Application of perfluoropolyether elastomers in microfluidic drug metabolism assays.

Recently, increasing attention has been paid to liver-on-a-chip models for both pharmacokinetics and toxicity (ADMET) screenings. Although polydimethylsiloxane (PDMS) is the most popular material for the fabrication of microfluidic devices, its extensive sorption of hydrophobic drugs limits its applications. Therefore, we investigated a chemically repellent material, perfluoropolyether (PFPE) elastomer, as an alternative to PDMS. Primary rat hepatocytes cultured in the PFPE microfluidic device were polygonal or cuboidal in shape and had one or two prominent nuclei, as when cultured in 96-well plates. When hepatocytes were cultured in the PFPE microfluidic device and exposed to dynamic flow, the production of albumin and urea increased 3.94- and 1.72-fold, respectively, compared with no dynamic flow. Exposure to dynamic flow did not result in obvious changes in the expression of cytochrome P450, but increased the metabolic activity of hepatocytes compared to under static conditions. PFPE devices did not absorb midazolam, which was extensively absorbed by PDMS devices. However, the sorption of bufuralol could not be avoided even with PFPE devices. Solvent swelling experiments highlighted much better chemical repellency with PFPE than with PDMS. Hansen solubility parameters and sphere radius were estimated from the solvent swelling experiments. The relative energy distance (RED) of bufuralol to PFPE was much smaller than that of other three drugs tested, reasonably explaining the high sorption of bufuralol to PFPE. Although sorption into PFPE cannot be completely avoided, PFPE microfluidic devices may provide a better performance in ADMET evaluation than PDMS.

Decreases in mean hemoglobin and serum albumin values in erythema nodosum leprosum and lepromatous and lepromatous leprosy

Changes in hemoglobin (HGB) and serum albumin (SA) concentration associated with the onset of symptomatic erythema nodosum leprosum (ENL) were studied by comparing the values obtained on the day thalidomide or prednisone therapy commenced, with each patients' preceding values. In three groups of ENL patients mean HGB values fell with statistical significance: 1) in 38 patients who had been begun on thalidomide in the decade of the 1990s and who had been receiving dapsone for a minimum of 6 months, mean HGB values fell from 13.19 gm/dl to 12.27 gm/dl, or 7.0%, p = 6.0 x 10(-6); 2) in 8 patients who were in the active patient file not overlapping with the preceding group, and who had been on dapsone for a minimum of 6 months, mean HGB values feel from 13.40 gm/dl to 11.96 gm/dl, or 10.7%, p = 0.0015; and 3) in 8 patients not overlapping with the preceding groups, who were treated with rifampin and minocylcine or clarithromycin mean HGB values fell from 13.25 gm/dl to 12.48 gm/dl, or 5.8%, p = 0.0035. In two groups of ENL patients SA values also fell with statistical significance: 1) in 34 patients who were begun on thalidomide in the decade of the 1990s and who had been on dapsone for a minimum of 6 months, mean SA values fell from 4.14 gm/dl to 3.77 gm/dl, or 8.9%, p = 1.2 x 10(-5); and 2) in 10 patients from the active file not overlapping with the preceding group, and who had been on dapsone for a minimum of 6 months, mean SA values fell from 4.45 gm/dl to 4.06 gm/dl, or 8.8%, p = 0.039. A brisk fall in HGB values was often accompanied by a fall in SA concentration, and vice versa. Recovery from extreme falls in HGB and SA values was complete in 13 weeks. Recovery occurred in the presence of continued dapsone treatment. The falls could be rapid, occurring too soon to be the result of decreased erythropoiesis or hepatic SA synthesis. This study provides no direct evidence as to the mechanism responsible for the fall in these two parameters, but an interleukin-6 mediated hemodilution is an attractive hypothesis. The ENL-associated fall in HGB values was distinct from dapsone-induced hemolysis and the anemia of chronic disease. The ENL-associated anemia is not a good reason to discontinue dapsone therapy.

Relación entre albúminas e inmunoglobulinas séricas y licuorales en hanseniano

Los resultados de mayor interés obtenidos sobre las muestras de LCD y suero de 7 casos de hanseniasis (H.D.) (2 borderline: B 3 lepromatosos: L de los cuales el 4 L grave y con déficit inmunitario; 2 tuberculoides: T), son: I.º) Los índices LCR/suero de la albúmina y de las IgG por tests cinético-nefelometría y de las IgG anti PGL-1 por ELISA, en cuanto separan los casos según sus tipos y forma mediante valores típicamente uniformes: los más bajos de albúmina para los L; los más bajos de IgG anti PGL-1 para los B; los medios de IgG para los T, siendo los B y L muy deformantes. II.º) Los index de LINK indican producción intratecal de IgG si superan el V.N. en nuestros casos los de IgG anti PGL-1 han resultado todos superiores y altos, sólo los B menos altos; los IgG todos inferiores; pero, hay que considerar que por la policlonía de la IgG, una parte de ellas podría resultar superior si fuese revelada aisladamente por su antígeno específico. III.º) Una mayor casuística con test de medidas homólogas para los dos de IgG podrá confirmar o no nuestros resultados, y también modificar nuestra de ducción por la cual los epítopes HLA-DR de los queratinocitos uniéndose con las IgG intratecales determinarían la respuesta al test lepromínico, es decir, negativa en los L por la falta de los HLA-DR; positiva la precoz en los B po la unión con la IgG; positiva la tardía y a menudo la precoz en los T por la unión con la IgG anti PGL-1 y las IgG. Otro caso de diagnosis incierta resulta positivo para la H.D. de tipo T, pero atípico o la debido a la asociación de otra enfermedad del S.N.C. como la esclerosis múltiple o la siringomielía.

Humoral defence factors in the breast milk of Ethiopian women with leprosy and healthy controls.

Secretory IgA, lactoferrin, albumin, and total protein were quantitated in colostrum and milk samples obtained from 215 Ethiopian nursing mothers over a period ranging from 1 day to 2 yr postparturition. IgG, IgM, C3, and C4 complement components were quantitated in 11 day 1 samples. The subjects were classified into three groups: lepromatous leprosy, borderline lepromatous leprosy, and a nonlepromatous group consisting of women with tuberculoid leprosy and healthy controls. Results obtained from the above groups were also compared with a group from Edinburgh. No major variation in levels of secretory IgA, lactoferrin, albumin, and total protein was found between the three groups of Ethiopian women. Results from the Edinburgh group were significantly higher, mainly in the level of total protein. When the individual proteins were expressed as a percentage of the total protein, there was no difference between the milk samples from the Ethiopian and Edinburgh mothers.

Estudo da precipitaçäo entre soros de portadores de Hanseníase / Precipitation among sera of patients with hansen's disease

Os autores estudaram a precipitaçäo de soros de leprosos que reagiram entre si. Para a realizçäo deste estudo empregaram o método de OUCHTERLONY. Examinaram 885 soros de pacientes nas três formas clínicas da doença. Entre os soros examinados somente 100 deles deram reaçöes positivas de precipitaçäo, sendo que o número deles que reagiu por mais de uma vez foi pequeno e dos que reagiram por um número menor vezes foi maior. Quanto à reatividade os soros, em relaçäo às formas clínicas de lepra mostrou ser maior na forma L, depois, na T e a seguir na forma I. Näo houve influência do tipo, nem do tempo de tratamento. Concluiu-se que os portadores de lepra nas três formas podem, em determinadas ocasiöes, portar antígenos ou anticorpos na circulaçäo sanguínea e que eles podem reagir entre si, dando faixas nítidas de precipitaçäo quando postos a reagir