Effect of once-daily generic ciclesonide on exhaled nitric oxide in atopic children with persistent asthma.

BACKGROUND: Ciclesonide (CIC) is an effective inhaled corticosteroid for treating asthmatic children. However, its effect on airway inflammation assessed by the fraction of exhaled nitric oxide (FENO) in children with persistent asthma is virtually unknown. We aimed to assess the effect of once-daily generic CIC, 80 or 160 µg, on FENO, lung function, asthma control and bronchial hyperresponsiveness, in atopic children with persistent asthma. METHODS: This was a 12-week, randomised, double-blind, parallel-group study. Sixty children with mild-to-moderate persistent asthma were recruited. Changes in FENO, asthma control score, lung function (FEV1) and bronchial hyperresponsiveness to methacholine (BHR) were used to assess the effects of both CIC doses. Non-normally distributed variables were log-transformed to approximate normality, and parametric tests were used for comparisons within and between groups at baseline and after 12 weeks of treatment. RESULTS: In the CIC 80 µg group, FENO decreased from 45.0 ppb (95% CI 37.8-53.7) to 32.7 ppb (95% CI 21.0-47.3) at the end of study (P=0.021), whereas in the CIC 160 µg group, FENO decreased from 47.3 ppb (95% CI 40.4-55.3) to 30.5 ppb (95% CI 24.1-38.7) (P<0.001). The difference between groups in FENO at the end of study was not significant (P=0.693). There was a significant improvement of asthma control with both CIC doses but there was no significant change in BHR or FEV1 in either group. CONCLUSION: Once-daily generic ciclesonide (80 µg or 160 µg), for 12 weeks, is effective to improve airway inflammation and asthma control in atopic children with persistent asthma.

Overnourishment during lactation induces metabolic and haemodynamic heart impairment during adulthood.

AIM: In this study, the effects of postnatal overfeeding on heart energy homoeostasis and cardiac haemodynamics in adult male Swiss mice were examined. METHODS AND RESULTS: During the suckling period, the mice were divided into four groups of control or overfed pups in combination with baseline or ischaemia/reperfusion treatments (control group baseline, CGBL; overfed group baseline, OGBL; control group ischaemia/reperfusion, CGIR; and overfed group ischaemia/reperfusion, OGIR). End diastolic pressure (EDP), heart contraction speed (Max dP/dt), relaxation speed (Min dP/dt), isovolumetric relaxation time (Tau) and frequency by beats per minute (BPM) were measured. During baseline and ischaemia/reperfusion, key proteins such as AKT1, AKT2, AKT3, pAKT, adenosine monophosphate-activated protein kinase (AMPK), pAMPK, insulin receptor beta (IRß), protein tyrosine phosphatase 1B (PTP1B), insulin receptor substrate 1 (IRS1), fatty acid binding protein (FABP), CD36, phosphoinositide 3-kinase (PI3K) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were studied. The expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), carnitine palmitoyltransferase 1 (CPT1) and uncoupling protein 3 (UCP3) was studied as a marker of cardiac hypertrophy and energetic metabolism. Cardiac fibrosis was analyzed by quantifying collagen deposition, which is increased in the OGBL and OGIR groups compared with the control groups. CONCLUSIONS: The OGBL group showed reduced EDP compared with the CGBL group and high Max dP/dt compared with the OGBL group. Ischaemia/reperfusion increased EDP and Min dP/dt in the intragroup comparison. By contrast, Tau and frequency were not significantly different among groups. The OGIR mice showed significant alterations in heart metabolism proteins, including AKT2, pAKT/AKT1, pAKT/AKT2, AMPK, pAMPK/AMPK, PTP1B, IRS1, FABP and CD36. Furthermore, alterations in ANP, BNP, CPT1 and UCP3 messenger RNA (mRNA) expression indicated hypertrophy and reduction in their efficiency, such that exclusive overnutrition in childhood induces a long-term effect on haemodynamics, metabolism and heart remodelling.

Fraction of exhaled nitric oxide in healthy Chilean schoolchildren aged 8-15 years.

BACKGROUND: The fraction of exhaled nitric oxide (FENO) measured using portable devices is increasingly used in the clinical setting to assess asthmatic children. However, there is little and variable information on the reference values obtained using these devices in healthy children from different populations. METHODS: 190 healthy non-smoker children (8-15 years old) were randomly selected from public schools participating in this study. The objective was to determine FENO reference values for healthy Chilean schoolchildren. Healthy individuals were identified by medical interview and parent questionnaire on the use of asthma medications, and current and past symptoms of asthma, rhinoconjunctivitis and eczema. FENO was measured at schools using a portable device with electrochemical sensor (NIO MINOX). Reference values of FENO were expressed as geometric mean and upper limit of the 95% reference interval (right-sided). The relationship of FENO with gender, age, height, body mass, and other factors was assessed by multiple regression, and the difference between groups was contrasted by ANOVA. RESULTS: The FENO geometric mean was 15.4ppb with a 95% reference interval upper limit (right-sided), of 27.4ppb (90%CI 25.6-29.2). The 5th and 95th percentiles were 9.0ppb and 28.0ppb, respectively. Height was the only factor significantly associated to FENO (p=0.022). There was no significant difference in mean FENO regarding age, gender, weight, parent reported rhinoconjunctivitis and eczema. CONCLUSION: This study suggests that FENO values higher than 27ppb are likely to be abnormal and would reflect airway inflammation in children as those in the present study.

Use of a mouse model of pancreatic neuroendocrine tumors to find pericyte biomarkers of resistance to anti-angiogenic therapy.

The successful introduction of rationally targeted agents into standard cancer care is a testimony of the vast knowledge base in tumor biology. However, in order to provide individually tailored therapy to patients and to identify small subsets of patients with a high likelihood to benefit from treatment, the identification of biomarkers for response or resistance to a particular therapeutic regimen is imperative. Herein, by the use of a genetically engineered mouse model of pancreatic neuroendocrine tumors, we have assessed the utility of pericyte characteristics in terms of differential marker expression to serve as surrogate markers for response or evasive resistance to anti-angiogenic therapy. We found that tumors refractory to therapy following long-term treatment with a vascular endothelial growth factor receptor-2 blocking antibody contained blood vessels with a prolific investment of pericytes expressing α-smooth muscle actin. Further analysis by simultaneous immunostaining for different pericyte markers led to the conclusion that the increased abundance of this particular subtype of blood vessels most likely occurred by co-option of vessels from the surrounding exocrine pancreas. Our findings may form the basis for retrospective analysis of pancreatic neuroendocrine tumors from patients having undergone treatment with anti-angiogenic agents in order to validate the occurrence of pericytes expressing α-smooth muscle actin as a biomarker for tumors refractory to therapy.

Is periodontal disease a risk factor for severe COVID-19 illness?

Periodontal disease (PD) comprises a group of diseases involving inflammatory aspects of the host and dysbiotic events that affect periodontal tissues and could have systemic implications. Diverse factors and comorbidities have been closely associated with PD such as diabetes, obesity, aging, hypertension, and so on; although, underlying mechanisms or causal associations have not been established completely. Interestingly, these same factors have been widely associated with progression or severe coronavirus disease 2019 (COVID-19), an illness caused by coronavirus SARS-CoV-2. Since inflammatory and dysbiotic factors as well as comorbidities affect systemic health, it is possible that periodontal status indicates the risk of complication of COVID-19. However, assessment of oral health history including periodontal status in COVID-19 patients has not been reported. Knowing PD is associated with severe COVID-19 could help identify risk groups and establish pertinent recommendations.

Heightened bronchial hyperresponsiveness in the absence of heightened atopy in children with current wheezing and low income status.

BACKGROUND: Although global studies such as the International Study of Asthma and Allergies in Childhood (ISAAC) have provided valuable data on the prevalence of asthma in children in Latin America, there is little information on the relationship between asthma symptoms, pulmonary function, bronchial hyperresponsiveness (BHR) and atopy in the region. METHODS: This study examined the relationship between self-reported wheezing in the past 12 months, pulmonary function, airway responsiveness and atopy in children from a low income population in a neighbourhood of Santiago, Chile. Two random samples (100 each) of children aged 13-14 years who participated in ISAAC phase I were selected according to whether or not they reported wheezing in the past 12 months. Spirometry, the methacholine bronchial challenge test and the prick test were performed in all individuals. RESULTS: Children who reported current wheezing had significantly higher BHR to methacholine compared with those without wheezing (71.6% vs 52.6%; p = 0.007) and no significant difference was found in forced expiratory volume in 1 s (116.7 (12.3)% vs 120.3 (14.5%); p = 0.11). The prevalence of atopy was not significantly different between those children who reported wheezing compared with those who did not (44.2% vs 42.3%; p = 0.89). Multiple regression analysis showed that only BHR to methacholine (OR 2.72, 95% CI 1.25 to 4.13; p = 0.01) and maternal asthma (OR 3.1, 95% CI 1.2 to 8.3, p = 0.03) were significant risk factors for current wheezing. CONCLUSIONS: Our results support previous findings suggesting that in adolescents from underprivileged populations, self-reported current wheezing is related to BHR but not to atopy.

Traumatic facial arteriovenous malformations.

Traumatic arteriovenous malformations (AVM) represent an abnormal communication between arteries and veins and are usually complex. They occur most commonly in the extremities and are noted most often in military casualties. In the literature there are approximately 25 cases of traumatic AVM of the facial region which are angiographically documented. To these are added five documented cases from this paper, one which was proven at surgery, and one which was suspected from classical signs and symptoms but not diagnosed. The trauma leading to the AVM may be: penetrating, blunt, postsurgical, or inflammatory. A swelling of the face, pulsatile tinnitus, throbbing headache and bleeding comprise the main presenting symptoms. A bruit and thrill are usually present. Doppler ultrasonography and selective arteriography will provide the essential diagnostic information. Embolization therapy may be a helpful preoperative adjunct or may be the total therapy if surgery cannot be performed. Proper identification of the feeder vessels, surgical control of these vessels, total excision of the AVM with functional and cosmetic reconstruction of the tissue defect remain the basic principles of therapy.

Chemical face peeling.

The author reviews his approach to the use of phenol for chemical face peeling. A discussion of preoperative, intraoperative, and postoperative care is included. Indications, benefits, and possible complications of the procedure are discussed.

Xylanase recovery by ethanol and Na2SO4 precipitation.

Xylans are the major components of the hemicellulosic fraction of lignocellulosic biomass and their hydrolysis can be obtained using xylanases from Penicillium janthinellum. In this work, sugarcane bagasse hemicellulosic hydrolysate was used as the substrate for producing xylanase. The precipitation of these enzymes was studied using ethanol and Na2SO4 as precipitating agents. Ethanol precipitation experiments were performed batchwise in concentrations ranging from 10 to 80%, pH 4.0 to 7.0, at 4 degrees C. The concentrations used in the precipitations with Na2SO4 were from 5 to 60% at pH 5.5 and 25 degrees C. Solubility curves as a function of xylanase activity and total protein for both precipitating agents were made. According to the results, Na2SO4 is not appropriate for precipitating xylanases in this medium since at salt concentrations higher than 25%, the enzyme was denaturated and at this concentration less than 80% of the enzyme and total protein were precipitated. Because of differences in xylanase and total protein solubility, a fractionated precipitation using ethanol can be performed, since with 40% ethanol, 49% of the total protein was precipitated and more than 95% of the enzyme was kept in solution. On the other hand approx 100% of the xylanases were recovered by precipitation after adding 80% ethanol.

Extraction by reversed micelles of the intracellular enzyme xylose reductase.

Xylose reductase enzyme (EC 1.1.1.21) produced by Candida guilliermondii in sugarcane bagasse was extracted by reversed micelles of N-benzyl-N-dodecyl-N-bis (2-hydroxyethyl) ammonium chloride cationic surfactant. An experimental design was employed to evaluate the influences of the following factors on the enzyme extraction: temperature, cosolvent, and surfactant concentration. A model was used to represent the enzyme recovery and fit of the experimental data. The extraction yielded a total recovery of 130%, and the purity increased 4.8-fold. This study demonstrates that liquid-liquid extraction by reversed micelles is a process able to recover and increase the enzymatic activity and purity of XR produced by C. guilliermondii.

Increased 99mTc-pyrophosphate uptake with radiation pneumonitis.

A case of radiation pneumonitis confirmed by tissue biopsy is presented with demonstration of increased uptake of 99mTc-pyrophosphate.

Progenitor cells and TNF-alpha involvement during morphological changes in pancreatic islets of obese mice.

Overnutrition during pregnancy and lactation lend increasing support to the development of obesity and several chronic diseases in adulthood such as type 2 diabetes mellitus, which leads to beta-cell dysfunction and insulin resistance. In this work, we aimed to study the effects of early life overnutrition on the development of obesity, analyzing the morphological changes, expression of TNF-α, and also the stem cell marker CD133 in the pancreatic islets of young and adult mice. Overnutrition during lactation phase was used as an experimental model to induce obesity. The animals were analyzed at 28 and 150 days of age, when pancreata were collected for histological, ultrastructural and western blotting analysis. The results showed that islet hypertrophy is established in obese groups at day 28 and remained until adulthood. CD133+ cells were observed as small cells within pancreatic islets in both control and obese young mice. However, at day 150, these cells were observed only in the islet peripheries and near ducts of the obese group. Furthermore, TNF-α expression in pancreatic islets was increased in both young and adult obese groups when compared to control groups. This work shows interesting data about CD133 receptor and TNF-α roles in the pancreas during obesity development.

Engineered high-affinity affibody molecules targeting platelet-derived growth factor receptor ß in vivo.

Platelet-derived growth factor receptor (PDGFR) ß is a marker of stromal pericytes and fibroblasts and represents an interesting target for both diagnosis and therapy of solid tumors. A receptor-specific imaging agent would be a useful tool for further understanding the prognostic role of this receptor in vivo. Affibody molecules constitute a class of very small binding proteins that are highly suited for in vivo imaging applications and that can be selected to specifically recognize a desired target protein. Here we describe the isolation of PDGFRß-specific Affibody molecules with subnanomolar affinity. First-generation Affibody molecules were generated from a large naive library using phage display selection. Subsequently, sequences from binders having a desired selectivity profile and competing with the natural ligand for binding were used in the design of an affinity maturation library, which was created using a single partially randomized oligonucleotide. From this second-generation library, Affibody molecules with a 10-fold improvement in affinity (K(d)=0.4-0.5 nM) for human PDGFRß and a 4-fold improvement in affinity (K(d)=6-7 nM) for murine PDGFRß were isolated and characterized. Complete reversible folding after heating to 90 °C, as demonstrated by circular dichroism analysis, supports tolerance to labeling conditions for molecular imaging. The binders were highly specific, as verified by dot blot showing staining reactivity only with human and murine PDGFRß, but not with human PDGFRα, or a panel of control proteins including 16 abundant human serum proteins. The final binder recognized the native conformation of PDGFRß expressed in murine NIH-3T3 fibroblasts and human AU565 cells, and inhibited ligand-induced receptor phosphorylation in PDGFRß-transfected porcine aortic endothelial cells. The PDGFRß-specific Affibody molecule also accumulated around tumoral blood vessels in a model of spontaneous insulinoma, confirming a potential for in vivo targeting.

El vivir de las mujeres en el climaterio: revisión sistemática de la literatura / The climacteric lives of women:a systematic literature review

La esperanza de vida superior a los 60 años de edad para 2020 revela una parte importante de mujeres que van a vivir el climaterio, lo que requiere medidas adecuadas de salud. Por lo tanto, esta revisión sistemática tiene por objetivo caracterizar en la literatura científica la experiencia de las mujeres que están en el climaterio. La búsqueda se llevó a cabo en la Biblioteca Virtual en Salud (BVS) con los descriptores climaterio y salud de la mujer, en un período de tiempo desde 2004 hasta 2010 y, posteriormente, fueron seleccionadas 13 investigaciones de campo en la base LILACS que abordaban la experiencia del climaterio. Del análisis surgieron las categorías: climaterio como etapa psico-fisiológica de la vida, busca de una vida saludable en el climaterio y acciones de salud dirigidas a las mujeres menopáusicas. Llegamos a la conclusión de que existe la necesidad de vincular eficazmente el fenómeno del climaterio a la política pública de salud en Brasil, y la expansión de los servicios de salud que permitan satisfacer la demanda y la atención integral a las mujeres que experimentan el climaterio (AU)

Life expectancy of over 60 years for 2020 reveals that an important nunber of women will experience the menopause, and this requires appropriate health measures. Therefore, this systematic review is to characterize the scientific literature on the experience of women in the climacteric. The search was conducted through the Virtual Health Library (VHL) with descriptors climacteric and women's health in a period from 2004 to 2010 and 13 field research papers in LILACS were subsequently selected, on account of their presenting experiences in the climacteric. The analysis found the folowing categories: climacteric as a psycho-physiological stage of life, for a healthy life in climacteric and health actions aimed at menopausal women. We conclude that there is a need to effectively link the phenomenon of menopause in public health policy in Brazil and the expansion of health services to meet the demand and comprehensive care to women undergoing menopause (AU)

La detección de la lepra y la humanización de la atención: acciones de enfermería en el programa de salud de la familia / No disponible

El municipio de São Gonçalo, en la Región Metropolitana de Río de Janeiro - Brasil es considerado una zona endémica de la lepra de acuerdo con el Ministerio de Salud. De esta observación, hemos tratado de identificar con este trabajo cuáles son las acciones realizadas por las enfermeras en El Programa de Salud Familiar (PSF) para detectar la lepra y qué tipo de atención prestan a las personas afectadas por la enfermedad, centrándose en la humanización. Así, se realizó investigación descriptiva, cualitativa y de campo en las unidades de salud de la familia de esa ciudad, con treinta y un enfermeros a través de entrevistas con preguntas abiertas. Emergiendo dos categorías: las acciones de detección de la enfermera del PSF, la atención prestada a las personas afectadas y la necesaria humanización de esos cuidados. Se concluyó que las medidas adoptadas por las enfermeras no siguen un estándar único y que algunas no tienen la capacitación necesaria para desenvolverse con los usuarios del PSF afectadas por la lepra (AU)

The Municipality of São Gonçalo in the Metropolitan Region of Rio de Janeiro - Brazil is considered an endemic area for leprosy according to the Ministry of Health. From this observation, we sought to identify with this work which actions are performed by nurses from Family Health Program (PSF) to detect leprosy and what care they provide to people affected by the disease, with the focus on humanization. Thus, we performed descriptive, qualitative and field units in the health of the family of that city, with thirty-one nurses through interviews with open questions. Two categories emerged: the detection actions made by the nurse, the care given to people affected and the humanization of care needed. It was concluded that the actions taken by the nurses do not follow a single standard and that some lack the necessary training to function with users of PSF affected by leprosy (AU)

Effect of once-daily generic ciclesonide on exhaled nitric oxide in atopic children with persistent asthma

BACKGROUND: Ciclesonide (CIC) is an effective inhaled corticosteroid for treating asthmatic children. However, its effect on airway inflammation assessed by the fraction of exhaled nitric oxide (FENO) in children with persistent asthma is virtually unknown. We aimed to assess the effect of once-daily generic CIC, 80 or 160 μg, on FENO, lung function, asthma control and bronchial hyperresponsiveness, in atopic children with persistent asthma. METHODS: This was a 12-week, randomised, double-blind, parallel-group study. Sixty children with mild-to-moderate persistent asthma were recruited. Changes in FENO, asthma control score, lung function (FEV1) and bronchial hyperresponsiveness to methacholine (BHR) were used to assess the effects of both CIC doses. Non-normally distributed variables were log-transformed to approximate normality, and parametric tests were used for comparisons within and between groups at baseline and after 12 weeks of treatment. RESULTS: In the CIC 80 μg group, FENO decreased from 45.0 ppb (95% CI 37.8-53.7) to 32.7 ppb (95% CI 21.0-47.3) at the end of study (P = 0.021), whereas in the CIC 160 μg group, FENO decreased from 47.3 ppb (95% CI 40.4-55.3) to 30.5 ppb (95% CI 24.1-38.7) (P < 0.001). The difference between groups in FENO at the end of study was not significant (P = 0.693). There was a significant improvement of asthma control with both CIC doses but there was no significant change in BHR or FEV1 in either group. CONCLUSION: Once-daily generic ciclesonide (80 μg or 160 μg), for 12 weeks, is effective to improve airway inflammation and asthma control in atopic children with persistent asthma

No disponible

Fraction of exhaled nitric oxide in healthy Chilean schoolchildren aged 8-15 years

BACKGROUND: The fraction of exhaled nitric oxide (FENO) measured using portable devices is increasingly used in the clinical setting to assess asthmatic children. However, there is little and variable information on the reference values obtained using these devices in healthy children from different populations. METHODS: 190 healthy non-smoker children (8-15 years old) were randomly selected from public schools participating in this study. The objective was to determine FENO reference values for healthy Chilean schoolchildren. Healthy individuals were identified by medical interview and parent questionnaire on the use of asthma medications, and current and past symptoms of asthma, rhinoconjunctivitis and eczema. FENO was measured at schools using a portable device with electrochemical sensor (NIO MINOX). Reference values of FENO were expressed as geometric mean and upper limit of the 95% reference interval (right-sided). The relationship of FENO with gender, age, height, body mass, and other factors was assessed by multiple regression, and the difference between groups was contrasted by ANOVA. RESULTS: The FENO geometric mean was 15.4 ppb with a 95% reference interval upper limit (right-sided), of 27.4 ppb (90%CI 25.6-29.2). The 5th and 95th percentiles were 9.0 ppb and 28.0 ppb, respectively. Height was the only factor significantly associated to FENO (p = 0.022). There was no significant difference in mean FENO regarding age, gender, weight, parent reported rhinoconjunctivitis and eczema. CONCLUSION: This study suggests that FENO values higher than 27 ppb are likely to be abnormal and would reflect airway inflammation in children as those in the present study

No disponible

Carrier ampholytes rehabilitated: gel isoelectric focusing on pH gradients visualized in real-time by automated fluorescence scanning in the HPGE-1000 apparatus.

All synthetic carrier ampholyte mixtures (SCAMs) contain some naturally fluorescing carrier ampholytes (CAs). The detection of these during isoelectric focusing (IEF), using gel electrophoresis apparatus with intermittent scanning of fluorescence, allows one to follow in real-time the "life cycle" of the pH gradient, i.e., its genesis, steady-state, and decay. The most prominently fluorescing CAs can be calibrated by pH measurement at or after the steady state ("calibration CAs"). By application of the calibration CAs, the fluorescence pattern of CAs can be interpreted in terms of pH gradient (p/s). Simultaneously with the visualization of the pH gradient in that way, protein samples can be detected by "fluorescence reduction" and assigned pH values in dependence on focusing time and, at or after the steady state of the protein, pI' values. The method remedies the inherent blindness of IEF with regard to the state of the pH gradient within its limited "life cycle". It allows one to load the sample at a time when the shape of the pH gradient is optimal for the purpose of its resolution from neighboring components. The visualization of the cathodic drift during IEF eliminates the danger to resolution and to loss of sample associated with "blind" IEF. Most importantly, the possibility to follow the pH in the position of the protein as a function of time provides an objective, accurate measure of the pI' not available from pH measurement at an arbitrary focusing time. The method therefore preempts the advantage of using an IEF method which is free of the pH gradient drift, i.e., immobilized pH gradient (IPG)-IEF. Moreover, it preserves the "natural pH gradient", does not present any of its sample entry problems and those due to very low conductance, and is compatible with agrose gels and their relatively diminished restrictiveness to migration.