<i>KISS1</i> and KISS1R expression in the human and rat carotid body and superior cervical ganglion

KISS1 and its receptor, KISS1R, have both been found to be expressed in central nervous system, but few data are present in the literature about their distribution in peripheral nervous structures. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of KISS1 and KISS1R in the rat and human carotid bodies and superior cervical ganglia, also with particular reference to the different cellular populations. Materials consisted of carotid bodies and superior cervical ganglia were obtained at autopsy from 10 adult subjects and sampled from 10 adult Sprague-Dawley rats. Immunohistochemistry revealed diffuse expression of KISS1 and KISS1R in type I cells of both human and rat carotid bodies, whereas type II cells were negative. In both human and rat superior cervical ganglia positive anti-KISS1 and -KISS1R immunostainings were also selectively found in ganglion cells, satellite cells being negative. Endothelial cells also showed moderate immunostaining for both KISS1 and KISS1R. The expression of both kisspeptins and kisspeptin receptors in glomic type I cells and sympathetic ganglion cells supports a modulatory role of KISS1 on peripheral chemoreception and sympathetic function. Moreover, local changes in blood flow have been considered to be involved in carotid body chemoreceptor discharge and kisspeptins and kisspeptin receptors have also been found in the endothelial cells. As a consequence, a possible role of kisspeptins in the regulation of carotid body blood flow and, indirectly, in chemoreceptor discharge may also be hypothesized

Measuring Airway Obstruction in Severe Asthma in Children

Lung function is an important tool in the diagnosis and monitoring of patients with asthma at all ages. Airway obstruction is a typical feature of asthma and it can be assessed with several lung function techniques. Spirometry, respiratory resistance and reactance, and lung volumes are available to measure it at different ages and in children. The assessment of a bronchodilator response is always recommended to show the reversibility of the obstruction. Poor lung function is a predictor of poor asthma outcome and a low Forced Expiratory Volume in the first second of expiration percent predicted measured with spirometry, has been shown to be associated with a higher risk of having an exacerbation during the following year independently of the presence of asthma symptoms. In severe asthma lung function assessment is used to distinguish different phenotypes, children with severe asthma have worse airflow limitation prior to administration of a bronchodilator than children with non severe asthma. Airway resistance and reactance are indirect measurements of airway obstruction and they can be measured with the forced oscillation technique, which is feasible also in non-collaborative children. This technique can be more informative in discriminating patients with asthma from healthy controls and is able to indicate a more peripheral involvement of the airways. The role of this technique in severe asthma is still debated. In conclusion lung function is useful in the clinical management of children with severe asthma

Caratterizzazione della taspina ed attività su cute umana coltivata di "sangre de grado" (<i>Croton lechleri</i> Müll. Arg.)

Tra le piante peruviane più interessanti per la loro azione antivirale ed immunomodulante spicca Croton lechleri (sangre de grado o de drago) al quale si attribuiscono effetti antinfiammatori, immunomodulatori ed antivirali che la rendono un candidato ideale per studi più approfonditi. Poiché Croton lechleri è una pianta da secoli conosciuta dalla popolazione peruviana come riparatore di ferite e disinfettante, abbiamo ritenuto interessante quantificare e caratterizzare la sostanza che viene considerata come la più importante per l’attività di questi estratti: la taspina

Sex differences in redox state, autophagy and lysosomal function

Modifications of the normal redox state are connected with numerous diseases and conditions such as cardiovascular diseases, diabetes mellitus and its complications, liver diseases, and aging which are characterized by numerous sex differences. Evidences suggest that redox state might be different in males and females. Autophagy is crucial for the maintaining cellular homeostasis process whereby cytoplasmic components are delivered to lysosomes for degradation. Alteration in constitutive autophagy is implicated in many pathological conditions, including heart diseases, diabetes mellitus and its complications, and liver diseases. A cross-talk between ROS and autophagy has been described. The current study was conducted to investigate the influence of sex on lipid and protein oxidation and autophagic response in the heart, the liver and the kidney obtained from young adult healthy male and female rats. 7 week old Sprague-Dawley rats were used to obtain heart, liver and kidneys. Malondialdehyde (MDA), and carbonylated proteins were measured by spectrophotometric methods for redox state assessment. The autophagy biomarkers Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3), the mammalian target of rapamycin (mTOR; checkpoint in autophagic process), and the lysosomal associated membrane protein (LAMP-1; biomarker of lysosomes) were evaluated by Western blotting. Immunofluorescence analysis was also performed for LC3 and LAMP-1 colocalization. In the heart, Beclin-1, LC3-II/LC3-I were higher in males than in females suggesting that male heart have a major constitutive autophagy and this was linked with higher levels of carbonyl groups, indicating that protein oxidation could play a role. In the liver, it was found that LAMP-1 was higher in males and greatly colocalized with LC3 indicating a larger number of autophagolysosomes. None of the above parameters was significantly different in the kidneys of both sexes with the exception of MDA, which was significantly higher in females. These results suggest that the sex determinant affects the autophagy process and oxidation of proteins and lipids in an organ specific manner. It seems that the protein oxidation is more linked with constitutive autophagy, at least in cardiac ventricles, in comparison with lipid peroxidation

Contributo alla conoscenza dei boschi a <i>Laurus nobilis</i> L. della Sardegna, habitat prioritario ai sensi della Direttiva 92/43/CEE

The results of the phytosociological study of the Sardinian Laurus nobilis L. stands are here presented. The statistical analysis of the surveys, carried out on the best known populations, allowed us to recognize four new plant communities, referred to one association and three subassociations. In Sardinia the Laurus nobilis L. stands are present on effusive and metamorphic substrata, on typic xerorthent or lithic xerorthent soils, in the oceanic pluviseasonal Mediterranean bioclimate. The investigated stands show a good conservation status and high recruitment levels, in relation to the high naturalness of the ravines and valleys in which they occur

Human umbilical endothelial cells (HUVECs) and sex differences

HUVECs are worldwide used to study the endothelial physiology and pathology that might be involved in sex and gender differences detected at the cardiovascular level. The present work characterised the phenotype of HUVECs in terms of morphology, proliferative and migratory capacity and in the gene expression of oestrogen and androgen receptors and nitric oxide synthase 3 (NOS3) to evaluated if they are sexually dimorphic. Moreover, autophagic process was analysed in male and female HUVECs (MHUVECs and FHUVECs), as autophagy is influenced by sex. Umbilical cords were obtained from healthy, normal weight, male and female neonates born to healthy non-obese and non-smoking women. HUVECs morphology was analysed by electron microscopy, and their function was investigated by proliferation, viability, wound healing and chemotaxis assays. Real-time PCR was used to evaluate gene expression for oestrogen and androgen receptors and for NOS3, while the expression of the primary molecules involved in autophagic process [(Akt, the mammalian target of rapamycin (mTOR), beclin-1 and microtubule-associated protein 1 light chain 3 (LC3)] and NOS3 were analysed by western blotting. FHUVECs showed significantly higher proliferation and migration rate, and NOS3 mRNA and protein expression than MHUVECs. Conversely, beclin-1 and the LC3-II/LC3-I ratio were higher in MHUVECs than in FHUVECs, indicating a higher autophagy in male cells as also indicated by ultrastructural analysis showing a buildup of autophagic vacuoles at different stages in MHUVECs. The expression of oestrogen and androgen receptor genes, the protein expression of Akt, mTOR, and cellular size and shape were not influenced by sex. Male and female neonates did not differ in body weight, but the weight of male babies was positively associated with the weight of the mother, suggesting that the weight of the mother may exert a different influence on male and female babies. Our findings indicate that sex differences exist from prenatal life and are parameter- specific, suggesting that a better quality of the research on the endothelium in vitro can be obtained by analyzing HUVECs of both sexes as well as its translational value. Moreover, the sex differences observed in HUVECs could help the diseases of adulthood because endothelial dysfunction has a key role in cardiovascular diseases, diabetes mellitus, neurodegeneration and immune diseases

Human umbilical endothelial cells (HUVECs) have a sex: characterisation of the phenotype of male and female cells

Background: Human umbilical endothelial cells (HUVECs) are widely used to study the endothelial physiology and pathology that might be involved in sex and gender differences detected at the cardiovascular level. This study evaluated whether HUVECs are sexually dimorphic in their morphological, proliferative and migratory properties and in the gene and protein expression of oestrogen and androgen receptors and nitric oxide synthase 3 (NOS3). Moreover, because autophagy is influenced by sex, its degree was analysed in male and female HUVECs (MHUVECs and FHUVECs). Methods: Umbilical cords from healthy, normal weight male and female neonates born to healthy non-obese and non-smoking women were studied. HUVEC morphology was analysed by electron microscopy, and their function was investigated by proliferation, viability, wound healing and chemotaxis assays. Gene and protein expression for oestrogen and androgen receptors and for NOS3 were evaluated by real-time PCR and Western blotting, respectively, and the expression of the primary molecules involved in autophagy regulation [protein kinase B (Akt), mammalian target of rapamycin (mTOR), beclin-1 and microtubule-associated protein 1 light chain 3 (LC3)] were detected by Western blotting. Results: Cell proliferation, migration NOS3 mRNA and protein expression were significantly higher in FHUVECs than in MHUVECs. Conversely, beclin-1 and the LC3-II/LC3-I ratio were higher in MHUVECs than in FHUVECs, indicating that male cells are more autophagic than female cells. The expression of oestrogen and androgen receptor genes and proteins, the protein expression of Akt and mTOR and cellular size and shape were not influenced by sex. Body weights of male and female neonates were not significantly different, but the weight of male babies positively correlated with the weight of the mother, suggesting that the mother’s weight may exert a different influence on male and female babies. Conclusions: The results indicate that sex differences exist in prenatal life and are parameter-specific, suggesting that HUVECs of both sexes should be used as an in vitro model to increase the quality and the translational value of research. The sex differences observed in HUVECs could be relevant in explaining the diseases of adulthood because endothelial dysfunction has a crucial role in the pathogenesis of cardiovascular diseases, diabetes mellitus, neurodegeneration and immune disease.</br

Severe asthma features in children: a case-control online survey

BACKGROUND: Very few studies have explored the distinguishing features of severe asthma in childhood in Europe, and only one study was conducted in Southern Europe. The aim of this study was to provide a detailed characterization of children with severe asthma treated in specialized pediatric asthma centers across Italy. METHODS: We conducted a web-based data collection of family, environmental, clinical and laboratory characteristics of 41 patients aged 6-17 years with severe asthma, defined according to the recent guidelines of the European Respiratory Society and the American Thoracic Society, and 78 age-matched peers with non-severe persistent asthma. The patients have been enrolled from 16 hospital-based pediatric pulmonology and allergy centers in Northern, Central, and Southern Italy. Logistic regression analysis assessed the relationship between patients' characteristics and severe asthma or non-severe persistent asthma. RESULTS: Features independently and significantly associated with severe asthma included lifetime sensitization to food allergens [Odds ratio (OR), 4.73; 95 % Confidence Interval (CI), 1.21-18.53; p = 0.03], lifetime hospitalization for asthma (OR, 3.71; 95 % CI, 1.11-12.33; p = 0.03), emergency-department visits for asthma during the past year (OR = 11.98; 95 % CI, 2.70-53.11; p = 0.001), and symptoms triggered by physical activity (OR = 12.78; 95 % CI, 2.66-61.40; p = 0.001). Quality-of-life score was worse in patients with severe asthma than in subjects with non-severe persistent asthma (5.9 versus 6.6, p = 0.005). Self-perception of wellbeing was compromised in more than 40 % of patients in both groups. Children with severe asthma had lower spirometric z scores than non-severe asthmatic peers (all p < 0.001), although 56 % of them had a normal forced expiratory volume in 1 s. No differences were found between the two groups for parental education, home environment, patients' comorbidities, adherence to therapy, exhaled nitric oxide values, and serum eosinophils and IgE . CONCLUSIONS: As expected, children with severe asthma had more severe clinical course and worse lung function than peers with non-severe persistent asthma. Unlike previous reports, we found greater sensitization to food allergens and similar environmental and personal characteristics in patients with severe asthma compared to those with non-severe persistent asthma. Psychological aspects are compromised in a large number of cases and deserve further investigation

Prevalence, severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes

The primary objective of this study was to investigate factors associated with fatigue severity in newly diagnosed patients with higher-risk myelodysplastic syndromes (MDS). The secondary objectives were to assess symptom prevalence and to examine the relationships between fatigue, quality of life (QoL) and overall symptom burden in these patients. The analyses were conducted in 280 higher-risk MDS patients. Pre-treatment patient-reported fatigue was evaluated with the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Female gender (P = 0·018), poor performance status (i.e., ECOG of 2-4) (P < 0·001) and lower levels of haemoglobin (Hb) (P = 0·026) were independently associated with higher fatigue severity. The three most prevalent symptoms were as follows: fatigue (92%), dyspnoea (63%) and pain (55%). Patients with higher levels of fatigue also had greater overall symptom burdens. The mean global QoL scores of patients with the highest versus those with the lowest levels of fatigue were 29·2 [standard deviation (SD), 18·3] and 69·0 (SD, 18·8), respectively and this difference was four times the magnitude of a clinically meaningful difference. Patient-reported fatigue severity revealed the effects of disease burden on overall QoL more accurately than did degree of anaemia. Special attention should be given to the female patients in the management of fatigue

First analysis of the Severe Paediatric Asthma Collaborative in Europe registry.

New biologics are being continually developed for paediatric asthma, but it is unclear whether there are sufficient numbers of children in Europe with severe asthma and poor control to recruit to trials needed for registration. To address these questions, the European Respiratory Society funded the Severe Paediatric Asthma Collaborative in Europe (SPACE), a severe asthma registry. We report the first analysis of the SPACE registry, which includes data from 10 paediatric respiratory centres across Europe. Data from 80 children with a clinical diagnosis of severe asthma who were receiving both high-dose inhaled corticosteroid and long-acting β2-agonist were entered into the registry between January 2019 and January 2020. Suboptimal control was defined by either asthma control test, or Global Initiative for Asthma criteria, or ≥2 severe exacerbations in the previous 12 months, or a combination. Overall, 62 out of 80 (77%) children had suboptimal asthma control, of whom 29 were not prescribed a biologic. However, in 24 there was an option for starting a licensed biologic. 33 children with suboptimal control were prescribed a biologic (omalizumab (n=24), or mepolizumab (n=7), or dupilumab (n=2)), and for 29 there was an option to switch to a different biologic. We conclude that the SPACE registry provides data that will support the planning of studies of asthma biologics. Not all children on biologics achieve good asthma control, and there is need for new trial designs addressing biologic switching