Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease in which much burden is geared towards end-of-life care. Particularly in the earlier stages of ALS, many people have found both physiological and psychological boosts from various types of physical exercise for disused muscles. Proper exercise is important for preventing atrophy of muscles from disuse-a key for remaining mobile for as long as possible-and as long as it is possible to exercise comfortably and safely, for preserving cardiovascular fitness. However, the typical neuromuscular patient features a great physical inactivity and disuse weakness, and for that reason many controversial authors have contested exercise in these patients during years, especially in ALS which is rapidly progressive. There is an urgent need for dissecting in detail the real risks or benefits of exercise in controlled clinical trials to demystify this ancient paradigm. Yet, recent research studies document significant benefits in terms of survival and quality of life in ALS, poor cooperation, small sample size, uncontrolled and short-duration trials, remain the main handicaps. Sedentary barriers such as early fatigue and inherent muscle misuse should be overcome, for instance with body-weight supporting systems or non-invasive ventilation, and exercise should be faced as a potential non-monotonous way for contributing to better health-related quality of life.
Neuromuscular disorders encompass a wide category of illnesses with a significant burden on the patient, family, and society. Telehome monitoring presents an alternative for closer follow-up, by ensuring timely transmission of data and prompting medical support before deterioration occurs. We used telehome monitoring devices for amyotrophic lateral sclerosis patients with respiratory failure in a clinic. This instrument directly acts as a digital recorder of parameters received from an external instrument, such as the bi-level ventilator, and contains an internal modem for direct connection to the Internet, thereby allowing bidirectional flexibility in collecting data and parameter changes whenever needed. The use and acceptance of the system was investigated with patients and all therapists involved. The instrument was found to be user-friendly and effective by the researchers, being practical for both patients and therapists. Therefore, it can be integrated into a routine home care application based on a large respiratory rehabilitation center. The device was extensively tested, and in an ongoing randomized controlled study it is being investigated whether this management strategy is able to hasten the ventilator adaptation process and to diminish the overall utilization of health services, with concurrent economic viability. We conclude that home telemonitoring represents a positive contribution to the management of chronic patients and raised awareness of it should be considered in a near future. This portable telemonitoring device provides an opportune approach to better understand and recognize a ventilatory pattern through long-term ventilation monitoring in the home environment.
Our objective was to measure direct (hospital and NHS) and indirect (patient/caregiver) costs of following up in-home compliance to non-invasive ventilation via wireless modem. We constructed a prospective controlled trial of 40 consecutive ALS home-ventilated patients, randomly assigned according to their residence area to G1 (nearby hospital, office-based follow-up) and G2 (outside hospital area, telemetry device-based follow-up). Total NHS direct cost encompassed costs related to outpatients' visits (office and emergency room) and hospitalizations. Hospital direct costs included transportation to/from hospital, office visit per hour cost and equipment maintenance. Non-medical costs considered days of wages lost due to absenteeism. G1 included 20 patients aged 60 ± 10 years and G2 included 19 patients aged 62 ± 13 years. Results showed that no differences were found regarding clinical/demographic characteristics at admission. NHS costs showed a 55% reduction in average total costs with a statistically significant decrease of 81% in annual costs per patient in G2. Hospital costs were found to be significantly higher in G2 with regard to total costs (64% average increase) but not annual costs (7%). No statistical difference was found with regard to expenses from absenteeism. In conclusion, at the cost of an initial financial constraint to the hospital per year (non-significant), telemonitoring is cost-effective, representing major cost savings to the NHS in the order of 700 euros/patient/year.
Acetylcholine is well known in the medical setting as one of the most exemplary neurotransmitters. Its ubiquity in nature otherwise suggests a theoretically diverse spectrum of action and an extremely early appearance in the evolutionary process. In humans, acetylcholine and its synthesizing enzyme, choline acetyltransferase, have been found in various nonneural tissues such as the epithelium, mesothelium, endothelium, muscle, immune cells and blood cells. The widespread expression of nonneuronal acetylcholine is accompanied by the ubiquitous presence of acetylcholinesterase and nicotinic/muscarinic receptors. Structural and functional dissimilarities are evident between the nonneuronal and neuronal cholinergic systems. An increasing body of evidence throughout the last few years has placed acetylcholine as a major cellular signaling molecule in many pathways. Furthermore, numerous erythrocyte physiological events in the microcirculation are strongly regulated by acetylcholine. Thus, it is time to revise our understanding of the role of vascular acetylcholine in humans. Its biological and pathobiological roles must be evaluated in more detail to eventually achieve novel therapeutical targets. The present article reviews recent findings about nonneuronal acetylcholine in red blood cells, with special regard to (1) red cell rheology, (2) plasma ion concentrations, (3) nitric oxide intracellular translocation and metabolism and (4) band 3 protein phosphorylation.
Experimental evidence has shown that plasma fibrinogen plays a key role as a major cardiovascular risk factor, acting directly to trigger erythrocyte aggregation in occlusive vascular disease. However, due to the complex and hitherto unclear interaction between fibrinogen and the erythrocyte membrane, no study has yet evaluated the effects of fibrinogen, under physiological range values, on the erythrocyte nitric oxide (NO) mobilization. Taking into consideration the potential NO-derived molecules, we have raised the hypothesis that fibrinogen, under physiological conditions, may act to influence blood flow via erythrocyte NO modulation. In this in vitro study whole-blood samples were harvested from healthy subjects, erythrocyte suspensions were incubated in the absence (control aliquots) and presence of different fibrinogen concentrations and levels of NO, nitrite, nitrate and S-nitroglutathione (GSNO) were determined. Our results showed, when compared with control aliquots, that the presence of fibrinogen modulates the NO mobilization in erythrocytes by (1) decreasing erythrocyte NO efflux levels (P < 0.001); (2) increasing levels of intraerythrocytic NO oxidative metabolites, namely, nitrite (P < 0.0001) and nitrate (P < 0.0001); and (3) enhancing the formation of GSNO (P < 0.001). In conclusion, this study provides new insights into an unknown mechanism by which fibrinogen modulates the erythrocyte capacity to supply NO, the effects of which on inflammation profiles (generally associated with blood hyperviscosity and hyperaggregation) still need to be elucidated. Also, increased erythrocyte GSNO levels may be associated with platelet NO metabolism, its activation status and hypotension, which may be extremely relevant in the clinical setting as biomarkers.
In the present article the authors make an approach over the applications of dithiothreitol (DTT) in its different clinicallaboratory, potential and up-to-date sources. Dithiothreitol is a chemical reagent with a wide actuation spectrum not only from a laboratorial view but also from a therapeutic standpoint, more clinical and practical. DTT (i) is frequently used in a variety of experiences that involve proteins or peptides, protecting sulfhydryl groups from oxidation and reducing disulfide bonds between cysteines; (ii) is also used in the study of disulfide exchange reactions of protein disulfides; (iii) is able to keep glutathione in the reduced state; (iv) acts as an "antidote" enabling the activity of detoxification systems; (v) participates in cellular mechanisms such as vesiculation, cell morphology, signal transduction pathways (hormone-'like' role), etc.; (vi) can be used in the treatment approach of diseases like cystinosis or medical conditions resulting from ion or metal toxicity. In erythrocytes, there's literature pointing that DTT may trigger changes on the normal discoid shape following metabolic depletion, and additionally modulate the exovesiculation kinetics as demonstrated by us. The present article dissects in detail recent findings in our Unit concerning the DTT influence on human erythrocytes.
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