Comparison of two mechanical insufflation-exsufflation devices in patients with amyotrophic lateral sclerosis: a preliminary study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease affecting upper and lower motor neurons and resulting in progressive skeletal muscle weakness. Weak cough and difficulty in clearing secretions are often the cause of pulmonary infections and acute respiratory failure. Cough assistance is commonly used to provide support in coughing for patients with ALS. METHODS: This was a preliminary parallel randomized study comparing two cough-assist devices: one utilizing mechanical insufflation/exsufflation (MI/E) and expiratory flow accelerator (EFA) technology, the other utilizing only MI/E technology. The aim was to compare the effectiveness, safety and acceptability of the two devices. Thirty patients with ALS and similar severity and functional scale were enrolled. The primary outcome was the change in respiratory function, respiratory muscle function, gas exchange, and peak cough expiratory flow as an indicator of cough efficacy. Secondary outcomes were the number of exacerbations at 1, 6 and 12 months of treatment, and the patient-perceived comfort/distress related to the interventions together with the perceived efficacy of cough. RESULTS: Thirty subjects were recruited and randomized into the two groups (1:1 ratio). Primary outcomes : respiratory function parameters decreased over time in both groups, but significantly less in the Kalos group, as did the respiratory muscle strength parameters and peak cough flows. Gas exchanges decreased over time in both groups with no clinically relevant differences between groups. Secondary outcomes : there were no significant differences between groups regarding the number of exacerbations over time. No adverse events were reported. All participants, in both groups, reported a similar increase in perceived cough efficacy and there was no significant difference in comfort and distress between the two treatments. CONCLUSIONS: The cough-assist device with EFA technology performed better than a traditional MI/E device in ALS patients regarding respiratory function and cough efficacy, although number of exacerbations and acceptability of the two devices was similar. Following these promising preliminary results, further investigation is required in a larger cohort to confirm the superiority of EFA technology associated with a MI/E device.

Effectiveness of expiratory flow acceleration in patients with Parkinson's disease and swallowing deficiency: A preliminary study.

OBJECTIVES: Parkinson's disease (PD) causes dysfunction both to swallowing and to the cough mechanism. Oropharyngeal dysphagia is the main cause of pneumonia, due to silent aspiration of food and saliva. Pneumonia is the leading cause of death in PD. Different strategies exist to reduce the risk of inhalation and associated lung infections, but evidence of their efficacy is still unclear. The aim of this preliminary study was to investigate if adding an expiratory flow acceleration (EFA®) technique to standard therapy (ST) for dysphagia can reduce the incidence of bronchopulmonary infections and improve quality of life, respiratory function parameters, cough, and airways encumbrance perception. MATERIALS AND METHODS: Twenty-five patients with PD were randomized to two groups: ST vs. ST + EFA. Patients were re-assessed at 30, 180 and 360 days from start of treatment. The primary outcome was the incidence of respiratory exacerbations together with quality of life score (PDQ-39). Secondary outcomes were changes in respiratory function tests, cough capacity (CPEF), perceived health status (Euro-QOL-VAS), cough, and upper airways encumbrance perception evaluated by visual numeric scale (VNS). RESULTS: Twenty patients concluded the study (10 each group). Albeit the difference was not significant, less respiratory infections, symptoms, hospital admissions and medical visits were found in the study group. Furthermore, there was a significant difference in cough effectiveness measured with the peak cough expiratory flow (PCEF) and other spirometry parameters (FEV1, FVC), and also in specific and generic health-related quality of life measures (PDQ-39, Euro-QoL-VAS). CONCLUSION: The results of this preliminary study support the use of EFA® technology in Parkinson's patients with dysphagia to reduce the risk of respiratory complications. Nevertheless, further studies are needed in a larger, more representative sample to definitively confirm the usefulness of this technique in PD patients.

The impact of long-term exposure to space environment on adult mammalian organisms: a study on mouse thyroid and testis.

Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis.In thyroids, volumetric ratios between thyrocytes and colloid were measured. cAMP production in 10(-7)M and 10(-8)M thyrotropin-treated samples was studied. Thyrotropin receptor and caveolin-1 were quantitized by immunoblotting and localized by immunofluorescence. In space-exposed animals, both basal and thyrotropin-stimulated cAMP production were always higher. Also, the structure of thyroid follicles appeared more organized, while thyrotropin receptor and caveolin-1 were overexpressed. Unlike the control samples, in the space samples thyrotropin receptor and caveolin-1 were both observed at the intracellular junctions, suggesting their interaction in specific cell membrane microdomains.In testes, immunofluorescent reaction for 3ß- steroid dehydrogenase was performed and the relative expressions of hormone receptors and interleukin-1ß were quantified by RT-PCR. Epididymal sperm number was counted. In space-exposed animals, the presence of 3ß and 17ß steroid dehydrogenase was reduced. Also, the expression of androgen and follicle stimulating hormone receptors increased while lutenizing hormone receptor levels were not affected. The interleukin 1 ß expression was upregulated. The tubular architecture was altered and the sperm cell number was significantly reduced in spaceflight mouse epididymis (approx. -90% vs. laboratory and ground controls), indicating that the space environment may lead to degenerative changes in seminiferous tubules.Space-induced changes of structure and function of thyroid and testis/epididymis could be responsible for variations of hormone levels in human during space missions. More research, hopefully a reflight of MDS, would be needed to establish whether the space environment acts directly on the peripheral glands or induces changes in the hypotalamus-pituitary-glandular axis.

Feeding behavior in mammals including humans.

The complex control of food intake and energy metabolism in mammals relies on the ability of the brain to integrate multiple signals indicating the nutritional state and the energy level of the organism and to produce appropriate responses in terms of food intake, energy expenditure, and metabolic activity. Central regulation of feeding is organized as a long-loop mechanism involving humoral signals and afferent neuronal pathways to the brain, processing in hypothalamic neuronal circuits, and descending commands using vagal and spinal neurons. Sensor mechanisms or receptors sensitive to glucose and fatty acid metabolism, neuropeptide and cannabinoid receptors, as well as neurotransmitters and neuromodulators synthesized and secreted within the brain itself are all signals integrated in the hypothalamus, which therefore functions as an integrator of signals from central and peripheral structures. Homeostatic feedback mechanisms involving afferent neuroendocrine inputs from peripheral organs, like adipose tissue, gut, stomach, endocrine pancreas, adrenal, muscle, and liver, to hypothalamic sites thus contribute to the maintenance of normal feeding behavior and energy balance. In addition to transcriptional events, peripheral hormones may also alter firing and/or connection (synaptology) of hypothalamic neuronal networks in order to modulate food intake. Moreover, intracellular energy sensing and subsequent biochemical adaptations, including an increase in AMP-activated protein kinase activity, occur in hypothalamic neurons. Understanding the regulation of appetite is clearly a major research effort but also seems promising for the development of novel therapeutic strategies for obesity.

GnRH immunodetection in the brain of the holocephalan fish Chimaera monstrosa L.: correlation to oocyte maturation.

Chimera monstrosa (rabbit fish) like other holocephalans is a rare, delicate deep sea fish. Owing to the difficulty of sampling individuals in good shape, there is a paucity of information available on the morphology and physiology of this species especially concerning reproduction. In holocephalans, a hypothalamus-pituitary-gonadal axis has been postulated and a GnRH molecule identical to cGnRH II has been identified. The aim of the present study was to correlate the presence of steroidogenic enzymes in the ovarian follicles with the presence of GnRH in the hypothalamus. Estrogens, the steroids that trigger the accumulation of yolk (vitellogenesis) in the oocytes are synthesized by the somatic cells of the follicle in the vitellogenic stages via a cascade of steroid dehydrogenases involving 3 beta-hydroxysteroid-dehydrogenase (3 beta-HSD; in the inner thecal layer) and aromatase cytochrome (P450; granulosa layer). Our results showed that 3 beta-HSD is present concomitant with the presence of cGnRH II in the preoptic area and in the ventral hypothalamus. Another form of immunoreactive GnRH, mGnRH is also present in the brain of C. monstrosa. It is localized in the ventral telencephalon and in the midbrain caudal diencephalon (boundary between ventral thalamus and tegmentum of the mesencephalon). This form of GnRH is probably correlated with sexual behaviour.

Galanin and its binding sites in the brain of eels subjected to different osmolar conditions.

A galanin (GAL)-like peptidergic system was investigated in the brain of Anguilla anguilla subjected to hyperosmolar and hypoosmolar conditions, by using antisera raised against porcine 1-29 GAL. A group of immunoreactive perikaria was identified in the periventricular hypothalamus, in the ventral thalamus, in the pretectal areas and in the optic tectum. Immunoreactive perikaria were present in the nucleus lateralis of the torus semicircularis in seawater (SW) adapted eels, and were absent in the freshwater (FW) adapted eels. Galaninergic fibres were observed in many areas of the brain. The immunoreactive perikaria and fibres, when localised in the same areas, were more strongly labelled and numerous in the SW adapted eels in comparison to the FW adapted animals. GAL-specific binding sites, investigated by autoradiography using iodinated porcine GAL, occurred in several regions of the brain, in particular in the dorsal telencephalon, in the dorsal thalamus and in the torus semicircularis, where a high density of binding sites was observed in the SW adapted eels. Conversely, a higher density of binding sites was observed in the caudal substantia reticularis and in the corpus cerebelli in the FW adapted eels. We conclude that different distributions and intensity in immunoreactive elements occur in response to the two environmental conditions.

Clinorotation-induced weightlessness influences the cytoskeleton of glial cells in culture.

During and after spaceflight astronauts experience neurophysiological alterations. To investigate if the impairment observed might be traced back to cytomorphology, we undertook a ground based research using a random positioning machine (clinostat) as a simulation method for microgravity. The outcome of the study was represented by cytoskeletal changes occurring in cultured glial cells (C(6) line) after 15 min, 30 min, 1 h, 20 h and 32 h under simulated microgravity. Glia is fundamental for brain function and it is essential for the normal health of the entire nervous system. Our data showed that after 30 min under simulated microgravity the cytoskeleton was damaged: microfilaments (F-actin) and intermediate filaments (Vimentin, Glial Fibrillary Acidic Proteins GFAP) were highly disorganised, microtubules (alpha-tubulin) lost their radial array, the overall cellular shape was deteriorated, and the nuclei showed altered chromatin condensations and DNA fragmentation. This feature got less dramatic after 20 h of simulated microgravity when glial cells appeared to reorganise their cytoskeleton and mitotic figures were present. The research was carried out by immunohistochemistry using antibodies to alpha-tubulin, vimentin and GFAP, and cytochemical labelling of F-actin (Phalloidin-TRIC). The nuclei were stained with propidium iodide or 4,6-diamidino-2-phenylindole dihydrochloride (DAPI). The cells were observed at the conventional and/or the confocal laser scanning microscope. Samples were also observed at the scanning electron microscope (SEM). Our data showed that in weightlessness alterations occur already visible at the scale of the single cell; if this may lead to the neurophysiological problems observed in flight is yet to be established.