Background: Gaucher disease is a lysosomal storage disorder caused by functional glucocerebrosidase enzyme deficiency. Hepatosplenomegaly and hematological complications are found in both Gaucher disease and Acid Sphingomyelinase Deficiency, which is caused by acid sphingomyelinase dysfunction. The possible overlap in clinical presentation can cause diagnostic errors in differential diagnosis. For this reason, in patients with an initial clinical suspicion of Gaucher disease, we aimed to carry out a parallel screening of acid sphingomyelinase and glucocerebrosidase. Methods: Peripheral blood samples of 627 patients were collected, and enzymatic activity analysis was performed on both glucocerebrosidase and acid sphingomyelinase. The specific gene was studied in samples with null or reduced enzymatic activity. Specific molecular biomarkers helped to achieve the correct diagnosis. Results: In 98.7% of patients, normal values of glucocerebrosidase activity excluded Gaucher disease. In 8 of 627 patients (1.3%), the glucocerebrosidase enzymatic activity assay was below the normal range, so genetic GBA1 analysis confirmed the enzymatic defect. Three patients (0.5%) had normal glucocerebrosidase activity, so they were not affected by Gaucher disease, and showed decreased acid sphingomyelinase activity. SMPD1 gene mutations responsible for Acid Sphingomyelinase Deficiency were found. The levels of specific biomarkers found in these patients further strengthened the genetic data. Conclusions: Our results suggest that in the presence of typical signs and symptoms of Gaucher disease, Acid Sphingomyelinase Deficiency should be considered. For this reason, the presence of hepatosplenomegaly, thrombocytopenia, leukocytopenia, and anemia should alert clinicians to analyze both enzymes by a combined screening. Today, enzyme replacement therapy is available for the treatment of both pathologies; therefore, prompt diagnosis is essential for patients to start accurate treatment and to avoid diagnostic delay.
Distribution of T29C TGFβ1 gene polymorphism was analysed in 260 hypertensive and 134 normotensive subjects. Circulating TGFβ1 and procollagen type III levels, microalbuminuria, left ventricular geometry and function were evaluated in all the hypertensives subgrouped according to T29C TGFβ1 gene polymorphism. Circulating TGFβ1 by ELISA technique, procollagen type III by a specific radioimmunoassay, microalbuminuria by radioimmunoassay, left ventricular geometry and function by echocardiography were determined. All groups were comparable for gender, age and sex. Regarding T29C TGFβ1 gene polymorphism, prevalence of TC or CC genotypes was significantly (p<0.05) higher in hypertensives than normotensives. TC and CC hypertensives were characterized by a higher prevalence of subjects with microalbuminuria (p<0.001 TC vs TT; p<0.05 CC vs TT), left ventricular hypertrophy (p<0.01 TC and CC vs TT), and by increased levels of procollagen type III (p<0.05 TC and CC vs TT). TC hypertensives were also characterized by a significant increase (p<0.05) of LVM and LVM/h2.7 and of urinary albumin excretion (p<0.05) values than those detectable in TT hypertensives. Our data suggest that T29C TGFβ1 gene polymorphism was associated to clinical characteristics suitable to recognize hypertensives with a higher severity of hypertension.
Therapeutic attempts to cure allergic diseases reduce symptoms without circumventing the onset of the allergic reaction. Specific immunotherapy (SIT), is the most commonly used treatment. Nevertheless, SIT may account for various adverse events. Therefore, different therapies have been developed in order to treat and prevent allergic reactions. Among these therapies, there is an increased interest in studying recombinant peptides mutated in the IgE binding site. Several studies have shown two major allergens of Parietaria judaica (Pj) named Par j 1 and Par j 2, which have been cloned and characterized by us. In our study we have fragmented the Par j 2 protein in order to determine the major epitopes recognized by human IgE and we used site-directed mutagenesis to identify potential amino acid residues involved in IgE binding. The IgE binding activity of the recombinant peptides was tested and the results showed that site-specific mutagenesis at positions K41, T42, T43, and C52 caused a loss of IgE binding. The goal of this work is to synthesize molecules which can induce a protective immune response against Pj. These molecules will be used in immunotherapy in order to create new vaccines for the treatment of Parietaria pollen allergy.
The outcomes of Coronavirus disease-2019 (COVID-19) vary depending on the age, health status and sex of an individual, ranging from asymptomatic to lethal. From an immunologic viewpoint, the final severe lung damage observed in COVID-19 should be caused by cytokine storm, driven mainly by interleukin-6 and other pro-inflammatory cytokines. However, which immunopathogenic status precedes this “cytokine storm” and why the male older population is more severely affected, are currently unanswered questions. The aging of the immune system, i.e., immunosenescence, closely associated with a low-grade inflammatory status called “inflammageing,” should play a key role. The remodeling of both innate and adaptive immune response observed with aging can partly explain the age gradient in severity and mortality of COVID-19. This review discusses how aging impacts the immune response to the virus, focusing on possible strategies to rejuvenate the immune system with stem cell-based therapies. Indeed, due to immunomodulatory and anti-inflammatory properties, multipotent mesenchymal stem cells (MSCs) are a worth-considering option against COVID-19 adverse outcomes.
The concept of Vascular Dementia (VaD) has been recognized for over a century, but its definition and diagnostic criteria remain unclear. Conventional definitions identify the patients too late, miss subjects with cognitive impairment short of dementia, and emphasize consequences rather than causes, the true bases for treatment and prevention. We should throw out current diagnostic categories and describe cognitive impairment clinically and according to commonly agreed instruments that document the demographic data in a standardized manner and undertake a systematic effort to identify the underlying aetiology in each case. Increased effort should be targeted towards the concept of and criteria for Vascular Cognitive Impairment and Post-Stroke Dementia as well as for genetic factors involved, especially as these categories hold promise for early prevention and treatment.
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