Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses

Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin- converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50 mg/kg and PO at doses 0 (placebo), 0.25, 0.50 and 1.00 mg/kg. Blood pressures (BP) were measured and blood samples were obtained at different times in order to measure serum drug concentrations and serum ACE activity, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of benazeprilat after PO benazepril was 3-4%. Maximum ACE inhibitions from baseline were 99.63% (IV benazepril), 6.77% (placebo) and 78.91%, 85.74% and 89.51% (for the three PO benazepril doses). Significant differences in BP were not found. Although oral availability was low, benazeprilat 1.00 mg/kg, reached sufficient serum concentrations to induce long lasting serum ACE inhibitions (between 88 and 50%) for the first 48 h. Additional research on benazepril administration in equine patients is indicated

Using the FVB strain of mice for the evaluation of clinical and experimental ketamine (IP) associated with phenothiazines, benzodiazepines and α2-agonists

El objetivo de este trabajo ha consistido en evaluar el estado fisiológico de los animales mediante el control de las frecuencias respiratoria y cardiaca así como la tasa de saturación de oxígeno durante la anestesia con ketamina asociada a otros fármacos. Para ello hemos utilizado 40 ratones FVB consanguíneos (20 machos y 20 hembras) de 11 semanas de edad, a los que se les administró por vía intraperitoneal ketamina asociada a un depresor del sistema nervioso central: acepromazina, diazepam, medetomidina, midazolam o xilazina. Obtuvimos resultados que difirieron mucho entre sexos, concluyendo que en machos los mejores resultados obtenidos fueron con la asociación a los α2-agonistas, mientras que en las hembras, al menos a las dosis empleadas, no pudimos afirmar que ninguna de las asociaciones fuese óptima.The aim of this work has been to evaluate the physiological status of animals by controlling the respiratory rate and heart rate and oxygen saturation during anesthesia with ketamine in combination with other drugs. We have used 40 consanguine FVB mice (20 males and 20 females) from 11 weeks of age, who were administered intraperitoneally with a ketamine-associated central nervous system depressant:acepromazina, diazepam, medetomidine, midazolam or xylazine. We obtained results that differed greatly between the sexes, in males, concluding that the best results were obtained with the association of α2- agonists, while in females, at least at the doses employed, did not say that none of the associations were optima

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

Seguimiento de las guías españolas para el manejo del asma por el médico de atención primaria: un estudio observacional ambispectivo

Objetivo Evaluar el grado de seguimiento de las recomendaciones de las versiones de la Guía española para el manejo del asma (GEMA 2009 y 2015) y su repercusión en el control de la enfermedad. Material y métodos Estudio observacional y ambispectivo realizado entre septiembre del 2015 y abril del 2016, en el que participaron 314 médicos de atención primaria y 2.864 pacientes. Resultados Utilizando datos retrospectivos, 81 de los 314 médicos (25, 8% [IC del 95%, 21, 3 a 30, 9]) comunicaron seguir las recomendaciones de la GEMA 2009. Al inicio del estudio, 88 de los 314 médicos (28, 0% [IC del 95%, 23, 4 a 33, 2]) seguían las recomendaciones de la GEMA 2015. El tener un asma mal controlada (OR 0, 19, IC del 95%, 0, 13 a 0, 28) y presentar un asma persistente grave al inicio del estudio (OR 0, 20, IC del 95%, 0, 12 a 0, 34) se asociaron negativamente con tener un asma bien controlada al final del seguimiento. Por el contrario, el seguimiento de las recomendaciones de la GEMA 2015 se asoció de manera positiva con una mayor posibilidad de que el paciente tuviera un asma bien controlada al final del periodo de seguimiento (OR 1, 70, IC del 95%, 1, 40 a 2, 06). Conclusiones El escaso seguimiento de las guías clínicas para el manejo del asma constituye un problema común entre los médicos de atención primaria. Un seguimiento de estas guías se asocia con un control mejor del asma. Existe la necesidad de actuaciones que puedan mejorar el seguimiento por parte de los médicos de atención primaria de las guías para el manejo del asma. Objective: To assess the degree of compliance with the recommendations of the 2009 and 2015 versions of the Spanish guidelines for managing asthma (Guía Española para el Manejo del Asma [GEMA]) and the effect of this compliance on controlling the disease. Material and methods: We conducted an observational ambispective study between September 2015 and April 2016 in which 314 primary care physicians and 2864 patients participated. Results: Using retrospective data, we found that 81 of the 314 physicians (25.8%; 95% CI 21.3–30.9) stated that they complied with the GEMA2009 recommendations. At the start of the study, 88 of the 314 physicians (28.0%; 95% CI 23.4–33.2) complied with the GEMA2015 recommendations. Poorly controlled asthma (OR, 0.19; 95% CI 0.13–0.28) and persistent severe asthma at the start of the study (OR, 0.20; 95% CI 0.12–0.34) were negatively associated with having well-controlled asthma by the end of the follow-up. In contrast, compliance with the GEMA2015 recommendations was positively associated with a greater likelihood that the patient would have well-controlled asthma by the end of the follow-up (OR, 1.70; 95% CI 1.40–2.06). Conclusions: Low compliance with the clinical guidelines for managing asthma is a common problem among primary care physicians. Compliance with these guidelines is associated with better asthma control. Actions need to be taken to improve primary care physician compliance with the asthma management guidelines

Impaired health-related quality of life in idiopathic inflammatory myopathies: a cross-sectional analysis from the COVAD-2 e-survey

Objectives To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Methods Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. Results We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10–15] IIMs vs 13 [11–15] non-IIM AIRDs vs 15 [13–17] nrAIDs vs 17 [15–18] controls, P < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10–15) IIMs vs 15 (13–17) controls, P < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Conclusion Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs

Estudio de la unión de oxitetraciclina (OT) a seroalbúminas humana (HSA) y bovina (BSA)

Interactions between oxytetracyline (OT) and human and bovine serum albumins (HSA and BSA) were studied by equilibrium dialysis. The OT determination method was the proposed by Garrat (1964). The OT binds to the HSA and the BSA by 0,2 and1 binding sites per molecule respectively. The association constant ranges from 2,5 x 105 y 1,0 x 106M-1 and from 1,5 x 104 y 1,8 x 104M-1 for the respective HS and BS albumins.Se estudia la interacción entre oxitetracilina (OT) y seroalbúminas humana (HSA) y bovina (BSA) mediante diálisis en el equilibrio. El método de determinación de OT ha sido el propuesto por Garrat (1964). La OT se fija a la HSA en 0,2 centros de unión por molécula con una constante de asociación comprendida entre 2,5 x 105 y 1,0 x 106M-1, en tanto que se une a la BSA en 1 centro de unión por molécula con una constante de asociación comprendida entre 1,5 x 104 y 1,8 x 104M-1

A study of the binding of silymarin to plasmatic proteins. I. Bovine proteins

The binding of the silymarin--antihepatotoxic principle from Sylibum marianum (L.) Gaertn - to the plasmatic proteins has been studied by equilibium dialysis. From the results obtained it is inferred that 68,21 + 1,61 per cent of the silymarin is adsorved on the plasmatic proteins qhen the dialysis is carried out at 4ºC.Se estudia la unión de la silimarina, principal antihepatotóxico del Sylibum marianum (L.) Gaertn, a las proteínas plasmáticas de bovino mediante diálisis al equilibrio. De los resultados obetnidos se deduce que el 68,21 + 1,61 por ciento d la silimarina se encuentra adsorbida por las prote´nas del plasma cuando la diálisis se realiza a 4ºC

Study of the silymarin binding to the plasmatic proteins. II. Proteins of the pig, sheep, goat, cattle and man

The rate of binding of silymarin to pig, sheep, goat, cattle and mar plasmatic proteins has been calculated by the equilibrium dialysis method. The analytical procedure has been carried out at 18°C. The binding rate has been averaged for three series of each species at 7 concentration levels of silymarin ranging from 3.72 to 74.46 mg/l. For the human plasma protein this value was 90.61±1.98 percent, and for the remaining species 75.00±3.74, 57.48+4.16, 92.96+3.00 and 84.20+2.90 respectively.Se estudia la tasa de unión de la silimarina a las proteínas plasmaticas de cerdo, ovino, caprino, bovino y hombre, por el procedimiento de diálisis al equilibrio. Dicha tasa se ha promediado sobre tres series con 7 niveles de concentr=ación del fármaco, que van desde 3.72 hasta 74.46 mg/1, para cada especie. Para la proteína plasmática humana este valor fue del 90.61 + 1.98 p.100. Para las restantes especies fue del 75.00 + 3.74, 57.48 + 4.16, 92.96 + 3.00 y 84.20 + 2.90 p.100, respectivamente. Las experiencias se han realizado a 18© C de temperatura ambiente

Estudio de la unión de silimarina y (+)-cianidanol-3 a las proteínas plasmáticas de pollo.

The binding of silymarin and (+ )-cyanidol-3 to plasmatic proteins of poultry by equilibIÍum dialysis at room temperature has been studied. Binding percentages have fluctuated for silymarin between 92'65 and 98'75 (mean value 94'53) and flor (+ )-cyanidol-3 between 92'65 and 98'75 (mean value 94'53) and for (+ )-cyanidol-3 between 44'50 and 89'89 (mean value 64'10).Se estudia comparativamente la unión de la silimarina y del (+ )-cianidanol-3 a las proteínas plasmáticas del pollo de carne mediante diálisis de equilibrio a temperatura ambiente. Para la silimarina, los porcentajes de unión han oscilado entre 92'65 y 98'75 (valor medio de 94'53), en tanto que para el (+ )-cianidanol-3 el rango ha oscilado entre márgenes mayores, 44'50 y 89'89 con un valor medio de 64'10