Serum properdin consumption as a biomarker of C5 convertase dysregulation in C3 glomerulopathy.

Properdin (P) stabilizes the alternative pathway (AP) convertases, being the only known positive regulator of the complement system. In addition, P is a pattern recognition molecule able to initiate directly the AP on non-self surfaces. Although P deficiencies have long been known to be associated with Neisseria infections and P is often found deposited at sites of AP activation and tissue injury, the potential role of P in the pathogenesis of complement dysregulation-associated disorders has not been studied extensively. Serum P levels were measured in 49 patients with histological and clinical evidence of C3 glomerulopathy (C3G). Patients were divided into two groups according to the presence or absence of C3 nephritic factor (C3NeF), an autoantibody that stabilizes the AP C3 convertase. The presence of this autoantibody results in a significant reduction in circulating C3 (P < 0·001) and C5 levels (P < 0·05), but does not alter factor B, P and sC5b-9 levels. Interestingly, in our cohort, serum P levels were low in 17 of the 32 C3NeF-negative patients. This group exhibited significant reduction of C3 (P < 0·001) and C5 (P < 0·001) and increase of sC5b-9 (P < 0·001) plasma levels compared to the control group. Also, P consumption was correlated significantly with C3 (r = 0·798, P = 0·0001), C5 (r = 0·806, P < 0·0001), sC5b-9 (r = -0·683, P = 0·043) and a higher degree of proteinuria (r = -0·862, P = 0·013). These results illustrate further the heterogeneity among C3G patients and suggest that P serum levels could be a reliable clinical biomarker to identify patients with underlying surface AP C5 convertase dysregulation.

Interlaboratory assessment of the bovine corneal opacity and permeability (BCOP) assay.

A multinational interlaboratory study to investigate the bovine corneal opacity and permeability (BCOP) assay is presented. The aim of this work was to determine the capability and possible limitations of this method to predict ocular irritancy of a large set of chemicals. The assays were carried out in 12 European laboratories with different types of activity. In each of these laboratories 52 substances, with a wide range of structure, physical form and irritant properties, were tested and in vitro scores were compared with those obtained from concurrent rabbit eye (Draize) tests. The technique was easily learned by workers in the participating laboratories, as shown by the fact that there were consistent responses between treated corneas within an individual laboratory. Interlaboratory variability was also very good. It was found that a given laboratory had a 96% chance of classifying irritants or non-irritants similarly to the other laboratories. In addition, it was observed that corneas preserved overnight responded similarly to freshly prepared tissues, thus allowing flexibility for those laboratories where the availability of corneas is limited. Comparisons between in vivo and in vitro data showed that the BCOP data correctly predicted whether a compound would be irritating or non-irritating for 44 of the 52 compounds (84.6%). Specificity and sensitivity were also greater than 84%, and the same number of substances were overestimated as were underestimated (four out of 52). All of the false negatives were solids whereas most of false positives were liquids, indicating that some adjustment in the protocol may be required depending on the physical state of the substance to be tested. All of the substances selected could be evaluated, with no limitation such as colour, insolubility, low or high pH. Given the number of products evaluated and the reproducibility within and among the laboratories involved, the overall results are quite satisfactory and therefore confirm the usefulness of the assay for screening chemicals for ocular irritation.

[Carbohydrate metabolism derangements in patients with morbid obesity: weight loss impact]. / Estudio del metabolismo hidrocarbonado en pacientes con obesidad mórbida: influencia de la pérdida de peso.

OBJECTIVE: Examination of carbohydrate metabolism derangements in patients with morbid obesity and the influence of weight reduction through nutritional intervention. Assessment of gender influence on carbohydrate metabolism derangements and on response to diet. PATIENTS AND METHOD: 59 patients with morbid obesity were studied with anthropometric assessment and with carbohydrate metabolism assessment through an oral glucose overload and measurement of insulin resistance, before and after a dietary intervention alternating diets of very low caloric content with conventional low-calorie diets. RESULTS: A very significant global weight reduction in both sexes was observed (95% confidence interval [CI], 26.9 to 39.8 kg in males, and 13.5 to 20.3 kg in women). A significant improvement in basal blood glucose was found in both sexes (95% CI: males, 0.44 to 46.5 mg/dl; women, 9.5 to 32.8 mg/dl), and in 120 minute oral glucose tolerance test (OGTT) blood glucose in women (95% CI: 3.5 to 52.9 mg/dl). Both males and women showed significant improvement in basal insulinemia (95% CI: males, 1.6 to 14.2 microU/ml; women, 3.9 to 8.5 microU/ml) and in sex hormone-binding globulins (SHBG) (95% CI: males, -30.1 to -13.3 nmol/l; women, -54 to -19.4 nmol/l). Both males and women showed an improvement of sensitivity to insulin measured with HOMA (HOMAIR) (95% CI: males, 1.46 to 3.59; women, 0.67 to 2.24). CONCLUSION: In patients with morbid obesity carbohydrate metabolism derangements are common. Weight reduction led to a significant reduction of these derangements.

Ocular tolerance of sertaconazole gel.

The in vitro and in vivo tolerance of sertaconazole gel, a new topical azole antifungal, was studied. Ketoconazole gel (Panfungol) was used as a reference substance. The methods applied for tolerance assessment were the bovine corneal opacity and permeability test for the in vitro assay and a modified Draize test for the in vivo assay. The results obtained show that both substances can be classified as slightly irritant and with acceptable tolerance. However, unlike ketoconazole gel, sertaconazole gel did not cause a positive lesion index in vivo. Ketoconazole was 5.25 times more irritant in vitro than sertaconazole gel, whose effect was similar to that of saline solution. Consequently, the negligible irritant effect of sertaconazole gel on a type of epithelium that is extremely sensitive, i.e. the cornea, confirms the good tolerance of this new antifungal gel on other structures such as the skin and mucous membranes.

Estudio del metabolismo hidrocarbonato en pacientes con obesidad mórbida: influencia de la pérdida de peso / Carbohydrate metabolism derangements in patients with morbid obesity: weight loss impact

Objetivo. Analizar la presencia de alteraciones del metabolismo hidrocarbonado en pacientes con obesidad mórbida y la influencia de la reducción ponderal mediante intervención dietética sobre las mismas. Valorar la influencia del sexo en la presencia de dichas alteraciones y en la respuesta a la dieta. Pacientes y métodos. A 59 pacientes con obesidad mórbida se les realizó una valoración antropométrica y del metabolismo hidrocarbonado mediante la realización de sobrecarga oral de glucosa y medición de la insulinresistencia antes y después de una intervención dietética, alternando dietas de muy bajo contenido calórico con dietas hipocalóricas convencionales. Resultados. Se apreció una reducción ponderal global muy significativa en ambos sexos (intervalo de confianza [IC] al 95%: 26,9 a 39,8 kg en varones y 13,5 a 20,3 kg en mujeres). Se encuentra una mejoría significativa en ambos sexos de la glucemia basal (IC al 95%: varones, 0,44-46,5 mg/dl; mujeres, 9,5-32,8 mg/dl) y en las mujeres de la glucemia a los 120 min de la sobrecarga oral de glucosa (IC al 95%: 3,5 a 52,9 mg/dl). Tanto los varones como las mujeres presentan mejoría significativa de la insulinemia basal (IC al 95%: varones, 1,6 a 14,2 µU/ml; mujeres, 3,9 a 8,5 µU/ml) y de la globulina transportadora de hormonas sexuales (IC al 95%: varones, -30,1 a -13,3 nmol/l; mujeres, -54 a -19,4 nmol/l). Tanto varones como mujeres mostraron una mejoría de la sensibilidad a la insulina medida por Homeostasis Model Assessment (IC al 95%: varones, 1,46 a 3,59; mujeres, 0,67 a 2,24). Conclusión. En pacientes con obesidad mórbida existe una elevada presencia de alteraciones del metabolismo hidrocarbonado. Con la reducción ponderal obtenida hemos conseguido una Objetivo. Analizar la presencia de alteraciones del metabolismo hidrocarbonado en pacientes con obesidad mórbida y la influencia de la reducción ponderal mediante intervención dietética sobre las mismas. Valorar la influencia del sexo en la presencia de dichas alteraciones y en la respuesta a la dieta. Pacientes y métodos. A 59 pacientes con obesidad mórbida se les realizó una valoración antropométrica y del metabolismo hidrocarbonado mediante la realización de sobrecarga oral de glucosa y medición de la insulinresistencia antes y después de una intervención dietética, alternando dietas de muy bajo contenido calórico con dietas hipocalóricas convencionales. Resultados. Se apreció una reducción ponderal global muy significativa en ambos sexos (intervalo de confianza [IC] al 95%: 26,9 a 39,8 kg en varones y 13,5 a 20,3 kg en mujeres). Se encuentra una mejoría significativa en ambos sexos de la glucemia basal (IC al 95%: varones, 0,44-46,5 mg/dl; mujeres, 9,5-32,8 mg/dl) y en las mujeres de la glucemia a los 120 min de la sobrecarga oral de glucosa (IC al 95%: 3,5 a 52,9 mg/dl). Tanto los varones como las mujeres presentan mejoría significativa de la insulinemia basal (IC al 95%: varones, 1,6 a 14,2 µU/ml; mujeres, 3,9 a 8,5 µU/ml) y de la globulina transportadora de hormonas sexuales (IC al 95%: varones, -30,1 a -13,3 nmol/l; mujeres, -54 a -19,4 nmol/l). Tanto varones como mujeres mostraron una mejoría de la sensibilidad a la insulina medida por Homeostasis Model Assessment (IC al 95%: varones, 1,46 a 3,59; mujeres, 0,67 a 2,24). Conclusión. En pacientes con obesidad mórbida existe una elevada presencia de alteraciones del metabolismo hidrocarbonado. Con la reducción ponderal obtenida hemos conseguido una significativa reducción de estas alteraciones

Objective. Examination of carbohydrate metabolism derangements in patients with morbid obesity and the influence of weight reduction through nutritional intervention. Assessment of gender influence on carbohydrate metabolism derangements and on response to diet. Patients and method. 59 patients with morbid obesity were studied with anthropometric assessment and with carbohydrate metabolism assessment through an oral glucose overload and measurement of insulin resistance, before and after a dietary intervention alternating diets of very low caloric content with conventional low-calorie diets. Results. A very significant global weight reduction in both sexes was observed (95% confidence interval [CI], 26.9 to 39.8 kg in males, and 13.5 to 20.3 kg in women). A significant improvement in basal blood glucose was found in both sexes (95% CI: males, 0.44 to 46.5 mg/dl; women, 9.5 to 32.8 mg/dl), and in 120 minute oral glucose tolerance test (OGTT) blood glucose in women (95% CI: 3.5 to 52.9 mg/dl). Both males and women showed significant improvement in basal insulinemia (95% CI: males, 1.6 to 14.2 µU/ml; women, 3.9 to 8.5 µU/ml) and in sex hormone-binding globulins (SHBG) (95% CI: males, -30.1 to -13.3 nmol/l; women, -54 to -19.4 nmol/l). Both males and women showed an improvement of sensitivity to insulin measured with HOMA (HOMAIR) (95% CI: males, 1.46 to 3.59; women, 0.67 to 2.24). Conclusion. In patients with morbid obesity carbohydrate metabolism derangements are common. Weight reduction led to a significant reduction of these derangements