MOLECULAR RECOGNITION OF CHIRAL CONFORMERS: A ROTATIONAL STUDY OF THE DIMERS OF GLYCIDOL

K.-M. Marstokk, H. Mollendal and Y. Stenstrom,Acta Chem. Scand. 1992, 46, 432Author Institution: Dipartimento di Chimica "G. Ciamician" dell'Universita, Via Selmi 2, I-40126 Bologna, ItalyWe report for the first time the rotational spectra of dimers deriving from the combinations of different conformers of a chiral alcohol, glycidol. Its MW spectra has been reported, and two hydrogen bonded conformers, 1 and 2 have been identified.} Conformer 1 is more stable by 3.4 (4) kJ/mol. A pure chiral species (either R or S) can form seven hydrogen bonded homo - dimers, identified with the label Hom. They can be divided into two groups: one group where the hydrogen bonds form a ring involving 8 heavy atoms and another group where this ring involves only 5 heavy atoms, called 8Hom and 5Hom. Six (three Hom and three Het) conformers have the 8-heavy-atom-frame while eight (four Hom and four Het) conformers have the 5-heavy-atom-frame. Only the rotational spectra of species 8Hom-11 and 8Hom-12 have been observed. We recorded the FTMW spectra in a supersonic expansion. The relative energies and dynamics of formation of the dimers in the supersonic expansion will be discussed

Increased serum levels of ICAM-1 ELAM-1 and TNF-a in inflammatory disorders of peripheral nervous system

Endothelial intercellular adhesion molecule-1 (ICAM-1) and glycoprotein E-selectin (ELAM-1) allow the homing of leukocytes to inflammation sites. A circulating form of ICAM-1 markedly increases in inflammatory CNS disorders. In the present study, the serum levels of ICAM-1, ELAM-1 and tumor necrosis factor-α (TNF-α) were measured in patients with acute (AIDP) and chronic (CIDP) inflammatory demyelinating polyneuropathies and cryoglobulinemic neuropathy (CGN). Immunoenzymometric assays revealed increased sICAM-1 levels in some of these patients; furthermore, high titres of ELAM-1 and TNF-α were detected in two patients with AIDP and one patient with CGN. Our data extend previous observations on inflammatory PNS disorders by showing that, in addition to ICAM-1, ELAM-1 also represents a useful marker of endothelial activation and that, taken together, the two molecules may serve as an indicator of specific pathogenetic mechanisms. © 1994 Masson S.p.A

Secretome from senescent melanoma engages the STAT3 pathway to favor reprogramming of naive melanoma towards a tumor-initiating cell phenotype.

International audienceHere, we showed that the secretome of senescent melanoma cells drives basal melanoma cells towards a mesenchymal phenotype, with characteristic of stems illustrated by increased level of the prototype genes FN1, SNAIL, OCT4 and NANOG. This molecular reprogramming leads to an increase in the low-MITF and slow-growing cell population endowed with melanoma-initiating cell features. The secretome of senescent melanoma cells induces a panel of 52 genes, involved in cell movement and cell/cell interaction, among which AXL and ALDH1A3 have been implicated in melanoma development. We found that the secretome of senescent melanoma cells activates the STAT3 pathway and STAT3 inhibition prevents secretome effects, including the acquisition of tumorigenic properties. Collectively, the findings provide insights into how the secretome of melanoma cells entering senescence upon chemotherapy treatments increases the tumorigenicity of naïve melanoma cells by inducing, through STAT3 activation, a melanoma-initiating cell phenotype that could favor chemotherapy resistance and relapse

Amore e odio per l’Europa

Il Forum europeo tenutosi a Milano sul tema “Amore e odio per l’Europa” è stato un evento maggiore che ha riunito numerosi psicoanalisti provenienti dalle Scuole europee e mondiali del Campo freudiano, mettendoli a confronto con specialisti di diverse discipline, economisti, politologi, filosofi, storici, giuristi. La posta in gioco di questo straordinario dibattito era una riflessione, ormai urgente, sullo spazio europeo. Con questo si intende ovviamente non solo lo spazio geografico – tuttavia importante da definire concretamente nella prospettiva della globalizzazione – ma soprattutto lo spazio politico, di pensiero, di scambi che non possono limitarsi al mercato, se non vogliamo che l’Europa cada nell’indifferenza dei popoli che la abitano. In un’epoca in cui le tensioni ideali non sono più un motore vivo della storia, bisogna puntare a far nascere il desiderio per altre vie. Il capitalismo ha scelto il diluvio d’oggetti, quel che siamo soliti chiamare consumismo e che mostra la corda nei vicoli ciechi in cui ci ha condotti il neoliberismo. Con la psicoanalisi possiamo trovare nuove strade, possiamo aprire a un’erotizzazione del pensiero, un amore che resta attualmente soffocato dietro le forme di odio cui spesso abbiamo assistito negli ultimi tempi. L’insegnamento freudiano però non ci lascia ignari del fatto che né l’odio né l’amore sono mai puri, ed è con questo intreccio complesso che, in molti modi, i testi del libro cercano di confrontarsi

Determinants of virologic and immunologic outcomes in chronically HIV-infected subjects undergoing repeated treatment interruptions: The Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) study

BACKGROUND: Factors influencing the outcome of structured treatment interruptions (STIs) in HIV chronic infection are not fully elucidated. METHODS: In ISS-PART, 273 subjects were randomly assigned to arm A (137 assigned to continuous highly active antiretroviral therapy [HAART]) and arm B (136 assigned to 5 STIs of 1, 1, 2, 2, and 3 months' duration, each followed by 3 months of therapy). Main outcome measures were the proportion of subjects with a CD4 count >500 cells/mm, the rate of virologic failure, and the emergence of resistance at 24 months. RESULTS: The proportion of subjects with a CD4 count >500 cells/mm was higher in arm A than in arm B (86.5% vs. 69.1%; P = 0.0075). Pre-HAART CD4 cell count and male gender were independent predictors of a CD4 count >500 cells/mm in arm B. The overall risk of virologic failure was not increased in arm B; however, it was higher in the 38 subjects who had resistance mutations in the rebounding virus. Archived mutations at baseline and the use of a regimen that included an unboosted protease inhibitor (PI), compared with nonnucleoside reverse transcriptase inhibitor-based HAART, independently predicted the emergence of plasma mutations during STI (P = 0.002 for DNA mutations and P = 0.048 for PI-based HAART). CONCLUSIONS: Our results suggest that patients with preexisting mutations and treated with unboosted PI-based HAART should not be enrolled in studies of time-fixed treatment interruptions, being at higher risk of developing plasma mutations during STI and virologic failure at therapy reinstitution. © 2007 Lippincott Williams & Wilkins, Inc

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)