SARS-CoV-2 infection: NLRP3 inflammasome as plausible target to prevent cardiopulmonary complications?

NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome has recently become an intriguing target of several chronic and viral diseases. Here, we argue that targeting NLRP3 inflammasome could be a strategy to prevent cardiovascular outcomes [fulminant myocarditis, heart failure, venous thromboembolism (VTE)] and acute respiratory distress syndrome (ARDS) in patients with SARS-CoV-2 infection. We discuss the rationale for NLRP3 targeting in clinical trials as an effective therapeutic strategy aimed to improve prognosis of COVID-19, analyzing the potential of two therapeutic options (tranilast and OLT1177) currently available in clinical practice.

Comparative genotoxicity of cobalt nanoparticles and ions on human peripheral leukocytes in vitro.

Owing to the increasing development of nanotechnology, there is a need to assess how engineered nanomaterials can interact with living cells. The main purpose of the present study was to assess whether metal cobalt nanoparticles (CoNP 100-500 nm) are genotoxic compared to cobalt ions (Co(2+)). Uptake experiments were carried out by incubating peripheral blood leukocytes (PBLs) with (57)Co(2+) (added to stable Co(2+) 10(-2) M to obtain concentrations in the range of 10(-5) to 10(-4) M) or with (60)CoNP for 24 and 48 h. Whereas intracellular Co(2+) showed slight or no variations over the baseline levels, CoNP were taken up efficiently leading to intracellular CoNP concentrations of 485 +/- 106.1 and 970 +/- 99 fg per cell after 24 and 48 h, respectively. The genotoxicity end points considered in this study were the frequency of binucleated micronucleated (BNMN) cells and the percentage of tail DNA (% Tail DNA) fragmentation by means of the comet assay. Genotoxic effects were evaluated by incubating PBLs of three healthy donors with subtoxic concentrations (10(-5) to 8 x 10(-5)M) of Co(2+) in the form of cobalt chloride, CoNP and 'washed' CoNP, the latter to exclude any interference by Co(2+). On a group basis, Co(2+) induced a clear trend in the increase of the BNMN frequency, whereas CoNP showed only minor changes. Moreover, we observed a high variability among donors in the induction of micronuclei. The comet assay showed a statistically significant dose-related increase in % Tail DNA for CoNP (P < 0,001), whereas Co(2+) did not induce significant changes over control values. These findings suggest that nanosized Co can be internalized by human leukocytes and can interact with DNA leading to the observed genotoxic effects, which are, however, modulated both by donor's characteristics and/or by Co(2+) release.

Quality of eggs from Lohmann Brown Classic laying hens fed black soldier fly meal as substitute for soya bean.

Soya bean is the main protein source in poultry feed but rising prices make an alternative protein source necessary. Insects, such as the black soldier fly (Hermetia illucens), may be an attractive solution for hens, although little information is available on their effect on egg quality. The present study aims to fill this gap by testing the effect of 100% replacement of soya bean with H. illucens larva meal in the diet of Lohmann Brown Classic laying hens for 21 weeks. At the end of the trial, the eggs were characterized for parameters such as weight, colour, proximate composition of albumen and yolk, and content of carotenoids, tocopherols and cholesterol. The fatty acid profile of yolks was also determined. Hens fed the insect-based diet produced eggs (HIM group) with a higher proportion of yolk than the group fed the soya bean-based diet (SBM group). HIM was associated with redder yolks (red index 5.63 v. 1.36) than SBM. HIM yolks were richer in γ-tocopherol (4.0 against 2.4 mg/kg), lutein (8.6 against 4.9 mg/kg), ß-carotene (0.33 against 0.19 mg/kg) and total carotenoids (15 against 10.5 mg/kg) than SBM yolks. The fatty acid composition of HIM yolks was almost identical to that of SBM yolks. Finally, HIM yolks contained 11% less cholesterol than SBM yolks. These results suggest that H. illucens larva meal is a suitable total substitute for soya bean meal in the diet of Lohmann Brown Classic laying hens. A sustainable alternative to the plant protein source therefore seems feasible.

Differential effects of beclobrate on lipid/lipoprotein distribution in normal and hypercholesterolemic rats.

Beclobrate, a new fibric acid derivative, displays remarkable lipid lowering activity in rodents. In order to evaluate changes in the distribution and liver handling of lipoproteins, beclobrate was tested in rats fed on a normal or hypercholesterolemic diet. On the normal diet, beclobrate lowered total plasma cholesterol by 22-33.4% (10-50 mg/kg); the cholesterol reduction occurred mainly in high density lipoproteins (HDL) (by 24-45% with the three tested doses). The metabolic clearance of 125I-labelled beta-very low density lipoproteins (beta-VLDL) injected into these animals almost doubled (0.20 1/h vs. 0.13 1/h in controls) after treatment with 20 mg/kg of beclobrate. In addition, beclobrate administration dramatically increased the activity of the high-affinity receptors for beta-VLDL in isolated liver membranes (Bmax: 208 +/- 17.6 vs. 146 +/- 2.6 ng/mg of protein for controls). On the hypercholesterolemic diet, beclobrate treatment (50 mg/kg) was associated with a 25% reduction in total cholesterol accompanied, however, by a 166% rise in HDL cholesterol. In these animals, the composition of VLDL, typically cholesterol-enriched, became close to normal. The increased HDL was characterized by a remarkable enrichment with particles containing apolipoprotein E (apo E), which is compatible with either an improved peripheral cholesterol removal or an enhanced direct secretion of apo E. The two models offer different opportunities for evaluating the mechanism of action of this new lipid lowering agent. Lipoprotein catabolism and receptor-mediated clearance were characteristically improved in normolipidemic rats whereas major effects on HDL metabolism could be demonstrated in hypercholesterolemic rats.

Comparison between diurnal changes and changes induced by hydrocortisone and epinephrine in circulating myeloid progenitor cells (CFU-GM) in man.

A significant increase from 8 AM to 3 PM was found in both myeloid progenitor cell (CFU-GM) and polymorphonuclear leukocyte (PMN) blood concentration in 45 normal subjects. Diurnal blood (CFU-GM and PMN changes were significantly correlated. Spontaneous diurnal changes in blood CFU-GM levels and in PMN were compared with the changes induced by i. v. administration of hydrocortisone (16 normal volunteers) and of epinephrine (10 normal volunteers). Diurnal changes in CFU-GM and PMN seem to follow a pattern similar to that induced by epinephrine administration. These findings suggest that diurnal changes in CFU-GM reflect mainly a shift of these cells between different blood compartments.

Transtympanic drains in the treatment of serous otitis in children; anatomical versus functional long term results.

The long term results are reported of transtympanic drains in 391 ears of 258 children affected by serous otitis; 150 ears have been evaluated at the end of a 3-7-year observation period. (1) A high percentage of ears with major anatomical lesions was found (46.6%), especially in the higher age group (greater than 7 years). (2) Functional hearing results are better than anatomical results; 84.6% of the subjects had a hearing level better than 20 dB (0-10 dB: 53.3%; 11-20 dB: 31.3%). (3) Anatomical and functional results are worse in case of recurrence (2 or more drains). (4) It is imperative to control periodically those children with major tympanic lesions and present good hearing.

[4'-epidoxorubicin: its cardiotoxicity. Possible cardiac protection with gallopamil, a drug with calcium-antagonist action]. / La 4'-epidoxorubicina: sua cardiotossicità. Eventuale cardioprotezione con il gallopamil, farmaco ad azione calcioantagonista.

The 4'-EPI-doxorubicin (4'-EDX) has shown antitumoral activity against a broad spectrum of human tumors. The same clinical reports have shown therapeutic activity comparable to doxorubicin (adriamycin), but a lower cardiac toxicity. 4'-EDX cardiotoxicity appears after highest cumulative doses: 935 mg/m2 bs for 4'-EDX vs 550 mg/m2 bs for adriamycin. Moreover we have observed a protective action of the calcium antagonist gallopamil. We have found an improvement in ventricular performance after using gallopamil, and a reduction of 4'-EDX cardiotoxicity. Cardiac function was evaluated by EKS, STI, echography, myocardial scintigraphy course. Our result indicates the possibility of treating tumors without serious cardiotoxic by 4'-EDX and gallopamil.

[Scanning electron microscopy in malignant uveal melanomas (author's transl)]. / Mélanomes malins de l'uvée observés au microscope électronique à balayage.

Four malignant uveal melanomas, of which two were of fascicular (subtype B) type one of epithelioid type and one of mixed-type, were examined under a scanning electron microscope. Within the tumors, we can distinguish cells having long cytoplasmatic processes and cells without processes, which correspond to the fusiform and epithelioid cells respectively. The cells also show a more or less marked development of the microvillosities of the cell surface.

[Chronic kidney failure: dialysis and kidney transplantation. The medicolegal and social considerations]. / Insufficienza renale cronica: dialisi e trapianto renale. Considerazioni medico-legali e sociali.

The authors carried out a research on the social and labour problems of the people affected by chronic renal failure, either on dialysis treatment or already transplanted since two years. It has been given a questionnaire based on questions about the person, the working position, the social insurance situation, the family and personal problems. The results show a good social reinsert and a good recover of the transplanted in opposition of the many problems had by those on dialysis; in particular it has been considered also the problem of the periodic absences from work. It has been also considered the italian law situation regarding the people affected by chronic renal failure in some different social insurance fields.

[Medico-legal aspects of chronic respiratory insufficiency under long-term oxygen inhalation therapy]. / Aspetti medico-legali dell'insufficienza respiratoria cronica con ossigeno terapia a lungo termine.

Ninety-one subjects affected by severe pulmonary insufficiency necessitating continuous treatment with oxygen were studied. The social and professional realities and their status within the national health service were determined. The results of the research, obtained through the use of the questionnaires, showed that the lives of these subjects are very much influenced by their pathology. Among the factors considered were necessity for home assistance, scarce or absence of autonomy and contact with the outside world and extremely reduced work capacity. Elevated public spending for assistance was analyzed in reference to public health insurance as regards each single subject and the type of lung dysfunction from which the subject suffered.

Airbag and hearing loss: our experience.

The international literature reports sporadic cases of sudden sensorineural hearing loss associated with Airbag inflation in subjects involved in car accidents, who had never suffered from hearing loss and had no history of pathologies that could otherwise explain the hearing loss. The authors have studied the actual incidence of this possibility, analysing 25 subjects submitted to an airbag inflation. Only subjects who had never suffered from previous otological pathology were considered for the study. The examination was carried out 3 to 10 days after the accident. Otoscopical examination, tympanometry and audiometry were normal in all the examined subjects. The Author's opinion is that traumatic hearing loss following airbag inflation is a rare or exceptional incident that probably occurs in subjects with a particular susceptibility and sensitivity.

Immunohistochemical analysis of dendritic cells in skin lesions: correlations with survival time.

The response to wounds until healing requires the activity of many cell types coordinate in space and time, so that the types of cells in a wound and their localization may be of help to date lesions with respect to death, which would be useful in forensic pathology. Cells reacting to injury include dendritic cells; the early reaction of these cells to skin wounding has not yet been investigated in humans, which was the aim of this study. Samples of wounded and control skin were taken at autopsy and analyzed by affinity histochemistry. Both epidermal and dermal MHC-II+ cells increased transiently in number within the first hour after wounding, then decreased. In the epidermis the increase affected also CD1a+ cells, i.e. well differentiated Langherhans cells, which however increased less, earlier and for a shorter time period than MHC-II+ cells. Dermal MHC-II+ cells became part of a perivascular mononuclear cell infiltrate visible in the subpapillary dermis by 60 min after wounding, which contained also mast cells. The immediately perivascular MHC-II+ cells were DC-SIGN- and CD11c-, while MHC-II+, DC-SIGN+, CD11c+ dendritic cells were predominantly located at the periphery of infiltrates and some were near the epidermis. Mast cells underwent degranulation, besides increase in number, in the first hours after wounding. The results suggest that skin dendritic cells, including Langerhans cells, participate to the early response to wounding in concert with mast cells, and that subpapillary blood vessels are primary sites of cell infiltration during that response in humans. The results show that the ratio between CD1a positive and MHC-II positive cells in the epidermis, the degranulation index of mast cells and the relative volume of MHC-II positive cells in the dermis can be added to the tools useful to distinguish vital from post mortem lesions and, the first two of them, to estimate the interval between a lesion and death.