Дослідження специфічної токсичності аналгетичного засобу для диких копитних тварин на основі мелоксикаму

Laboratory studies were conducted to determine the subacute toxicity of the veterinary drug Loksidev on white rats and dogs. The meloxicam-based Loxidev drug is used for diseases of the European doe animal treatment system for non-infectious diseases of the musculoskeletal system (acute aseptic myositis to reduce the symptoms of lameness and inflammation), as well as for diseases of the respiratory organs (in case of appropriate antibiotic therapy). Red deer: treatment of animals for non-infectious diseases of the musculoskeletal system (arthritis of the metatarsal joint to reduce symptoms of lameness and inflammation). When administered subcutaneously to rats, the drug Loxidev (for injections), under the conditions of a subacute toxicological experiment, in doses of 0.03; 0.15 and 0.3 ml/kg of body weight, does not cause hemo-, hepato- and nephrotoxic effects on the body of laboratory animals. The exception was the tendency to decrease the concentration of total hemoglobin and the hematocrit indicator, as well as a probable decrease (P < 0.05) in the number of erythrocytes and leukocytes by 6.5 and 7.2 %, respectively, relative to the control in the blood and an increase (P < 0.05) enzymatic activity of ALT and AST and concentration of urea in blood serum of rats, after three days of administration of the drug, at a dose of 0.30 mg/kg of body weight by 11.8; 11.0 and 10.3 %, respectively. However, after 7 days, after stopping the administration of the drug, these indicators probably did not differ from the control. Subcutaneous administration of the drug Loxidev (for injections) to dogs in doses of 0.03; 0.15 and 0.3 ml/kg of body weight for 3 days generally does not affect the clinical and biochemical parameters of the blood and does not cause hepatotoxic and nephrotoxic effects on the animal body, under the conditions of a subacute toxicological experiment. The exception was the tendency to decrease the concentration of total hemoglobin, the hematocrit index and the number of erythrocytes, as well as a probable decrease (P < 0.05) in the number of leukocytes by 6.6 %, respectively, relative to the control in the blood and an increase (P < 0.05) in enzymatic activity ALT and AST and the concentration of urea in the blood serum of dogs, after three days of administration of the drug at a dose of 0.30 mg/kg of body weight by 19.4; 19.3 and 14.5 %, respectively, but 7 days after stopping the administration of the drug, these indicators probably did not differ from the control. Further studies will be the next stage of pre-registration tests aimed at studying the irritant effect, allergenic properties of “Loksidev”, which is mandatory material of the “Safety and residue studies” section of the dossier for this veterinary drug.Проведено лабораторні дослідження з визначення підгострої токсичності ветеринарного препарату Локсидев на білих щурах і собаках. Препарат Локсидев на основі мелоксикаму застосовують при захворюваннях лані європейської лікування тварин за неінфекційних захворювань опорно-рухового апарату (гострі асептичні міозити для зменшення симптомів кульгавості та запалення), а також при захворюваннях органів дихання (в разі проведення відповідної антибіотикотерапії). Олені благородні: лікування тварин за неінфекційних захворювань опорно-рухового апарату (артрит заплесново-плеснового суглоба для зменшення симптомів кульгавості та запалення). При підшкірному введенні щурам препарат Локсидев (для ін’єкцій), за умов підгострого токсикологічного експерименту в дозах 0,03; 0,15 і 0,3 мл/кг маси тіла, не спричинює гемо-, гепато- та нефротоксичної дії на організм лабораторних тварин. Виняток становили тенденції до зниження концентрації загального гемоглобіну і показника гематокриту, а також вірогідне зниження (Р < 0,05) кількості еритроцитів і лейкоцитів на 6,5 і 7,2 % відповідно, відносно контролю в крові та підвищення (Р < 0,05) ензиматичної активності АЛТ і АСТ та концентрації сечовини в сироватці крові щурів, після трьох діб введення препарату, у дозі 0,30 мг/кг маси тіла на 11,8; 11,0 і 10,3 % відповідно. Проте через 7 діб, після припинення введення препарату, дані показники вірогідно не відрізнялися від контролю. Підшкірне введення собакам препарату Локсидев (для ін’єкцій) у дозах 0,03; 0,15 і 0,3 мл/кг маси тіла протягом 3-х діб у цілому не впливає на клініко-біохімічні показники крові та не спричинює гепато- та нефротоксичної дії на організм тварин, за умов підгострого токсикологічного експерименту. Виняток становили тенденції до зниження концентрації загального гемоглобіну, показника гематокриту і кількості еритроцитів, а також вірогідне зниження (Р < 0,05) кількості лейкоцитів на 6,6 % відповідно, відносно контролю в крові та підвищення (Р < 0,05) ензиматичної активності АЛТ і АСТ та концентрації сечовини в сироватці крові собак, після трьох діб введення препарату у дозі 0,30 мг/кг маси тіла на 19,4; 19,3 і 14,5 % відповідно, проте через 7 діб після припинення введення препарату дані показники вірогідно не відрізнялися від контролю. Подальші дослідження будуть черговим етапом передреєстраційних випробувань, спрямованих на вивчення подразнювальної дії, алергенних властивостей “Локсидев”, що є обов’язковим матеріалом розділу “Дослідження щодо безпеки і залишків” досьє на даний ветеринарний препарат

The risk of incident depression when assessed with the Lifestyle and Well-Being Index.

OBJECTIVES Novel findings indicate links between unhealthy lifestyles and depression based on active inflammatory processes. Thus, identifying participants with poor habits could reveal differences in trends of incident depression. This study aimed to examine the association between an objective lifestyle assessment, as measured by the Lifestyle and Well-Being Index (LWB-I), and incident depression in healthy participants of a Spanish cohort. STUDY DESIGN This was a longitudinal analysis of a subsample of 10,063 participants from the Seguimiento Universidad de Navarra cohort study. METHODS Group comparisons and Cox proportional hazard models were conducted using the LWB-I, which categorizes the sample into groups with healthy and unhealthy lifestyles and well-being. The main outcome was incident depression as well as secondary outcomes. RESULTS Those classified to the transition category of LWB-I were associated with a hazard ratio of 0.67 (95% confidence interval: 0.52-0.87), and those in the excellent category showed a hazard ratio of 0.44 (95% confidence interval: 0.33-0.58), which in both groups reflects a significantly lower risk of incident depression compared with the group including those classified in the poor LWB-I level. Moreover, the available sensitivity analyses concerning time of depression diagnosis or antidepressant treatment further supported the role of nutrition and physical activity on incident depression. Interestingly, throughout the follow-up, incident depression was inversely related to healthier daily habits as measured by the LWB-I. CONCLUSIONS A global assessment of lifestyles such as the LWB-I provides valuable insight into the complex relationship between lifestyle factors and their link to depression risk

The risk of incident depression when assessed with the lifestyle and well-being index

Objectives: Novel findings indicate links between unhealthy lifestyles and depression based on active inflammatory processes. Thus, identifying participants with poor habits could reveal differences in trends of incident depression. This study aimed to examine the association between an objective lifestyle assessment, as measured by the Lifestyle and Well-Being Index (LWB-I), and incident depression in healthy participants of a Spanish cohort. Study design: This was a longitudinal analysis of a subsample of 10,063 participants from the Seguimiento Universidad de Navarra cohort study. Methods: Group comparisons and Cox proportional hazard models were conducted using the LWB-I, which categorizes the sample into groups with healthy and unhealthy lifestyles and well-being. The main outcome was incident depression as well as secondary outcomes. Results: Those classified to the transition category of LWB-I were associated with a hazard ratio of 0.67 (95% confidence interval: 0.52-0.87), and those in the excellent category showed a hazard ratio of 0.44 (95% confidence interval: 0.33-0.58), which in both groups reflects a significantly lower risk of incident depression compared with the group including those classified in the poor LWB-I level. Moreover, the available sensitivity analyses concerning time of depression diagnosis or antidepressant treatment further supported the role of nutrition and physical activity on incident depression. Interestingly, throughout the follow-up, incident depression was inversely related to healthier daily habits as measured by the LWB-I. Conclusions: A global assessment of lifestyles such as the LWB-I provides valuable insight into the complex relationship between lifestyle factors and their link to depression risk.Funding was received from the Spanish Government-Instituto de Salud Carlos III , the European Regional Development Fund (FEDER; RD 06/0045, CIBER-OBN, grants PI10/02658, PI10/02293, PI13/00615, PI14/01668, PI14/01798, PI14/01764, PI17/01795, PI20/00564 and G03/140), the Navarra Regional Government (27/2011, 45/2011, 122/2014), the National Plan on Drugs (2020/021), and the University of Navarra

Sentimiento de sobrecarga y apoyo social en cuidadores familiares de enfermos crónicos

Se evalúa si la estructura de la red social, el apoyo percibido y su nivel de satisfacción personal inciden en el sentimiento de sobrecarga del cuidador, derivado de la asistencia de un hijo o de un progenitor anciano con una enfermedad crónica invalidante. Con tal fin, fueron administrados a 143 cuidadoras -50,3% madres y 49,7% hijas- el Cuestionario sobre Apoyo Social de Mannheim (1986) y el Cuestionario sobre Sentimiento de Carga de Zarit y Zarit (1999). A partir de las pruebas multivariadas de significación estadística, se puede concluir que las madres presentan una red de parientes mayor que las hijas, aunque no se diferencian significativamente en la percepción del apoyo social. En ellas, el tamaño de la red de parientes, el apoyo instrumental cotidiano y psicológico en crisis aminora el sentimiento de sobrecarga, mientras que en las hijas lo disminuye la mayor intensidad de apoyo instrumental en crsis percibido por ellas

Sentimiento de sobrecarga y apoyo social en cuidadores familiares de enfermos crónicos

We evaluate if the social network structure, the percei ved support and the personal satisfaction acts on the caregiver's feeling of burden, coming from the caring of a child oran older parent with chronic invalidating illness. We used Mannheim's Instrument for Social Support (1986) and the Feeling of Burden Questionnaire (Zarit & Zarit, 1999) with 143 caregivers -50,3% mothers and 49,7% daughters. Taking into account the multivariate statistical tests, we can conclude that mothers have a larger relatives network than daughters, even though they don't significantly differ in the perception of social support. In mothers, the size of the relatives network, the everyday instrumental and the psychological crisis support diminishes the feeling of burden, as for the daughters the more intense crisis instrumental perceived support diminishes the same feeling.Se evalúa si la estructura de la red social, el apoyo percibido y su nivel de satisfacción personal inciden en el sentimiento de sobrecarga del cuidador, derivado de la asistencia de un hijo o de un progenitor anciano con una enfermedad crónica invalidante. Con tal fin, fueron administrados a 143 cuidadoras -50,3% madres y 49,7% hijas- el Cuestionario sobre Apoyo Social de Mannheim (1986) y el Cuestionario sobre Sentimiento de Carga de Zarit y Zarit (1999). A partir de las pruebas multivariadas de significación estadística, se puede concluir que las madres presentan una red de parientes mayor que las hijas, aunque no se diferencian significativamente en la percepción del apoyo social. En ellas, el tamaño de la red de parientes, el apoyo instrumental cotidiano y psicológico en crisis aminora el sentimiento de sobrecarga, mientras que en las hijas lo disminuye la mayor intensidad de apoyo instrumental en crisis percibido por ellas

A quantitative measure of lifestyle and well-being based on health related quality of life

-

A quantitative measure of lifestyle and well-being based on health related quality of life

-

An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy

Ozlem Goker-Alpan,1 Nicola Longo,2 Marie McDonald,3 Suma P Shankar,4,5 Raphael Schiffmann,6 Peter Chang,7 Yinghua Shen,7 Arian Pano7 1Lysosomal Disorders Unit, Fairfax, VA, 2University of Utah, Salt Lake City, UT, 3Department of Pediatrics, Duke University, Durham, NC, 4Department of Ophthalmology, 5Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 6Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, 7Shire, Lexington, MA, USA Background: Following a drug manufacturing process change, safety/efficacy of agalsidase alfa were evaluated in enzyme replacement therapy (ERT)-naïve children with Fabry disease. Methods: In an open-label, multicenter, Phase II study (HGT-REP-084; Shire), 14 children aged ≥7 years received 0.2 mg/kg agalsidase alfa every other week for 55 weeks. Primary endpoints: safety, changes in autonomic function (2-hour Holter monitoring). Secondary endpoints: estimated glomerular filtration rate, left ventricular mass index (LVMI), midwall fractional shortening, pharmacodynamic parameters, and patient-reported quality-of-life. Results: Among five boys (median 10.2 [range 6.7, 14.4] years) and nine girls (14.8 [10.1, 15.9] years), eight patients experienced infusion-related adverse events (vomiting, n=4; nausea, n=3; dyspnea, n=3; chest discomfort, n=2; chills, n=2; dizziness, n=2; headache, n=2). One of these had several hypersensitivity episodes. However, no patient discontinued for safety reasons and no serious adverse events occurred. One boy developed immunoglobulin G (IgG) and neutralizing antidrug antibodies. Overall, no deterioration in cardiac function was observed in seven patients with low/abnormal SDNN (standard deviation of all filtered RR intervals; <100 ms) and no left ventricular hypertrophy: mean (SD) baseline SDNN, 81.6 (20.9) ms; mean (95% confidence interval [CI]) change from baseline to week 55, 17.4 (2.9, 31.9) ms. Changes in SDNN correlated with changes in LVMI (r=-0.975). No change occurred in secondary efficacy endpoints: mean (95% CI) change from baseline at week 55 in LVMI, 0.16 (-3.3, 3.7) g/m2.7; midwall fractional shortening, -0.62% (-2.7%, 1.5%); estimated glomerular filtration rate, 0.15 (-11.4, 11.7) mL/min/1.73 m2; urine protein, -1.8 (-6.0, 2.4) mg/dL; urine microalbumin, 0.6 (-0.5, 1.7) mg/dL; plasma globotriaosylceramide (Gb3), -5.71 (-10.8, -0.6) nmol/mL; urinary Gb3, -1,403.3 (-3,714.0, 907.4) nmol/g creatinine, or clinical quality-of-life outcomes. Conclusion: Fifty-five weeks’ agalsidase alfa ERT at 0.2 mg/kg every other week was well tolerated. Disease progression may be slowed when ERT is started prior to major organ dysfunction. Trial registration: https://ClinicalTrials.gov identifier NCT01363492. Keywords: agalsidase alfa, efficacy, enzyme replacement therapy, Fabry disease, pediatric study, safet

Nutritional determinants of quality of life in a mediterranean cohort: The SUN study

Health related quality of life (HRQoL) is a subjective appreciation of how personal characteristics and health influence well-being. This cross-sectional analysis aimed to quantitatively measure the influence of dietary, lifestyle, and demographic factors on HRQoL. A sub-sample of the Seguimiento Universidad de Navarra (SUN) Project, a Mediterranean cohort, was analyzed (n = 15,674). Through self-administered questionnaires the relationship between HRQoL and dietary patterns (Mediterranean-diet (MedDiet) and provegetarian food pattern (FP) assessment), lifestyles (sleeping hours, physical activity) and demographic characteristics were measured. Multivariate linear regression and flexible regression models were used to estimate the pondered effect of personal factors on Short Form-36 (SF-36) scores. Coefficients for MedDiet and provegetarian scores (β-coefficient for global SF-36 score: 0.32 (0.22, 0.42); 0.09 (0.06, 0.12) respectively for every unit increase), physical activity (β: 0.03 (0.02, 0.03) for every metabolic equivalent of task indexes (MET)-h/week) had a positive association to HRQoL. The female sex (β: −3.28 (−3.68, −2.89)), and pre-existing diseases (diabetes, β: −2.27 (−3.48, −1.06), hypertension β: −1.79 (−2.36, −1.22), hypercholesterolemia β: −1.04 (−1.48, −0.59)) account for lower SF-36 scores. Adherence to MedDiet or provegetarian FP, physical activity and sleep are associated with higher HRQoL, whereas the female sex, “other” (versus married status) and the presence of chronic diseases were associated with lower SF-36 scores in this sample

Nutritional determinants of quality of life in a mediterranean cohort: The SUN study

Health related quality of life (HRQoL) is a subjective appreciation of how personal characteristics and health influence well-being. This cross-sectional analysis aimed to quantitatively measure the influence of dietary, lifestyle, and demographic factors on HRQoL. A sub-sample of the Seguimiento Universidad de Navarra (SUN) Project, a Mediterranean cohort, was analyzed (n = 15,674). Through self-administered questionnaires the relationship between HRQoL and dietary patterns (Mediterranean-diet (MedDiet) and provegetarian food pattern (FP) assessment), lifestyles (sleeping hours, physical activity) and demographic characteristics were measured. Multivariate linear regression and flexible regression models were used to estimate the pondered effect of personal factors on Short Form-36 (SF-36) scores. Coefficients for MedDiet and provegetarian scores (β-coefficient for global SF-36 score: 0.32 (0.22, 0.42); 0.09 (0.06, 0.12) respectively for every unit increase), physical activity (β: 0.03 (0.02, 0.03) for every metabolic equivalent of task indexes (MET)-h/week) had a positive association to HRQoL. The female sex (β: −3.28 (−3.68, −2.89)), and pre-existing diseases (diabetes, β: −2.27 (−3.48, −1.06), hypertension β: −1.79 (−2.36, −1.22), hypercholesterolemia β: −1.04 (−1.48, −0.59)) account for lower SF-36 scores. Adherence to MedDiet or provegetarian FP, physical activity and sleep are associated with higher HRQoL, whereas the female sex, “other” (versus married status) and the presence of chronic diseases were associated with lower SF-36 scores in this sample