benefit obese individuals with impaired energy expenditure. HUM5007 and 7-Keto were generally well tolerated and no serious adverse events were reported.
Assuntos
Ácido Ascórbico/farmacologia , Metabolismo Basal/efeitos dos fármacos , Colecalciferol/farmacologia , Desidroepiandrosterona/análogos & derivados , Ácidos Nicotínicos/farmacologia , Extratos Vegetais/farmacologia , Adulto , Ácido Ascórbico/administração & dosagem , Restrição Calórica , Camellia sinensis , Colecalciferol/administração & dosagem , Desidroepiandrosterona/administração & dosagem , Desidroepiandrosterona/farmacologia , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Nicotínicos/administração & dosagem , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/farmacologia , Sobrepeso , Extratos Vegetais/administração & dosagemRESUMO
We have investigated the influence of charge and lipid concentration on the in-vivo percutaneous absorption of a model compound, methyl nicotinate (MN), from liposomal vesicles. MN-loaded liposomes were produced by the reverse-phase evaporation method (REV) using different concentrations of phosphatidyl choline (PC), in association with surfactants such as dioctadecyl dimethyl ammonium bromide (DDAB18) and dicetyl phosphate (DCP), which impart a positive or negative charge to the systems, respectively. The liposomal suspensions were then processed to hydrogels and used to study in-vivo the MN permeation profile. MN was chosen as the model compound since it was capable of causing cutaneous erythema, the intensity and duration of which was proportional to the amount entering the living epidermis over time. The extent of the erythema was monitored by reflectance spectrophotometry, a non-invasive technique. In-vivo findings showed an interesting MN delayed release, which was proportional to the amount of phospholipids in each liposomal formulation. Furthermore, it could be noted that the erythematous effect was more prolonged when MN was delivered from neutral or negatively-charged liposomal forms.
Assuntos
Lipídeos/química , Ácidos Nicotínicos/efeitos adversos , Ácidos Nicotínicos/metabolismo , Absorção Cutânea/efeitos dos fármacos , Administração Tópica , Área Sob a Curva , Química Farmacêutica/métodos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Eritema/induzido quimicamente , Humanos , Lipídeos/farmacologia , Lipossomos , Ácidos Nicotínicos/administração & dosagem , Fosfatidilcolinas/química , Fosfatidilcolinas/farmacologia , Absorção Cutânea/fisiologia , Espectrofotometria/métodos , Tecnologia Farmacêutica/métodosRESUMO
Atherosclerosis is a complex vascular disease initiated by abnormal accumulation of plasma lipoproteins in the subendothelial space. Elevated levels of plasma triglycerides (TG) and low-density lipoprotein (LDL)-cholesterol as well as low concentrations of high-density lipoprotein (HDL) play a causal role in the development and progression of atherosclerotic lesions. We have shown that apolipoprotein E-deficient (apo E-KO) mice have elevated triglyceride levels plus diminished HDL concentrations. Drugs such as fenofibrate and nicotinic acid are well known to reduce TG and increase HDL levels in humans. In this study, we investigated the beneficial effects of fenofibrate and niacin on lipid profile and atherogenesis in apo E-KO mice and their wild-type counterparts. Animals were fed with a cholesterol-enriched diet supplemented with fenofibrate (0.1% wt/wt, n = 8) or nicotinic acid (0.5% wt/wt, n = 8) for 14 weeks. Body weights were recorded weekly, and plasma lipid profiles were determined at 4-week intervals. The hearts and aortas were collected and fixed for histologic and morphometric evaluations of atherosclerotic lesions. Fenofibrate treatment in apo E-KO mice paradoxically increased total cholesterol and TG by 65% and 44%, respectively, and decreased HDL-cholesterol levels by 35% as compared with controls. Similar effects of fenofibrate on cholesterol levels, but not on TG concentrations, were observed in C57BL/6 mice. Fenofibrate-treated mice had lower body weight as compared with controls. Niacin had no effect on body weight gain but failed to decrease TG or to increase HDL levels in either apo E-KO mice or their wild-type counterparts. Neither fenofibrate nor niacin significantly influenced atherogenesis in apo E-KO mice as compared with controls. In conclusion, this study shows that neither niacin nor fenofibrate has beneficial lipid-modifying and antiatherosclerosis activities in mice. Identification of mechanisms underlying paradoxical effects of fenofibrate on lipoprotein metabolisms in apo E-KO mice merits further investigation.
Assuntos
Apolipoproteínas E/deficiência , Fenofibrato/farmacologia , Ácidos Nicotínicos/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Apolipoproteínas E/genética , Arteriosclerose/sangue , Arteriosclerose/etiologia , Arteriosclerose/prevenção & controle , Peso Corporal/efeitos dos fármacos , Colesterol na Dieta/administração & dosagem , HDL-Colesterol/sangue , Fenofibrato/administração & dosagem , Humanos , Hipolipemiantes/administração & dosagem , Hipolipemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ácidos Nicotínicos/administração & dosagem , Triglicerídeos/sangue , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/farmacologiaRESUMO
BACKGROUND: Topical skin-directed therapies are used to induce remissions in early-stage mycosis fungoides (MF). They are rarely curative, and responding patients are subject to frequent relapses, emphasizing the need for alternative therapies. OBJECTIVE: We sought to evaluate the efficacy and tolerability of topical tazarotene 0.1% gel as adjuvant therapy in the treatment of refractory MF lesions. METHODS: A total of 20 adult patients with early patch or plaque MF limited to less than 20% body surface area (BSA) involvement whose lesions were either stable or refractory to therapy for at least 8 weeks enrolled in an open-label pilot study. Tazarotene 0.1% gel was applied to MF lesions once daily for 24 weeks. Continued concomitant use of other medications such as low- to mid-potency topical corticosteroids was permitted for the alleviation of skin irritation. Global improvement, overall disease severity, percent BSA involvement, and pruritus were evaluated every 4 weeks. Up to 6 index lesions were followed up for area, plaque elevation, scaling, and erythema scores. Skin biopsy specimens were to be taken at baseline, week 8, and week 24. Evaluable specimens were stained with hematoxylin and eosin, CD8 antibody, and CD45RO antibody. RESULTS: In all, 20 patients enrolled, 19 received treatment, and 16 completed at least 4 weeks of topical treatment. By intent-to-treat analysis, 11 of 19 patients (58%) achieved at least a moderate (>50%) global improvement in BSA, and 35% of 99 index lesions cleared completely. Significant reductions (mean differences) were also found in the median lesional area score (-37, P =.0013), mean plaque elevation score (-.67, P =.016), mean scaling (-0.70, P =.033), and mean erythema score (-1.03, P =.002). Analysis of overall disease also disclosed statistical differences in percent of change for BSA involvement of 22% (P =.013) and of mean overall disease severity score of 34% (P =.011). Of 19 patients, 16 (84%) experienced mild or moderate local skin irritation manifested by peeling, erythema, burning, and tenderness that was managed successfully with topical steroids or reducing the frequency of treatment. Histopathology and immunohistochemistry results showed reductions in lymphocytic infiltrates and percentage of CD45RO(+) lymphocytes, and increases in the percentage of CD8(+) lymphocytes during the course of therapy. CONCLUSION: In this small pilot study, tazarotene 0.1% gel was a well-tolerated and effective adjuvant topical for the treatment of refractory MF lesions by clinical and histologic assessments.
Assuntos
Micose Fungoide/tratamento farmacológico , Ácidos Nicotínicos/administração & dosagem , Retinoides/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Administração Tópica , Antígenos CD8/análise , Feminino , Géis , Humanos , Imuno-Histoquímica , Antígenos Comuns de Leucócito/análise , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/imunologia , Micose Fungoide/patologia , Ácidos Nicotínicos/efeitos adversos , Projetos Piloto , Retinoides/efeitos adversos , Pele/patologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologiaRESUMO
Tazarotene (Tazorac, Allergan, Inc.) is the first topical retinoid approved for the treatment of plaque psoriasis. It has a similar onset of action compared to potent topical steroids and has the advantage of a longer remission. The common side effects associated with the drug include skin irritation (including pruritus), erythema and a burning sensation. To overcome some of these shortcomings, it has been used in combination with steroids, calcipotriene and phototherapy. Combination therapy not only results in a decrease in adverse side effects, but also enhanced efficacy. Clinical study data have shown that combination therapy is just as important as tazarotene monotherapy, if not more.
Assuntos
Fármacos Dermatológicos/uso terapêutico , Ácidos Nicotínicos/uso terapêutico , Psoríase/terapia , Retinoides/uso terapêutico , Administração Cutânea , Ensaios Clínicos como Assunto , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Estabilidade de Medicamentos , Quimioterapia Combinada , Humanos , Ácidos Nicotínicos/administração & dosagem , Ácidos Nicotínicos/efeitos adversos , Fototerapia , Psoríase/tratamento farmacológico , Retinoides/administração & dosagem , Retinoides/efeitos adversosRESUMO
Tazarotene is a receptor-selective retinoid, which is efficacious in the treatment of patients with psoriasis, acne vulgaris, and photoaging. It normalizes keratinocyte differentiation, reverses keratinocyte hyperproliferation, and has anti-inflammatory effects. Clinical studies have shown that tazarotene 0.1% gel has greater comedolytic activity than tretinoin (Retin-A 0.025% gel, Retin-A Micro 0.1%) and adapalene (Differin) 0.1% gel. Although it is efficacious as monotherapy, tazarotene is more commonly used as part of combination therapy with a topical antibacterial in patients with acne vulgaris, and with a mid- or high-potency topical corticosteroid or with phototherapy in patients with psoriasis. Combination therapy enhances efficacy and tolerability. Tazarotene 0.1% gel, used in combination with mometasone furoate 0.1% cream, was shown in psoriasis clinical trials to be more efficacious than calcipotriene (calcipotriol) ointment used twice daily, or mometasone furoate 0.1% cream used twice daily. Use of tazarotene in conjunction with broad band UVB, narrow band UVB or bath psoralens + UVA (PUVA) results in greater efficacy than with phototherapy alone. Tazarotene should not be administered during pregnancy or in women who are not practicing adequate contraception. Adverse events consist primarily of irritation, peeling, erythema, dryness, burning, and itching. They are most common during the first 1-2 weeks of therapy and can be minimized with use of the cream formulation, alternate day application, short contact therapy, mild cleansers, and combination therapy.