La "grandiosa opera": il ponte Vecchio di Ragusa (1812-1844). La storia e le rappresentazioni.

L'articolo ricostruisce la storia del ponte dei Cappuccini di Ragusa, attraverso nuove acquisizioni documentarie e iconografie inedite

Effects of low pH on synthesis and release of catecholamines in the cat carotid body in vitro

Producción CientíficaThe rates of dopamine and noradrenaline synthesis in the cat carotid body (c.b.) are 5.9 _+ 0.58 pmol/c.b./2 h and 0.3 + 0.02 pmol/c.b./2 h, respectively. The synthesis is doubled when the organs are incubated at pH 7. Similarly, low pH induces a release of dopamine from the c.b. which is proportional to increased activity in the carotid sinus nerve

Synthesis and Release of Catecholamines by the Cat Carotid Body in Vitro: Effects of Hypoxic Stimulation

Producción CientíficaThe role of catecholamines (CAs) in cat carotid body chemoreception has been controversial. On the basis of pharmacological experiments, it would appear that endogenous dopamine (DA) may act either as an inhibitory or excitatory transmitter. Neurochemical studies on the effects of natural stimulation on the release of carotid body CAs in the cat have also been inconclusive. In the present study, we have characterized the synthesis and release of CAs in the in vitro cat carotid body preparation in response to different levels of hypoxic stimulation and have correlated these measures with the chemosensory activity of the carotid sinus nerve. The synthesis of [3H]DA and [3H]norepinephrine was linear for at least 4 h in carotid bodies incubated with their natural precursor [~H]tyrosine. Synthesis of both [3H]CAs plateaued when the [3H]tyrosine concentration in the media reached 40 uM, which is a concentration similar to that found in cat plasma. Exposure of the animals to an atmosphere of 10% 02 in N~ for 3 h prior to removal and incubation of the carotid bodies with [3H]tyrosine resulted in an approximately 100% increase in the rate of [3H]DA synthesis but no change in [3H]norepinephrine synthesis. This selective increase in [3H]DA synthesis was not detected when [3H]dihydroxyphenylalanine was used as precursor. Carotid bodies first incubated with [3H]tyrosine and later superfused with solutions equilibrated with different gas mixtures (0 100% 0 2 in N2) exhibited an increase in [3H]DA release and carotid sinus nerve discharge which were inversely related to the oxygen concentration. This relationship was strongest for the weaker stimuli (between 50% and 20% O 2 in N2), where both nerve activity and [3H]DA release increased almost in parallel. With lower oxygen concentrations (10% O 2 and 0% 02 equilibrated solutions), the increase in the release of [3H]DA was proportionally greater than the increase in carotid sinus nerve discharge. Our results demonstrate that hypoxic stimulation increases both the rate of synthesis and release of DA in the cat carotid body. Although the precise role of DA in this chemoreceptor organ is presently unknown, our findings suggest that this biogenic amine plays a direct role in generating or controlling the electrical activity in the carotid sinus nerve. INTRODUCTION The mammalian carotid body is an arterial chemoreceptor organ activated by low paO2, low pH and high p~CO2 (ref. 21). Structurally, the receptor complex is formed by clusters of two types of cells, the type I and type II cells; the clusters lie within a supporting connective tissue matrix containing a dense capillary net24, 41. Sensory fibers of the carotid sinus nerve (CSN) penetrate these cell clusters to end in synaptic apposition with type I cells, which are considered to be preneural (receptor) elements. Two perennial issues pertaining to arterial chemoreception, concern first, whether the type 1 cells are in fac

Transfusional approach in multi-ethnic Sickle Cell patients: real-world practice data from a Multicenter survey in Italy

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies. Although we observed a similar proportion of Caucasian (47.9%) and African (48.7%) patients, Italian SCD patients clustered into two distinct overall groups: children of African descent and adults of Caucasian descent. We found a subset of SCD patients requiring more intensive therapy with a combination of HC plus chronic transfusion regimen, due to partial failure of HC treatment alone in preventing or reducing sickle cell-related acute manifestations. Notably, we observed a higher use of acute transfusion approaches for SCD patients of African descent when compared to Caucasian subjects. This might be related to (i) age of starting HC treatment; (ii) patients' low social status; (iii) patients' limited access to family practitioners; or (iv) discrimination. In our cohort, alloimmunization was documented in 135 patients (8.5%) and was more common in Caucasians (10.3%) than in Africans (6.6%). Alloimmunization was similar in male and female and more frequent in adults than in children. Our study reinforces the importance of donor-recipient exact matching for ABO, Rhesus, and Kell antigen systems for RBC compatibility as a winning strategy to avoid or limit alloimmunization events that negatively impact the clinical management of SCD-related severe complications

Italian patients with hemoglobinopathies exhibit a 5-fold increase in age-standardized lethality due to SARS-CoV-2 infection.

Since the beginning of the COVID-19 pandemic, concerns have been expressed worldwide for patients with hemoglobinopathies and their vulnerability to SARS-CoV-2 infection. Data from Lebanon confirmed a role of underlying comorbidities on COVID-19 severity, but no deaths among a cohort of thalassemia patients.1 Patients with sickle cell disease (SCD) displayed a broad range of severity after SARS-CoV-2 infection, spanning from a favorable outcome unless pre-existing comorbidities (UK cohort)2 to high case mortality in US.3 History of pain, heart, lung, and renal comorbidities was identified as risk factors of worse COVID-19 outcomes by the US SECURE-SCD Registry.4 While Italy experienced a death rate in the general population among the highest in the world, preliminary data from the first wave of the pandemic showed a lower than expected number of infected thalassemia patients (updated up to April 10, 2020), likely due to earlier and more vigilant self-isolation compared to the general population.

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). Results A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. Conclusions In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms