The in vivo effect of L-arginine on skin elasticity in mice

ABSTRACT The human skin aging process is a complex mechanism that can be induced both by intrinsic and extrinsic factors. Observations include a decrease in the biosynthetic and proliferative capacity of cells, increased expression of matrix metalloproteinases, reduction in collagen type I expression, and the progressive disappearance of elastic tissue in the papillary dermis. L-arginine, the substrate of nitric oxide synthesis, is involved in angiogenesis and cell proliferation, as well as an indirect precursor of collagen synthesis via the proline pathway. The aim of this study was to examine the tensile strength, histology, and immunohistochemistry of female and male mice skin receiving different concentrations of topically applied L-arginine, in order to evaluate the possibility of using L-arginine as an active cosmetic ingredient in antiaging products. The results suggest that the application of L-arginine improves the mechanical resistance of skin from older female mice (20 weeks old) and promotes the formation of a larger amount of collagen and elastic fibers in the skin when applied at a concentration of 15%.

Oral or topical administration of L-arginine changes the expression of TGF and iNOS and results in early wounds healing

ABSTRACT PURPOSE: To evaluate the contribution of L-arginine oral or topical rout of administration in the surgical wound healing process. METHODS: L-arginine was orally or topically administrated to mice after a laparotomy model procedure. The wounds were analyzed to evaluate the granulation tissue by HE analysis, collagen deposition, iNOS and cytokines production by immunochemisyry on wound progress. Mice used in this model were healthy, immunosupressed or diabetic and all of them were treated with different concentration of L-arginine and rout of administration. RESULTS: Suggested that groups treated with L-arginine orally or topically improved wound repair when compared with non-treatad mice. L- arginine treatment stimulated TGF-β and restricted NO production leading to a mild Th1 response and collagen deposition in injured area, when it was orally administrated. Topical administration decreased IL-8 and CCR1 expression by wound cells but did not interfere with TNF-α and IL-10 production, ratifying the decrease of inflammatory response, the oral administration however, presented a higher iNOS and TGF-β expression then. L-arginine treatment also improved the improved the wound healing in immunosupressed or diabetic mice. CONCLUSION: L-arginine administrated orally or topically can be considered an important factor in the recuperation of tissues.

influência de excipientes farmacêuticosem reações adversas a medicamentos / Influence of pharmaceutical excipients on adversereactions to drugs

Excipientes são substâncias adicionadas às formulaçõesfarmacêuticas, excluindo-se os fármacos,e têm a função de garantir a estabilidade eas propriedades biofarmacêuticas dos medicamentos,além de melhorarem as característicasorganolépticas e, assim, a aceitação dos medicamentospelos pacientes. Porém, diversos estudostêm demonstrado que esses compostos não estãoisentos do risco de causar reações adversas. O objetivodeste estudo é abordar algumas das reaçõesadversas já descritas para excipientes comumenteutilizados na indústria farmacêutica. Observa-seque o aspartame e a sacarina estão relacionadosao aparecimento de tipos de câncer, como linfomase hiperplasias do urotélio em ratos, respectivamente.O sorbitol e a lactose podem produzirreações no trato gastrointestinal, como diarreia eflatulências e, assim, dificultar a absorção do fármaco.O cloreto de benzalcônio, muito utilizadoem formulações oculares e descongestionantesnasais, pode causar prolongada broncoconstriçãoe o aumento progressivo de lesões córneas.Já o corante amarelo de tartrazina e os parabenos,por serem estruturalmente semelhantes aoácido acetilsalicílico, estão relacionados a reaçõesde hipersensibilidade, pois pessoas sensíveis a essefármaco também podem apresentar reaçõesalérgicas a tais excipientes. Em conclusão, apesarde conceitualmente inertes, não existe ausênciade risco comprovada na utilização de adjuvantesfarmacêuticos. Apesar de alguns estudos apresentaremresultados controversos com relação àpromoção de efeitos adversos relacionada à utilizaçãode alguns excipientes, pode-se concluir que,quando possível, a adição desses compostos develimitar-se à estritamente necessária para mantera qualidade do medicamento e a função do fármaco,para evitar possíveis reações adversas.

Excipients are substances added to pharmaceutical formulations,with the exclusion of drugs, which have thefunction of guaranteeing the stability and biopharmaceuticalproperties of the drug, in addition to improvingits organoleptic characteristics and, thus, acceptanceof the medication by patients. However, several studieshave shown that these compounds may cause adversereactions. The objective of this study is to discuss theadverse effects caused by excipients commonly usedby the pharmaceutical industry. It is possible to noticethat aspartame and saccharin are associated with theonset of cancers, such as lymphomas and hyperplasticurothelium in rats, respectively. Sorbitol and lactosemay produce reactions in the gastrointestinal tract suchas diarrhea and flatulence and, thereby, hinder drugabsorption. Benzalkonium chloride, often used in ocularformulations and nasal decongestants, can cause prolongedbronchoconstriction and a progressive increasein corneal injury. Because they are structurally similarto aspirin, the yellow dye tartrazine and parabens areassociated with hypersensitivity reactions, as individualssensitive to this drug may also have allergic reactionsto these excipients. In conclusion, although conceptuallyinert, we cannot rule out the risks associated with theuse of pharmaceutical adjuvants. Even though somestudies have presented conflicting results regarding theadverse effects caused by the use of certain excipients, itis possible to conclude that the use of these compoundsmust be limited to that strictly necessary. This way,thequality of the product and the function of the drug aremaintained and possible adverse reactions are avoided.

Validation of HPLC, DPPH• and nitrosation methods for mesalamine determination in pharmaceutical dosage forms

Mesalamine (5-aminosalicylic acid, 5-ASA) is used because of its local effects in the treatment of inflammatory bowel disease. Therefore, the aims of this work were to compare and validate three analytical methods for the quality control of commercial coated tablets containing 5-ASA: high performance liquid chromatography (HPLC), 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH•) and nitrosation. The parameters linearity, precision and accuracy were studied in this work. HPLC with ultraviolet detection at 254 nm was carried out with a C18 column and a mobile phase constituted of 30 mmol/L monobasic phosphate buffer (pH 7.0) and methanol (70:30; v/v), with 25 percent tetrabutylammonium hydrogen sulphate. The DPPH• method was performed at 517 nm and using 100 mmol/L acetate buffer, pH 5.5, ethanol and 250 æmol/L ethanolic solution of DPPH•. The nitrosation method was accomplished by using a platinum electrode and standard 0.1 mol/L sodium nitrite as titrant solution. Repeatability (intra-day) and intermediate precision (inter-day), expressed as RSD, were lower than 3 percent. The experimental recoveries were between 72.5 and 99.9 percent. Statistical analysis by one-way ANOVA, followed by the multiple comparison test of Bonferroni showed no significant difference among the three methods. All proposed methods can be used for the reliable quantitation of 5-ASA in pharmaceutical dosage forms.

Mesalazina (ácido 5-aminosalicílico, 5-ASA) é utilizado devido seu efeito local no tratamento de doença inflamatória intestinal. Assim, o objetivo deste trabalho foi comparar e validar três métodos analíticos para o controle de qualidade de comprimidos comerciais revestidos contendo 5-ASA: cromatografia líquida de alta eficiência (CLAE), radical 1,1-difenil-2-picril-hidrazil (DPPH•) e nitrosação. Os parâmetros linearidade, precisão e exatidão foram estudados neste trabalho. CLAE com detecção ultravioleta em 254 nm foi realizada utilizando coluna C18 e a eluição em fase móvel constituída de tampão fosfato monobásico 30 mmol/L (pH 7,0) e metanol (70:30; v/v), com 25 por cento de sulfato hidrogênio de tetrabutilamônio. Para o método de DPPH• utilizou-se tampão acetato 100 mmol/L, pH 5,5, álcool etílico e 250 æmol/L solução etanólica de DPPH• a 517 nm. Para o método de nitrosação utilizou-se um eletrodo de platina e um padrão de nitrito de sódio 0.1 mol/L como solução titulante. Repetibilidade (intra-dia) e precisão intermediária (inter-dia), expressado como DPR, foi menor que 3 por cento. A recuperação experimental foi entre 72,5 e 99,9 por cento. Análise estatística por "one-way" ANOVA, seguida de comparação múltipla do teste de Bonferroni, não mostrou significância entre os três métodos. Os métodos propostos podem ser usados para análise quantitativa do5-ASA em formas farmacêuticas.