Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial).

PURPOSE: To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Inclusion criteria comprised patients with COVID-19-related moderate-severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. RESULTS: Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X­ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. CONCLUSIONS: LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.

Prebiotics and phytogenics functional additives in low fish meal and fish oil based diets for European sea bass (Dicentrarchus labrax): Effects on stress and immune responses.

The use of terrestrial raw materials to replace fish meal (FM) and fish oil (FO) in marine fish diets may affect fish growth performance and health. In the last years functional additives have been profiled as good candidates to reduce the effects on health and disease resistance derived from this replacement, via reinforcement of the fish immune system. In the present study, three isoenergetic and isonitrogenous diets with low FM and FO (10% and 6% respectively) were tested based on supplementation either with 0.5% galactomannanoligosaccharides (GMOS diet) or 0.02% of a mixture of essential oils (PHYTO diet), a non-supplemented diet was defined as a control diet. Fish were fed the experimental diets in triplicate for 9 weeks and then they were subjected to a stress by confinement as a single challenge (C treatment) or combined with an experimental intestinal infection with Vibrio anguillarum (CI treatment). Along the challenge test, selected stress and immunological parameters were evaluated at 2, 24 and 168h after C or CI challenges. As stress indicators, circulating plasma cortisol and glucose concentrations were analyzed as well as the relative gene expression of cyp11b hydroxylase, hypoxia inducible factor, steroidogenic acute regulatory protein, heat shock protein 70 and heat shock protein 90 (cyp11b, hif-1α, StAR, hsp70 and hsp90). As immune markers, serum and skin mucus lysozyme, bactericidal and peroxidase activities were measured, as well as gene expression of Caspase-3 (casp-3) and interleukin 1ß (il-1ß). The use of functional additives induced a significant (p < 0.05) reduction of circulating plasma cortisol concentration when confinement was the unique challenge test applied. Supplementation of PHYTO induced a down-regulation of cyp11b, hif-1α, casp-3 and il-1ß gene expression 2h after stress test, whereas StAR expression was significantly (p < 0.05) up-regulated. However, when combination of confinement stress and infection was applied (CI treatment), the use of PHYTO significantly (p < 0.05) down-regulated StAR and casp-3 gene expression 2h after challenge test, denoting that PHYTO diet reinforced fish capacity of stress response via protection of head kidney leucocytes from stress-related apoptotic processes, with lower caspase-3 gene expression and a higher il-1ß gene expression when an infection occurs. Additionally, dietary supplementation with GMOS and PHYTO compounds increased fish serum lysozyme after infection. Both functional additives entailed a better capability of the animals to cope with infection in European sea bass when fed low FM and FO diets.

Suplementos de calcio y riesgo de enfermedad cardiovascular: ¿fin de la controversia? / Calcium supplements and cardiovascular disease risk: end of the controversy?

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Guía de la Academia Europea de Neurología sobre terapia de neuroestimulación central en condiciones de dolor crónico / European Academy of Neurology guidelines on central neurostimulation therapy in chronic pain conditions

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Un algoritmo de tratamiento farmacológico para el dolor neuropático localizado / A pharmacological treatment algorithm for localised neuropathic pain

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¿Existe evidencia científica para el empleo de la capsaicina tópica en el dolor de la osteoartritis? / Is there scientific evidence for the use of topical capsaicin in osteoarthritis pain?

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Cannabis en el tratamiento del dolor: consideraciones clínicas y de investigación / Cannabis in pain treatment: clinical and research considerations

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Vitamina D y dolor crónico / Vitamin D and chronic pain

La vitamina D, una vitamina liposoluble que se encuentra en algunas fuentes de alimentos naturales, se sintetiza en la piel humana después de la exposición al sol. La insuficiencia y la deficiencia de vitamina D son muy frecuentes en el mundo, lo cual se cree que contribuye a una gran variedad de problemas de salud. La vitamina D durante mucho tiempo ha sido utilizada en combinación con el calcio para mejorar la salud ósea y reducir el riesgo de fracturas. Los suplementos de vitamina D se han relacionado con la prevención de la hipertensión arterial, cáncer y otras enfermedades. Investigaciones recientes también La vitamina D, una vitamina liposoluble que se encuentra en algunas fuentes de alimentos naturales, se sintetiza en la piel humana después de la exposición al sol. La insuficiencia y la deficiencia de vitamina D son muy frecuentes en el mundo, lo cual se cree que contribuye a una gran variedad de problemas de salud. La vitamina D durante mucho tiempo ha sido utilizada en combinación con el calcio para mejorar la salud ósea y reducir el riesgo de fracturas. Los suplementos de vitamina D se han relacionado con la prevención de la hipertensión arterial, cáncer y otras enfermedades. Investigaciones recientes también apuntan a una posible asociación entre la deficiencia de vitamina D y el dolor crónic (AU)

Vitamin D, a fat-soluble vitamin found in few natural food sources, is synthesized in human skin after sun exposure. Insufficient and deficiency of vitamin D is very common in the world, which is thought to contribute to a wide range of health issues. Vitamin D has long been utilized in combination with calcium to improve bone health and reduce the risk of fractures. Vitamin D supplementation has been linked to the prevention of high blood pressure, cancer, and other diseases. Recent research also points to a possible association between vitamin D deficiency and chronic pain (AU)

Capsaicina 8 % parche frente a pregabalina oral en pacientes con dolor neuropático periférico / Capsaicin 8% patch versus oral pregabalin in patients with peripheral neuropathic pain

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Efficacy of colistin versus beta-lactams, aminoglycosides, and rifampin as monotherapy in a mouse model of pneumonia caused by multiresistant Acinetobacter baumannii.

The treatment of life-threatening infections due to carbapenem-resistant Acinetobacter baumannii has become a serious challenge for physicians worldwide. Often, only colistin shows in general good in vitro activity against these carbapenem-resistant strains, but its antibacterial efficacy in comparison with the antibiotics most used in clinical practice is not well known. We studied the efficacy of colistin versus those of imipenem, sulbactam, tobramycin, and rifampin in an experimental pneumonia model with immunocompetent mice. We used three strains of A. baumannii corresponding to the main clones (A, D, and E) involved in the outbreaks of our hospital, with different grades of resistance to imipenem (imipenem MICs of 1, 8, and 512 microg/ml, respectively) and to the other antibiotics. The MIC of colistin was 0.5 microg/ml for the three strains. Reduction of log(10) CFU/g in lung bacterial counts, clearance of bacteremia, and survival versus results with controls were used as parameters of efficacy. Imipenem and sulbactam (Deltalung counts: -5.38 and -4.64 log(10) CFU/ml) showed the highest level of bactericidal efficacy in infections by susceptible and even intermediate strains. Tobramycin and rifampin (-4.16 and -5.15 log(10) CFU/ml) provided good results against intermediate or moderately resistant strains, in agreement with killing curves and pharmacodynamics. On the contrary, colistin showed the weakest antibacterial effect among the antibiotics tested, both in killing curves and in the in vivo model (-2.39 log(10) CFU/ml; P < 0.05). We conclude that colistin did not appear as a good option for treatment of patients with pneumonia due to carbapenem-resistant A. baumannii strains. Other alternatives, including combinations with rifampin, may offer better therapeutic profiles and thus should be studied.

Estudio genotóxico in vivo de 6 extractos de plantas medicinales en células de la médula ósea de roedores / Genotoxity study in vivo of six plants extracts in bone marrow cells of rodents

Se estudió el efecto mutagénico in vivo de 6 extractos de plantas medicinales, mediante el ensayo de micronúcleos en ratones. Los extractos fueron administrados por vía oral. Como controles negativo y positivo se utilizaron agua y cilofosfamida (40 mg/kg) respectivamente. Al final del tratamiento los animales fueron sacrificados y procesada la médula ósea para obtener las preparaciones. Sólo uno de los seis extractos ensayados indujo micronúcleos en las células somáticas de los animales tratados (AU)

F(2)-isoprostanes mediate high glucose-induced TGF-beta synthesis and glomerular proteinuria in experimental type I diabetes.

BACKGROUND: The recently discovered arachidonic acid derivatives, isoprostanes, are increased in pathological conditions associated with oxidative stress, such as diabetes. No role has yet been described for isoprostanes during the development of diabetic nephropathy. Cell culture in high ambient glucose has been used as a model in elucidating cellular mechanisms underlying diabetic nephropathy. Among the growth factors involved in the effect of high glucose, transforming growth factor-beta (TGF-beta) has been described as playing a key role in the development of nephropathy. METHODS: Streptozotocin-induced diabetic rats were supplemented in their diet with the antioxidant vitamin E (1000 U/kg diet). Blood and urine samples were taken to determine renal function and isoprostane concentration, as determined by gas chromatography/mass spectrometry. Glomerular mesangial and endothelial cells were cultured in high ambient glucose to determine the synthesis of isoprostanes and the role of isoprostanes in high glucose-induced synthesis of TGF-beta. RESULTS: Streptozotocin-induced diabetic rats had marked increases in plasma levels and urinary excretion rates of F(2)-isoprostanes. Dietary supplementation with vitamin E normalized (plasma) and reduced (urine) isoprostane levels and, surprisingly, improved proteinuria and blood urea nitrogen (BUN) levels. High ambient glucose increased F(2)-isoprostane synthesis in glomerular endothelial and mesangial cells in culture. Incubation of glomerular cells with F(2)-isoprostanes stimulated the production of TGF-beta. CONCLUSIONS: Increased F(2)-isoprostane synthesis during diabetes appears to be responsible in part for the increase in renal TGF-beta, a well-known mediator of diabetic nephropathy.

Effects of the cholecystokinin receptor antagonist L-364,718 on pancreatitis induced by a deficient in choline and supplemented with ethionine (CDE) diet in the rat.

The role of cholecystokinin (CCK) in the development of a necrotizing acute pancreatitis induced by a diet deficient in choline and supplemented with ethionine (CDE) has been evaluated in the rat by using a potent CCK receptor antagonist L-364,718. Acute pancreatitis was induced by administration of CDE diet for 14 days. L-364,718 administration was carried out by subcutaneous injections at dose of 0.1 mg/kg/day. Pancreatic exocrine secretion (flow, protein, amylase and trypsin outputs) in resting and under infusion of 1.25 microgram/kg/h of CCK-8 were used to evaluate the pancreatic functionality. Others parameters (serum amylase, percentage fluid in pancreas, haematocrit and mortality) evaluated the severity of pancreatitis. L-364,718 slightly reduced the mortality and the increases of percentage of fluid accumulated in pancreas in CDE diet acute pancreatitis. Basal and CCK stimulated pancreatic secretion was significantly depressed 36 hours after L-364,718 treatment. A slight response to CCK was observed. Nevertheless it was lower than usually observed in control rats. Our results demonstrate that in the rat, chronic L-364,718 treatment did not completely restore pancreatic activity in acute pancreatitis induced by CDE diet. Hence CCK cannot be considered as the main factor involved in the development of this pancreatitis model.

Acute necrotizing pancreatitis induced by a CDE diet in the rat: a morphologic and functional study.

We studied the effect on the rat pancreas of a choline-deficient diet supplemented with ethionine administered over different time periods. The study was carried out in several groups of male Wistar rats weighing 300 gm and fed for 60, 104, 195, 250, and 336 hours with a choline-deficient diet supplemented with ethionine (CDE). Analysis of pure exocrine pancreatic secretion in animals fed the CDE for 60 hours revealed a decrease in total protein, amylase, and trypsin as compared with animals fed a standard diet. After cholecystokinin stimulation, a gradual decrease in secretion was observed as the duration of the CDE was increased, such that after 336 hours no response to cholecystokinin was found, indicating the lack of pancreatic functionality. Analysis of pancreas preparations by light microscopy showed the existence of infiltration, edema, and hemorrhagic foci after 60 hours of CDE administration. As the duration of the treatment increased, pancreatic morphology deteriorated, with the appearance of vacuolization and foci of necrosis at 195 hours. This deterioration became more pronounced after 250 to 336 hours, progressing to a considerable degree of hemorrhage and necrosis of the acinar tissue. These results clearly confirm the existence of acute necrotizing and hemorrhagic pancreatitis in rats fed a CDE for 250 to 336 hours.

Urinary solute transport by ileal segments. I. Effects of nicotinic acid.

This study was conducted to quantify urinary solute transport by the ileum, using an in vivo human model, and to determine the effect of nicotinic acid on this process. Patients were studied under both basal conditions and niacin therapy. The rates of solute transport were established by analysis of excretion indexes for each solute. Potassium and ammonium were absorbed by the ileum, while phosphorus, sodium and bicarbonate were secreted. The percentage excretion index of sodium and bicarbonate increased by approximately 100 and 600% respectively, causing a significant rise in urinary pH. Although not statistically significant, there was a tendency for chloride to be absorbed and for water to pass into the bowel lumen. Nicotinic acid 3 g/day had no significant effect on urinary solute transport.