Immunohistological Description of Nongestational Ovarian Choriocarcinoma in Two Female Mice With Conditional Loss of Trp53 Driven by the Tie2 Promoter.

Nongestational ovarian choriocarcinoma (NGCO) is a tumor of germ cell origin seldom described in nonhuman species. Few spontaneous cases are reported in macaques and mice, with the B6C3F1 strain overrepresented. This report describes 2 cases of ovarian choriocarcinoma in nulliparous female mice with conditional loss of Trp53 under the Tie2 promoter. The mouse line was maintained on a mixed genetic background including Crl: CD1(ICR) and 129X1/SvJ strains. In both cases, affected ovary was partially replaced by blood-filled lacunae lined by neoplastic trophoblast-like giant cells. Immunohistochemically, neoplastic cells expressed folate-binding protein and prolactin and were invariably negative for p53. To the authors' knowledge, this is the first report characterizing this entity in a genetically engineered mouse (GEM) line. Considering that germ cells (the cell population from which NGCO originates) constitutively express Tie2 receptor, it can be speculated that Tie2-driven deletion of Trp53 may have played a role in the development of these tumors.

One-year surveillance for hypervirulent Klebsiella pneumoniae detected carbapenem-resistant superbugs.

Hypervirulent Klebsiella pneumoniae (hvKp) can cause infections in clinically healthy people, such as young and immunocompetent patients. Genes involved in the capsule synthesis or those encoding the siderophores have been adopted as predictors of hvKp. Certain sequence types, such as ST23 and ST86, have been associated with hvKp strains, too. The aim of this study was to investigate the presence of hvKp among 354 K. pneumoniae strains isolated from clinical samples of patients admitted to an Italian 900-bed hospital between 21 May 2021 and April 2022. All the isolates were screened by PCR for the amplification of virulence loci. Whole genome sequencing was performed in strains tested positive for at least one target gene. Thirteen out of 354 (3.7%) were hvKp. Five were wild type and belonged to the hypervirulent clones ST23, ST86, ST5, and ST375 and to the new clone ST6310. Six strains carried the blaKPC gene: three belonged to ST101, two to ST512, and one to ST395. Two isolates were ST147 and carried the blaNDM gene. Although hvKp isolation is not frequent, their presence should be systematically investigated to avoid the spreading of both virulent strains and strains with combined increase in virulence and resistance to antibiotics. PCR-based protocols are essential for surveillance of these strains, which do not always show a recognizable phenotype. Moreover, hvKp strains were isolated also from patients without history of recent foreign travels, indicating an increased spreading of these strains as well as an underestimated of their circulation so far.IMPORTANCEKlebsiella pneumoniae is a healthcare-associated pathogen frequently resistant to antibiotics. Hypervirulent strains of pneumoniae (hvKp) can spread from the primary site of infection to multiple sites causing life-threatening infections also in young otherwise healthy individuals. This study described the isolation of 13 isolates of K. pneumoniae with increased virulence in a large tertiary hospital over a 1-year period. Among them, eight strains were multidrug resistant and hypervirulent. Although these hypervirulent strains are still rare in Italy, their presence is particularly concerning since they can cause difficult-to-treat life-threatening infections. Moreover, not all the hypervirulent isolates were positive by the string test, so hvKp isolates were not always phenotypically detectable. Molecular biology techniques such as PCR amplification and next generation sequencing are therefore necessary for the detection of hvKp isolates, and surveillance programs exploiting molecular techniques are highly desirable.

Wild rats as urban detectives for latent sources of asbestos contamination.

Based on a large body of evidence asbestos minerals have been classified as carcinogens. Despite the Italian ban on asbestos in 1992 and the subsequent remediation activities, latent sources of contamination may still represent a hazard where asbestos were particularly used. Using wild rats as sentinel animals, this study aimed at uncovering sites with the greatest potential for non-occupational exposure to asbestos in the city of Casale Monferrato (Piedmont Region, Italy), where the largest Italian manufacturing plant of asbestos-cement had been active. During the study period (2013-2015) a total of 40 wild rats were captured from 16 sampling capture points. The lungs of wild rats have been investigated by using scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS). The SEM-EDS detected the presence of asbestos fibers (tremolite/actinolite, amosite, and chrysotile) in rats' lungs from 11 sampling points. The hypothetical rats' home-range and the observed site-specific concentration of asbestos fibers per gram of dry lung tissue were used to identify areas to be targeted by additional search of latent sources of asbestos. In conclusion, our results showed that the use of wild rats as sentinel animals may effectively integrate the strategies currently in use to reduce the exposure to asbestos.

Ultrastructural damage to heart tissue from repeated oral exposure to yessotoxin resolves in 3 months.

Yessotoxin (YTX), an algal toxin contaminating edible shellfish, was previously shown to induce ultrastructural changes in some cardiac muscle cells of mice after acute (1 and 2mg/kg) or daily repeated oral exposure (1 and 2mg/kg/day, for 7 days). Therefore, the temporal evolution of the ultrastructural myocardial alterations and the development of other signs of toxicity induced by a repeated daily oral administration of YTX (1mg/kg/day, for 7 days) to mice were evaluated within 3 months after the treatment. Symptoms, food consumption, body weight, gross pathology and histopathology of the main organs and tissues were observed, and plasma levels of transaminases, lactate dehydrogenase, creatinine and creatinine phosphokinase were measured. Heart, liver, kidneys and cerebellum were also analysed by transmission electron microscopy. In addition, the blood concentration of YTX was determined by a direct enzyme linked immunosorbent assay (ELISA) 24h after the last toxin administration. No mortality or other treatment-related changes, including histological or hematoclinical parameters, were recorded in mice administered with YTX. Similarly, electron microscopy did not reveal any ultrastructural alteration in the liver, kidneys, and cerebellum associated with YTX treatment. In contrast, changes in cardiac muscle cells near to the capillaries (clusters of rounded mitochondria and disorganization of myofibrils) were observed 24h after the treatment. These changes were also noted 30 days after the toxin administration, while after 90 days no differences in cardiac muscle cells between control and YTX-treated mice were observed, which indicated a recovery of the ultrastructural alterations induced by the toxin.

[Ankylosing spondylitis and osteoporosis]. / Spondylarthrite ankylosante et ostéoporose.

PURPOSE: Ankylosing Spondylitis (AS) is an inflammatory rheumatism characterized by its disease course with flares leading to progressive ankylosis of the spine related to paravertebral ligamentous and discal structures ossification. AS patients suffer significantly more vertebral fractures than control groups. These fractures could affect cervical spine. They are due to either ankylosis-related flawed spine compliance or AS-induced osteoporosis. CURRENT KNOWLEDGE AND KEY POINTS: The physiopathology of this osteoporosis is multi-factorial, but essentially linked to AS-related inflammatory phenomenons. It is marked by reduced bone density (at lumbar spine and femoral neck), increased bone turnover (with increased urinary C-telopeptide cross-linked collagen type 1), but without any significant change in phosphocalcic blood parameters. Histological features are depressed bone formation, with either maintained or increased resorption. FUTURE PROSPECTS: The screening of this osteoporosis is based upon investigating people at risk (progressive inflammatory AS) using dual-energy x-ray absorptiometry and biochemical markers of bone turnover. Treatment is based upon a modulation of both inflammatory phenomenons and bone remodelling using bisphosphonates and anti-TNF alpha.

[Andrologic surgery]. / La chirurgia andrologica.

The need of an economic and social low costs drive more and more surgeons towards the day surgery. The always growing diffusion of local anesthetic supports this trend. The drugs used as local anaesthetics are: carbocaine, procaine, lidocaine and bipivacaine. The Day Surgery can be largely employed in the therapy of andrological pathologies. In fact the anatomical placement of male genital apparatus allows easy possibilities of anaesthetical and surgical approach. It is so possible perform the following operations: meatotomy, section and plasty of fraenum, extirpation of Papovavirus lesions, circumcision, paraphymosis setting, corpora cavernosa drainage in priapism, section and ligation of deep dorsal vein, corporopexi, glandulopexi, cavernous crural plication, endocavernous penile prosthesis' implant, congenital or acquired penile recurvatum correction, blandulectomy, hepidydimis' cyst excision, testicle's biopsy, subcapsular orchiectomy sec. Higgins, testicular prosthesis' implant, resection and eversion of vaginal tunic of testicle in hydrocele's therapy, vasotomy and section and ligation of internal spermatic vein in varicocele's surgery. The Authors describe the anaesthetical and surgical techniques for bring forward these operations in Day Surgery.

[Paradoxical cutaneous reactions associated with tocilizumab therapy]. / Réactions cutanées paradoxales sous traitement par tocilizumab.

INTRODUCTION: Tocilizumab (TCZ) is a humanized antihuman interleukin (IL)-6 receptor antibody recommended for the treatment of moderate to severe active rheumatoid arthritis, adult-onset Still disease, Castleman disease and more recently, systemic juvenile idiopathic arthritis. Like anti-TNFα, rituximab and less frequently abatacept, TCZ can induce paradoxical cutaneous eruption like psoriasis with predominantly palmoplantar presentation. CASE REPORT: We report a 47-year-old woman with psoriastic arthritis who developed under anti-TNFα therapy and later under tocilizumab a paradoxical palmoplantar eruption. CONCLUSION: The specific underlying mechanisms of this side effect are unclear but relapse of these lesions seems to be observed with certain biological agents.

Repeated oral co-exposure to yessotoxin and okadaic acid: a short term toxicity study in mice.

The polyethers yessotoxin (YTX) and okadaic acid (OA) are two marine algal toxins frequently associated as edible shellfish contaminants. Seafood contamination by these compounds, also at low concentrations and for a long period of time, can increase the possibility of their simultaneous and repeated ingestion, with possible synergistic toxic effects. Thus, in vivo toxicity by repeated oral exposure to a combination of fixed doses of YTX and OA (1 mg YTX/kg and 0.185 mg OA/kg, daily for 7 days) was investigated in mice, in comparison to that of each toxin alone. No mortality, signs of toxicity, diarrhea or hematological changes was induced by the toxins co-administration or by the single toxins. Light microscopy revealed changes at gastric level (multifocal subacute inflammation, erosions and epithelial hyperplasia) in 2/5 mice co-administered with the toxins. In animals dosed only with OA, epithelial hyperplasia of forestomach and slight focal subacute inflammation of its submucosa were noted. No changes were induced by the treatment with YTX. Ultrastructural analysis of the heart revealed some cardiomyocytes with "loose packing" of myofibrils and aggregated rounded mitochondria in mice co-administered with the toxins or with YTX; OA-treated mice showed only occasional mitochondrial assemblage and dilated sarcomeres. Thus, the combined oral doses of YTX (1 mg/kg/day) and OA (0.185 mg/kg/day) did not exert cumulative or additive toxic effects in mice, in comparison to the single toxins.

Acute oral toxicity in mice of a new palytoxin analog: 42-hydroxy-palytoxin.

The acute oral toxicity of a new palytoxin congener, 42-hydroxy-palytoxin (42-OH-PLTX), was investigated in female CD-1 mice. The toxin (300-1697 µg/kg), administered by gavage, induced scratching, jumping, respiratory distress, cyanosis, paralysis and death of mice, with an LD50 of 651 µg/kg (95% confidence limits: 384-1018 µg/kg) within 24 h. Hematoclinical analyses showed increased plasma levels of lactate dehydrogenase and aspartate-aminotransferase at doses of 600 µg/kg and above, as well as of alanine-aminotransferase, creatine phosphokinase and potassium ions at ≥ 848 µg/kg. Histology revealed inflammatory lesions in the non-glandular area of the stomach of mice that survived up to 24 h after gavage (424-1200 µg/kg). Although no histological alterations were seen in skeletal and cardiac muscles, changes in some plasma biomarkers (creatine phosphokinase, lactate dehydrogenase) suggested involvement of these tissues in 42-OH-PLTX oral toxicity, in agreement with epidemiological data on seafood poisonings ascribed to palytoxins. Complete recovery of the tissue and hematological changes was observed two weeks post-exposure. Furthermore, 42-OH-PLTX induced in vitro delayed erythrocyte hemolysis at concentrations similar to those of PLTX (EC50 = 7.6 and 13.2 x 10⁻¹² M, respectively). This hemolysis could be completely neutralized by a monoclonal anti-PLTX antibody. The in vivo data, together with the in vitro data recorded for 42-OH-PLTX, seem to indicate Na+/K+-ATPase as one of the key cellular targets of this toxin.

Palytoxin toxicity after acute oral administration in mice.

The acute oral toxicity of palytoxin (PLTX), a highly toxic compound associated with seafood intoxication in tropical and subtropical areas, was investigated in mice. After gavage administration (300-1697 microg/kg) to groups of five female CD-1 mice, signs of toxicity and lethality were recorded for 24 h. The LD(50) was 767 microg/kg (95% confidence limits: 549-1039 microg/kg) and the main symptoms observed were scratching, jumping, respiratory distress and paralysis. Hematoclinical analyses showed increased levels of creatine phosphokinase and lactate dehydrogenase at doses of 600 microg/kg and above, and aspartate transaminase at 848 microg/kg and above. Histological analysis revealed acute inflammation of the forestomach in mice surviving up to 24h after administration (424-1200 microg/kg). Other histological alterations were observed in the liver and pancreas, while cardiac and skeletal muscle cells revealed only ultrastructural alterations visible by transmission electron microscopy. Ultrastructural and hematoclinical findings suggest an involvement of skeletal and/or cardiac muscle as targets of PLTX, according to the observed human symptoms. A NOEL of 300 microg/kg can be estimated from this acute oral toxicity study.