197 research outputs found
Nazioni Unite - Il Protocollo aggiuntivo alla Convenzione contro la tortura e gli altri trattamenti crudeli, inumani e degradanti (di V. Fiorese, in: I Diritti dell'Uomo, 2003 n.1)
No full textEnhanced tissue factor expression by blood eosinophils from patients with hypereosinophilia: a possible link with thrombosis.
No full textThrombotic risk is increased in eosinophil-mediated disorders, and several hypotheses have been proposed to link eosinophilia and thrombosis. In particular, eosinophils have been described as source of tissue factor (TF), the main initiator of blood coagulation; however, this aspect is still controversial. This study was aimed to evaluate whether TF expression varies in eosinophils isolated from normal subjects and patients with different hypereosinophilic conditions. Eosinophils were immunologically purified from peripheral blood samples of 9 patients with different hypereosinophilic conditions and 9 normal subjects. Western blot analysis and real-time polymerase chain reaction (RT-PCR) were performed to test eosinophil TF expression. For comparison, TF expression was evaluated in monocytes from blood donors and in human endothelial (ECV304) and fibroblast (IMR90) cell lines. Western blot analysis revealed a major band of 47,000 corresponding to native TF in homogenates of purified eosinophils with a higher intensity in the 9 patients than in the 9 controls (p<0.0001). According to RT-PCR cycle threshold (Ct), TF gene expression was higher in eosinophils from patients than in those from controls, median (range) 35.10 (19.45-36.50) vs 37.17 (35.33-37.87) (p = 0.002), and was particularly abundant in one patient with idiopathic hypereosinophilic syndrome and ischemic heart attacks (Ct: 19.45). TF gene expression was moderate in monocytes, Ct: 31.32 (29.82-33.49) and abundant in endothelial cells, Ct: 28.70 (27.79-29.57) and fibroblasts, Ct: 22.77 (19.22-25.05). Our results indicate that human blood eosinophils contain variable amounts of TF. The higher TF expression in patients with hypereosinophilic disorders may contribute to increase the thrombotic risk
Pseudoscopas carbonelli Matiotti
No full textPseudoscopas carbonelli Matiotti da Costa, n. sp. (Figs 1-4) Etymology. The specific epithet refers to a tribute to the great orthopterologist Carlos Salvador Carbonell, in memorial who dedicated his life to working brilliantly with Neotropical grasshopper taxonomy. Diagnosis. Close to P. nigrigena, but differentiated by coloration of the body, epiproct without protuberances in median region and absence of sclerotization in edge of the cerci. Combination of the following characteristics: (i) Epiproct triangular with deep median sulci in apical portion with five conspicuous protuberances in the median region and edge of the apical region sclerotized and curved; (ii) furculae divided in two small lobes; (iii) pallium lobes small; (iv) male cerci triangular, wide and robust at the base, and with sclerotized acute apex, curving inward; (v) hind edge of the female subgenital plate forming two large lobes on both sides; (vi) plan bridge with median reentrancy; (vii) ancorae larger in size than of the anterior projections; (viii) lophi prominent and sclerotized. Body morphology and coloration Description. Male Holotype (Figs. 1–3). Body medium in size (18 mm length), moderately robust and deeply pubescent, especially the femorae and tibiae. Braquipterous. Head. Front subvertical, slightly oblique (Fig. 3A) and conspicuously larger than usual (Fig. 3B). Antennae filiform, with 18 antennomeres surpassing the posterior margin of pronotum. Eyes globular, laterally salient and not exceeding the vertex. Interocular space narrow (Fig. 3A). Face little retreating. Frontal costa plan (Fig.3A). Occiput smooth (Fig. 3B). Fastigium of the vertex subtriangular, shorter, with apex of vertex slightly rounded (Fig.2A). Thorax. Pronotum with median carina slightly marked, and lateral absent (Fig. 2A); metazona shorter than prozona; pronotum disc crossed by three transverse sulci; pronotum lateral edges parallel, slightly expanding in the metazona; anterior margin straight and the posterior with slight median emargination (Fig. 2A). Prosternal process spiniform. Mesosternal lobes rounded. Tegmen short, lobuliform, reaching to the second abdominal segment (Fig. 2A). Legs. Hind femur slender, the upper keel smooth, the end of lower knee lobes rounded. Hind tibiae pubescent with 7 outer and 8 inner dorsal spines; absence of hind femur’s terminal spinous projection on the dorsal genicular lobes (Fig. 2A). Abdomen. Tympanum large. Abdomen thickened in distal region. Epiproct triangular, longer than wider with deep median sulci in apical portion and five conspicuous protuberances in the median region; edge of the apical region sclerotized and curved apex rounded; furculae divided in two small lobes (Fig. 3C). Pallium with small and salient lobes (Fig. 3C). Cerci triangular, robust, conic, pubescent, strongly curved, exceeding the epiproct apex; acute and sclerotized apex (Fig. 3D). Subgenital plate cupuliform, short, curved up, apex rounded and pubescent (Fig. 3D). Phallic complex. Cingulum with long apodemes, arch developed; gonophore with a rectangular ventral projection (Fig. 4A); aedeagus long with upper and lower valves of the same size and median longitudinal sulci in the apical valves; sclerites of aedeagus covered by the wide and highly lobulated ectophallic sheath (Fig. 4A). Epiphallus with plan bridge and median reentrancy; ancorae larger in size than of the anterior projections; lophi prominent and sclerotized; without internal conical protuberance (Fig. 4B). Body brown light color (Figs 1A, 2A, 3 A-B). Head mostly yellow color with a black pair of retro-ocular bands that take part of the genae, and continue in the dorsal half of the pronotum lateral lobes, tegmina, pleural and sides of the abdomen. Scape, pedicel, and antennal flagellum brown color. Fastigium of the vertex with five brown spots (Fig. 2A). Occiput marked with brown spots. Face, clypeus, and genae yellowish color; mandible and labrum black color; labial and maxillary palpi yellowish color with black tip (Fig. 3B). Light brown antennae. Pronotum dorsally with several punctures and brown spots (Fig. 2A). Lateral lobes of the pronotum with a yellow ivory band on the lower abdomen (Fig. 3A). Tegmen with veins light brown, a narrow ivory band surrounding the dorsal portion of the wing (Fig. 2A). Genicular lunules black. Legs I and II green, with pretarsus tip, arolium and claws brown color; femur III yellow-green, with genicular lobe black; tibiae III light-blue, with tarsomeres light green, and tarsal claws and arolium brown. Lateral sclerites of the abdomen yellowed from the second segment. Dorsal and ventral abdominal segments and pallium brown. Female. Larger in size to male, robust (body length 21mm) (Fig. 1B, 2B). Same color as male, but the head more yellowish (Fig. 2B); fastigium more prominent and wider than in males and with brown color spots; eyes more prominent. Interocular space wider. Pronotum dorsally light green, with several punctures and brown punctuation spots. Lateral lobes of the pronotum with a reddish, yellow-green and ivory bands, from upper to lower portion (Fig. 1B). Abdomen sides with a black spot in between segments 3-6. Ovipositor valves short in lateral view and serrulated margins absent (Fig. 3E); dorsal valve of the ovipositor robust and apical tooth of the external ventral valve of ovipositor little prominent. Hind edge of the female subgenital plate forming two large lobes on both sides and without sclerotization (Fig. 3F). Legs I and II less robust than in males. Cerci short, conical, not reaching the epiproct tip (Fig.3E). Epiproct subtriangular with median sulcus well marked, interrupted transversely in the median region. Habitat and Habits. Individuals of P. carbonelli n. sp. were collected mainly during the day, being active on bushes and grasses of the edge of the forest in more open places and with lower canopy cover (Fig.6), usually between 11am to 5pm. The records of the genus Pseudoscopas are between the Pampean and Parana provinces, but P. carbonelli is found only in the southeast of the Parana province. (Morrone 2001; 2006). Measurements (mm): Males (n=7): BL= 18.1 (17.4–18.1); PL = 0.3 (0.2–0.3); FL3 = 0.8 (0.7–0.8); TL = 0.3 (0.2–0.3). Females (n = 8): BL = 21.1 (19.2–21.1); PL = 0.5 (0.4–0.5); FL3 = 0.9 (0.8–0.9); TL = 0.4 (0.3 – 0.4). Type material. Holotype ♂. BRAZIL: Rio Grande do Sul, municipality of São Francisco de Paula, (29°24’44.16”S 50°12’30.44”W), 27-30.i.2020, Zefa, E.; Acosta R.C. & Tim, V., 7♂ and 8♀ (MCTP). Holotype condition: genitalia were extracted and maintained in holotype’s tube. Chromosomes (Figs. 5 A-D). Diploid chromosome number of 2n=23, X0 ♂ /24, XX ♀; all chromosomes acrocentrics, grouped in two chromosome pairs large (L 1 –L 2), two pairs medium large (ML 3 – ML 4), five medium (M 5 –M 9), and two small (S 10 –S 11) (Fig. 5A); the X chromosome belongs to the ML group, and the megameric to the M group, both showing positive heteropiknosis until diplotene phase (Fig. 5C, D). Metaphase I chiasmata position: L 1, proximal and intersticial; L 2, proximal and intersticial; ML 3, proximal and subterminal; ML 4, subterminal; M 5, terminal; M 6, terminal; M 7, terminal; M 8, intersticial; M 9, intersticial; S 10, terminal; S 11, terminal (Fig. 5B). The size relationship between chromosomes can be better seen in (Fig. 5E), which includes a metaphase II. Genus distribution. Brazil (Paraná; Santa Catarina; Rio Grande do Sul); Argentina (Misiones, Concepción); Paraguay (Sapucay, Caaguazú); Uruguay (Caraguatay, Cuchilla Negra, Tacuarembó) (Cigliano et al. 2021; Ronderos 1987; Mesa et al. 1982; Monné 2018) (Table 1, Fig. 7).Published as part of Costa, Maria Kátia Matiotti Da, Acosta, Riuler Corrêa, Timm, Vítor Falchi, Demari, Christian Peter, Carvalho, Gervásio Silva & Zefa, Edison, 2021, Pseudoscopas carbonelli n. sp. (Orthoptera: Acrididae: Melanoplinae) from southern Brazil, including chromosome complement, pp. 127-140 in Zootaxa 4975 (1) on pages 128-133, DOI: 10.11646/zootaxa.4975.1.4, http://zenodo.org/record/480527
Esteri alchilsolforici con attività antiproliferativa da diverse specie di ascidie del Mediterraneo
No full textStudio chimico condotto su campioni di Ascidia mentula, Microcosmus vulgaris, Halocynthia papillosa e Sidnyum turbinatu
Co‐occurrence of IgE and IgG autoantibodies in patients with chronic spontaneous urticaria
No full textChronic spontaneous urticaria (CSU) pathogenesis shows a complex and still unclear interplay between immunoglobulin (Ig)G- and IgE-mediated autoimmunity, leading to mast cell and basophil degranulation and wheal formation. The objective of this study was to evaluate at the same time IgE- and IgG-reactivity to well recognized and recently reported autoantigens in CSU patients, and to assess the effects of such reactivity on response to the anti-IgE monoclonal antibody omalizumab. Twenty CSU patients underwent omalizumab treatment. Urticaria activity score 7 (UAS7) was recorded at baseline and at different drug administration time-points for categorizing early-, late- or non-responders. At baseline, sera from the 20 patients and from 20 controls were tested for IgE and IgG autoantibodies to high- and low-affinity IgE receptors (FcεRI and FcεRII), tissue factor (TF) and thyroglobulin (TG) by immunoenzymatic methods. Antibody levels were compared with those of controls and analysed according to response. Eighteen patients were omalizumab responders (11 early and seven late), while two were non-responders. More than 50% of patients had contemporary IgE and IgG to at least to one of the four different autoantigens. Late responders showed higher levels of both anti-TF IgE and IgG than early responders (P = 0·011 and P = 0·035, respectively). Twenty-five per cent of patients had levels of anti-FcεRI IgE, exceeding the upper normal limit, suggesting that it could be a novel auto-allergen in CSU. In CSU, there is an autoimmune milieu characterized by the co-existence of IgE and IgG autoantibodies to the same antigen/allergen, particularly in late responders to omalizumab, possibly explaining the slower response
Therapeutic Options in Hereditary Optic Neuropathies
No full textOptions for the effective treatment of hereditary optic neuropathies have been a long time coming. The successful launch of the antioxidant idebenone for Leber’s Hereditary Optic Neuropathy (LHON), followed by its introduction into clinical practice across Europe, was an important step forward. Nevertheless, other options, especially for a variety of mitochondrial optic neuropathies such as dominant optic atrophy (DOA), are needed, and a number of pharmaceutical agents, acting on different molecular pathways, are currently under development. These include gene therapy, which has reached Phase III development for LHON, but is expected to be developed also for DOA, whilst most of the other agents (other antioxidants, anti-apoptotic drugs, activators of mitobiogenesis, etc.) are almost all at Phase II or at preclinical stage of research. Here, we review proposed target mechanisms, preclinical evidence, available clinical trials with primary endpoints and results, of a wide range of tested molecules, to give an overview of the field, also providing the landscape of future scenarios, including gene therapy, gene editing, and reproductive options to prevent transmission of mitochondrial DNA mutations
Immunomodulation of polymorphonuclear leukocytes by D53 Immucytal and its constitutive fractions
No full textIL-10 up-regulates human monocyte phagocytosis in the presence of IL-4 and IFN-gamma
No full textInterleukin-10 (IL-10), a cytokine produced by type 2 helper T (Th2) cells, inhibits the microbicidal effector function of interferon-γ (IFN-γ)-activated macrophages. However, recent observations indicate that IL-10, like IFN-γ, increases FcγRI expression and FcγR-mediated cytotoxic activity on human monocytes, suggesting that this cytokine cannot be classified purely as a monocyte deactivator. The present study found that incubation for 40 h of human monocytes or monocyte-derived macrophages in the presence of IL-10 caused a significant enhancement of their capacity to ingest particles coated with immunoglobulin G (FcγR-mediated ingestion) or with C3b/C3bi fragments of the complement system (CR1/CR3-mediated ingestion). The number of phagocytosing cells (% phagocytosis) and the number of ingested particles per cell (phagocytic index) were both significantly higher after 40-h incubation of monocytes with IL-10 concentrations ≥1 U/ml. This up-regulating activity on phagocytosis was completely reversed by anti-IL-10 monoclonal antibody (mAb). As previously reported, IL-10 stimulated FcγRI expression on monocytes but did not induce the expression of FcγRII, FcγRIII, CR1, and CR3. IFN-γ, like IL-10, up-regulated only FcγRI expression but significantly reduced both FcγR- and CR-mediated ingestion. IL-10 almost completely reversed the IFN-γ-induced inhibition of both FcγR- and CR-mediated phagocytosis, without concomitant changes in membrane expression of phagocytic receptors. Exposure of monocytes to IL-4 reduced the membrane expression of all three FcγRs and also inhibited FcγR-mediated ingestion. On the other hand, IL-4 up-regulated both CR3 expression and CR-mediated ingestion on cultured monocytes. IL-10 not only neutralized the down-regulatory effect of IL-4 on FcγR expression but also completely reversed the IL-4-induced suppression of FcγR-mediated phagocytosis. Exposure of monocytes to a combination of IL-10 and IL-4 resulted in a synergistic effect on CR-mediated ingestion, even though no additive effects were observed on CR membrane expression. Finally, culture of monocytes in medium containing anti-IL-10 mAb significantly reduced their capacity to ingest IgG- or C3b/C3bi-coated particles, suggesting a role for endogenously produced IL-10 in the modulation of phagocytosis by human monocytes. These results demonstrate that IL-10 is a potent up-regulator of the phagocytic activity of human mononuclear phagocytes and indicate that this function may be in sensitive balance with the relative concentration of IL-10, IL-4, and IFN-γ
Involvement of the IgE-basophil system and mild complement activation in haemophilia B with anti-factor IX neutralizing antibodies and anaphylaxis
No full textIntroduction: Patients with haemophilia B who develop factor IX (FIX) neutralizing antibodies (inhibitors) after FIX infusion are at high risk of hypersensitivity reactions upon FIX re-exposure, but the underlying mechanisms are incompletely understood. Aim: To investigate biomechanisms of FIX hypersensitivity. Methods: A cellular antigen stimulation test (CAST) was employed to evaluate leukotriene C4 (LTC4) release from basophils stimulated by FIX in three treated children with haemophilia B, one of whom developed FIX inhibitor and experienced anaphylaxis following FIX re-exposure. Anti-FIX IgE and IgG antibodies and markers of complement activation (C5b9, C3d and iC3b) were measured in plasma, the last also after FIX infusion. Ten healthy children served as controls. Results: The patient who developed anti-FIX inhibitors and anaphylaxis had a nonsense mutation in FIX gene (p.Arg298Stop) and, compared to controls, had higher plasma levels of specific anti-FIX IgE (2.285 vs 0.084 OD492 nm), with marked LTC4 release from his FIX-stimulated basophils (519.8 vs 39.9 pg/mL). Further, he had higher plasma levels of anti-FIX IgG of all the four subclasses (total IgG 1.180 vs 0.120 OD492 nm) with FIX neutralizing activity (1.5 BU); mild complement activation occurred during FIX-induced anaphylaxis (C5b9 increased from 258.5 to 351.1 ng/mL). The same parameters were normal in the two patients who tolerated FIX infusion. Conclusion: In the patient with haemophilia B who experienced anaphylaxis after FIX, but not in the patients with haemophilia B who tolerated FIX, the CAST assay showed FIX-induced LTC4 release, which was associated with high plasma levels of specific anti-FIX IgE and IgG antibodies
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