Safety, Tolerability, and Effects of Sodium Bicarbonate Inhalation in Cystic Fibrosis.

BACKGROUND: Among the many consequences of loss of CFTR protein function, a significant reduction of the secretion of bicarbonate (HCO3-) in cystic fibrosis (CF) is a major pathogenic feature. Loss of HCO3- leads to abnormally low pH and impaired mucus clearance in airways and other exocrine organs, which suggests that NaHCO3 inhalation may be a low-cost, easily accessible therapy for CF. OBJECTIVE: To evaluate the safety, tolerability, and effects of inhaled aerosols of NaHCO3 solutions (4.2% and 8.4%). METHODS: An experimental, prospective, open-label, pilot, clinical study was conducted with 12 CF volunteer participants over 18 years of age with bronchiectasis and pulmonary functions classified as mildly to severely depressed. Sputum rheology, pH, and microbiology were examined as well as spirometry, exercise performance, quality-of-life assessments, dyspnea, blood count, and venous blood gas levels. RESULTS: Sputum pH increased immediately after inhalation of NaHCO3 at each clinical visit and was inversely correlated with rheology when all parameters were evaluated: [G' (elasticity of the mucus) = - 0.241; G″ (viscosity of the mucus) = - 0.287; G* (viscoelasticity of the mucus) = - 0.275]. G* and G' were slightly correlated with peak flow, forced expiratory volume in 1 s (FEV1), and quality of life; G″ was correlated with quality of life; sputum pH was correlated with oxygen consumption (VO2) and vitality score in quality of life. No changes were observed in blood count, venous blood gas, respiratory rate, heart rate, peripheral oxygen saturation of hemoglobin (SpO2), body temperature, or incidence of dyspnea. No adverse events associated with the study were observed. CONCLUSION: Nebulized NaHCO3 inhalation appears to be a safe and well tolerated potential therapeutic agent in the management of CF. Nebulized NaHCO3 inhalation temporarily elevates airway liquid pH and reduces sputum viscosity and viscoelasticity.

Physical and chemical analysis of commercial nystatin / Análises físico-químicas da nistatina comercial

Nystatin (NYS) is a fermentation-produced antibiotic of the polyene group. Commercial NYS is a mixture of compounds named NIS A1, A2 and A3. Current analysis undertook physical and chemical analyses in two samples of commercial nystatin (NYS I and NYS II). Moisture (Karl Fischer), spectroscopic (IR, UV and fluorescence) and thermal analyses (TGA and DSC) were conducted. The moisture was respectively 9.2% and 8.8% for samples I and II. Absorption spectrum in the UV/VIS region had a vibronic structure with three max.. The mirror image rule was not complied with in the fluorimetric analysis. Spectroscopy analysis in the IV region indicated that samples showed spectra similar one to another, analogous to crystal type A. Thermal analyses by DSC provided a wide, single endothermal peak and, therefore, similarities among the samples. DTG shows that samples undergo decomposition at three phases within the temperature range under analysis. Results show that samples are impure and not polymorphic, constituted by a mixture of the compounds A1, A2 and A3.

A nistatina (NIS) é um antibiótico do grupo dos poliênicos produzido por fermentação. A NIS comercial consiste numa mistura de compostos denominados NIS A1, A2 e A3. O presente trabalho teve por objetivo realizar análises físico-químicas de duas amostras de nistatina comercial (NIS I e NIS II). Foram realizadas análises de umidade (Karl Fischer), espectroscópicas (IV, UV e fluorescência) e térmicas (TGA e DSC). A umidade encontrada foi de 9,2% e 8,8% para as amostras I e II, respectivamente. O espectro de absorção na região do UV/VIS apresentou estrutura vibrônica com três máxs.. Na análise fluorimétrica não se observou obediência à regra da imagem espelho. A análise por espectroscopia na região do IV mostrou que as amostras apresentam espectros semelhantes entre si, análogos ao cristal do tipo A. As análises térmicas por DSC apresentaram um pico endotérmico, largo, único, sugerindo semelhanças entre as amostras. O DTG indica que as amostras sofrem decomposição em três fases no intervalo de temperatura estudado. Dos resultados obtidos, concluiu-se que que as amostras são impuras e não polimorfas, constituindo-se de uma mistura dos compostos A1, A2 e A3.

MCM-41 and Na-magadiite silicates internal voids probed by pyrene fluorescence spectroscopy.

Investigation of the properties of two different silicate materials, namely MCM-41, with one-dimensional, cylindrical pores (4.04 nm diameter), and Na-magadiite, with a bidimensional, layered structure (1.67 nm between layers) was carried out. These materials may be used as sorbents, and their polarity is determinative to the kind of applications they may be employed at. Pyrene, which presents a vibronically resolved emission spectrum, was used as a fluorescent probe to give information on the polarity of these silicates voids. The ratio of band intensity at 383 nm (band 3) to that at 373 nm (band 1) is known to diminish as the polarity of the medium increases. Pristine sorbents and pyrene-adsorbed ones were characterized by thermogravimetric analysis and X-ray diffraction. UV-VIS emission spectra of included pyrene were recorded at temperatures ranging from 10 to 300 K, and from comparing the I(3) : I(1) ratio it was found that Na-magadiite internal sites correspond to a less polar medium than those in MCM-41. This is in accordance with the thermogravimetric data, which shows that a larger amount of pyrene was included in Na-magadiite, despite its smaller dimensions. Yet, excimer emission, usually a concentration dependent phenomenon, was mainly observed for the MCM-41 samples. Upon temperature lowering, pyrene molecules move to other sites of different polarities, towards an intermediary value for both materials.

Lipid membrane with low proton permeability.

This work reports the production of a liposomal formulation, having a lipidic membrane with known chemical composition and a low proton permeability, as confirmed by physicochemical characterization of the maintenance of a transmembranic pH gradient. These liposomes consist of DSPC, DSPE-PEG, DSPG and cholesterol, with low internal pH. To verify the low proton permeability of these liposomal bilayers, a study of proton migration according to the fluorescence quenching of 9-aminoacridine (9AA), as well as CPT-11 encapsulation, were used to monitor the acidification of the intravesicular space. Both experiments showed that this liposomal formulation is able to maintain a transmembranic proton gradient.