Silent thyroiditis following vaccination against COVID-19: report of two cases.

PURPOSE: It is well established that thyroiditis and other thyroid disorders can be induced by COVID-19 infection, but there is limited information about the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We report two cases of thyrotoxicosis following SARS-CoV-2 vaccine. METHODS AND RESULTS: Two young health care peoples (wife and husband) received a first dose of SARS-CoV-2 vaccine, and few weeks later developed clinical manifestations of thyroid hyperactivity, with increased thyroid hormone levels on thyroid function tests, suppressed thyroid-stimulating hormone and negative antithyroid antibodies, despite being healthy before vaccination. They were diagnosed at the 4th week after first dose of SARS-Cov-2 vaccine as silent thyroiditis and followed without treatment, since their symptoms were not severe. At the 6th week, the patients became wholly asymptomatic and their thyroid function returned to normal. CONCLUSIONS: Thyrotoxicosis can occur after SARS-CoV-2 vaccination probably related to silent thyroiditis.

Comparison of the impact of ships to size-segregated particle concentrations in two harbour cities of northern Adriatic Sea.

Detailed information on in-harbour shipping contribution to size segregated particles in coastal cities are scarce, especially in the busy Mediterranean basin. This poses issues for human exposure and air quality in urban harbour agglomerates, where only criteria pollutants (i.e. PM10 and/or PM2.5) are usually monitored. In this work, particle number and mass size distributions, in a large size range (0.01-31 µm), were obtained in two coastal cities of northern Adriatic Sea: Venice (Italy) and Rijeka (Croatia). Three size ranges were investigated: nanoparticles (diameter D < 0.25 µm); fine particles (0.25 1 µm). Absolute concentrations were larger in Venice for all size ranges showing, using analysis of daily trends, a large influence of local meteorology and boundary-layer dynamics. Contribution of road transport was larger (in relative terms) in Rijeka compared to Venice. The highest contributions of shipping were in Venice, mainly because of the larger ship traffic. Maximum impact was on nanoparticles 7.4% (Venice) and 1.8% (Rijeka), the minimum was on fine range 1.9% (Venice) and <0.2% (Rijeka) and intermediate values were found in the coarse fraction 1.8% (Venice) and 0.5% (Rijeka). Contribution of shipping to mass concentration was not distinguishable from uncertainty in Rijeka (<0.2% for PM1, PM2.5, and PM10) and was about 2% in Venice. Relative contributions as function of particles size show remarkable similitudes: a maximum for nanoparticles, a quick decrease and a successive secondary maximum (2-3 times lower than the first) in the fine range. For larger diameters, the relative contributions reach a minimum at 1-1.5 µm and there is a successive increase in the coarse range. Size distributions showed a not negligible contribution of harbour emissions to nanoparticle and fine particle number concentrations, compared to PM2.5 or PM10, indicating them as a better metric to monitor shipping impacts compared to mass concentrations (PM2.5 or PM10).

Characterisation of atmospheric pollution near an industrial site with a biogas production and combustion plant in southern Italy.

Although biogas production can have some benefits, there is a research gap on potential influence of biogas plant emissions on local air quality, thus an accurate and comprehensive evaluation of impacts of this technology is needed. This study deals with this issue by means of a characterisation of air pollution near an industrial area including a biogas production (from biomass) and combustion plant located in South Italy. The methodology consists in advanced statistical analysis on concentration of gaseous pollutants, particles concentration and size distribution in number and mass, and PM2.5 chemical composition. High-temporal resolution measurements, supported by ancillary meteorological parameters, and source apportionment of PM2.5 using Positive Matrix Factorization (PMF) receptor model, are performed. The integrated approach provides the emissive picture consisting in different anthropogenic sources (i.e. traffic, biomass burning, and industrial facilities) with particular focus on biogas plant emissions. Results showed that CO and nitrogen oxides were influenced by vehicular traffic and biomass combustion, however, a contribution of the plant to NO was observed. SO2 was influenced mainly by transport from the industrial zone, but a second local contribution compatible with the emissions of the biogas plant was detected. Number particle concentrations were analysed in four size ranges: nanoparticles (D < 0.05 µm), ultrafine particles (D < 0.3 µm), accumulation (0.3 < D < 1 µm) and coarse particles (D > 1 µm). Nanoparticles and ultrafine particles were mainly influenced by vehicular traffic and biomass burning, instead, a contribution of the plant was individuated in the accumulation mode. PMF5 identified the contribution of six sources: crustal (14.7% ± 2.1% of measured PM2.5); marine aerosol (aged) (12.9% ± 2.3%); biomass burning (32.8% ± 1.4%); secondary sulphate (19.7% ± 2.4%); primary industrial emissions (5.4% ± 2.3%); traffic and secondary nitrate (17.0% ± 3.9%). The plant is likely to contribute to both sources, the industrial and the traffic plus secondary nitrate.

Short communication: A comparison of cow cleanliness, fly population, and fly avoidance behaviors among docked, switch-trimmed, and switch-intact dairy cows in 3 commercial dairy herds.

Tail docking is a controversial practice in the dairy industry. Proponents claim that tail docking keeps the udder cleaner, and therefore improves milk quality and decreases somatic cell count. Opponents of tail docking cite that it causes unnecessary pain, backed by multiple studies that demonstrate no positive benefits of tail docking and that tail docking increases aggravation from flies. The objective of this study was to evaluate and compare cow cleanliness, fly population, and fly-avoidance behaviors among cows with docked, switch-trimmed, and switch-intact tails. A total of 206 cows from 3 Kentucky dairy herds were included in the longitudinal observational study. Each farm included previously docked cows, switch-intact cows, and cows whose switches were trimmed at the initial farm visit. Researchers visited each farm every 2 wk for 8 wk to record cow cleanliness, teat cleanliness, fly population, and fly-avoidance behavior scores. No significant differences were found in cow cleanliness scores, teat cleanliness scores, fly population scores, skin twitching, or foot stomping counts among docked, switch-trimmed, or switch-intact cows. Although the fly population scores did not differ, the amount of tail swings among docked, switch-intact, and switch-trimmed cows were significantly different. The odds of exhibiting tail swinging were 2.63 times greater for docked cows than for switch-trimmed cows and 1.92 times greater than for switch-intact cows. Overall, switch trimming resulted in similar outcomes to tail docking, although neither showed improvements over intact tails.

Deposition in St. Mark's Basilica of Venice.

Atmospheric pollutants may cause damage to monuments and historical buildings. Besides air contaminants, soluble salts are also responsible for stone deterioration and decay in outdoor and indoor monuments. The problem of how to conserve works of arts thus requires a deep knowledge of contaminants' concentration and distribution inside buildings. In this work, water-soluble ions inside St. Mark's Basilica in Venice were studied, with the aim of understanding their principal source and distribution inside the building. With the aid of Fourier transform infrared spectroscopy and scanning electron microscopy analysis, the interaction between ions and surface's material was also investigated. Ion chromatographic analysis of depositions highlighted a large amount of "deteriorating agents" such as sulphates and chlorides. A possible source in the innermost area of the basilica has been found for formates and nitrates. On the contrary, a decrease of chloride, from the entrance to the innermost area, has been found, which indicates that the source is outside the building. It is emphasized that different contaminants behave differently on different material, and the effect of pollution inside churches and monuments is not easy to predict. Wood and brick seem to react differently than stone and mortar to the damaging action of salts and pollutants. The present work should be considered a useful tool for the future preservation of St. Mark's Basilica in Venice.

Increasing incidence of thyroid cancer in Basilicata: an Italian study.

OBJECTIVE: In recent years many authors have reported an increase in thyroid cancer (TC) incidence in several countries. The cause of such phenomenon remains unclear. DESIGN: This study was designed to estimate the incidence of TC in Basilicata, the smallest region of Southern Italy with a population of 596,546 people, between 2001 and 2004. MAIN OUTCOME: A total of 302 cases of TC were identified. The annual incidence of TC changed over the years, from 10.0 per 100,000 people in 2001 to 15.7 per 100,000 people in 2004. The number of new TC cases per 100,000 people increased an average of 16% per yr. Median age at diagnosis was 49 yr. The most frequent histotype was papillary TC (PTC) (73.2%). In 20 (6.6%) patients with PTC, we identified at least one first-degree relative affected by differentiated TC. CONCLUSIONS: The present study shows a high incidence of sporadic and familial non-medullary TC in Basilicata. The reason for this finding may be related to several factors discussed in the paper. Further studies evaluating the trends in the incidence of TC in Basilicata in the future could provide some answers for the potential pathogenetic hypothesis.

Autoimmune hepatitis during intravenous glucocorticoid pulse therapy for Graves' ophthalmopathy treated successfully with glucocorticoids themselves.

We report a case of acute hepatitis of autoimmune origin which occurred in a 43-yr-old woman during iv glucocorticoid (GC) pulse therapy for Graves' ophthalmopathy (GO). Prior to therapy, liver function tests were normal with no previous history of liver disorders or conditions predisposing to GC-associated liver damage. After the administration of a 4.7-g cumulative dose of methylprednisolone acetate, there was a marked increase of liver enzymes, prompting immediate discontinuation of iv GC. Nevertheless, liver enzymes increased further, reaching a peak 45 days later, with values 30- to 50-fold greater than those prior to therapy, associated with evidence of impaired liver function. Liver biopsy showed a marked lymphocytic infiltration, likely indicating an autoimmune hepatitis. Based on the assumption that following GC-induced immune suppression, autoimmune hepatitis might have been precipitated by sudden re-activation of the immune system during interpulse periods, we treated the patient with im and then oral GC, in order to re-induce immune suppression. Within three days from re-institution of GC therapy, there was a marked reduction of liver enzymes and amelioration of liver function. Complete normalization was achieved two months later, while the patient was still receiving a low maintenance dose of oral prednisone.

Novel aspects of immunosuppressive and radiotherapy management of Graves' ophthalmopathy.

Treatment of severe Graves' ophthalmopathy (GO) is a complex therapeutic challenge and, in spite of any efforts, about one third of patients are disappointed with the outcome of treatment. Glucocorticoids (GC), orbital radiotherapy (RT), or a combination of both, are most frequently used for their immunosuppressive effects. Novel immunosuppressive treatment procedures (or novel modalities of established treatments) are reviewed in the present article. GC has recently been used by the i.v. route and this treatment modality has been shown to be more effective and better tolerated than the oral route. Promising preliminary results have been reported by some authors with somatostatin analogs, octreotide and lanreotide. The number of patients treated so far is limited, most of the results have been obtained in nonrandomized or uncontrolled studies, and comparison with other validated methods of treatment is also needed. Because of the pathogenic role of cytokines, cytokine antagonists, currently evaluated in other autoimmune diseases, have been tested with positive results also in a small series of GO patients. The use of antioxidants might also be envisioned in the future, since in vitro studies have shown that oxygen free radicals might be involved in GO. Based on the shared antigen(s) theory, total thyroid ablation, by removing the bulk of shared antigens(s), might be beneficial for the course of GO. New data on recently performed placebo-controlled studies on orbital radiotherapy are discussed, together with studies on long-term safety of orbital radiotherapy.

Impaired thyroglobulin (Tg) secretion by FRTL-5 cells transfected with soluble receptor associated protein (RAP): evidence for a role of RAP in the Tg biosynthetic pathway.

Secretion of thyroglobulin (Tg) by thyrocytes requires several endoplasmic reticulum (ER)-resident molecular chaperones. The receptor-associated protein (RAP), a known molecular chaperone, binds to Tg in thyroid cells shortly after biosynthesis. Here we investigated whether RAP is involved in Tg secretion by FRTL-5 cells. For this purpose, we studied Tg secretion by FRTL-5 cells transfected with a soluble RAP chimera, as a mean for interfering with endogenous RAP. We used a RAP-human IgG Fc (RAP-Ig) chimeric cDNA, which was designed in order to exclude the ER retention sequence of RAP and to allow generation of a secreted form of RAP. FRTL-5 cells were transiently transfected with the RAP-Ig cDNA or, as control, with a CD8-Ig cDNA. Media were collected at 24, 48 and 72 h after transfection. Secretion of fusion proteins and of Tg in the media was measured by ELISA. As expected, under standard culture conditions, RAP was not secreted into the media by FRTL-5 cells, even though it could be detected by Western blotting in cell extracts. In transfection experiments, fusion proteins were present in the media of FRTL-5 cells transfected with either RAP-Ig or CD8-Ig, indicating that transfection was successful. Although Tg was found in the media of FRTL-5 cells transfected with either CD8-Ig or RAP-Ig, a lower amount was found in cells transfected with RAP-Ig. Therefore, we concluded that RAP is involved in Tg secretion by FRTL-5 cells suggesting that RAP may function as a Tg molecular chaperone.

Effect of propionyl-L-carnitine treatment on membrane phospholipid fatty acid turnover in diabetic rat erythrocytes.

In this work we have examined the effect of the oral administration of propionyl-L-carnitine (PLC) on the membrane phospholipid fatty acid turnover of erythrocytes from streptozotocin-induced diabetic rats. A statistically significant reduction in radioactive palmitate, oleate, and linoleate, but not arachidonate, incorporation into membrane phosphatidylcholine (PC) of diabetic rat erythrocytes with respect to control animals was found. Changes in radioactive fatty acid incorporation were also found in diabetic red cell phosphatidylethanolamine (PE), though they were not statistically significant. Oral propionyl-L-carnitine (PLC) treatment of diabetic rats partially restored the ability of intact red cells to reacylate membrane PC with palmitate and oleate, and reacylation with linoleate was fully restored. The analysis of the membrane phospholipid fatty acid composition revealed a consistent increase of linoleate levels in diabetic rat red cells, a modest decrease of palmitate, oleate and arachidonate. The phospholipid fatty acid composition of diabetic red blood cells was not affected by the PLC treatment. Lysophosphatidylcholine acyl-CoA transferase (LAT) specific activity measured with either palmitoyl-CoA or oleyl-CoA was significantly reduced in diabetic erythrocyte membranes in comparison to controls. In addition, LAT kinetic parameters of diabetic erythrocytes were altered. The reduced LAT activity could be partially corrected by PLC treatment of diabetic rats. Our data suggest that the impaired erythrocyte membrane physiological expression induced by the diabetic disease may be attenuated by the beneficial activity of PLC on the red cell membrane phospholipid fatty acid turnover.

Endothelins urinary excretion is increased in spontaneously diabetic rats: BB/BB.

Previously we reported (1) an increase of endothelin-1,2 (ET) content, in urine of rats made diabetic with streptozotocin (STZ), starting three days and up to 20 weeks from diabetes induction. The increased ET excretion was considered as an early marker of endothelial damage. To ascertain if this phenomenon was present also in a strain of spontaneously diabetic rats, endothelin-1,2 urinary excretion was determined in BB/BB diabetic rats, and their control (BB/WB), at different times after the onset of diabetes, (two, four, six and twelve weeks). BB/BB diabetic rats showed elevated urinary excretion of endothelins as compared to BB/WB control rats, starting two weeks after diabetes onset, and up to twelve weeks. In the same animals, Nerve Conduction Velocity (NCV), was monitored at the same time as an index of the occurrence of a diabetes complication (peripheral neuropathy). NCV resulted to be impaired in the BB/BB diabetic rats as compared to control rats; however the increase of ET in urine, is earlier in comparison to peripheral neuropathy. These data suggest the hypothesis that endothelial damages preceed the overt manifestations of peripheral neuropathy associated to diabetes.

Serum and urine levels of levocarnitine family components in genetically diabetic rats.

Serum concentration and urinary excretion of levocarnitine (L-carnitine, CAS 541-15-1) family components were evaluated in a Wistar derived strain of genetically diabetic rats BB/BB, in comparison with normal Wistar rats, and their control rats BB/WB of both sexes. BB/BB diabetic animals have lower serum concentration of total-L-carnitine (TC), L-carnitine (LC), acetyl-L-carnitine (ALC), and short chain L-carnitine esters (SCLCE) than both the strains of non-diabetic rats, as previously observed in streptozotocin diabetic rats. No or marginal variations between control and diabetic rats were detected in cumulative urinary excretion of L-carnitine family components. A strain difference was observed between Wistar and BB/WB non-diabetic rats, BB/WB showing higher serum concentration and lower cumulative urinary excretion of LC and TC than Wistar animals. Renal clearance of L-carnitine components proved to be markedly higher in BB/BB diabetic rats, as previously shown in streptozotocin rats. The reduction of serum concentration of the carnitines endogenous pool may explain this finding. The lack of an increased urinary excretion of L-carnitine components in diabetic animals despite the high increase of diuresis suggests that the saturable tubular reabsorption of L-carnitine family components also in diabetes is the primary mechanism to preserve the homeostatic equilibria of the L-carnitine family, the variation in serum concentration being attributable to the complex systemic metabolic alterations typical of diabetes. In agreement with previous investigations, male animals of all the strains showed higher serum concentration and urinary excretion of L-carnitine components as compared to females.

Elevated urinary excretion of endothelins in streptozotocin diabetic rats.

Endothelin-1,2 urinary excretion, has been determined in control and streptozotocin diabetic rats at different times after diabetes induction. Diabetic rats showed increased urinary excretion of endothelins as compared to control rats, already three days after diabetes induction and up to 20 weeks.

Effect of acetyl-L-carnitine treatment on the levels of levocarnitine and its derivatives in streptozotocin-diabetic rats.

The effect of diabetes induced by streptozotocin and that of acetyl-L-carnitine (ALC) hydrochloride (CAS 5080-50-2) treatment on the homeostasis of the levocarnitine (L-carnitine) moiety was investigated in Sprague-Dawley rats. The diabetic status was ascertained by measuring blood glucose. L-carnitine (LC), total acid soluble L-carnitine (TC) and ALC were measured in serum, tissues and urine by radioenzymatic methods. Short-chain L-carnitine esters (SCLCE) were obtained by subtracting LC from TC. Serum concentration of L-carnitine moiety was decreased in diabetic when compared to normal rats; whereas ALC oral treatment (50 and 150 mg/kg p.o. for 4 weeks) in diabetic rats increased, dose-dependently, all the components of L-carnitine moiety, SCLCE and ALC being completely restored. In the liver of diabetic rats all the analytes proved to be higher than in normal rats, mainly LC and TC. A similar trend was observed in skeletal muscle, at least with LC and TC, whereas SCLCE and ALC were not affected. The treatment with ALC increased the liver concentration of all the analytes in a dose-related way whereas in skeletal muscle only LC and TC showed an increase with the highest dose of ALC. Myocardium and kidneys showed a decrease of all the analytes in diabetes; the treatment with ALC normalized the situation in kidneys, in a dose-related way, but not in the myocardium. Urinary excretion and renal clearance of L-carnitine moiety increased in diabetes; an additional dose-related increase was observed with the ALC treatment.

Acetyl-L-carnitine effect on nerve conduction velocity in streptozotocin-diabetic rats.

Measurement of nerve conduction velocity (NCV) is a useful and sensitive tool for evaluating diabetes related neurological dysfunctions. The method used allows to monitor the parameter at different times in the same group of rats, so that it is possible to observe simultaneously the development of the damage in time, and to evaluate the improvement related to the treatment. The repeated oral treatment with acetyl-L-carnitine (ALC, CAS 5080-50-2) 250 mg/kg caused an improvement in NCV of the diabetic rats; the effect was higher when the treatment started early with respect to the diabetes induction. The improvement in NCV was constant in time and comparable from 2 to 6 weeks of the treatment. In conclusion, oral treatment with ALC was able to normalize the impairment of NCV in streptozotocin rats, the effect being constant in time from 2 to 6 weeks of treatment and up to 8 weeks after induction when administration started in early stage of diabetes (2-3 weeks after induction); however, at this time the NCV is already significantly decreased.

Biochemical diagnosis of mucopolysaccharidoses: experience of 297 diagnoses in a 15-year period (1977-1991).

We report the results over 15 years (1977-1991) for biochemical diagnoses of patients referred from throughout Italy and suspected of having a mucopolysaccharidosis. Of these, 147 patients were diagnosed as being homozygous or hemizygous for a specific lysosomal enzyme deficiency; 74 pregnancies at risk were monitored in their families; 76 heterozygote diagnoses were performed on their relatives, with a total of 48 positive diagnoses. We also report the analysis of genomic DNA from 11 unrelated Italian Hunter patients, using pc2S15 probe. DNA from two patients, digested with Pst-I, showed a variant pattern of hybridization caused by deletion or rearrangement of the gene.

High-performance liquid chromatographic evaluation of Med 15 and its metabolites Med 5 and tolmetin in rat plasma.

A simple and reliable high-performance liquid chromatographic method is described for the quantitative analysis of the new non-steroidal anti-inflammatory agent Med 15 and its metabolites Med 5 and tolmetin in rat plasma. After selective extraction the three analytes and an internal standard (p-phenyl-phenol) were separated on a reversed-phase Ultrasphere 5 micron column using potassium dihydrogenphosphate (0.05 M)-acetonitrile (52:48) (pH 4.7) as the mobile phase. The analytes were detected at 313 nm; the sensitivity of the method proved to be 0.05 microgram/ml for all three compounds. The method has been applied to investigate Med 15 pharmacokinetics in rats.

Homeostatic equilibrium of L-carnitine family before and after i.v. administration of propionyl-L-carnitine in humans, dogs and rats.

Propionyl-L-carnitine is a minor component of L-carnitine family which, when exogenously administered, proved to possess interesting cardiovascular activities. In this paper the pharmacokinetics of propionyl-L-carnitine was investigated in humans, dogs and rats after intravenous administration. In all the three species the base homeostatic equilibrium was carefully investigated in plasma and in urine during the 24 h period before the administration. Propionyl-L-carnitine, acetyl-L-carnitine, L-carnitine and total acid soluble L-sensitive were assayed in plasma and urine with very sensitive enantioselective radioenzyme assay. After dosing propionyl-L-carnitine rapidly increased, and then decreased reaching the base value within 6 h or more, depending on the species and the dose. Also L-carnitine in all the three species and acetyl-L-carnitine in rats and dogs increased, but the increase was more sustained when compared to propionyl-L-carnitine. Urinary excretion paralleled plasma concentration, reaching the highest value in the 24 h-period after dosing. Renal clearance also increased reflecting the behaviour of plasma concentration and urinary excretion. Results obtained all the conclusion that two homeostatic equilibrium of L-carnitine family components, namely the inter-exchange between L-carnitine and its esters catalyzed by carnitine acyl transferases, and a saturable tubular reabsorption process with differentiated threshold for each component.

Biochemical diagnosis of Hunter syndrome on Epstein-Barr virus-transformed lymphoblastoid cell lines.

Long-term lymphoblastoid cell lines have been established from a patient with Hunter syndrome, from his mother, an obligate heterozygote, and from several control individuals. Biochemical analyses show that lymphoblastoid cells represent a suitable biological material for the diagnosis of hemizygous, affected males and for heterozygous females: clonal analysis demonstrates the mosaicism predicted by the Lyon hypothesis.