Prevention of the spread of SARS COV-2 by Rapid Antigenic Tests on the passengers entering an Italian seaport.

Abstract: Out of 38,282 passengers entering Italy at a major seaport, submitted to SARS-CoV-2 rapid antigenic test, 272 (0.6%) resulted positive and 212 (93.4%) were confirmed positive by qRT-PCR, leaving a 0.6% of false positive. Those resident in the area under control of the same Local Health Authority of the seaport were immediately submitted to isolation and investigated for contact tracing, the others notified to their Local Health Authority which did the same in the following day. This procedure was made possible by a full-time dedication of the local healthcare workers who managed all the passengers disembarking around the clock along the months of the emergency.

ICH3, a selective alpha7 nicotinic acetylcholine receptor agonist, modulates adipocyte inflammation associated with obesity.

PURPOSE: The alpha7 nicotinic acetylcholine receptor (α7nAChR), involved in the modulation of inflammation and insulin sensitivity, is downregulated in white adipose tissue (WAT) of obese patients. This study aims to test the ability of a selective synthetic α7nAChR agonist, the spirocyclic Δ2-isoxazoline derivative (R)-(-)-ICH3 (ICH3), to counteract acute inflammation and obesity-associated modifications in WAT. METHODS: We employed the LPS-septic shock murine model, human primary adipocytes and diet-induced obese (DIO) mice. Inflammatory factor expression was assessed by ELISA and quantitative real-time PCR. Flow cytometry was employed to define WAT inflammatory infiltrate. Insulin signaling was monitored by quantification of AKT phosphorylation. RESULTS: In the septic shock model, ICH3 revealed antipyretic action and reduced the surge of circulating cytokines. In vitro, ICH3 stimulation (10 µM) preserved viability of human adipocytes, decreased IL-6 mRNA (P < 0.05) and blunted LPS-induced peak of TNFα (P < 0.05) and IL-6 (P < 0.01). Chronic administration of ICH3 to DIO mice was associated with lower numbers of CD8+ T cells (P < 0.05) and to changed WAT expression of inflammatory factors (Hp, P < 0.05; CD301/MGL1, P < 0.01; Arg-1, P < 0.05). As compared to untreated, ICH3 DIO mice exhibited improved insulin signaling in the skeletal muscle (P < 0.01) mirrored by an improved response to glucose load (ipGTT: P < 0.05 at 120 min). CONCLUSIONS: We proved that ICH3 is an anti-inflammatory drug, able to reduce inflammatory cytokines in human adipocytes and to blunt the effects of obesity on WAT inflammatory profile, on glucose tolerance and on tissue insulin sensitivity.

Health tourism: an opportunity for sustainable development.

In February 2017, the "Programma Mattone Internazionale Salute" (ProMis), that is the Italian Program for Internationalization of Regional Health Systems of the Ministry of Health (MoH), presented the first version of its Position Paper on Health Tourism, which embeds a first shared approach to the recommendations expressed by the European Committee of Regions (CoR) on "Age-Friendly" tourism. The CoR stresses the importance of local and regional authorities in the coordination of multi-sectoral policies such as healthcare, social assistance, transport, urban planning and rural development in relation to the promotion of mobility, security, accessibility of services, including health care and social services. "Age-friendly" tourism is an example of an innovative tourist offer that strives to meet the health needs of the entire "traveling" population, with an integrated and cross-sector approach that involves various organizations operating in sectors such as healthcare, accessibility and transport. The aim of the workshop was to explore the interest of the stakeholders to participate in a systemic action in the field of "health" tourism, and to identify priority implementation areas that offer opportunities to take advantage of validated, innovative experiences that strengthen the accessibility to health and social services in regional, national and international contexts. This effort provides the opportunity to take advantage of aligning the European Structural and Investment Funds (ESIF) to the development of tourism, coherently with the needs and resources of local and regional health authorities.

Immune sensitization of equine bronchus: glutathione, IL-1beta expression and tissue responsiveness.

BACKGROUND: Increasing clinical epidemiological and experimental evidence indicates that excess of production of reactive oxygen free radicals (ROS) induced by an oxidative stress is involved in the pathogenesis of a number of human airway disorders, as well as equine recurrent airway obstruction. Free-radicals modulate the activation of transcription factors, such as nuclear factor-(NF)-kappaB and activator protein (AP)-1, in several different cells. This activation leads to expression of many pro-inflammatory cytokines, including interleukin (IL)-1beta. We have hypothesized that equine airway sensitization might induce an oxidative stress and increase the ROS production, which in turn might enhance a production of IL-1beta and airway hyperresponsiveness. METHODS: We have examined the effect of passive sensitization on IL-1beta mRNA expression and electrical field stimulation (EFS)-induced contraction in equine isolated bronchi, and the potential interference of reduced-glutathione (GSH), an antioxidant, with these responses. Bronchi passively sensitized with serum from animals suffering from heaves and having high total level of IgE, and control tissues, either pretreated or not with GSH (100 microM), were used to quantify IL-1beta mRNA. Other tissues were used to study the effect of EFS (3-10-25 Hz). RESULTS: Mean IL-1beta mRNA expression was higher in passively sensitized than in control rings. GSH significantly (p < 0.05) reduced the IL-1beta mRNA expression only in passively sensitized bronchi. ELF induced a frequency-dependent contraction in both non-sensitized and passively sensitized tissues, with a significantly greater response always observed in sensitized tissues. GSH did not modify the EFS-induced contraction in non-sensitized bronchi, but significantly (p < 0.05) decreased it in passively sensitized tissues. CONCLUSION: Our data indicate that the passive sensitization of equine bronchi induces inflammation and hyperresponsiveness. These effects might be due to an oxidative stress because a pretreatment with GSH decreased the increased IL-1beta mRNA expression and responsiveness to EFS of passively sensitized bronchi.

Effect of chronic opioid antagonism on the hypothalamic-pituitary-ovarian axis in hyperprolactinemic women.

Short term naloxone infusion studies have suggested that enhanced endogenous opioid activity may play a role in inhibiting GnRH and gonadotropin secretion in hyperprolactinemic patients. Because it was not known whether long term opioid antagonism would lead to persistent stimulation of LH with a subsequent ovarian response, we administered the long-acting oral opiate antagonist, naltrexone (NTX), to six hyperprolactinemic amenorrheic women. Blood was drawn from all subjects every 15 min for 10 h on a control day and again on the next day after the administration of 50 mg NTX. Five subjects continued NTX (50 mg daily) for 3-8 weeks. There was a significant increase in the mean concentration of LH (6.7 +/- 1.1 to 12.2 +/- 1.6 IU/L), area under the LH curve (200%), and LH pulse amplitude (3.2 +/- 0.6 to 7.2 +/- 1.0 IU/L) on the first NTX day compared to the control day (P < 0.02). Estradiol levels also increased on the first NTX day (P < 0.01). The mean peak estradiol level increased from 76 +/- 9.9 pmol/L on the control day to 138 +/- 21 pmol/L during NTX treatment (P < 0.02). NTX stimulated LH release in five of six patients, followed by a rise in estradiol in four of these five patients. This initial increase in estradiol was not sustained in most cases, and the mean estradiol level during the entire NTX treatment period was not significantly different from the control level. One patient achieved an estradiol level of 187 pmol/L after 3 weeks of NTX treatment and reported withdrawal bleeding after stopping NTX. No patient ovulated. PRL levels did not change on the first NTX day vs. the control day (166 +/- 79 vs. 167 +/- 67 micrograms/L); however, PRL did increase over time with continued NTX treatment (P < 0.05). The mean PRL level during chronic NTX treatment was 255 +/- 121 micrograms/L. We conclude that treatment of hyperprolactinemic amenorrheic women with NTX results in a prompt partial reactivation of the hypothalamic-pituitary-gonadal axis, as indicated by increased gonadotropin and subsequent estradiol release. The effect of opioid antagonism, however, did not lead to a sustained increase in estradiol secretion with chronic treatment. Thus, although endogenous opioids appear to play a key role in mediating PRL-induced gonadal suppression, chronic opioid antagonism with NTX does not appear to be an effective treatment for amenorrhea in these patients.

Aromatization is not required for androgen induced changes in proopiomelanocortin gene expression in the hypothalamus.

Testosterone regulation of POMC mRNA and peptide levels has been previously demonstrated in the medial basal hypothalamus (MBH) of the rat. Although both dihydrotestosterone (DHT) and estradiol are known to affect POMC peptide levels in the MBH, it is unclear if the effects of testosterone on POMC gene expression are due to conversion by aromatization to estradiol or due to independent androgen actions. We have therefore compared the effects of the nonaromatizable androgen DHT and estradiol on POMC gene expression and beta-endorphin (beta-EP) levels in the MBH of castrated male rats. We have also examined the effect of the dopamine agonist, pergolide, on POMC in the DHT and estradiol treated animals in light of previous studies in female rats. In the first study POMC mRNA in the MBH, as measured by a solution hybridization assay, was 0.85 +/- 0.07 pg/microgram RNA 3 weeks after castration and decreased to 0.64 +/- 0.07 pg and 0.65 +/- 0.07 pg in the DHT treated rats with and without pergolide (P < 0.05). In the second study the mean POMC mRNA concentration in the MBH was 0.95 +/- 0.10 pg/microgram RNA and decreased to 0.68 +/- 0.06 pg and 0.70 +/- 0.08 pg in the estradiol treated rats with and without pergolide (P < 0.05). In both studies significant changes in beta-EP peptide levels paralleled the changes in POMC mRNA levels. We conclude that both androgens and estrogens can affect POMC mRNA levels in the male rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of chronic prolactin infusion on pituitary prolactin and hypothalamic proopiomelanocortin.

Although there is evidence that endogenous opioids, and in particular beta-endorphin (beta-EP), may mediate some of the suppressive effects of hyperprolactinemia on the hypothalamic-pituitary-gonadal (HPG) axis, there is controversy about the effects of prolactin (PRL) on beta-EP and its precursor, proopiomelanocortin (POMC), in the hypothalamus. In this study we have therefore examined the effects of chronic peripheral and intracerebroventricular (i.c.v.) infusion of ovine PRL on POMC gene expression and beta-EP levels in the medial basal hypothalamus (MBH) of castrated male and female rats. Endogenous pituitary and plasma PRL levels were determined by RIA with an antiserum to rat PRL which does not crossreact with oPRL. Suppression of endogenous rPRL levels was used as a confirmation of the biological effectiveness of the infused oPRL. POMC mRNA was measured in the MBH by solution hybridization assay. In the first experiment oPRL (5 microg/microl/h) or vehicle was infused for 2 weeks by osmotic minipump into the right lateral ventricle of ovariectomized rats. The mean plasma concentration of rPRL declined from 3.7+/-1.0 ng/ml in the controls to 1.4+/-0.13 ng/ml in the oPRL infused animals (P<0.05); pituitary rPRL content similarly decreased from 39.1+/-4.6 microg to 20.4+/-3.7 microg (P<0.02). There was no significant change in the concentration of POMC mRNA or beta-EP in the MBH of the oPRL treated animals. In the second experiment oPRL was infused for 1 week into the third ventricle of orchiectomized rats. Again despite a fall in endogenous PRL levels, there was no significant change in POMC or beta-EP in the MBH. In the third experiment oPRL was infused subcutaneously into orchiectomized rats for 2 weeks. Mean plasma oPRL levels were 150+/-7.3 ng/ml after 1 week and 58+/-7.5 ng/ml after 2 weeks. Pituitary rPRL content was again suppressed in the oPRL treated animals but no change in POMC or beta-EP was detected in the MBH. We conclude that oPRL can be infused both peripherally and centrally for up to 2 weeks with resulting suppression of endogenous pituitary PRL content and release. Under these conditions no effects on the concentrations of POMC mRNA or beta-EP could be demonstrated in the hypothalamus. These results suggest that either PRL has nongenomic effects on hypothalamic beta-EP or that endogenous opioids other than beta-EP mediate the suppressive effects of PRL on the HPG axis.

Sonographic evolution of cornual pregnancies treated without surgery.

Transvaginal sonography allows early and accurate diagnosis of cornual pregnancy, as well as providing a means for puncture injection treatment of certain ectopic pregnancies. We describe four cases of cornual pregnancy managed nonsurgically and followed with transvaginal sonography for 47-64 weeks. Sonographic evidence of cornual pregnancy persisted throughout the period of follow-up, despite resumption of normal menstrual cyclicity. We conclude that some early live cornual pregnancies can be managed by puncture injection, and cornual pregnancies in which the embryo has died can be followed conservatively.

Effects of teicoplanin on human platelet aggregation in vitro and ex vivo.

The effects of teicoplanin on adenosine-diphosphate (ADP)-induced human platelet aggregation in vitro and on both ADP- and ristocetin-induced human platelet aggregation ex vivo were investigated. In the in vitro study carried out on platelets from 7 healthy volunteers, teicoplanin had no effect on platelet function even at a concentration (1 mg/ml) 10 times higher than the peak level found in the in vivo state, but at the highest concentration (10 mg/ml), which is 100 times higher than that reached in vivo, it inhibited ADP-induced platelet aggregation. In the ex vivo studies carried out in 10 healthy volunteers, teicoplanin, following single intravenous doses of 400 mg and 800 mg, did not produce any effect on platelet function up to 6 hours after administration. After 12 hours, teicoplanin, when given at 800 mg i.v., reduced ADP-induced platelet aggregation.

Effects of cefonicid on platelet aggregation.

Beta-lactam antibiotics may interfere with platelet aggregation by inhibiting the binding of agonists of platelet aggregation, such as ADP and collagen, to specific receptor sites. The aim of this study was to evaluate in vitro the effects of cefonicid, a semi-synthetic cephalosporin, on platelet aggregation. Spontaneous platelet aggregation and platelet aggregation induced by ADP and collagen were assessed. Platelets from healthy subjects were incubated with cefonicid at final concentrations of 0.1 mg/ml, 1 mg/ml and 10 mg/ml (0.1 mg/ml is the concentration of cefonicid achieved in humans at therapeutic doses). When compared with saline, cefonicid at a concentration of 0.1 mg/ml had no effect on platelet aggregation, but at 1 mg/ml it inhibited ADP-induced aggregation and at 10 mg/ml it also inhibited aggregation induced by collagen. These findings suggest that therapeutic doses of cefonicid do not affect platelet aggregation.

Antitracheobronchospastic interaction in vitro and in vivo between salbutamol and flunisolide.

Salbutamol and flunisolide, when administered in association, are able to potentiate their effects both in vitro and in vivo on relaxation of the tracheobronchial smooth muscle of the guinea-pig.

Experimental analysis of antihypertensive properties of S 5984 and its constituents: tertatolol and indapamide.

S 5984 is a combination of tertatolol (S 2395-1) and indapamide. A positive synergism between these two constituents with regard to antihypertensive activity was demonstrated in the rat and the dog.

[Analysis of a case of multiple myeloma with late dissemination of skin nodules]. / Analisi di un caso di mieloma multiplo con disseminazione nodosa cutanea tardiva.

A case of a 55 years old woman suffering from multiple myeloma with strong bone marrow proplasmocytic infiltration, several osteolytic and osteoporotic lesions and high seric M-component level and hypertensive heart failure is described. After 32 months of partial remission obtained with cyclic chemotherapy, large cutaneous tumors arose. Despite of a new therapeutic trial, in the last 8 months, an increase of bone marrow and seric signs was observed without involvement of the lungs or kidneys or expression of plasma-cell leukemia. Death occurred at 50th month because of sepsis and heart failure. A real cutaneous tropism, late occurred and without cytohistological changes, is stressed. The meaning of the rich vascularization of the skin over the tumors in absence of inflammation and necrosis remains unclear.

Experimental documentation of presence of purinergic receptors at human atria.

Our experimental data suggest the likelihood that there is a purinergic inhibition on human atria; it appears that inhibition is mediated via P1/Ri (A-1/Ri) and P-2 receptors. Adenosine and ATP produced inhibitory effects on chronotropism and inotropism via P1/Ri (A-1/Ri) and P-2 receptors respectively.

3,5-Diphenyl-1H-pyrazole derivatives. V--1-Acetyl-4-hydroxy-3,5-diphenyl-2-pyrazoline esters, 4-hydroxy-3,5-diphenyl-1H-pyrazole esters and N-substituted 4-(3-amino-2-hydroxy-1-propoxy)-1-methyl-3,5-diphenyl-1H-pyrazoles with antiarrhythmic, sedative and platelet antiaggregating activities.

The synthesis of 1-acetyl-4-hydroxy-3,5-diphenyl-2-pyrazoline esters 3, 4-hydroxy-3,5-diphenyl-1H-pyrazole esters 5 and N-substituted 4-(3-amino-2-hydroxy-1-propoxy)-1-methyl-3,5-diphenyl-1H-pyrazoles 7, starting from 4-hydroxy-3,5-diphenyl-2-pyrazoline is described. Some of compounds 3, 5 and 7 showed a considerable antiarrhythmic and sedative activity in rats and mice, respectively, as well as a remarkable in vitro platelet antiaggregating activity. Moreover, the above compounds usually exhibited moderate antihypertensive, local anesthetic, analgesic and antiinflammatory activities in rats and mice.

[Preparation and pharmacologic activity of N-oxides of 4'-(benzotriazol-2-yl-phenylalkanoic and -phenoxyalkanoic acids]. / Preparazione e attività farmacologica di n-ossidi di acidi 4'-(benzotriazol-2-il)-fenilalcanoici e-fenossialcanoici.

A number of N-oxides of 4'-(benzotriazol-2-yl)-phenylalkanoic and -phenoxyalkanoic acids bearing various substituents on position 6 of benzotriazole together with 4'-(benzotriazol-2-yl) phenylacetic acid were prepared and subjected to a wide pharmacological screening. Several compounds exhibited significant antiinflammatory and diuretic activities, while one was endowed with antihypertensive activity.

3,5-Diphenyl-1H-pyrazole derivatives. III--Esters from 1-(2-hydroxyethyl)-3,5-diphenyl-1H-pyrazole and its 4-bromo derivative with hypotensive, depressant, antiarrhythmic and analgesic activities.

The synthesis of dialkylaminoalkyl ethers (III a-g) by reaction of 1-(2-hydroxyethyl)-3,5-diphenyl-1H-pyrazole (I) sodium salt with a series of omega-chloroalkyldialkylamines is described. Cyanoethylation of alcohol (I) and its 4-bromo derivative (II) gave 2-cyanoethyl ethers (III h, i), one of which (III h) was hydrolyzed to the corresponding carboxylic acid. Cyanoethylation of 3,5-diphenylpyrazole (IV) and its 4-bromo derivative (V) yielded nitriles (VI) and (VII), respectively, which were hydrolyzed to the corresponding carboxylic acids (VIII) and (IX). Some of the above compounds showed considerable hypotensive, depressant, antiarrhythmic and analgesic activities in mice and rats, as well as a remarkable platelet antiaggregating activity in vitro. Moreover, the above compounds usually exhibited a moderate antiinflammatory activity in rats and infiltration anesthesia in mice.

Dopamine and sex steroid regulation of POMC gene expression in the hypothalamus.

Previous studies have shown that POMC mRNA and peptide levels are increased in the medial basal hypothalamus (MBH) of the chronically castrated rat and are suppressed with sex steroid replacement. In a parallel time course, hypothalamic dopamine turnover similarly changes after chronic castration and sex steroid replacement. In this study we have examined the effects of dopamine on POMC in the MBH and questioned whether the increase in dopamine activity which occurs in the MBH of chronically castrated rats is responsible for the stimulation of POMC seen under these conditions. We have therefore measured POMC gene expression and peptide content in the MBH of chronically castrated male and female rats in response to the dopamine antagonist haloperidol, and in intact or sex steroid replaced animals in response to the dopamine agonist pergolide. Adult male and female rats were studied 3-4 weeks after castration with and without testosterone (T) or estradiol (E2) replacement. POMC mRNA was measured by a solution hybridization S1 nuclease protection assay; beta-endorphin (beta-EP) and alpha-MSH were measured by RIA. In the first study 4 groups of ovariectomized (OVX) rats were treated with saline, haloperidol, E2 or E2 + pergolide. The mean POMC mRNA concentration in the MBH was 0.85 +/- 0.04 pg/microgram RNA in the saline group and decreased to 0.62 +/- 0.06 pg/microgram with haloperidol (p < 0.01). A similar decrease to 0.53 +/- 0.03 pg/microgram was seen with E2 (p < 0.01); pergolide however prevented the E2 induced decrease in POMC mRNA. In the second study ORCX rats received saline or haloperidol and sham-ORCX rats received saline or pergolide.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of tetanus toxin, Salmonella typhimurium porin, and bacterial lipopolysaccharide on platelet aggregation.

Endotoxins may interfere with platelet aggregation by interacting with the platelet membrane. The aim of this study was to evaluate the effects of tetanus toxin, Salmonella typhimurium porin, and bacterial lipopolysaccharide (LPS) on platelet aggregation induced by ADP and thrombin in vitro. Spontaneous platelet aggregation and platelet aggregation induced by ADP and thrombin were measured. Our results show that Salmonella typhimurium porin and bacterial LPS enhanced human and rabbit platelet aggregation induced by ADP and thrombin. Tetanus toxin did not affect platelet aggregation.