The clinical efficacy of low-dose whole-lung irradiation in moderate-to-severe COVID-19 pneumonia: RTMX-20 trial.

This is a paired prospective comparative cohort study with 58 patients, in order to analyze the clinical LD-WLI in patients with moderate or severe COVID19 pneumonia. The results of this study show that the Radiotherapy could be an option to improve the clinical response for patients with COVID-19.

Overexpression of NaV 1.6 channels is associated with the invasion capacity of human cervical cancer.

Functional activity of voltage-gated sodium channels (VGSC) has been associated to the invasion and metastasis behaviors of prostate, breast and some other types of cancer. We previously reported the functional expression of VGSC in primary cultures and biopsies derived from cervical cancer (CaC). Here, we investigate the relative expression levels of VGSC subunits and its possible role in CaC. Quantitative real-time PCR revealed that mRNA levels of Na(V) 1.6 α-subunit in CaC samples were ∼40-fold higher than in noncancerous cervical (NCC) biopsies. A Na(V) 1.7 α-subunit variant also showed increased mRNA levels in CaC (∼20-fold). All four Na(V) ß subunits were also detected in CaC samples, being Na(V) ß1 the most abundant. Proteins of Na(V) 1.6 and Na(V) 1.7 α-subunits were immunolocalized in both NCC and CaC biopsies and in CaC primary cultures as well; however, although in NCC sections proteins were mainly relegated to the plasma membrane, in CaC biopsies and primary cultures the respective signal was stronger and widely distributed in both cytoplasm and plasma membrane. Functional activity of Na(V) 1.6 channels in the plasma membrane of CaC cells was confirmed by whole-cell patch-clamp experiments using Cn2, a Na(V) 1.6-specific toxin, which blocked ∼30% of the total sodium current. Blocking of sodium channels VGSC with tetrodotoxin and Cn2 did not affect proliferation neither migration, but reduced by ∼20% the invasiveness of CaC primary culture cells in vitro assays. We conclude that Na(V) 1.6 is upregulated in CaC and could serve as a novel molecular marker for the metastatic behavior of this carcinoma.

Evidence against alpha-adrenoceptors mediating relaxation in rat thoracic aortae: alpha-agonists relaxation depends on interaction with alpha-adrenoceptors.

In rat aorta, the presence of functional alpha(2)-adrenoceptors (alpha(2)-AR) was investigated in ring preparations preconstricted with alpha(1)-adrenergic and non- alpha(1)-adrenergic agonists. Particularly, the hypothetical interference of alpha(2)-AR agonists with alpha(1)-AR-mediated vasoconstriction was evaluated. Relaxant and contractile responses to alpha(2)-AR agonists were obtained. In endothelium-intact and endothelium-denuded aortic rings preconstricted with phenylephrine (1 x 10(-6) m), the imidazoline derivatives, clonidine and UK14304, induced relaxations with similar order of potencies (-log EC(50)) and maxima relaxant effects respectively. Pretreatment with the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) had no effect on the relaxant responses to clonidine and UK14304. In phenylephrine-constricted rings with endothelium, relaxations to clonidine and UK 14304 were not antagonized by the selective alpha(2)-AR antagonist, rauwolscine (< or =1 x 10(-6) m). Clonidine and UK 14304 induced only contractions on endothelium-intact and endothelium-denuded aortic rings contracted with prostaglandin F(2alpha) (3 x 10(-7) m). Moreover, clonidine and UK 14304-induced relaxation of endothelium-denuded arteries precontracted with methoxamine but not with serotonin. Finally, the concentration-contraction curves to clonidine and UK 14304 in endothelium-denuded aortic rings were significantly shifted to the right by the alpha(1D)-AR selective antagonist, BMY 7378, and rauwolscine. The pA(2) and pK(B) values for BMY 7378 and rauwolscine, respectively, against endothelium-independent actions of clonidine and UK 14304 were characteristic of an effect on the alpha(1D)-AR. The other selective alpha(2)-AR agonist tested BHT 933 (an azepine derivative), lacks considerable relaxant and contractile effects in rat aorta. The results provide no evidence for the presence of functional alpha(2)-AR in rat aorta. Respectively, the relaxant and contractile effects of the imidazoline derivatives, clonidine and UK 14304, may be due to an adjustable (in relation to the agonist-dependent active state of the alpha(1)-AR), inhibitory and excitatory, interaction with alpha(1)-ARs.

Impairment of smooth muscle function of rat thoracic aorta in an endothelium-independent manner by long-term administration of N(G)-nitro-L-arginine methyl ester.

In this study, we aimed to elucidate whether the daily hypertensive dose of long-term N(G)-nitro-l-arginine methyl ester (l-NAME) treatment, could make a difference between endothelial and smooth muscle functions in rat thoracic aorta. We test the hypothesis that high-dose, long-term l-NAME treatment has a depressive effect on vascular smooth muscle contractile activity which is not related with nitric oxide (NO) synthesis inhibition. After 14 days of treatment, isometric tension and (45)Ca(2+) influx were measured in aortic tissues isolated from l-NAME(10) and l-NAME(100) hypertensive (10 and 100 mg/kg/day, systolic blood pressures 167 +/- 7 and 172 +/- 10 mmHg, respectively) and control normotensive rats (132 +/- 7 mmHg). In l-NAME(10)- and l-NAME(100)-treated rats, acetylcholine-induced relaxation in aortic rings was suppressed with no significant difference between the treatments. l-NAME(100) (but not l-NAME(10)) treatment, significantly inhibited contractile responses to phenylephrine, angiotensin II, and K(+) (80 mm) in endothelium-intact tissues. The effect of l-NAME(100) on phenylephrine-induced contractile responses was not observed after 3 days of treatment. In endothelium-denuded aortic tissues of l-NAME(100) (but not l-NAME(10))-treated rats, phenylephrine (1 x 10(-6) m)- and K(+) (80 mm)-induced contractions and (45)Ca(2+) influxes were significantly reduced. In Ca(2+)-free medium (0.1 mm EDTA), on the contrary, the transient contractions obtained by either phenylephrine (1 x 10(-6) m) or caffeine (1 x 10(-2) m), or the sustained contractions induced by 12-o-tetradecanoylphorbol-13-acetate (1 x 10(-6) m; a protein kinase C activator) in endothelium-denuded aortic rings, were not modified by both l-NAME treatments. These results indicate that in aortic rings from l-NAME hypertensive rats, low and high doses, long-term l-NAME administration may be associated with equivalent inhibition in NO-dependent vasodilator tone (corresponding to equivalent hypertension values); whereas only high-dose, long-term l-NAME administration produces an endothelium-independent decrease in vasocontrictor activity, at least partly explained by a reduction in extracellular Ca(2+) influx.