Carcinoma sieroso papillare del peritoneo in paziente già operata di carcinoma mammario. Caso clinico

Il carcinoma sieroso papillare del peritoneo (PPSC) è un tumore raro che si riscontra più frequentemente nel sesso femminile. L?età media al momento della diagnosi è di 56 anni. Si diffonde coinvolgendo il peritoneo, la superficie delle ovaie e la pelvi. L?istologia è indistinguibile dall?analogo tumore ovarico, cioè il carcinoma sieroso papillare (PSCO). L?istogenesi del PPSC è probabilmente correlata all?epitelio celomatico embrionale. Sintomi e segni clinici tipici sono distensione addominale, costipazione, nausea, vomito, riduzione dell?appetito, malessere generale e perdita di peso. La chirurgia citoriduttiva, in aggiunta alla chemioterapia con cisplatino e ad altre terapie come l?immunoterapia e la radioterapia, aumenta la sopravvivenza dei pazienti affetti da PPSC. Viene descritto il caso di una paziente di 51 anni, già operata di carcinoma mammario, nella quale si manifestavano alcuni dei segni e sintomi descritti. L?intervento chirurgico dimostrò le localizzazioni sierose caratteristiche. Si fece una larga exeresi ma la malata morì 14 mesi dopo per la fatale progressione della malattia. English version The peritoneal papillary serous carcinoma (PPSC) is a rare tumor more frequently revealed in female. The onset mean age is 56 years. It implicate peritoneum, ovary?s surface and pelvis. The histology of this disease is similar to papillary serous carcinoma ovary (PSCO). The PPSC histogenesis is probably correlated to coelomatic embryonal epithelium. Clinical characteristics are abdominal swelling, constipation, nausea, emesis, inappetence, feel unwell, lose weight. The cytoreductive surgery and the cisplatinum chemotherapy, and other treatments like immunotherapy and radiotherapy, increase the PSCP patient survival. A case of a 51 years old patient with previous surgery for breast cancer is here described. She show some of the yet described clinical findings. At the surgery we found the typically serous peritoneal localizations. We performed a debulking, and the patient died 14 months after the operation due to the disease progression

Peptide gH625 enters into neuron and astrocyte cell lines and crosses the blood-brain barrier in rats.

Peptide gH625, derived from glycoprotein H of herpes simplex virus type 1, can enter cells efficiently and deliver a cargo. Nanoparticles armed with gH625 are able to cross an in vitro model of the blood-brain barrier (BBB). In the present study, in vitro experiments were performed to investigate whether gH625 can enter and accumulate in neuron and astrocyte cell lines. The ability of gH625 to cross the BBB in vivo was also evaluated. gH625 was administered in vivo to rats and its presence in the liver and in the brain was detected. Within 3.5 hours of intravenous administration, gH625 can be found beyond the BBB in proximity to cell neurites. gH625 has no toxic effects in vivo, since it does not affect the maximal oxidative capacity of the brain or the mitochondrial respiration rate. Our data suggest that gH625, with its ability to cross the BBB, represents a novel nanocarrier system for drug delivery to the central nervous system. These results open up new possibilities for direct delivery of drugs into patients in the field of theranostics and might address the treatment of several human disease

Tumore desmoide della parete addominale in una donna in età fertile: cosa possiamo fare?

Il tumore desmoide (TD) è una neoplasia dei tessuti molli loca - lizzata più frequentemente nella parete addominale anteriore in gio - vani donne in età fertile. Inoltre a causa della sua frequente inciden - za in donne con recente gravidanza, la stimolazione alla proliferazio - ne dei tessuti muscolo-aponeurotici è stata messa in relazione col trau - ma del parto. L’intervento chirurgico radicale è il trattamento di scelta per pre - venire recidive locali. Molti autori sottolineano il ruolo della radioterapia nella regres - sione del tumore e nel controllo delle recidive locali in pazienti che hanno ricevuto una resezione incompleta. Molti altri invece racco - mandano l’uso della chemioterapia o della terapia antiestrogenica anche in presenza di tumori con recettori per gli estrogeni negativi. Il TD, d’altra parte, pur essendo un tumore con un’altissima incidenza di recidiva locale, non dà mai metastasi, per tale motivo in una giovane donna appare razionale, qualora realizzabile, un tratta - mento chirurgico che, senza lasciare residuo macroscopico di malattia, miri a preservare le strutture e la funzione. Inoltre i dati in letteratu - ra evidenziano che la positività istologica dei margini di resezione non è correlata con la comparsa di recidiva locale e che la gravidanza non rappresenta di per sé un fattore di rischio. In una donna in età fertile, dopo un’exeresi primaria di un TD, anche in presenza di margini microscopici positivi, potrebbero per - tanto essere evitate la radioterapia, la chemioterapia o la terapia antiestrogenica e può essere ragionevolmente presa in considerazione la sola osservazione clinica

3,5-diiodo-L-thyronine regulates glucose-6-phosphate dehydrogenase activity in the rat.

Thyroid hormones influence the activity of lipogenic enzymes such as malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PD). The effect of T3 on ME is exerted at the transcriptional level, but it is unclear if its effect on G6PD is also nuclear mediated. Furthermore, other iodothyronines that have been shown to posses biological activity (such as diiodothyronines) could contribute to this enzyme's regulation. In this study the effects of 3,5-diiodothyronine (T2) on the aforementioned enzymes were examined and compared with those of T3. Rats made hypothyroid by propylthiouracil and iopanoic acid treatment were used throughout. Enzyme activities were determined spectrophotometrically, and G6PD messenger RNA (mRNA) expression was analyzed by Northern blotting using a human G6PD complementary DNA probe. Injections of T2 to hypothyroid animals significantly enhanced the activity of both enzymes. The effect of T2on ME was nuclear mediated and mimicked the effect of T3. The effects of T2 and T3on G6PD differed. INjection of T3 into hypothyroid rats induced an increase in both enzyme activity and G6PD mRNA expression, indicating a nuclear-mediated effect. The effect of T2 on G6PD activity, on the other hand, was not nuclear mediated. The injection of T2 into hypothyroid animals did not change G6PD mRNA expression, and the strong increase in the enzyme's activity (from +70% to +300%) was unaffected by simultaneous injection of protein synthesis inhibitors. As the lowest dose of 1 μg T2/100 g BW affects G6PD activity 3-5 times more than the same dose of T3, these data provide the first evidence that T2 is a factor capable of regulating G6PD activity

Pathways affected by 3,5-diiodo-l-thyronine in liver of high fat-fed rats: evidence from two-dimensional electrophoresis, blue-native PAGE, and mass spectrometry.

3,5-Diiodo-l-thyronine (T2) powerfully reduces adiposity in rats fed a high-fat diet (HFD), stimulating (in the liver) fatty acid oxidation and mitochondrial uncoupling, and strongly counteracting steatosis, a condition commonly associated with diet-induced obesity. Proteomics offer unique possibilities for the investigation of changes in the levels and modifications of proteins. Here, combining 2D-E, mass spectrometry, and blue native (BN) PAGE, we studied how the subcellular hepatic phenotype responds to HFD and T2-treatment. By identifying differentially expressed proteins and analyzing their interrelation [using the Ingenuity Pathway Analysis (IPA) platform], we obtained an integrated view of the phenotypic/metabolic adaptations occurring in the liver proteome during HFD with or without T2-treatment. Interestingly, T2 counteracted several HFD-induced changes, mostly in mitochondria. BN-PAGE and subsequent in-gel activity analysis of OXPHOS complexes revealed a modified profile of individual complexes in HFD mitochondria vs. normal ones. This pattern was re-normalized in mitochondria from T2-treated HFD animals. These data indicate that in HFD rats, the effects of T2 on the liver proteome cause it to resemble that associated with a non-steatotic condition. The identified metabolic pathways (mainly at the mitochondrial level) may be responsible for the beneficial effects of T2 on liver adiposity and metabolism

Residual respiratory impairment after COVID-19 pneumonia

Introduction: The novel coronavirus SARS-Cov-2 can infect the respiratory tract causing a spectrum of disease varying from mild to fatal pneumonia, and known as COVID-19. Ongoing clinical research is assessing the potential for long-term respiratory sequelae in these patients. We assessed the respiratory function in a cohort of patients after recovering from SARS-Cov-2 infection, stratified according to PaO2/FiO2 (p/F) values. Method: Approximately one month after hospital discharge, 86 COVID-19 patients underwent physical examination, arterial blood gas (ABG) analysis, pulmonary function tests (PFTs), and six-minute walk test (6MWT). Patients were also asked to quantify the severity of dyspnoea and cough before, during, and after hospitalization using a visual analogic scale (VAS). Seventy-six subjects with ABG during hospitalization were stratified in three groups according to their worst p/F values: above 300 (n = 38), between 200 and 300 (n = 30) and below 200 (n = 20). Results: On PFTs, lung volumes were overall preserved yet, mean percent predicted residual volume was slightly reduced (74.8 ± 18.1%). Percent predicted diffusing capacity for carbon monoxide (DLCO) was also mildly reduced (77.2 ± 16.5%). Patients reported residual breathlessness at the time of the visit (VAS 19.8, p < 0.001). Patients with p/F below 200 during hospitalization had lower percent predicted forced vital capacity (p = 0.005), lower percent predicted total lung capacity (p = 0.012), lower DLCO (p < 0.001) and shorter 6MWT distance (p = 0.004) than patients with higher p/F. Conclusion: Approximately one month after hospital discharge, patients with COVID-19 can have residual respiratory impairment, including lower exercise tolerance. The extent of this impairment seems to correlate with the severity of respiratory failure during hospitalization