Recognizing the new disorder "idiopathic hypocryoglobulinaemia" in patients with previously unidentified clinical conditions

A considerable number of patients with high clinical suspicion for cryoglobulinaemic vasculitis either show negative results for the detection of cryoglobulins or show only trace amounts which cannot be characterized for composition. We aimed at establishing whether the failure to detect or the detection of trace amounts of cryoglobulin with conventional methods either identifies a peculiar subset of low level cryoglobulinaemia (from now on hypocryoglobulinaemia) or represents a separate entity. Using a modified precipitation technique in hypo-ionic medium, we prospectively identified between 2008 and 2021 237 patients (median age 60.8 years [22–97], 137 females) having < 0.5% cryocrit and clinical suspicion of autoimmune disorder. Of these 237 patients, only 54 (22.7%) had a history of HCV infection. One hundred and sixty-nine out of 237 patients (71%) had an established underlying disease, while 68 patients (28.6%) (median age 62.9 years [29–93], 35 females) did not show either laboratory markers or clinical symptoms consonant with an underlying aetiology. These 68 cases with only trace amounts of cryoglobulins were defined as having a putatively idiopathic hypocryoglobulinaemia. Nineteen of these 68 patients (27.9%) had a history of HCV infection. Twenty-four patients out of 68 (35.3%) were positive for rheumatoid factor (RF), while 25 (36.7%) patients had signs of complement consumption (i.e., C4 < 15 mg/dl and/or C3 < 80 mg/dl ), and 36 (52.9%) had increased inflammatory indexes. Seven patients only had arthralgia and constitutional symptoms while 61 out of 68 (89.7%) presented with at least one of the three cardinal signs of cryoglobulinaemic vasculitis including skin lesions, peripheral nerve involvement, and glomerulonephritis. Seventy-five percent of the subjects had type III hypocryoglobulins. In patients with hypocryoglobulinaemia the histologic features of glomerulonephritis (also examined by electron microscopy) resembled those of mixed cryoglobulinaemia-associated glomerulonephritis. In conclusion, hypocryoglobulins are often polyclonal and are mainly unrelated to HCV infection. Patients who present high clinical suspicion for vasculitis, especially glomerulonephritis and yet test negative for cryoglobulinaemia detected by standard techniques, could require deeper investigation even in the absence of HCV infection, RF activity or signs of complement consumption

Highly dispersed Fe3+-Al2O3 for the Fenton-like oxidation of phenol in a continuous up-flow fixed bed reactor: enhancing catalyst stability through operating conditions

A highly dispersed Fe3+-Al2O3 catalyst (6 wt% Fe) was used for the catalytic wet hydrogen peroxide oxidation of phenol (1 g/L) in an up-flow fixed bed reactor (UFBR) under continuous operation. To enhance catalytic performance, three simple synthesis strategies were combined: two-stage impregnation of iron citrate, acid washing with CH3COOH and thermal treatment at 900 °C. Solid samples were characterized in depth by several techniques: N2 Physisorption, XRD, SEM–EDAX, TEM, TGA, PZC, TPD of pyridine, XPS and Mössbauer. Peroxidation experiments were performed in an UFBR over a wide range of operating parameters in order to evaluate their influence on phenol mineralization and catalyst stability. Under selected operating condition (T = 90 °C, Wcat = 20 g, QL = 1.2 mL/min and [H2O2]:[Phenol] = 16.8), complete phenol conversion and remarkable TOC reduction of 90% were achieved, with a high H2O2 consumption efficiency (η = 76%) and low Fe leaching ( 70%) but the cumulative iron loss was calculated to be c.a. 20% of the initial Fe loaded in the UFBR. The catalyst was susceptible to leaching due to the accumulation of complexing intermediates such as carboxylic acids. However, acceptable iron leaching values ( 80%). The presence of chelating by-products favored also the Fe redistribution inside the catalyst pellets. Nevertheless, catalyst decay in the long-term operation was mainly due to the occurrence and permanence of chelating organic acids. This process was specially promoted by the amphoteric character of the alumina-based catalyst. However, adsorbed species were promptly eliminated by calcination at 500 °C, recovering steady state conversion profiles.Centro de Investigación y Desarrollo en Ciencias Aplicada

Synthesis, in vitro activity and in vivo toxicity of the new 2,3-dinitrobutadiene derivative (1E,3E)-1,4-bis(2-naphthyl)-2,3-dinitro-1,3-butadiene

Abstract Our interesting results on the antiproliferative (in vitro) and antitumour (in vivo) activities of (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (1-Naph-DNB) have more recently induced us to design and synthesize some new 1,4-diaryl-2,3-dinitro-1,3-butadienes characterized by a common arylnitrobutadiene array but with different geometric and/or functional properties. This task was undertaken with the aim to obtain new compounds with an enhanced antiproliferative activity and, possibly, a different specificity with respect to the original (lead) compound. (1E,3E)-1,4-Bis(2-naphthyl)-2,3-dinitro-1,3-butadiene (2-Naph-DNB) is one of the molecules so obtained, a structural isomer of 1-Naph-DNB provided with a different spatial arrangement. When analyzed in vitro for its inhibition of cell proliferation 2-Naph-DNB showed a remarkable activity in the range of micromolar concentrations, with significant differences, with respect to 1-Naph-DNB, against some cell lines. Furthermore, it was able to significantly trigger apoptosis, to up-regulate p53, to block cells in the G2/M phase of the cell cycle and, finally, to slightly bind to DNA forming interstrand cross-links (ISCL). 2-Naph-DNB was then analyzed for its toxic activity in vivo in CD1 mice. This allowed the determination of toxicity parameters such as the lethal doses (LD) and the maximal tolerated dose (MTD) together with the definition of the spectrum of tissue alterations due to its administration i.v. Altogether our data suggest that the idea of modifying the geometry of the lead compound 1-Naph-DNB deserves further investigation aimed at synthesizing new molecules with similar chemical functionalities but with different spatial requirements, hopefully characterized by still enhanced activities in terms of inhibition of cell proliferation and apoptosis