RESUMO
BACKGROUND/OBJECTIVE: Newborn infant skin is functional but immature, and diapering products can play a significant role in infant diapered skin health. Previous work demonstrated a regimen consisting of a diaper with an emollient and apertures on the inner liner (topsheet) with an acidic, pH-buffered wipe (Regimen A) lowered newborn skin pH and reduced the enzymatic activity on skin post-stool cleaning versus a regimen without these features (Regimen B). This study extends these findings to determine the impact of Regimen A on diaper area erythema severity over a 2-week use period. METHODS: This IRB-approved, blinded, randomized, crossover study enrolled newborn infants >7 days and ≤8 weeks. Participants exclusively used two unique diaper and wipe combinations, Regimen A and Regimen B (non-emollient, non-aperture containing topsheet and wipe with limited buffering capacity), each for 14 days and preceded by a 3-day washout regimen. RESULTS: Diapered skin pH was reduced during Regimen A use to values similar to that of a non-diapered control site (chest), while use of Regimen B was associated with a more alkaline skin pH. Regimen A resulted in significantly fewer severe erythema episodes. At the site of highest erythema, the perianal space, the average erythema score was significantly lower and more newborns were free of erythema while using Regimen A vs. Regimen B (P < .05). CONCLUSIONS: These findings demonstrate that diapering products can have a significant impact on newborn skin. They reinforce the need to support the physiological normalization of skin pH and protection from skin irritation and damage.
Assuntos
Dermatite das Fraldas , Eritema , Estudos Cross-Over , Dermatite das Fraldas/tratamento farmacológico , Dermatite das Fraldas/prevenção & controle , Eritema/etiologia , Humanos , Concentração de Íons de Hidrogênio , Lactente , Recém-Nascido , Pele , Higiene da PeleRESUMO
BACKGROUND/OBJECTIVES: Diaper dermatitis is one of the most frequent skin conditions affecting infants and is associated with elevated skin pH, exposure to urine and feces, and increased fecal protease and lipase activity, resulting in stratum corneum barrier damage and increased risk of infection. The study aim was to determine the impact of two diaper and wipe regimens on newborn infant skin pH and residual enzyme activity after stool cleaning. METHODS: Two diaper and wipe regimens were compared in a randomized, single-blinded crossover study. Regimen A paired an emollient-containing diaper with an acidic, pH-buffered wipe. Regimen B was a non-emollient diaper and wipe with limited buffering capacity. A 3-day washout period preceded each 3-day regimen use period. Skin pH at the perianal/buttocks interface (PBI), genital region, and undiapered chest control were measured at baseline and day 3. Skin swabs were collected for residual enzyme activity after a stool cleaning event. RESULTS: Diapered skin pH at the PBI was similar to undiapered skin after 3 days of use for Regimen A, while PBI pH for Regimen B was elevated versus control. PBI pH was lower for Regimen A versus Regimen B. After a stool cleaning, PBI skin pH for Regimen A was lower immediately and had lower residual enzyme activity versus Regimen B (P < .05), and the pH-lowering effect was sustained up to 60 minutes. CONCLUSIONS: These results suggest that the use of an emollient-containing diaper with a pH-buffered wipe creates conditions favorable to optimum diapered skin health.
Assuntos
Dermatite das Fraldas , Emolientes , Criança , Estudos Cross-Over , Dermatite das Fraldas/tratamento farmacológico , Dermatite das Fraldas/prevenção & controle , Humanos , Concentração de Íons de Hidrogênio , Lactente , Cuidado do Lactente , Recém-NascidoRESUMO
We have identified a novel series of potent MCH-R1 antagonists based on l-arginine. As predicted by computational methods, there was an activity dependence on the pi-electronic character of the aromatic systems corresponding to the amino-terminus of these molecules. These results have enhanced our understanding of the MCH-R1 receptor and the potential for a predictive homology model.
Assuntos
Arginina/farmacologia , Receptores de Somatostatina/antagonistas & inibidores , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Humanos , Luciferases/genética , Modelos Moleculares , Conformação Molecular , Relação Estrutura-AtividadeRESUMO
The synthesis and biological testing of novel classes of potent melanin-concentrating hormone (MCH-R1) antagonists based on pyrazolopiperazinone and pyrrolopiperazinone scaffolds are described.
Assuntos
Piperazinas/síntese química , Pirazóis/síntese química , Pirróis/síntese química , Receptores de Somatostatina/antagonistas & inibidores , Células CACO-2 , Humanos , Indicadores e Reagentes , Modelos Moleculares , Conformação Molecular , Piperazinas/farmacologia , Pirazóis/farmacologia , Pirróis/farmacologia , Ensaio Radioligante , Receptor 5-HT2C de Serotonina/efeitos dos fármacosRESUMO
Aminomethyl tetrahydronaphthalene biphenyl carboxamide MCH-R1 antagonists with greater selectivity over hERG were identified. SAR studies addressing two distinct alternatives for structural modifications leading to improve hERG selectivity are described.
Assuntos
Compostos de Bifenilo/farmacologia , Canais de Potássio Éter-A-Go-Go/efeitos dos fármacos , Naftalenos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Receptores de Somatostatina/antagonistas & inibidores , Compostos de Bifenilo/síntese química , Canal de Potássio ERG1 , Ergolinas/farmacologia , Humanos , Indicadores e Reagentes , Mianserina/farmacologia , Naftalenos/síntese química , Receptor 5-HT2C de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Relação Estrutura-AtividadeRESUMO
The design, synthesis, and biological studies of a novel class of MCH-R1 antagonists based on an aminotetrahydronaphthalene ketopiperazine scaffold is described. Compounds within this class promoted significant body weight reduction in mouse diet induced obesity studies. The potential for hERG blockage activity and QT interval studies in anesthetized dogs are discussed.
Assuntos
Piperazinas/farmacologia , Receptores de Somatostatina/antagonistas & inibidores , Animais , Cães , Avaliação Pré-Clínica de Medicamentos , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Modelos Moleculares , Piperazinas/química , Relação Estrutura-AtividadeRESUMO
A direct correlation between hERG binding and QTc prolongation was established for a series of aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists. Compounds within this class with greater selectivity over hERG were developed. Compound 4h proved to have the best profile, with MCH-R1 Ki = 16 nm and hERG IC50 = 25 microM.