Pensiero materialista e fisica quantistica: Alexandre Kojève tra “dualismo ontologico” e “principio di indeterminazione”

The aim of my contribution is to show how Alexandre Kojève, through a heterodox Hegelian Marxism, attempted to thematize a form of ontological dualism based on “dualistic” and “indeterministic” materialism. To this end, I divide my essay into three parts. In the first, we’ll see how Kojève attempted to redefine the “ontological” presuppositions of both Hegel’s and Marx’s thought; in the second part, I’ll focus on the Kojèveian project of Hegelianism’s mise à jour considering the new discoveries of quantum physics; in the third and last part, I’ll try to bring out some purely aporetic aspects of Kojève’s theories.O objetivo deste artigo é mostrar como Alexandre Kojève, através de um Hegelo-Marxismo decididamente heterodoxo, tentou tematizar uma forma de dualismo ontológico que poderia ser baseada em um materialismo ao mesmo tempo ‘dualista’ e essencialmente ‘indeterminista’. Para este fim, divido meu ensaio em três partes. Na primeira, veremos como Kojève tentou redefinir os pressupostos ‘ontológicos’ do pensamento tanto do Hegel quanto do de Marx; na segunda parte, focalizarei o projeto de Kojève de mise à jour do hegelianismo também à luz das novas descobertas da física quântica; na terceira e última parte, tentarei fazer emergir, de forma crítica, alguns aspectos puramente aporéticos das teorias de Kojève. &nbsp

Eric Weil e la «fine della storia»

The aim of my article is to how Eric Weil (1904-1977) suggested a “Kantian-post-Hegelian” version of the famous thesis onthe “End of History”, elabored by Alexandre Kojève (1902-1968) from the 1930s. We’ll see how this aspect of the Weilian thought, emerged clearly from the specific studies on Kant that Weil developed since the early 1960s. Therefore, will be clear how the “practical” implications of this Weilian re-undestanding indicated the way a new political philosophy, eminently critical and anti-dogmatic.O artigo visa mostrar como Eric Weil (1904-1977) recompreendeu a famosa tese do “fim da história”, elaborada por Alexandre Kojève (1902-1968) desde os anos de 1930, propondo uma nova versão de caráter essencialmente “kantiano pós-hegeliano”: um elemento teórico fundamental do inter histórico- filosófico weiliano, que emergiria claramente dos estudos específicos sobre Kant aos quais Weil se dedicou de modo pontual a partir da década de 1960.  Veremos, portanto, como as reviravoltas “práticas” de tal recompreensão tenham de fato indicado a estrada para a constituição de uma nova filosofia política, eminentemente crítica e antidogmática

Eric Weil: la storia come problema filosofico

The aim of my contribution is to show how Eric Weil (1904-1977) tried to re-propose a systematic thought capable of problematizing the relationship between history and philosophy, reality and discourse, particularity and universality. In the first part I’ll analyze the essential structure of Weil's most significant work, the Logique de la philosophie; in the second one, I’ll present the essential contents of De l’intérêt que l’on prend a l’histoire – a text where was already problematized the relationship between the universality of the historical-philosophical discourse and concrete particularity. Finally in the third and last part through analyzing Valeur et dignité du récit historiographique, we will see how Weil gave essential importance to the positive function of historical narratives, inexhaustible sources of  meaningful images for the philosopical discourse. Keywords: Philosophy; History; Dialectics; Philosophical system; Meaning

Losartan counteracts the hyper-reactivity to angiotensin II and ROCK1 over-activation in aortas isolated from streptozotocin-injected diabetic rats

<p>Abstract</p> <p>Background</p> <p>In streptozotocin-injected rats (STZ-rats), we previously demonstrated a role for angiotensin II (AT-II) in cardiac remodelling and insulin resistance partially counteracted by <it>in vivo </it>treatment with losartan, an AT-II receptor antagonist.</p> <p>We now aimed to investigate the effect of treating diabetic STZ-rats with losartan on diabetes vascular response to vasoconstrictors.</p> <p>Methods</p> <p>Male Wistar rats were randomly divided in four groups, two of them were assigned to receive losartan in the drinking water (20 mg/kg/day) until the experiment ending (3 weeks afterward). After 1 week, two groups, one of which receiving losartan, were injected in the tail vein with citrate buffer (normoglycemic, N and normoglycemic, losartan-treated, NL). The remaining received a single injection of streptozotocin (50 mg/kg in citrate i.v.) thus becoming diabetic (D) and diabetic losartan-treated (DL). Plasma glycaemia and blood pressure were measured in all animals before the sacrifice (15 days after diabetes induction).</p> <p>In aortic strips isolated from N, NL, D and DL rats we evaluated i) the isometric concentration-dependent contractile response to phenylephrine (Phe) and to AT-II; ii) the RhoA-kinase (ROCK1) activity and expression by enzyme-immunoassay and Western blot respectively.</p> <p>Key results</p> <p>The concentration-dependent contractile effect of Phe was similar in aortas from all groups, whereas at all concentrations tested, AT-II contraction efficacy was 2 and half and 1 and half times higher in D and DL respectively in comparison with N and NL. AT-II contracture was similarly reduced in all groups by AT-II receptor antagonists, irbesartan or irbesartan plus PD123319. HA-1077 (10 μM), an inhibitor of ROCK1 activity, reduced AT-II efficacy (Δmg/mg tissue w.w.) by -3.5 ± 1.0, -4.6 ± 1.9, -22.1 ± 2.2 and -11.4 ± 1.3 in N, NL, D and DL respectively). ROCK1 activity and expression were higher in D than in N/NL and DL aortas.</p> <p>Conclusion and implications</p> <p>Aortas isolated from STZ-rats present hyper-contracture to AT-II mainly dependent on the up-regulation of ROCK1 expression/activity. In vivo losartan treatment partially corrects AT-II hyper-contracture, limiting the increase in ROCK1 expression/activity. These data offer a new molecular mechanism supporting the rationale for using losartan in the prevention of diabetic vascular complications.</p

Restoration of Cardiomyocyte Functional Properties by Angiotensin II Receptor Blockade in Diabetic Rats

Recent evidence suggests that blockade of the renin-angiotensin system ameliorates diabetes-induced cardiac dysfunction, but the mechanisms involved in this process remain elusive. We investigated the effect of treatment with an angiotensin II receptor blocker, losartan, on the metabolic and electrophysiological properties of cardiomyocytes isolated from streptozotocin-induced diabetic (STZ) rats. Glucose uptake and electrophysiological properties were measured in ventricular cardiomyocytes from normoglycemic and STZ-induced diabetic rats given vehicle or 20 mg · kg−1 · day−1 losartan for 8 weeks. Insulin and β-adrenergic stimulation failed to increase the glucose uptake rate in STZ cardiomyocytes, whereas the α-adrenergic effect persisted. Concurrently, a typical prolongation of action potential duration (APD) and a decrease of transient outward current (Ito) were recorded in patch-clamped STZ myocytes. Treatment with losartan did not affect body weight or glycemia of diabetic or control animals. However, in losartan-treated STZ-induced diabetic rats, β-adrenergic−mediated enhancement of glucose uptake was completely recovered. APD and Ito were similar to those measured in losartan-treated control rats. A significant (P &lt; 0.0001) correlation between metabolic and electrophysiological parameters was found in control, diabetic, and losartan-treated diabetic rats. Thus, angiotensin receptor blockade protects the heart from the development of cellular alterations typically associated with diabetes. These data suggest that angiotensin receptor blockers may represent a new therapeutic strategy for diabetic cardiomyopathy

Pharmacological effects of 3-iodothyronamine (T1AM) in mice include facilitation of memory acquisition and retention and reduction of pain threshold

BACKGROUND AND PURPOSE: 3-Iodothyronamine (T1AM), an endogenous derivative of thyroid hormones, is regarded as a rapid modulator of behaviour and metabolism. To determine whether brain thyroid hormone levels contribute to these effects, we investigated the effect of central administration of T1AM on learning and pain threshold of mice either untreated or pretreated with clorgyline (2.5 mg•kg-1, i.p.), an inhibitor of amine oxidative metabolism. EXPERIMENTAL APPROACH: T1AM (0.13, 0.4, 1.32 and 4 mg•kg-1) or vehicle was injected i.c.v. into male mice, and after 30 min their effects on memory acquisition capacity, pain threshold and curiosity were evaluated by the following tests: passive avoidance, licking latency on the hot plate and movements on the hole-board platform. Plasma glycaemia was measured using a glucorefractometer. Brain levels of triiodothyroxine (T3), thyroxine (T4) and T1AM were measured by HPLC coupled to tandem MS. ERK1/2 activation and c-fos expression in different brain regions were evaluated by Western blot analysis. RESULTS: T1AM improved learning capacity, decreased pain threshold to hot stimuli, enhanced curiosity and raised plasma glycaemia in a dose-dependent way, without modifying T3 and T4 brain concentrations. T1AM effects on learning and pain were abolished or significantly affected by clorgyline, suggesting a role for some metabolite(s), or that T1AM interacts at the rapid desensitizing target(s). T1AM activated ERK in different brain areas at lower doses than those effective on behaviour. CONCLUSIONS AND IMPLICATIONS: T1AM is a novel memory enhancer. This feature might have important implications for the treatment of endocrine and neurodegenerative-induced memory disorders

Inflammatory Microenvironment in Early Non-Small Cell Lung Cancer: Exploring the Predictive Value of Radiomics

Patient prognosis is a critical consideration in the treatment decision-making process. Conventionally, patient outcome is related to tumor characteristics, the cancer spread, and the patients’ conditions. However, unexplained differences in survival time are often observed, even among patients with similar clinical and molecular tumor traits. This study investigated how inflammatory radiomic features can correlate with evidence-based biological analyses to provide translated value in assessing clinical outcomes in patients with NSCLC. We analyzed a group of 15 patients with stage I NSCLC who showed extremely different OS outcomes despite apparently harboring the same tumor characteristics. We thus analyzed the inflammatory levels in their tumor microenvironment (TME) either biologically or radiologically, focusing our attention on the NLRP3 cancer-dependent inflammasome pathway. We determined an NLRP3-dependent peritumoral inflammatory status correlated with the outcome of NSCLC patients, with markedly increased OS in those patients with a low rate of NLRP3 activation. We consistently extracted specific radiomic signatures that perfectly discriminated patients’ inflammatory levels and, therefore, their clinical outcomes. We developed and validated a radiomic model unleashing quantitative inflammatory features from CT images with an excellent performance to predict the evolution pattern of NSCLC tumors for a personalized and accelerated patient management in a non-invasive way

Sustained Exendin-4 Secretion through Gene Therapy Targeting Salivary Glands in Two Different Rodent Models of Obesity/Type 2 Diabetes.

Exendin-4 (Ex-4) is a Glucagon-like peptide 1 (GLP-1) receptor agonist approved for the treatment of Type 2 Diabetes (T2DM), which requires daily subcutaneous administration. In T2DM patients, GLP-1 administration is reported to reduce glycaemia and HbA1c in association with a modest, but significant weight loss. The aim of present study was to characterize the site-specific profile and metabolic effects of Ex-4 levels expressed from salivary glands (SG) in vivo, following adeno-associated virus-mediated (AAV) gene therapy in two different animal models of obesity prone to impaired glucose tolerance and T2DM, specifically, Zucker fa/fa rats and high fed diet (HFD) mice. Following percutaneous injection of AAV5 into the salivary glands, biologically active Ex-4 was detected in the blood of both animal models and expression persisted in salivary gland ductal cell until the end of the study. In treated mice, Ex-4 levels averaged 138.9±42.3 pmol/L on week 6 and in treated rats, mean circulating Ex-4 levels were 238.2±72 pmol/L on week 4 and continued to increase through week 8. Expression of Ex-4 resulted in a significant decreased weight gain in both mice and rats, significant improvement in glycemic control and/or insulin sensitivity as well as visceral adipose tissue adipokine profile. In conclusion, these results suggest that sustained site-specific expression of Ex-4 following AAV5-mediated gene therapy is feasible and may be useful in the treatment of obesity as well as trigger improved metabolic profile

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients