ABSTRACT
The adequate formulation of topical vehicles to treat skin diseases is particularly complex. A desirable formulation should enhance the accumulation of the active drugs in the target tissue (the skin), while avoiding the penetration enhancement to be so large that the drugs reach the systemic circulation in toxic amounts. We have evaluated the transcutaneous penetration of three drugs chosen for their widely variable physicochemical properties: Amphotericin B, Imiquimod and Indole. We incorporated the drugs in fluid or ultra-flexible liposomes. Ultra-flexible liposomes produced enhancement of drug penetration into/through human skin in all cases in comparison with fluid liposomes without detergent, regardless of drug molecular weight. At the same time, our results indicate that liposomes can impede the transcutaneous penetration of molecules, in particular small ones.
Subject(s)
Amphotericin B/pharmacokinetics , Imiquimod/pharmacokinetics , Indoles/pharmacokinetics , Administration, Cutaneous , Amphotericin B/administration & dosage , Amphotericin B/chemistry , Animals , Drug Delivery Systems , Drug Stability , Humans , Imiquimod/administration & dosage , Imiquimod/chemistry , Indoles/administration & dosage , Indoles/chemistry , Liposomes , Mice , Skin AbsorptionABSTRACT
Dried herbal preparations, based on "Zornia latifolia," are commonly sold on web, mainly for their supposed hallucinogenic properties. In this work, we demonstrate that these commercial products contain a different Fabacea, i.e., Stylosanthes guianensis, a cheaper plant, widely cultivated in tropical regions as a fodder legume. We were provided with plant samples of true Zornia latifolia from Brazil, and carried out a thorough comparison of the two species. The assignment of commercial samples was performed by means of micro-morphological analysis, DNA barcoding, and partial phytochemical investigation. We observed that Z. latifolia contains large amounts of flavonoid di-glycosides derived from luteolin, apigenin, and genistein, while in S. guianensis lesser amounts of flavonoids, mainly derived from quercetin, were found. It is likely that the spasmolytic and anxiolytic properties of Z. latifolia, as reported in traditional medicine, derive from its contents in apigenin and/or genistein.
Subject(s)
Drug Contamination , Fabaceae/chemistry , Flavonoids/analysis , Plant Extracts/analysis , Apigenin , Brazil , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Luteolin , Plants , QuercetinABSTRACT
In 2011, the Spanish Association of Pediatrics decided to support the most ambitious project of its newly created Committee for Medicinal Products: Pediamécum. This is the first free on-line database with information on medicinal products for pediatric use in Spain. The web page http://pediamecum.es/ started on December 17 December 2012. One year later, Pediamécum includes 580 registered drugs. The website achieved more than one million page views by the end of 2013. Because of the first anniversary of Pediamécum, a survey was performed to request the feeling of users. Four hundred eighty-three responses were obtained. Ninety-five percent believed that it is easy to navigate through the web, and 74% said that their doubts about the use of medicines in children were always resolved. The overall rating of Pediamécum is 7.5/10. The aims of Pediamécum are being accomplished; which is reflected essentially due to it becoming a useful tool for all professionals who care for children in their daily clinical practice.
Subject(s)
Databases, Factual , Internet , Mobile Applications , Pediatrics , Prescription Drugs , Child , Humans , Societies, Medical , Spain , Surveys and Questionnaires , Time FactorsABSTRACT
We have screened the formation of complexes between ethylendiamine (EDA) core polyamidoamine (PAMAM) dendrimers (D) and a short interfering RNA (siRNA) as a function of three variables: the ionic strength of the medium (lacking or containing 150 mM NaCl), the D generation (G4, G5, G6 and G7) and the N/P ratio (nitrogen amines in D/phosphate in siRNA). It was observed that all D formed complexes with siRNA, being the size of the complexes strictly dependent on the ionic strength of the media. The strong electrostatic interactions occurring in NaCl lacking medium made siRNA-D complexes (siRNA-D) smaller than those obtained in NaCl containing medium (30-130 nm, +25 mV zeta potential vs. several microm-800 nm, 0 zeta potential, respectively). Not surprisingly, both the uptake and inhibition of EGFP expression in cell culture, resulted dependent on siRNA-D size. siRNA-D prepared in NaCl containing medium were poorly captured and presented a basal activity on phagocytic (J-774-EGFP) cells, being inactive on non-phagocytic cells (T98G-EGFP). However, the smaller siRNA-D prepared in NaCl lacking medium were massively captured, exhibiting the highest inhibition of EGFP expression at 50 nM siRNA (non-cytotoxic concentration). Remarkably, siRNA-G7 produced the highest inhibition of EGFP expression both in T98G-EGFP (35%) and J-774-EGFP (45%) cells, in spite of inducing a lower protection of siRNA against RNase A degradation. Taken together, our results showed that modifying the chemical structure of D is not the only way of achieving siRNA-D suitable for silencing activity. The simple use of a low ionic strength preparation media has been critical to get small siRNA-D that could be captured by cells and in particular, siRNA-G7 but not those formed by lower generation D, possessed structural constraints other than size that could favor its silencing activity.
Subject(s)
Dendrimers/chemical synthesis , Drug Carriers/chemical synthesis , Drug Compounding/methods , Ethylenediamines/chemistry , Polyamines/chemistry , RNA Interference/drug effects , RNA, Small Interfering , Cell Line, Transformed , Cell Survival/drug effects , Dendrimers/chemistry , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Stability , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Osmolar Concentration , RNA, Small Interfering/chemistry , RNA, Small Interfering/pharmacokinetics , RNA, Small Interfering/pharmacologyABSTRACT
Hydrophobic ([tetrakis(2,4-dimetil-3-pentyloxi)-phthalocyaninate]zinc(II)) (ZnPc) and hydrophilic ([tetrakis(N,N,N-trimethylammoniumetoxi)-phthalocyaninate]zinc(II) tetraiodide) (ZnPcMet) phthalocyanines were synthesized and loaded in ultradeformable liposomes (UDL) of soybean phosphatidylcholine and sodium cholate (6:1, w/w, ratio), resulting 100 nm mean size vesicles of negative Zeta potential, with encapsulation efficiencies of 85 and 53%, enthalpy of phase transition of 5.33 and 158 J/mmol for ZnPc and ZnPcMet, respectively, indicating their deep and moderate partition into UD matrices. Matrix elasticity of UDL-phthalocyanines resulted 28-fold greater than that of non-UDL, leaking only 25% of its inner aqueous content after passage through a nanoporous barrier versus 100% leakage for non-UDL. UDL-ZnPc made ZnPc soluble in aqueous buffer while kept the monomeric state, rendering singlet oxygen quantum yield (Phi(Delta)) similar to that obtained in ethanol (0.61), whereas UDL-ZnPcMet had a four-fold higher Phi(Delta) than that of free ZnPcMet (0.21). Free phthalocyanines were non-toxic at 1 and 10 microM, both in dark or upon irradiation at 15 J/cm2 on Vero and J-774 cells (MTT assay). Only liposomal ZnPc at 10 microM was toxic for J-774 cells under both conditions. Additionally, endo-lysosomal confinement of the HPTS dye was kept after irradiation at 15 J/cm2 in the presence of UDL-phtalocyanines. This could lead to improve effects of singlet oxygen against intra-vesicular pathogen targets inside the endo-lysosomal system.
Subject(s)
Indoles/chemistry , Liposomes/chemistry , Radiation-Sensitizing Agents/chemistry , Animals , Calorimetry, Differential Scanning , Cell Survival/drug effects , Chlorocebus aethiops , Indoles/administration & dosage , Indoles/chemical synthesis , Isoindoles , Leishmaniasis, Cutaneous/drug therapy , Liposomes/administration & dosage , Liposomes/chemical synthesis , Macrophages/drug effects , Macrophages/metabolism , Macrophages/radiation effects , Mice , Microscopy, Electron, Transmission , Nanotechnology , Photochemotherapy/methods , Radiation-Sensitizing Agents/administration & dosage , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet , Vero CellsSubject(s)
Klebsiella Infections/diagnosis , Klebsiella oxytoca , Liver Abscess/microbiology , Aged , Humans , MaleABSTRACT
To test the hygienic functional hypothesis of allogrooming in the white-crowned mangabey (Cercocebus torquatus lunulatus), we analyzed the distribution of such behavior over the body surface in the individuals of two captive groups of this species (N = 9 and N = 8). To sample the data, we used focal animal sampling and continuous recording. Before analyzing the data, we measured a representative subject in order to calculate the body surface area occupied by each site, defined accessibility rigorously (distinguishing among three categories of sites: easy to reach, difficult to reach, and inaccessible), and tested empirically the classification proposed. To determine whether allogrooming was likely to concentrate on the body sites with accessibility problems, we ran three successive analyses, each of with was increasingly specific: grouping types of sites, analyzing each site separately, and analyzing each subject's reception profile. The results obtained show that in both groups inaccessible sites received more allogrooming than predicted by their actual surface area; sites that were difficult to reach received an amount of allogrooming proportional to the body surface area they occupied, and those easy to reach received less allogrooming than expected. This complementarity between the distribution of auto- and allogrooming is consistent with the hygienic functional hypothesis of allogrooming. However, not all inaccessible sides nor those difficult-to-reach were allogroomed equally: Allogrooming concentrated primarily on dorsal and caudal regions, whose care is incompatible with a ventral/ventral orientation between groomer and groomee. The strong distributional selectivity of allogrooming and the interindividual variability in preferred allogrooming sites suggest that the hygienic functional hypothesis cannot fully account for all the aspects of the corporal distribution of such behavior. Thus, in support of the multifunctional nature of allogrooming, we conclude that there must be more than cleaning involved in Cercocebus torquatus lunulatus' allogrooming.
Subject(s)
Cercocebus/physiology , Grooming/physiology , Hygiene , Animals , Body Surface Area/veterinaryABSTRACT
OBJECTIVES: To determine the distribution of lipoprotein(a) levels and prevalence of hyperLp(a) in diabetes mellitus type I (IDDM). To analyze the effect of glycemic control and microalbuminuria on Lp(a) levels. METHODS: Cross-sectional study of 263 subjects with IDDM with a mean age of 19.2 +/- 11.6 years and an evolutive course of 6.3 +/- 6.5 years. Apart from Lp(a), measurements were obtained from serum levels of lipids, apolipoproteins AI and B, fructosamine, glycosilated hemoglobin (HbA1c), and albuminuria in all patients. RESULTS: Mean serum concentrations of Lp(a) were 16.5 +/- 18.1 mg/dl and 18.5% of patients had Lp(a) levels > 30 mg/dl [hyperLp(a)]. With a multivariate regression analysis, the only variable correlated with Lp(a) levels was cholesterol LDL (p < 0.001). Patients with hyperLp(a) did not differ from the other patients in any of the other variables analyzed, and patients with HbA1c higher and lower than 8% had similar mean serum Lp(a) concentrations (14.0 +/- 16 vs. 17.9 +/- 20). Lp(a) concentration was also similar among patients with albuminuria higher and lower than 20 micrograms/min (16.6 +/- 20 vs. 17.7 +/- 16). CONCLUSIONS: Control of glycemia and microalbuminuria have no effect on Lp(a) concentrations in diabetes mellitus type I. HyperLp(a) is not indicative of a poor glycemic control.
Subject(s)
Diabetes Mellitus, Type 1/blood , Lipoprotein(a)/blood , Adolescent , Adult , Age Factors , Aged , Albuminuria/diagnosis , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Regression Analysis , Time FactorsSubject(s)
Paraganglia, Nonchromaffin/cytology , Adult , Animals , Carotid Body/cytology , Cats , Chemoreceptor Cells/cytology , Ganglia, Autonomic/cytology , Humans , Infant , Iodides , Male , Methods , Mice , Neurofibrils , Osmium , Paraganglia, Nonchromaffin/embryology , Photomicrography , Staining and Labeling , Vagus Nerve/cytology , ZincSubject(s)
Pyoderma/etiology , Streptomycin/therapeutic use , Viruses/isolation & purification , Animals , Anuria/complications , Child , Femur , Fever/complications , HeLa Cells/cytology , Humans , Male , Microscopy, Electron , Nephritis/complications , Powders , Pyoderma/complications , Rabbits , Skin Diseases, Infectious/pathologyABSTRACT
De una manera esquemática -para no hacer una amplia descripción de los hechos hemos preferido una amplia documentación gráfica-, hemos reseñado las alteraciones generales de los centros nerviosos en la lepra. Confirmamos en general los datos conocidos de los autores: degeneraciones electivas de los tramos radiculares posteriores, de los cordones posteriores medulares (predominantemente en el de goll) y en menor intensidad alteraciones no sistematizadas en el cordeon lateral, parecendo comenzar estos trastornos por la vaina mielínica. En tramos más altos del eje encefálico, discretos procesos degenerativos de las celulas nerviosas y la conocidas gliosis marginales y perivasculares. Las alteraciones se limitan en lo sistematizado al territorio de la neurona sensitiva periferica. Mas junto a estos hechos, queremos resenar los infiltrados perivasculares medulares, y junto a ellos nos referimos especialmente a las transformaciones neurolglicas degenerativas que conducen a las clasmatodendrosis por nosotros desritas, y a las alteraciones degenerativas de la microglia y oligodendroglia. Resaltamos estos hechos últimos encontrados por nosotros por cuanto la imagem morfologica corresponde a las en general conocidas alteraciones degenerativas toxicas de los centros. En general, la respuesta de los centros nerviosos a los más varios tipos de tóxicos conduce inicialmente a gliosis, y más tarde a los fenómenos degenerativos descritos. Finalmente referimos de una manera principalmente gráfica las alteraciones degenerativas del nervio óptico y los fenómenos de edema agudo oligodendroglial en el nervio óptico y quiasma que no hemos encontrado referidos hasta el momento en la literatura. Creemos, en suma, que el cuadro histopatológico que acabamos de delimitar obedece en parte a lesiones periféricas que tuvieron su origem en los glanglios y en los nervios, y en parte a procesos de impregnación tóxica, semejantes a los que pueden encontrarse en otras afecciones crónicas, sin caracteres de especificidad.
