The furosemide stress test and computational modeling identify renal damage sites associated with predisposition to acute kidney injury in rats.

Acute kidney injury (AKI) diagnosis relies on plasma creatinine concentration (Crpl), a relatively insensitive, surrogate biomarker of glomerular filtration rate that increases only after significant damage befalls. However, damage in different renal structures may occur without increments in Crpl, a condition known as subclinical AKI. Thus, detection of alterations in other aspects of renal function different from glomerular filtration rate must be included in an integral diagnosis of AKI. With this aim, we adapted to and validated in rats (for preclinical research) the furosemide stress test (FST), a tubular function test hitherto performed only in humans. We also tested its sensitivity in detecting subclinical tubular alterations. In particular, we predisposed rats to AKI with 3 mg/kg cisplatin and subsequently subjected them to a triggering insult (ie, 50 mg/kg/d gentamicin for 6 days) that had no effect on nonpredisposed animals but caused an overt AKI in predisposed rats. The FST was performed immediately before adding the triggering insult. Predisposed animals showed a reduced response to the FST (namely, reduced furosemide-induced diuresis and K+ excretion), whereas nonpredisposed animals showed no alteration, compared to the controls. Computational modeling of epithelial transport of solutes and water along the nephrons applied to experimental data suggested that proximal tubule transport was only minimally reduced, the sodium-chloride symporter was upregulated by 50%, and the renal outer medullary potassium channel was downregulated by 85% in predisposed animals. In conclusion, serial coupling of the FST and computational modeling may be used to detect and localize subclinical tubular alterations.

Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model.

The sleep apnea-hypopnea syndrome (SAHS) involves periods of intermittent hypoxia, experimentally reproduced by exposing animal models to oscillatory PO2 patterns. In both situations, chronic intermittent hypoxia (CIH) exposure produces carotid body (CB) hyperactivation generating an increased input to the brainstem which originates sympathetic hyperactivity, followed by hypertension that is abolished by CB denervation. CB has dopamine (DA) receptors in chemoreceptor cells acting as DA-2 autoreceptors. The aim was to check if blocking DA-2 receptors could decrease the CB hypersensitivity produced by CIH, minimizing CIH-related effects. Domperidone (DOM), a selective peripheral DA-2 receptor antagonist that does not cross the blood-brain barrier, was used to examine its effect on CIH (30 days) exposed rats. Arterial pressure, CB secretory activity and whole-body plethysmography were measured. DOM, acute or chronically administered during the last 15 days of CIH, reversed the hypertension produced by CIH, an analogous effect to that obtained with CB denervation. DOM marginally decreased blood pressure in control animals and did not affect hypoxic ventilatory response in control or CIH animals. No adverse effects were observed. DOM, used as gastrokinetic and antiemetic drug, could be a therapeutic opportunity for hypertension in SAHS patients' resistant to standard treatments.

EXPLORATION OF SCORE AGREEMENT ON A MODIFIED UPPER QUARTER Y-BALANCE TEST KIT AS COMPARED TO THE UPPER QUARTER Y-BALANCE TEST.

BACKGROUND/PURPOSE: Physical performance measures (PPMs) such as The Star Excursion Balance Test (SEBT) and the Y-Balance Test (YBT) are functional movement tests used to assess participants' dynamic balance, which can be a vital component in physical exams to identify predisposing factors for risk of injury. The YBT is a functional assessment tool for the upper and lower body. It evolved from the SEBT, which has been previously used in research as a lower body functional assessment. It is comprised of fewer movement directions, which help limit fatigue. The YBT kit is a commercialized tool, which may pose barriers for clinicians with limited budgets and/or strict approval process for purchasing capital items in their clinics, especially healthcare providers in the secondary school setting. The cost may also pose a barrier for researchers with limited budgets. A less expensive, easy to make kit, may provide clinicians an opportunity to integrate functional testing into their evaluation or research. The purpose of this pilot study was to describe a cost efficient method to gather participant's upper quarter YBT (UQYBT) measurements and examine the inter- and intra-rater score agreement between this method and the commercial YBT measurements. METHODS: A convenience sample of 20 physically active participants volunteered to participate in a comparison study of the of Upper Quarter Y-Balance Test (UQYBT) using the commercialized kit and the Modified Upper Quarter Y-Balance Test kit (mUQYBT) made with three cloth tape measures, athletic tape, a goniometer and three 2x4x8 wood blocks. A Pearson Product Moment correlation and Bland-Altman analyses were used to examine the relationship between intra-rater scores comparing the UQYBT and mUQYBT. Inter-rater scores were analyzed using intraclass correlation coefficients (ICC) (2,1) and Bland-Altman analyses. RESULTS: All Pearson Product Moment r-values for intra-rater scores were greater than .96 and statistically significant at p<0.05. Coefficients of determination suggest that the mUQYBT scores account for approximately 92% of the UQYBT composite score when analyzing intra-rater comparisons. Bland-Altman plots suggest moderate agreement between the two tests with a potential bias towards higher composite scores in the mUQYBT. Inter-rater ICC scores were all greater than .98, while Bland-Altman plot analyses suggest moderate agreement between the raters. CONCLUSION: The mUQYBT produced similar results in both inter- and intra-rater measurements when compared to the commercialized YBT kit and offers a cost-effective alternative for assessing upper quarter PPMs for clinicians with limited budgets. LEVEL OF EVIDENCE: 2b.

The effects of intermittent hypoxia on redox status, NF-κB activation, and plasma lipid levels are dependent on the lowest oxygen saturation.

Obstructive sleep apnea syndrome (OSAS) is described as repetitive obstructions of the upper airways during sleep, causing concomitant episodes of systemic hypoxia and associated cardiovascular and metabolic pathologies. The mechanisms generating these pathologies are controversial. Because recurrent hypoxia is the element of inadequate respiration that leads to the pathology, experimental models of OSAS consist in the exposure of the animals to intermittent hypoxia (IH) by cycling O2 percentages in their habitats. A proposed mechanism linking the IH of OSAS to pathologies is the increased production of reactive oxygen species (ROS). However, it has been argued that many patients seem to lack oxidative stress and that, to augment ROS in IH animals, intense hypoxia, seldom encountered in patients, has to be applied. To solve the controversy, we have exposed rats to two intensities of IH (cycles of 10 or 5% O2, 40s, and then 21% O2, 80s; 8h/day, 15 days). We then measured reduced and oxidized glutathione and lipid peroxide levels, aconitase and fumarase activities, and ROS-disposal enzyme activity in liver, brain, and lung. Liver levels of nuclear NF-κB-p65 and plasma C-reactive protein (CRP), as well as lipid levels, were also assessed. Lowest hemoglobin saturations were 91.7 ± 0.8 and 73.5 ± 1.4%. IH caused tissue-specific oxidative stress related to hypoxic intensity. Nuclear NF-κB-p65 and lipid content in the liver and CRP in the plasma all increased with IH intensity, as did both plasma triglycerides and cholesterol. We conclude that IH, even of moderate intensity, causes oxidative stress probably related to the pathologies encountered in OSAS patients.

Bioequivalencia de una dosis de levofloxacina de laboratorios Leti (LL) comprimidos de 500 mg frente a levofloxacina de laboratorios sanofi aventis: tavanic® (LSA) tabletas de 500 mg, administrados en dosis única en voluntarios sanos / Bioequivalence of a dose of levofloxacin Leti laboratories (LL) tablets of 500 mg versus levofloxacin Sanofi Aventis laboratorie: tavanic® (LSA) tablets of 500 mg administered in single dose in healthy volunteers

Evaluar la Bioequivalencia en 12 voluntarios sanos de la Levofloxacina de Laboratorios LETI (LL) comprimidos de 500 mg en dosis única, producto test, con la del producto de referencia: Levofloxacina de Laboratorios SANOFI AVENTIS, Tavanic® (LSA) tabletas de 500 mg. El grupo test recibió un comprimido de Levofloxacina de Laboratorios LETI (LL) de 500 mg, y el grupo de referencia recibió una tableta de Levofloxacina de Laboratorios SANOFI AVENTIS: Tavanic® (LSA) de 500 mg. Terminada esta primera fase de tratamiento, los voluntarios no recibieron medicación por 6 días consecutivos (período de lavado). Luego se procedió al cruce de los tratamientos, los voluntarios del grupo test recibieron la medicación del grupo referencia y viceversa. La extracción de sangre venosa se realizó a la hora 0, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 14, 18 y 24 horas. Se determinaron los niveles plasmáticos de Levofloxacina de las muestras plasmáticas procedentes del estudio clínico, mediante el método cromatográfico por HPLC desarrollado y validado. Se obtuvo una Cmax de 1253.40+/-562.58 μg/mL para LL vs. 1317.42+/-439.64 μg/mL para LSA, el AUC0-24 fue de 9188.43+/-2406.64 μg/mL/h vs 8780.22+/-2305.99 μg/mL/h; y para el AUC0-∞ el resultado fue de 9933.17+/-2488.52 μg/mL/h vs. 9433.47+/-2399.71 μg/mL/h respectivamente. Las medias y sus intervalos de confianza para la Cmax y el AUC0-24 y AUC0-∞ se mantuvieron en los rangos aceptados para la demostración de bioequivalencia. Ambos productos son bioequivalentes y por lo tanto intercambiables.

To evaluated the bioequivalence in 12 healthy volunteers of the LETI Laboratories Levofloxacin (LL) tablets 500 mg single dose, test product with the product Reference: SANOFI AVENTIS Laboratories Levofloxacin, Tavanic® (LSA) 500 mg tablets. The test group received one tablet of levofloxacin LETI Laboratories (LL) of 500 mg, and the control group received a tablet Levofloxacin SANOFI AVENTIS Laboratories: Tavanic® (LSA) of 500 mg. After this first treatment phase, volunteers received no medication for 6 consecutive days (washout period). Then he proceeded to the crossing of the treatments, the volunteers of the group test group received the medication reference and viceversa. The venous blood collection was performed at time 0, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 14, 18 and 24 hours. We determined plasma levels of levofloxacin in plasma samples from the clinical study, using HPLC chromatographic method developed and validated. Cmax of 1253.40 + / -562.58 μg/mL for the LL vs. 1317.42 + / -439.64 μg/mL for LSA, the AUC0-24 was 9188.43 + / -2406.64 μg/mL/h vs. 8780.22 + / -2305.99 μg/mL/h, and the AUC0-∞ the result was 9933.17 + / -2488.52 μg/mL/h vs. 9433.47 + / -2399.71 μg/mL/h, respectively. The mean and confidence intervals for Cmax and AUC0-24 and AUC0-∞ were maintained in the range accepted for the demonstration of bioequivalence. Both products are bioequivalent and therefore interchangeable.

Bioequivalencia de una dosis de levofloxacina de laboratorios Leti: proxime® (LL) comprimidos de 500 mg frente a levofloxacina de laboratorios Sanofi Aventis: tavanic® (LSA) tabletas de 500 mg, administrados en dosis única en voluntarios sanos / Bioequivalence of dose of levofloxacin Leti laboratories: proxime® (LL) 500 mg tablets of levofloxacin aganist Sanofi Aventi: tavanic® (LSA) 500 mg tablets given as a single dose in healthy volunteers

Evaluar la Bioequivalencia en 12 voluntarios sanos de la Levofloxacina de Laboratorios LETI: Proxime® (LL) comprimidos de 500 mg en dosis única, producto test, con la del producto de referencia: Levofloxacina de Laboratorios SANOFI AVENTIS, Tavanic® (LSA) tabletas de 500 mg. El grupo test recibió un comprimido de Levofloxacina de Laboratorios LETI: Proxime® (LL) de 500 mg, y el grupo de referencia recibió una tableta de Levofloxacina de Laboratorios SANOFI AVENTIS: Tavanic® (LSA) de 500 mg. Terminada esta primera fase de tratamiento, los voluntarios no recibieron medicación por 6 días consecutivos (período de lavado). Luego se procedió al cruce de los tratamientos, los voluntarios del grupo test recibieron la medicación del grupo referencia y viceversa. La extracción de sangre venosa se realizó a la hora 0, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 14, 18 y 24 horas. Se determinaron los niveles plasmáticos de Levofloxacina de las muestras plasmáticas procedentes del estudio clínico, mediante el método cromatográfico por HPLC desarrollado y validado. Se obtuvo una Cmax de 1253.40+/-562.58 para la LL vs. 1317.42+/-439.64 para LSA, el AUC 0-24 fue de 9188.43+/-2406.64 vs 8780.22+/-2305.99; y para el AUC 0-∞ el resultado fue de 9933.17+/-2488.52 vs. 9433.47+/-2399.71 respectivamente.Las medias y sus intervalos de confianza para la Cmax yel AUC 0-24 y AUC 0-∞ se mantuvieron en los rangos aceptados para la demostración de bioequivalencia. Ambos productos son bioequivalentes y por lo tanto intercambiables

To evaluated the bioequivalence in 12 healthy volunteers of the LETI Laboratories Levofloxacin: Proxime® (LL) tablets 500 mg single dose, test product with the product Reference: SANOFI AVENTIS Laboratories Levofloxacin, Tavanic® (LSA) 500 mg tablets. The test group received one tablet of levofloxacin LETI Laboratories: Proxime® (LL) of 500 mg, and the control group received a tablet Levofloxacin SANOFI AVENTIS Laboratories: Tavanic® (LSA) of 500 mg. After this first treatment phase, volunteers received no medication for 6 consecutive days (washout period). Then he proceeded to the crossing of the treatments, the volunteers of the group test group received the medication reference and viceversa. The venous blood collection was performed at time 0, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 14, 18 and 24 hours. We determined plasma levels of levofloxacin in plasma samples from the clinical study, using HPLC chromatographic method developed and validated. Cmax of 1253.40 + / -562.58 for the LL vs. 1317.42 + / -439.64 for LSA, the AUC 0-24 was 9188.43 + / -2406.64 vs. 8780.22 + / -2305.99, and the AUC 0-∞ the result was 9933.17 + / -2488.52 vs. 9433.47 + / -2399.71, respectively. The mean and confidence intervals for Cmax and AUC 0-24 and AUC 0-∞ were maintained in the range accepted for the demonstration of bioequivalence. Both products are bioequivalent and therefore interchangeable

Determinación de inmunoglobulina E y de subclases de inmunoglobulina G en escolares con hiperreactividad de la vía aérea: consulta de neumonología pediátrica Ciudad Hospitalaria "Dr. Enrique Tejera" Valencia octubre a diciembre 1997 / Immunoglobuline E determination and immunoglobuline G subclas in schoolars with hiperreactivity of aereal ways: consult of pediatric neumonology Hospitalary City

Se conoce que la hiperreactividad de la vía aérea en niños es una patología compleja y multifactorial, caracterizada por un cuadro inflamatorio de la vía aérea, con una morbi-mortalidad en ascenso a pesar de los avances terapéuticos, a la cual se le involucra una base inmunológica cierta, se realizó un estudio comparativo y transversal en pacientes con edades comprendidas entre 6 y 12 años de edad, con hiperreactividad de la vía aérea, que acuden a la consulta de Neumonología Pediátrica de la Ciudad Hospitalaria "Dr. Enrique Tejera", Valencia, octubre-diciembre 1997. Cumpliéndose los criterios de inclusión, se determinaron los valores séricos de subclases de IgG e IgE, tanto en el grupo en estudio como en el control. Se aplicó la "t" de Student, demostrando una diferencia estadísticamente significativa sólo para IgG1, la cual estuvo disminuida en los pacientes al comparar con controles (p<0,05). Se aplicó el Coeficiente de Correlación de Pearson, obteniéndose valores significativos positivos altos sólo en el grupo en estudio: IgG2-IgG3 (0,88), IgG2-IgG4 (0,70) e IgG3-IgG4 (0,74), más no para IgE. Es necesario realizar más estudios para definir parámetros de diagnóstico pronóstico y eficacia del tratamiento indicado, así como valores basales normales en la población infantíl venezolana

HLA, grupo sanguineo, factor secretor, pepsinogeno I y helicobacter pylori en ulcerosos duodenales / HLA, blood group, secretor factor, pepsinogen I and helicobacter pylori in duodenal ulcer patients

La Ulcera duodenal es una entidad multifactorial en donde la predisposición genética y elementos extrínsecos parecen concurrir en su producción. Se determinaron una serie de marcadores genéticos y extrínsecos en 50 ulcerosos duodenales y 50 controles, pareados por edad, sexo y origen socieconómico. La detención del antígeno HLA no mostró diferencias significativas. Predominó el grupo sanguíneo ORh+ (p < 0.01). El factor secretor de antígeno ABO en saliva fue positivo en el 70 por ciento de los ulcerosos (p < 0.001). El Pepsinógeno I sérico resultó elevado en 85 por ciento de los pacientes (p < 0.001). La Inmunoglobina G anti H. pylori fue positiva en 62 por ciento de los ulcerosos (p < 0.001). La mayor sensibilidad y valor predictivo negativo lo tuvo el Pepsinógeno elevado (85 por ciento ) y la mayor especificidad y valor predictivo positivo la IgG anti H. pylori (90 y 86 por ciento ). Estos resultados, al mostrar positividad de marcadores genéticos e infecciosos afirman el carácter poligénico de la enfermedad ulcerosa duodenal