Low aerobic capacity in McArdle disease : A role for mitochondrial network impairment?

McArdle disease is caused by myophosphorylase deficiency and results in complete inability for muscle glycogen breakdown. A hallmark of this condition is muscle oxidation impairment (e.g., low peak oxygen uptake (VO)), a phenomenon traditionally attributed to reduced glycolytic flux and Krebs cycle anaplerosis. Here we hypothesized an additional role for muscle mitochondrial network alterations associated with massive intracellular glycogen accumulation. We analyzed in depth mitochondrial characteristics-content, biogenesis, ultrastructure-and network integrity in skeletal-muscle from McArdle/control mice and two patients. We also determined VO in patients (both sexes, N = 145) and healthy controls (N = 133). Besides corroborating very poor VO values in patients and impairment in muscle glycolytic flux, we found that, in McArdle muscle: (a) damaged fibers are likely those with a higher mitochondrial and glycogen content, which show major disruption of the three main cytoskeleton components-actin microfilaments, microtubules and intermediate filaments-thereby contributing to mitochondrial network disruption in skeletal muscle fibers; (b) there was an altered subcellular localization of mitochondrial fission/fusion proteins and of the sarcoplasmic reticulum protein calsequestrin-with subsequent alteration in mitochondrial dynamics/function; impairment in mitochondrial content/biogenesis; and (c) several OXPHOS-related complex proteins/activities were also affected. In McArdle disease, severe muscle oxidative capacity impairment could also be explained by a disruption of the mitochondrial network, at least in those fibers with a higher capacity for glycogen accumulation. Our findings might pave the way for future research addressing the potential involvement of mitochondrial network alterations in the pathophysiology of other glycogenoses

Ozone therapy versus surgery for lumbar disc herniation : A randomized double-blind controlled trial

Altres ajuts: Ministerio de Sanidad (Madrid); Ilustre Colegio de Médicos de Las Palmas (I19/18).Objectives: Surgery is the treatment of choice for symptomatic disc herniation after conservative management. Several studies have suggested the potential utility of intradiscal ozone infiltration in this pathology. The aim of this trial was to compare intradiscal ozone infiltration vs. oxygen infiltration vs. surgery. Design and interventions: This was a randomized, double-blinded, and controlled trial in patients on a waiting list for herniated disc surgery. There were three treatment groups: surgery; intradiscal ozone infiltration (plus foraminal infiltration of ozone, steroids, and anesthetic); intradiscal oxygen infiltration (plus foraminal infiltration of oxygen, steroids, and anesthetic). Main outcome measures: The requirements for surgery. Results: Five years after the treatment of the last recruited patient (median follow-up: 78 months), the requirement for further surgery was 20 % for patients in the ozone group and 60 % for patients in the oxygen group. 11 % of patients initially treated with surgery also required a second surgery. Compared to the surgery group, the ozone group showed: 1) significantly lower number of inpatient days: median 3 days (interquartile range: 3-3.5 days) vs. 0 days (interquartile range: 0-1.5 days), p = 0.012; 2) significantly lower costs: median EUR 3702 (interquartile range: EUR 3283-7630) vs. EUR 364 (interquartile range: EUR 364-2536), p = 0.029. Conclusions: Our truncated trial showed that intradiscal ozone infiltrations decreased the requirements for conventional surgery, resulting in decreased hospitalization durations and associated costs. These findings and their magnitude are of interest to patients and health services providers. Further validation is ongoing

Efeitos das condições ambientais no período entre a postura e o armazenamento de ovos de matrizes pesadas sobre o rendimento de incubação Effect on time between oviposition and the beginning of cool storage on hatchability of broiler breeder eggs

Avaliou-se o efeito das condições ambientais no período entre a postura e o armazenamento de ovos sobre o rendimento de incubação de 2.742 ovos de matrizes pesadas da linhagem Ross com 31 semanas de idade. Os tratamentos foram definidos pelo período de permanência dos ovos sob temperatura ambiente do galpão antes do armazenamento. Para cada tratamento foram utilizados 860 ovos, distribuídos em 10 repetições de 86 ovos cada. No tratamento A, os ovos foram enviados para a sala fria imediatamente após a coleta; no B, foram enviados para a sala fria após cinco horas de permanência no galpão; e, no C, permaneceram no galpão por 10 horas, antes de serem enviados para a sala fria. As condições ambientais da sala fria foram: temperatura 18,2 a 21,0 ºC e umidade relativa do ar de 72,8 a 76,8%. O período de armazenamento dos ovos foi de quatro dias. A mortalidade embrionária no tratamento A foi maior que no tratamento B (P<0,05). A eclosão dos ovos do tratamento B foi maior que aquela do tratamento A (P<0,05). O peso dos pintos do tratamento A foi maior que aqueles do tratamento C (P<0,05). O melhor rendimento de incubação foi obtido quando os ovos foram resfriados cinco horas após a postura.<br>The effect on hatchability of time post-oviposition until initiation of cool storage was examined using 2,742 eggs from 31-week-old Ross hens. Treatments were defined by the length of time that eggs remained at breeder house temperature, prior to cool storage. In treatments A, B and C, respectively, eggs were taken to the cooling room immediately after collection, after 5 hours in the aviary or after 10 hours in the aviary. From each treatment, 860 eggs were distributed into 10 replicates of 86 eggs each and stored for 4 days at 18.2 - 21.0ºC and 75% humidity. After cool storage, they were incubated. Embryo mortality in treatment A was higher than in B (P<0.05). The hatchability of eggs of treatment B was higher (P<0.05) than that of treatment A. Average chick weight at hatching was higher for treatment A than for treatment C (P<0.05). Eggs that were cooled beginning five hours after oviposition produced the highest incubation yield