Search

Introduction: The SARS-CoV-2 pandemic has deeply revolutionized our lives and consequently the management of patients, specifically ones with severe asthma.Objective: A survey was conducted to evaluate the effects on adherence, exacerbations and quality of life in patients with severe asthma during the COVID-19 pandemic period.Methods: 100 severe asthma patients, who accepted to participate to the survey, were asked to respond to different questionnaires in order to assess asthma symptoms (Asthma Control Test - ACT, and Asthma Control Quality - ACQ) and rino-sinusal ones (Sino-nasal outcome test - SNOT-22).Results: 31 out of 100 patients reported worsening of respiratory symptoms requiring a step-up in therapy dosage or frequency during the observational period; however, exacerbation rate was very low. Only 17 (17%) of the 100 participants experienced a severe asthma exacerbation. Moreover, there was no confirmed diagnosis of COVID-19 in this population.Conclusion: Patients with severe asthma did not show higher rates of exacerbations during the pandemic outbreak as well as no increased risk of contracting COVID-19 infection or developing the disease. Self-administration of biological drugs could be useful to maintain high rates of adherence to therapy, and, at the same time, to decrease the risk of exacerbations or Intensive Care Unit (ICU) room access.

Plant lipid transfer proteins (LTPs) are widespread plant food allergens, highly resistant to food processing and to the gastrointestinal environment, which have been described as the most common food allergens in the Mediterranean area. LTP allergy is widely described in adults, but it represents an emerging allergen also in the pediatric population. Little is known about the real prevalence and the clinical features of this allergy in children and it still often remains underdiagnosed in these patients. An early identification and a deeper knowledge of this allergy in childhood can avoid severe systemic reactions and improve the child's quality of life. Pediatricians should always consider the possibility of LTP involvement in cases of plant-derived food allergy.

Rheumatological systemic autoimmune diseases, such as connective tissue diseases, rheumatoid arthritis or spondyloarthritis, are characterized by the presence of joint involvement associated with extra-articular manifestations. Among them, cutaneous diseases are often the most relevant and representative clinical manifestation, as in psoriatic arthritis, scleroderma or systemic lupus erythematosus. In this context, it is useful for rheumatologists to understand better skin diseases and their histopathological features. Evaluation of skin biopsy specimens can be helpful not only to confirm the diagnosis in both classic and clinically atypical variants, but also to improve further our knowledge of the pathogenetic mechanisms and the close link between skin and articular diseases. In this review, we discuss the clinical features, diagnostic evaluation and the histopathological features of skin manifestation of the most relevant rheumatological autoimmune diseases.

The newborn immune system is characterized by an impaired Th1-associated immune response. Hepatitis B virus (HBV) transmitted from infected mothers to newborns is thought to exploit the newborns’ immune system immaturity by inducing a state of immune tolerance that facilitates HBV persistence. Contrary to this hypothesis, we demonstrate here that HBV exposure in utero triggers a state of trained immunity, characterized by innate immune cell maturation and Th1 development, which in turn enhances the ability of cord blood immune cells to respond to bacterial infection in vitro. These training effects are associated with an alteration of the cytokine environment characterized by low IL-10 and, in most cases, high IL-12p40 and IFN-α2. Our data uncover a potentially symbiotic relationship between HBV and its natural host, and highlight the plasticity of the fetal immune system following viral exposure in utero., The ability to fight infections matures after birth and is thus termed ‘trained immunity’. Here the authors show that cord blood cells from hepatitis B virus-infected mothers respond more strongly to bacterial infections, suggesting that viral exposure in utero promotes trained immunity in newborns.

Objective: Several theorists have hypothesized that stressful situations may trigger abnormal eating and even eating disorders in predisposed people. The purpose of this study was to assess whether a stressful situation would reveal an association between perfectionism and low self-esteem, and measures of eating disorder symptoms in male high school students. Method: A sample of 61 male high school students completed the Eating Disorder Inventory, the Multidimensional Perfectionism Scale, and the Self Liking and Competence Scale three times: on an average school day, on the day of an exam and on the day the subjects received the results of that exam. Linear regression analysis was carried out to verify whether the dimensions of perfectionism were associated with the measures of eat- ing disorders. Results: Interoceptive awareness was associated with 'Bulimia' only during the stressful situation and with 'Drive for thinness' both in stress and non stress situations. Other results were contradictory and difficult to interpret. Discussion: The results suggest that in nonclinical male individuals stress might bring out a previously absent association between some psychological predisposing factors for eating disorders and an actual desire or plan for ED related thoughts and behaviours. Such a finding suggests that stress may stimulate behaviours related to eating disorders in a predisposed personality. A central role may be played by interoceptive awareness in male subjects.

The low-density lipoprotein receptor-related protein 1 (LRP1) is an ubiquitously expressed endocytic receptor that, among its several functions, is involved in the catabolism of coagulation factor VIII (FVIII) and in the regulation of its plasma concentrations. Although LRP1/CD91 polymorphisms have been associated with increased FVIII levels and a consequent thrombotic risk, no data are available on LRP1/CD91 expression in patients with inherited FVIII deficiency. With the aim of elucidating this issue, 45 consecutive patients with haemophilia A (HA) (18 severe, 5 moderate and 22 mild HA) were enrolled in this cross-sectional, single-centre survey. The LRP1/CD91 mean fluorescence intensity (MFI) in monocytes from HA patients was significantly higher than that detected in 90 healthy blood donors (105 vs. 67, P < 0.001). This over-expression was independent of hepatitis C virus infection status and varied according to the severity of the haemophilia, being higher in patients with more severe FVIII deficiency. In conclusion, our study documents for the first time that LRP1/CD91 is over-expressed on monocytes from HA patients, with the intensity of expression varying according to the severity of the FVIII deficiency. Further studies are needed to assess the clinical implications of these findings.

Objective Systemic sclerosis (SSc) is a disorder characterized by vascular damage and fibrosis of the skin and internal organs. Despite marked tissue hypoxia, there is no evidence of compensatory angiogenesis. The ability of mesenchymal stem cells (MSCs) to differentiate into endothelial cells was recently demonstrated. The aim of this study was to determine whether impaired differentiation of MSCs into endothelial cells in SSc might contribute to disease pathogenesis by decreasing endothelial repair. Methods MSCs obtained from 7 SSc patients and 15 healthy controls were characterized. The number of colony-forming unit–fibroblastoid colonies was determined. After culture in endothelial-specific medium, the endothelial-like MSC (EL-MSC) phenotype was assessed according to the surface expression of vascular endothelial growth factor receptors (VEGFRs). Senescence, chemoinvasion, and capillary morphogenesis studies were also performed. Results MSCs from SSc patients displayed the same phenotype and clonogenic activity as those from controls. In SSc MSCs, a decreased percentage of VEGFR-2+, CXCR4+, VEGFR-2+/CXCR4+ cells and early senescence was detected. After culturing, SSc EL-MSCs showed increased expression of VEGFR-1, VEGFR-2, and CXCR4, did not express CD31 or annexin V, and showed significantly decreased migration after specific stimuli. Moreover, the addition of VEGF and stromal cell–derived factor 1 to cultured SSc EL-MSCs increased their angiogenic potential less than that in controls. Conclusion Our data strongly suggest that endothelial repair may be affected in SSc. The possibility that endothelial progenitor cells could be used to increase vessel growth in chronic ischemic tissues may open up new avenues in the treatment of vascular damage caused by SSc.

Detection of hepatitis C virus (HCV)-specific T cell response after exposure to hepatitis C in anti-HCV-positive or anti-HCV-negative patients has been associated with an ability to successfully control the infection. However, cross-reactivity between common human pathogens and HCV sequences has been demonstrated. The aim of this study was to investigate the impact of T cell cross-reactivity on HCV-specific T cell responses and their detection in HCV infected and non-infected subjects. The magnitude, function, and cross-reactivity of HCV peptide reactive T cells were studied in non-HCV-infected newborns and adults using a broad array of HCV peptides (601 peptides) spanning the entire HCV sequence. Comparisons were made with responses present in recovered and in chronically HCV-infected patients. HCV peptide reactive T cells are detectable in adults irrespective of previous HCV exposure and cross-reactivity between HCV peptides, and sequences of common pathogens, such as human herpes virus 1, can be demonstrated. Furthermore, the comprehensive magnitude of HCV-peptide reactive T cells present in chronically HCV-infected patients is similar and in some cases even lower than that of HCV-peptide reactive T cell response found in HCV-negative adults. In conclusion, the presence of oligo-specific HCV-peptide reactive T cells in humans does not always reflect a demonstration of previous HCV contact, whereas cross-reactivity with other common pathogens can potentially influence the HCV-specific T cell profile. The conspicuous deficit of HCV-peptide-specific T cells found in chronically HCV-infected patients confirms the profound collapse of virus-specific T cell response caused by HCV persistence.

Chronic hepatitis C virus (HCV) infection is associated with impaired proliferative, cytokine, and cytotoxic effector functions of HCV-specific CD8 + T cells that probably contribute significantly to viral persistence. Here, we investigated the potential role of T cells with a CD4 + CD25 + regulatory phenotype in suppressing virus-specific CD8 + T-cell proliferation during chronic HCV infection. In vitro depletion studies and coculture experiments revealed that peptide specific proliferation as well as gamma interferon production of HCV-specific CD8 + T cells were inhibited by CD4 + CD25 + T cells. This inhibition was dose dependent, required direct cell-cell contact, and was independent of interleukin-10 and transforming growth factor beta. Interestingly, the T-cell-mediated suppression in chronically HCV-infected patients was not restricted to HCV-specific CD8 + T cells but also to influenza virus-specific CD8 + T cells. Importantly, CD4 + CD25 + T cells from persons recovered from HCV infection and from healthy blood donors exhibited significantly less suppressor activity. Thus, the inhibition of virus-specific CD8 + T-cell proliferation was enhanced in chronically HCV-infected patients. This was associated with a higher frequency of circulating CD4 + CD25 + cells observed in this patient group. Taken together, our results suggest that chronic HCV infection leads to the expansion of CD4 + CD25 + T cells that are able to suppress CD8 + T-cell responses to different viral antigens. Our results further suggest that CD4 + CD25 + T cells may contribute to viral persistence in chronically HCV-infected patients and may be a target for immunotherapy of chronic hepatitis C.

Pulmonary endothelium is considered the compartment most susceptible to preservation damage. This investigation was designed to analyze the efficacy of an original, University of Parma low-potassium-albumin solution (SPAL UP) on cultured human pulmonary artery endothelial cells (HPAEC) and to compare its effects with those of University of Wisconsin solution (UW) and Euro-Collins solution (EC). Cryopreserved HPAEC tertiary cultures were inoculated at the density of 5000 cells/cm2 in 9-cm2 well-plates; subcultures were then incubated at 10 degrees C for 6 hr and 16 hr in 2 ml/well of SPAL UP, UW, and EC. The HPAEC viability after incubation was assessed by evaluating the total protein content and the expression of cytotoxicity, and by analyzing the rate of protein synthesis and expression of cellular functionality after stress. Results after 6 hr of preservation showed that SPAL UP had a less significant cytotoxic effect than EC, exerted a less depressing effect on cellular metabolism, and enhanced functional recovery of endothelial cells compared with UW. At the second time interval (16 hr), SPAL UP provided a less cytotoxic effect than UW; besides, SPAL UP-induced cytotoxicity was similar to that of warm control. In conclusion, in vitro preliminary data regarding the use of SPAL UP in HPAEC preservation suggest its suitability as solution for prolonged lung protection.

Cell-mediated immune responses to hepatitis B (HBV) and hepatitis C virus (HCV) antigens are vigorous and multispecific in acute, self-limited infections. Moreover, the prevalent cytokine pattern of circulating virus-specific T cells from patients who recover spontaneously from acute hepatitis is Th1-like. Longitudinal analysis of the T cell response to HCV antigens from the early stages of HCV infection in patients who recover from hepatitis and those who do not indicates that weaker responses and a prevalent Th2 pattern of cytokine production is associated with viral persistence and chronic evolution of disease. Although similar sequential studies are missing in hepatitis B, the observation that HBV-specific T cell responses are very weak or totally undetectable in the peripheral blood of patients with long-lasting chronic hepatitis B suggests that strength and quality of virus-specific T cell responses at the early stages of infection may influence the final outcome of both hepatitis B and C. While T cell hyporesponsiveness seems to be an important determinant for HBV persistence once chronic hepatitis has developed, this mechanism appears to be less critical in chronic HCV infection, because the vigor and quality of HCV-specific T cell responses seem to improve as a function of the duration of infection. This is shown by the finding that HCV-specific CD4- and CD8-mediated responses are easily detectable in the peripheral blood of patients with long-lasting chronic hepatitis C and that production of Th1 cytokines predominates within their livers. HCV therefore seems to be able to persist even in the face of an active T cell response and to acquire the capacity to survive within a host environment apparently unfavorable to its persistence. The high variability of HCV may explain its efficiency in escaping immune surveillance.

The lack of an ideal heart-lung preservation solution is one of the principal factor that limits the wide spread of transplantation. The aim of this work was to investigate the efficacy of Haemaccel (HM) on isolated human pulmonary artery endothelial cells comparing its effects with those of University of Wisconsin (UWS). Subcultures of HPAEC were inoculated at the density of 5,000 cells per cm2 in 9 cm2 well-plates. Cells were incubated with HM and UWS for 6 hrs at 10 degrees C. Cellular viability was analysed by the total protein content (cytotoxicity index) and by the rate of protein synthesis (metabolic index). The results showed that HM and UWS did no show a significant differences in the toxicity when compared with the control; on the contrary, HM seems to determine a less inhibitory effect on cellular metabolism permitting a more rapid cellular metabolic recovery than UWS. Thus, HM appears to be more suitable for the preservation of isolated HPAEC than UWS.

Human leukemia/lymphoma cells maintained in culture medium without provision of fresh nutrients lose viability and die by a process resembling apoptosis within a few days. Upon incubation in an FCS-supplemented RPMI 1640 medium containing 2 mM L-glutamine CEM, Namalwa, HL-60 and U937 cells, seeded at initial densities of 0.2 to 1 x 10(6) cells/ml, ceased growing within 3-5 days and progressively entered an apoptotic pathway, as assessed by nucleosomal DNA fragmentation and morphology. Both the major energy-source nutrients in the medium, glucose and glutamine, became rapidly exhausted during the incubation. Further studies were performed using CEM cells. Incubation in glutamine-free or glucose-free medium renewed every 24 h showed that glutamine deprivation is associated with cell death by apoptosis independent of energetic failure, whereas glucose deprivation is followed by rapid loss of mitochondrial function with sharp drop of intracellular ATP and cell death by necrosis. A 12-24 h incubation in glutamine-depleted medium was required to direct the cells toward the apoptotic pathway. Growth arrest followed by apoptotic death was detected in CEM cells when medium glutamine concentration remained below 0.3-0.4 mM for at least 24 h, but a reinstatement of medium glutamine to 2 mM within this period rescued the cells from growth arrest and death.

The attempt to synthesise efficacious solution to prolong lung preservation is, at present one of the most interesting challenges in transplant research. Recently, several issues emphasise the central role of ionic composition of lung-flush solutions, underlining, however, that colloid-free solutions are clearly detrimental. We have been studying a complex extracellular type solution (SPAL UP) synthesised to minimise the pathological events that occur during both preservation and reperfusion period. We report the results of toxicity of SPAL UP on normal human fibroblasts obtained from foetal lung (WI-38). WI-38 cells were seeded at 1.4 x 10(4)/cm2 in disposable plastic 12-well plates. After 3 days, cells were incubated in SPAL UP, Beltzer (UWS), Low Potassium Dextran (LPD) and Eurocollins (ECS) solutions for 6 hours at 10 degrees C. Cellular viability was evaluated by the rate of protein synthesis exploiting the incorporation of 35S-Methionine (2 microCi/ml) in growth medium with 10 mM unlabelled Methionine during 30 minutes incubation at 37 degrees C. The results were expressed as nmol. 35S-Methionine/mg of proteins/minute, and presented as means +/- SD of data of three (n = 3) well for each solution studied.the viability at time 0 before incubation (considered as control) was 1.65 +/- 0.1; after hypothermic preservation the data were respectively as follow: SPAL UP 0.51 +/- 0.09; UW 0.24 +/- 0.02; ECS 0.19 +/- 0.01; LDP 0.19 +/- 0.05.in this "in vitro" model SPAL UP solution provides a significantly (p0.05) better cell preservation than regular UW, ECS and LPD solutions.

Several and different solutions have been used for lung preservation but, at present, fluids and solutions are quite alike. In the last years extracellular type solutions have been progressively tested in experimental researches and have shown a better protection vs intracellular one. In this research we have studied the effect of a low-potassium solution normally used as plasma expander (Haemmaccel, HM) on isolated foetal human fibroblasts (WI-38). HM has been compared with Belzer solution (UWS) after 16 hrs incubation at 10 degrees C and low-potassium solutions with dextran 2% and 5% after 6 hrs and 16 hrs incubation at 10 degrees C. Wi-38 cells have been seeded at the density of 9x10(4)/cm2 onto plastic well plates. Cellular viability was measuring using the rate of protein synthesis through the incorporation of 3H leucine in growth medium during a 1 hr incubation at 37 degrees C. The results were expressed as nmol 3 H leu/mg of proteins/minute and presented as means +/- SD; the comparison has been performed by the one way variance analysis test. After 16 hrs incubation at 10 degrees C HM preserves WI-38 cells significantly better than UWS. Comparing HM with LPD 2% and 5% a significant difference both at 6 hrs and at 16 hrs was observed. Our preliminary in vitro results confirm that low-potassium solutions are less toxic on isolated lung cells than intracellular one. Polygelin contained in HM could be considered a suitable colloidal substance that determine a better preservation if compared with Low-Potassium Dextran solutions.

1. The hypotensive effect of spironolactone has been studied in twenty-four patients with various forms of hypertension. 2. In essential hypertension a greater fall of blood pressure was achieved in patients with renin activity hyporesponsive to postural change than in those in whom renin responded normally to posture. 3. A poor hypotensive response was observed in patients with renal or renal arterial disease and secondary aldosteronism. 4. The variable hypotensive response seen in patients with primary aldosteronism predicted the response to adrenal surgery. 5. Blood pressure was not lowered by spironolactone in one case of 17-hydroxylation deficiency or in one case of malignant ovarian arrhenoblastoma producing aldosterone.