Effects of long-term diet supplementation with Gliricidia sepium foliage mixed with Enterolobium cyclocarpum pods on enteric methane, apparent digestibility, and rumen microbial population in crossbred heifers

In the last decades, strategies have been evaluated to reduce rumen methane (CH4) production by supplementing tropical forages rich in secondary compounds; however, most of these beneficial effects need to be validated in terms of their persistence over time. The aim of this study was to assess CH4 emissions over time in heifers fed with and without Gliricidia sepium foliage (G) mixed with ground pods of Enterolobium cyclocarpum(E). Two groups of four crossbred (Bos taurus x Bos indicus) heifers (284 ±17 kg initial weight) were fed with two diets (0 and 15% of a mixture of the pods and foliage [E+G:0 and E+G:15, respectively] over 80 days, plus two weeks before the experiment, in which every animal was fed a legume and pod-free diet. Every 14 days, CH4 production, apparent digestibility, volatile fatty acids (VFA), and microbial population were quantified for each animal. The experiment was conducted with a repeated measurements design over time. Diets fed differed in terms of their crude protein (CP), condensed tannins (CT) and saponins content supplied by E. cyclocarpum and G. sepium. For most of the experiment, dry matter intake (DMI) and digestible dry-matter intake (DDMI) were 6.3 kg DMI/d and 512 g DDMI/kg, respectively for both diets (Diet: P>0.05). Apparent digestible crude protein (DCP) was reduced by 21 g DCP/kg DM when the diet was supplemented with E+G:15 (P=0.040). Molar proportions of VFA’s in the rumen did not differ between diets or in time (P>0.05). Daily methane production, expressed in relation to DMI was 23.95 vs 23.32 g CH4/kg DMI for the diet E+G:0 and E+G:15 respectively (Diet: P=0.016; Time: P>0.05). Percent gross energy loss as CH4 (Ym) with grassonly diets was above 8.1%, whereas when feeding heifers with the alternate supplementation, Ym values of 7.59% (P=0.016) were observed. The relative abundance of total bacterial, protozoa, and methanogenic archaeal replicates was not affected by time nor by the incorporation of legume and pods into the diet (P>0.05). Results suggest that addition of G. sepium mixed with E. cyclocarpum pods can reduce CH4 production in heifers and this response remains over time, without effect on microbial population and VFA concentration and a slight reduction in crude protein digestibility

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The 6-hydroxydopamine model and parkinsonian pathophysiology: Novel findings in an older model

The neurotoxin 6-hydroxydopamine (6-OHDA) is widely used to induce models of Parkinson's disease (PD). We now know that the model induced by 6-OHDA does not include all PD symptoms, although it does reproduce the main cellular processes involved in PD, such as oxidative stress, neurodegeneration, neuroinflammation, and neuronal death by apoptosis. In this review we analyse the factors affecting the vulnerability of dopaminergic neurons as well as the close relationships between neuroinflammation, neurodegeneration, and apoptosis in the 6-OHDA model. Knowledge of the mechanisms involved in neurodegeneration and cell death in this model is the key to identifying potential therapeutic targets for PD. Resumen: El neurotóxico 6-hidroxidopamina (6-OHDA) ha sido utilizado para generar modelos de la enfermedad de Parkinson (EP). A la fecha se ha establecido que si bien el modelo neurodegenerativo inducido por la 6-OHDA no reproduce la totalidad de síntomas de la enfermedad, sí replica procesos celulares tales como el estrés oxidativo, la neurodegeneración, la neuroinflamación y la muerte neuronal por apoptosis. En esta revisión se contempla el análisis de los factores que influyen en la vulnerabilidad de las neuronas dopaminérgicas, así como la estrecha relación entre el proceso neurodegenerativo, el neuroinflamatorio y la apoptosis ocasionada por la 6-OHDA. El conocimiento de los mecanismos involucrados en la neurodegeneración y la muerte celular en este modelo es relevante para definir posibles blancos terapéuticos para EP. Keywords: Apoptosis, Nigrostriatal pathway, Neurodegeneration, Substantia nigra, Neuroinflammation, Oxidative stress, Palabras clave: Apoptosis, Vía nigroestriatal, Neurodegeneración, Substantia nigra, Neuroinflamación, Estrés oxidativ

El modelo de 6-hidroxidopamina y la fisiopatología parkinsoniana: nuevos hallazgos en un viejo modelo

Resumen: El neurotóxico 6-hidroxidopamina (6-OHDA) ha sido utilizado para generar modelos de la enfermedad de Parkinson (EP). A la fecha se ha establecido que si bien el modelo neurodegenerativo inducido por la 6-OHDA no reproduce la totalidad de síntomas de la enfermedad, sí replica procesos celulares tales como el estrés oxidativo, la neurodegeneración, la neuroinflamación y la muerte neuronal por apoptosis. En esta revisión se contempla el análisis de los factores que influyen en la vulnerabilidad de las neuronas dopaminérgicas, así como la estrecha relación entre el proceso neurodegenerativo, el neuroinflamatorio y la apoptosis ocasionada por la 6-OHDA. El conocimiento de los mecanismos involucrados en la neurodegeneración y la muerte celular en este modelo es relevante para definir posibles blancos terapéuticos para EP. Abstract: The neurotoxin 6-hydroxydopamine (6-OHDA) is widely used to induce models of Parkinson's disease (PD). We now know that the model induced by 6-OHDA does not include all PD symptoms, although it does reproduce the main cellular processes involved in PD, such as oxidative stress, neurodegeneration, neuroinflammation, and neuronal death by apoptosis. In this review we analyse the factors affecting the vulnerability of dopaminergic neurons as well as the close relationships between neuroinflammation, neurodegeneration, and apoptosis in the 6-OHDA model. Knowledge of the mechanisms involved in neurodegeneration and cell death in this model is the key to identifying potential therapeutic targets for PD. Palabras clave: Apoptosis, Vía nigroestriatal, Neurodegeneración, Substantia nigra, Neuroinflamación, Estrés oxidativo, Keywords: Apoptosis, Nigrostriatal pathway, Neurodegeneration, Substantia nigra, Neuroinflammation, Oxidative stres