Chloride and sodium ion concentrations in saliva and sweat as a method to diagnose cystic fibrosis / Dosagem da concentração dos íons cloreto e sódio na saliva e no suor para o reconhecimento de pacientes com fibrose cística

Abstract Objective: Cystic fibrosis diagnosis is dependent on the chloride ion concentration in the sweat test (≥ 60 mEq/mL - recognized as the gold standard indicator for cystic fibrosis diagnosis). Moreover, the salivary glands express the CFTR protein in the same manner as sweat glands. Given this context, the objective was to verify the correlation of saliva chloride concentration and sweat chloride concentration, and between saliva sodium concentration and sweat sodium concentration, in patients with cystic fibrosis and healthy control subjects, as a tool for cystic fibrosis diagnosis. Methods: There were 160 subjects enrolled: 57/160 (35.70%) patients with cystic fibrosis and two known CFTR mutations and 103/160 (64.40%) healthy controls subjects. Saliva ion concentration was analyzed by ABL 835 Radiometer® equipment and, sweat chloride concentration and sweat sodium concentration, respectively, by manual titration using the mercurimetric procedure of Schales & Schales and flame photometry. Statistical analysis was performed by the chi-squared test, the Mann -Whitney test, and Spearman's correlation. Alpha = 0.05. Results: Patients with cystic fibrosis showed higher values of sweat chloride concentration, sweat sodium concentration, saliva chloride concentration, and saliva sodium concentration than healthy controls subjects (p-value < 0.001). The correlation between saliva chloride concentration and sweat chloride concentration showed a positive Spearman's Rho (correlation coefficient) = 0.475 (95% CI = 0.346 to 0.587). Also, the correlation between saliva sodium concentration and sweat sodium concentration showed a positive Spearman's Rho = 0.306 (95% CI = 0.158 to 0.440). Conclusions: Saliva chloride concentration and saliva sodium concentration are candidates to be used in cystic fibrosis diagnosis, mainly in cases where it is difficult to achieve the correct sweat amount, and/or CFTR mutation screening is difficult, and/or reference methods for sweat test are unavailable to implement or are not easily accessible by the general population.

Resumo Objetivo: O diagnóstico da fibrose cística depende do valor da concentração de íons de cloreto no teste do suor (≥ 60 mEq/mL - reconhecido como o indicador-padrão para o diagnóstico da doença). Além disso, as glândulas salivares expressam a proteína RTFC igualmente às glândulas sudoríparas. Nesse contexto, nosso objetivo foi verificar a correlação da concentração de cloreto na saliva e a concentração de cloreto no suor e entre a concentração de sódio na saliva e a concentração de sódio no suor em pacientes com fibrose cística e indivíduos controles saudáveis, como uma ferramenta para diagnóstico de fibrose cística. Métodos: Contamos com a participação de 160 indivíduos [57/160 (35,70%) com fibrose cística e duas mutações no gene RTFC conhecidas e 103/160 (64,40%) indivíduos controles saudáveis]. A concentração de íons na saliva foi analisada pelo equipamento ABL 835 da Radiometer® e a concentração de cloreto no suor e sódio no suor, respectivamente, por titulação manual utilizando o método mercurimétrico de Schales & Schales e fotometria de chama. A análise estatística foi realizada pelo teste qui-quadrado, pelo teste de Mann-Whitney e pela correlação de Spearman. Alpha = 0,05. Resultados: Os pacientes com fibrose cística apresentaram maiores valores na concentração de cloreto no suor, concentração de sódio no suor, concentração de cloreto na saliva e concentração de sódio na saliva do que os indivíduos-controle saudáveis (valor de p < 0,001). A correlação entre as concentrações de cloreto na saliva e cloreto no suor mostrou Rho de Spearman (coeficiente de correlação) positivo = 0,475 (IC de 95% = 0,346 a 0,587). Além disso, a correlação entre concentração de sódio na saliva e concentração de sódio no suor mostrou Rho de Spearman positivo = 0,306 (IC de 95% = 0,158 a 0,440). Conclusões: A concentração de cloreto na saliva e a concentração de sódio na saliva são candidatas a ser usadas como diagnóstico de fibrose cística, principalmente em casos em que é difícil atingir a quantidade correta de suor, e/ou o exame da mutação RTFC é difícil e/ou o método de referência para o teste do suor não se encontra disponível ou não é de fácil acesso ao público em geral.

Thickeners sold in Brazil: analysis of the composition and suitability for children under the age of 3 / Espessantes comercializados no Brasil: análise da composição e da adequação para crianças menores de 3 anos

Introduction: Thickeners are used in the treatment of swallowing disorders, named dysphagia. In Brazil there is no specific product for the pediatric population who under the age of 3 years. Objective: To analyze the different types of thickeners available in Brazil, considering their chemical composition and their use in pediatrics. Methods: Quantitative study, with descriptive approach based on the data collection. The brands of existing thickeners were analyzed in Brazil and their composition in relation to the Codex Alimentarius and nutritional recommendations for children from 0 to 3 years. Results: Eight brands were studied, three of which proved to be inappropriate for pediatric use because they have gum in their formulation. Other thickeners brands did not present inadequacies for use in the age group from 0 to 3 years old regarding to the type of carbohydrate, sodium content and total caloric value. Conclusion: In Brazil, 5 thickeners brands present in their composition levels of sodium and profile of carbohydrate adequate for children from 0 to 3 years, even when they are associated with infant formulas.(AU)

Introdução: Os espessantes são utilizados no tratamento dos distúrbios de deglutição, denominados disfagia, porém, no Brasil, não há produto específico para a população pediátrica menor de 3 anos. Objetivo: Analisar os diferentes tipos de espessantes disponíveis no Brasil, considerando sua composição química e sua utilização em pediatria. Método: Estudo quantitativo, do tipo descritivo com base no levantamento de dados. Foram analisadas as marcas de espessantes existentes no Brasil quanto a sua composição em relação ao Códex Alimentarius e recomendações nutricionais para crianças de 0 a 3 anos. Resultados: Foram estudadas oito marcas, das quais três mostraram-se inadequadas para utilização pediátrica, por possuírem goma em sua formulação. As demais marcas de espessantes não apresentaram inadequações para uso na faixa etária de 0 a 3 anos de idade no que se refere ao tipo de carboidrato, teor de sódio e valor calórico total. Conclusão: No Brasil, 5 marcas de espessantes apresentam em sua composição teores de sódio e perfil de carboidratos adequados para crianças de 0 a 3 anos, mesmo quando associadas a fórmulas infantis.(AU)

Novel multi-layer APPPA microcapsules for oral delivery: preparation condition, stability and permeability.

Oral therapy utilizing cell microencapsulation has shown promise in the treatment of many diseases. Current obtainable microcapsule membranes, however, show inadequate stability in the gastrointestinal (GI) environment, thus restricting the general application of live cells for oral therapy. To overcome this limitation, we have previously developed a novel multi-layer alginate/poly-L-lysine/pectin/poly-L-lysine/alginate microcapsule (APPPA) with demonstrated improvement on membrane stability over the frequently reported alginate/poly-L-lysine/alginate (APA) microcapsules. In this study, we further examined the effects of preparation conditions on microcapsule formation, and assessed the membrane strength and GI stability. Results showed that increased membrane strength of the APPPA microcapsules was attained by using pectin with low degree of esterification as the mid-layer material, saline as the solvent for the preparation solutions and washing medium, and 0.1 M CaCl2 as the gelling solution for alginate cores. Resistance of this membrane to the simulated GI fluids was also investigated. Permeability of and release profiles from the APPPA microcapsules were found comparable to the APA microcapsules. These findings suggested that the multi-layer APPPA microcapsule formulation may have potential in oral delivery of proteins, live bacterial cells and other biomedical applications.

Effect of Na+ ions on pH-dependent conformational changes in brush border sucrase-isomaltase in mice intestine.

Intestinal brush border sucrase-isomaltase (sucrose D-glucosidase E.C. 3.2.1.48, E.C. 3.2.1.10) exhibits pH-dependent stimulatory or inhibitory effects in response to Na+ ions. However, whether the enzyme undergoes conformational modulations as a function of pH and in the presence of alkali metal ions is not known. In this paper, we investigated the structural and functional relationship of purified murine sucrase in response to pH and Na+ ions using UV-CD fluorescence and spectroscopic studies. Kinetic studies revealed that at pH 5.0, the enzyme activation by Na+ ions was V-type, which changed to K-type at pH 7.2, whereas at alkaline pH (8.5), Na+ ions inhibited the enzyme activity and inhibition was uncompetitive in nature, affecting both the Km and Vmax components. Far UV-CD spectra of protein at pH 7.2 in the absence and presence of Na+ were almost overlapping, suggesting that secondary structure of protein was not affected upon addition of the salt. However, near UV-CD spectra indicated marked alterations in the tertiary structure of protein in presence of 50 mM Na+ ions. Increase in pH from 7.2 to 8.5 resulted in a marked rise in fluorescence intensity and red shift in lambda max due to tryptophan residues in the enzyme molecule. These findings suggested that alterations in enzyme activity as a function of pH and Na+ ions was associated with ionization of key amino acid residues together with structural modifications in the enzyme conformation around neutral or alkaline pH.

Host-finding behavior of Strongyloides stercoralis infective larvae to sodium cation, human serum, and sweat.

The host-finding behavior of Strongyloides stercoralis infective larvae was examined by in vitro agarose assay method. As human body fluid contains 0.85% (ca 0.15 molar) NaCl, various concentrations of sodium chloride, from 0.5M to 0.01M (7 steps), were examined. Many larvae were attracted at concentrations between 0.5 and 0.05M of sodium chloride. The concentration of 0.05M attracted the most larvae. The concentration of 0.02M of sodium chloride showed greatly reduced larval attraction compared with 0.05M. Therefore, the threshold concentration was determined as 0.05M. Then, 0.05M of chemicals were examined in a further experiment. Chloride compounds (NaCl, KCl, CaCl2, MgCl2) were investigated. These chemicals are components of human body fluids. Distilled water was used as the control in all experiments. Only sodium chloride attracted the larvae. Next, alkaline compounds were examined [NaOH, KOH, Ca(OH)2, and Mg(OH)2]. Larvae accumulated only at the NaOH site. The results suggested that the Na cation is important for larval attraction. A high pH value did not influence attraction at all. Next, human serum was tested. The human serum used was from normal serum to 1:32 diluted sera by distilled water (7 steps). Hierarchical attraction was seen according to serum concentration. Next, human sweat was collected from a limited zone of chest skin where only eccrine glands were distributed. Non-diluted sweat attracted the most larvae. Sweat might act as one of the most probable factors for infection by this skin-penetrating nematode.

Double logarithmic, linear relationship between postmortem vitreous sodium/potassium electrolytes concentration ratio and time since death in subjects of Chandigarh zone of Northwest India.

Present authors had recently demonstrated a highly significant double logarithmic linear relationship between time since death and serum sodium/potassium concentration ratio and also with the serum chloride concentration in humans. Consecutively the present study was carried out to substantiate this disposition in vitreous humour. The data on postmortem vitreous sodium/potassium electrolytes concentration ratio in 1026 subjects, revealed a highly significant relationship between logarithm of vitreous sodium/potassium electrolytes concentration ratio and logarithm of time since death upto 66 hrs. of death. Postmortem interval can be predicted from vitreous sodium/potassium electrolytes concentration ratio with standard error of estimate 0.1800 hrs. However, factors like environmental temperature, age & gender also influences it significantly.

Effect of potassium channel modulators on toxicity of Cleistanthus collinus.

The study was conducted to determine the effects of boiled extract of Cleistanthus collinus on rats by observing ECG changes and electrolyte levels in serum and urine. Influence of minoxidil and glibenclamide on Cleistanthus collinus induced toxicity was determined. ED50 for arrhythmia, changes in contractility and heart rate were recorded using the isolated frog heart. Cleistanthus at low doses caused transient tachycardia and increase in contractility and at high dose caused arrhythmia and cardiac arrest in rat. LD50 was found to be 1690 mg/kg. Minoxidil potentiated cardiac toxicity, whereas glibenclamide did not produce any significant change. High concentration of potassium in Cleistanthus extract hindered comparison of its levels. There was excretion of sodium even in the presence of hyponatraemia. Cleistanthus at low dose caused transient tachycardia and increase in contractility and at high dose caused arrhythmia and cardiac arrest in isolated frog heart. ED50 for arrhythmia was found to be 1406 mg/kg. Acute toxicity was mainly due to depressive cardiac activity of Cleistanthus. It also caused renal failure. Potassium channel modulators did not have important role in acute cardiac toxicity treatment. Probably in chronic toxicity, electrolyte level changes are involved and potassium channel modulators might have a role.

Resistência à corrosão de amálgamas e de liga à base de gálio, sem e com adesivos, através do método de perda de peso e análise da rugosidade de superfície / Corrosion resistance of amalgams and gallium alloy, without and with adhesives, through of weight loss and analysis of surface roughness

Avaliou-se a resistência à corrosão pelos testes de perda em imersão alternada (solução-ar) e as consequentes alterações produzidas nas superficies dos três materiais restauradores (os amálgamas Dispersalloy e Tytin Plus, ambos de alto conteúdo de cobre, respectivamente do tipo fase dispersa e do tipo partícula única, assim como liga á base de gálio Galloy), não ou associados a dois sistemas adesivos (All-Bond 2 e PAAMA-2), observadas através da medição da rugosidade de superficie. Confeccionou-se dez corpos-de-prova, para cada condição específica, a partir de uma matriz metálica de aço inoxidável contendo cinco cavidades cilíndricas, com 10,7 mm de diâmetro por 3,0 mm de altura cada uma. Após o polimento, como é feito no caso de análises metalográficas, os espécimes foram pesados e levados ao rugosímetro para realizar as medições imediatamente. Estes foram submetidos à imersão alternada, na solução de sulfeto de sódio a 5%, por um período de 24 horas e novamente foi realizada a pesagem e obtidos os valores de perda de peso. Depois da pesagem, os corpos- de prova foram levados novamente ao rugosímetro para obtenção dos valores médios de rugosidade de superficie. Os resultados foram rgistrados e submetidos à análise de variânvcia, a dois criterios, e ao teste de contrastes de Tukey-Kramer. Dos resultados obtidos, concluiu-se que todos os espécimes perderam peso e tiveram sua rugosidade de superfície aumentada após a imersão em solução corrosiva, a liga Galloy mostrou valores maiores, tanto no método de perda como no de rugosidade de superfície, quando comparada aos dois amálgamas; a liga Tytin Plus alcançou os melhores resultados, houve diferença estatisticamente significante entre os materiais restauradores, mas não houve entre os sistemas adesivos utilizados, mostrando comportamentos diferentes dependendo da combinação desses fatores.

The resistance to the corrosion was evaluated through weight loss to an alternated immersion ( solution-air) and its consequent changes on the surface of three restoring materials (them amalgams Dispersalloy and Tytin Plus, both with high copper content, respectively dispersion phase and unique particle, as well as the alloy gallium base Galloy), associated or not to two adhesive systems (All-bond 2 and PAAMA-20, observed by measuring the surface roughness. Ten bodies-of-test were made, for each specific condition, in a metallic matrix of stainless steel with five cylindrical cavitie, measuring 10,7 mm in diameter and 3,0 mm thickness each one. After polishing, as in the metalographic analysis, the specimens were weighed and submitted to the rugosimeter to measuring initial. These were submitted to an alternated immersion in 5% sodium sulfide solution, for 24 hours and then the second weighting was performed and obtained the average values of weight loss. A second measure of the surface roughness was then peformed. The results were registered and submitted to the variance analysis, to two approaches, and to the test of contrasts of Tukey-Kramer. From the obtained results, it was concluded that all specimens lost weight and there was an increasing roughness surface after immersion in corrosive solution; Galloy showed higher values, both weight loss test and the roughness surface, compared to two amalgams; the alloy Tytin Plus obtained better resukts; there was significant statistical difference among the restoring materials, but not among adhesive systems, showing different behaviors according to arrangement of these factors.

Effects of Haemonchus contortus infection on sodium status of sheep

Oito cordeiros machos, com cinco meses de idade, receberam uma dieta com teores marginais de sódio (0,5 g Na/kg); quatro ovinos foram infectados com uma única dose de 4.600 L3/cordeiro de Haemonchus contortus e quatro foram mantidos como controles, näo infestados. Todos os animais foram sacrificados 30 dias após a infecçäo. O teor de sódio foi determinado no fluido abomasal. Foi estudado o balanço entre a ingestäo e a excreçäo de sódio fecal. A relaçäo Na:K foi determinada em saliva colhida nos seguintes dias do experimento: zero, 20 e 30. A carga parasitária média foi de 1390 vermes. A infecçäo aumentou o teor de sódio no conteúdo abomasal (p<0,02), porém näo ocorreu uma relaçäo significativa entre a carga parasitária e as concentraçöes de sódio abomasal (p>0,082) ou fecal (p>0,5). Quanto maior o teor abomasal de sódio, menor foi a excreçäo fecal de sódio (p<0,001). A digestibilidade aparente do sódio foi similar entre os grupos infestado ou näo. Foi constatada uma pequena diminuiçäo na relaçäo Na:K salivar, em todos os animais, ao término do experimento, causada pela dieta marginal de sódio e näo pelo parasitismo. Foi concluído que, embora a infestaçäo por H. contortus promovesse uma perda expressiva de sódio no abomaso, existiu, em seguida, uma maior absorçäo intestinal compensatória para prevenir que ocorresse um estado de deficiência desse macroelemento nos ovinos.

Effect of adjuvants on the antibody response of mice to Bothrops asper (Terciopelo) snake venom

The adjuvant of several immunostimulant molecules on the murine antibody response to Bothrops asper snake venom were evaluated. Mice receiving venom together with either sodium alginate, calcium alginate, aluminum hydroxide, muramyl dipeptide, killed Brucella abortus or B. abortus smooth lipopolysaccharide developed a similar antibody response. Despite the fact that in some cases animals injected with venom and Salmonella montevideo lipopolysaccharide developed a significantly higher antibody titer when compared to other experimental groups, no statistically significant differences were observed in most of the comparisons.

Spectrophotometric study of the relative affinities of teichoic acid for different metal ions.

Spectrophotometric study of the relative affinities of teichoic acid (TA) for Na+, Ca2+, Mg2+, Cd2+, Hg2+, Cu2+ and Pb2+ described on the basis of the disruption of metachromasia of dye 1,9-dimethyl methylene blue (DMMB)-polyanion (TA) system has revealed the following sequence of relative affinities of TA for these metals: Na+ < Ca2+ < or = Mg2+ < Cd2+ < Hg2+ < Cu2+ < Pb2+. Some of the metal ions particularly Pb2+ and Hg2+ have specific interactions with the dye, and induce distinct metachromatic band of the dye even in the absence of the polyanion.

Stool electrolytes in acute dehydrating gastroenteritis.

Stool electrolytes were studied in 100 cases of gastroenteritis. The duration of illness was 24-48 hours in 32% and 72-96 hours in 28% of the cases. On stool culture, 43% children had no growth, 23% had Enteropathogenic E. coli and 10% had cholera and rotavirus each. The stool sodium loss was more in cholera and shigella cases, diarrhea of shorter duration and in children between 24-30 months of age. Potassium loss in the stool was more in shiegella cases, diarrhea of short duration and in children between 30-36 months of age. In cases of gastroenteritis with severe malnutrition, stool sodium loss was less; stool potassium loss was not affected by the nutritional status. Total electrolytes lost in stools can be estimated by knowing purging rate and rehydration therapy can be planned accordingly.