Polydatin Reduces Cardiotoxicity and Enhances the Anticancer Effects of Sunitinib by Decreasing Pro-Oxidative Stress, Pro-Inflammatory Cytokines, and NLRP3 Inflammasome Expression

Renal cell carcinoma (RCC) represents the main renal tumors and are highly metastatic. Sunitinib, a recently-approved, multi-targeted Tyrosine Kinases Inhibitor (TKi), prolongs survival in patients with metastatic renal cell carcinoma and gastrointestinal stromal tumors, however a dose related cardiotoxicity was well described. Polydatin (3,4',5-trihydroxystilbene-3-beta-d-glucoside) is a monocrystalline compound isolated from Polygonum cuspidatum with consolidated anti-oxidant and anti-inflammatory properties, however no studies investigated on its putative cardioprotective and chemosensitizing properties during incubation with sunitinib. We investigated on the effects of polydatin on the oxidative stress, NLRP3 inflammasome and Myd88 expression, highlighting on the production of cytokines and chemokines (IL-1 beta, IL-6, IL-8, CXCL-12 and TGF-beta) during treatment with sunitinib. Exposure of cardiomyocytes and cardiomyoblasts (AC-16 and H9C2 cell lines) and human renal adenocarcinoma cells (769-P and A498) to polydatin combined to plasma-relevant concentrations of sunitinib reduces significantly iROS, MDA and LTB4 compared to only sunitinib-treated cells (P<0.001). In renal cancer cells and cardiomyocytes polydatin reduces expression of pro-inflammatory cytokines and chemokines involved in myocardial damages and chemoresistance and down-regulates the signaling pathway of NLRP3 inflammasome, MyD88 and NF-kappa B. Data of the present study, although in vitro, indicate that polydatin, besides reducing oxidative stress, reduces key chemokines involved in cancer cell survival, chemoresistance and cardiac damages of sunitinib through downregulation of NLRP3-MyD88 pathway, applying as a potential nutraceutical agent in preclinical studies of preventive cardio-oncology

Diabete Tipo 1, Tipo 2 e Tipo X

Il muro concettuale secondo il quale il diabete in età pediatrica ha preferibilmente una patogenesi autoimmune sta ormai definitivamente crollando. Il diabete in età infantile e adolescenziale è molto più eterogeneo dal punto di vista eziopatogenetico di quanto si pensasse. In presenza di una qualsiasi iperglicemia è ormai diventato importantissimo chiedersi la patogenesi di questo sintomo utilizzando tutti gli strumenti che abbiamo oggi a disposizione

A Case of Fatal Intestinal Infarct Preceded by Recurrent Ischaemic Colitis due to the Enterotoxic Effect of Sodium Polystyrene Sulfonate

Case description: A 64-year-old patient with chronic renal failure and persistent hyperkalaemia not corrected by dialysis, was prescribed sodium polystyrene sulfonate (SPS) at a low dose (30 g/day for 2 days a week during the long interdialytic interval). After 3 months of therapy, the patient developed intense abdominal pain with non-specific colitis identified with a colonoscopy. In addition, the biopsy specimens showed rhomboid SPS crystals in the intestinal mucosa. Fourteen months after discontinuing therapy, the patient again presented with colitis and persistent biopsy finding of SPS crystals. The patient died a few months later due to intestinal infarction. Discussion and conclusion: SPS is a cation exchange resin used to treat hyperkalaemia resistant to dialysis, but may cause inflammation and ischaemia of the colon. In our patient, a short 3-month course of low-dose SPS therapy (without sorbitol, which is used to counter iatrogenic constipation caused by SPS) induced relapsing colitis, which was followed by massive intestinal infarction a few months later. In light of frequent reports of its enterotoxic effects, SPS should be replaced with the new potassium chelators (patiromer and sodium zirconium cyclosilicate)

Property of Melatonin of Acting as an Antihypertensive Agent to Antagonize Nocturnal High Blood Pressure: A Meta-Analysis

Therapy of hypertension persisting in the course of nocturnal sleep has yielded rather disappointing results . Therefore, the research has focused on drugs such as melatonin acting in such a way so as to counteract the lack of fall in blood pressure during night time sleep.  A meta-analysis has been planned by gathering only randomized controlled trials( RCTs), where melatonin was administered as a single dose at bedtime and compared with placebo. The efficacy was the "night time variation in systolic blood pressure" and the "night time variation in diastolic blood pressure". Safety endpoint was the possible occurrence of serious adverse events. Seven studies with 221 participants were pooled in the meta-analysis. Melatonin use was a predictor of significant decrease in nocturnal systolic blood pressure[SBP]( difference in means[MD]= -5.74 mm Hg; 95% CI: -6.07 to- 5.41 mm Hg; p&lt;0.00001).This change was generated by the very steep decrease in nocturnal SBP detected in patients treated with controlled-release(CR) melatonin ( MD=-8.42 mm Hg; 95% CI: -8.82 to- 8.02 mm Hg; p&lt;0.00001); whereas the mean change in nocturnal SBP, found in patients taking fast -release (FR)melatonin, was nonsignificant (MD=-0.06 mm Hg; 95% CI: -0.64 to 0.52 mm Hg; p=0.84). Likewise, use of melatonin was associated with a fall in DBP( MD= -0.60 mm Hg; 95% CI=-1.12 to -0.08 mm Hg), driven by the pressure changes attained by the CR melatonin. No major adverse events occurred in the examined trials. Evening administration of CR melatonin has been shown to cause a significant pressure decrease over the nocturnal sleep. Thus, the CR melatonin preparations could find a place in the antihypertensive armamentarium for promoting the physiological fall of blood pressure levels during night time sleep

Property of Melatonin of Acting as an Antihypertensive Agent to Antagonize Nocturnal High Blood Pressure: A Meta-Analysis

Therapy of hypertension persisting in the course of nocturnal sleep has yielded rather disappointing results . Therefore, the research has focused on drugs such as melatonin acting in such a way so as to counteract the lack of fall in blood pressure during night time sleep. A meta-analysis has been planned by gathering only randomized controlled trials( RCTs), where melatonin was administered as a single dose at bedtime and compared with placebo.The efficacy was the "night time variation in systolic blood pressure" and the "night time variation in diastolic blood pressure". Safety endpoint was the possible occurrence of serious adverse events.Seven studies with 221 participants were pooled in the meta-analysis. Melatonin use was a predictor of significant decrease in nocturnal systolic blood pressure[SBP]( difference in means[MD]= -5.74 mm Hg; 95% CI: -6.07 to- 5.41 mm Hg; p&lt;0.00001).This change was generated by the very steep decrease in nocturnal SBP detected in patients treated with controlled-release(CR) melatonin ( MD=-8.42 mm Hg; 95% CI: -8.82 to- 8.02 mm Hg; p&lt;0.00001); whereas the mean change in nocturnal SBP, found in patients taking fast -release (FR)melatonin, was nonsignificant (MD=-0.06 mm Hg; 95% CI: -0.64 to 0.52 mm Hg; p=0.84). Likewise, use of melatonin was associated with a fall in DBP( MD= -0.60 mm Hg; 95% CI=-1.12 to -0.08 mm Hg), driven by the pressure changes attained by the CR melatonin. No major adverse events occurred in the examined trials. Evening administration of CR melatonin has been shown to cause a significant pressure decrease over the nocturnal sleep. Thus, the CR melatonin preparations could find a place in the antihypertensive armamentarium for promoting the physiological fall of blood pressure levels during night time sleep

Troubles of Atrial Mechanical Recovery after Electrical Cardioversion in Patients with Persistent or Long-Lasting Persistent Atrial Fibrillation

Background: In the present retrospective cohort study we have evaluated the missed or delayed atrial mechanical recovery in a population of patients with persistent or long-lasting persistent atrial fibrillation (AF) who achieved restoration of sinus rhythm on the ECG by electrical cardioversion (ECV).Methods: The endpoint of our study was the failure to recover the normal mechanics of the left atrium. Inclusion criterion was the persistent or long-lasting persistent AF successfully treated by means of ECV, provided that a pertinent documentation was made available, comprising ECG, conventional 2D echo-color-Doppler and speckle tracking echocardiography(STE) evaluation, with also a STE assessment of the atria at the days 1, 30 and 90 from the ECV freely available within the clinical record of the patient.Results: Out of a total of 80 patients with persistent or long-standing persistent AF, retrospectively enrolled, as many as 22.5% of them did not achieve the normalization of their atrial STE profile, even though they had been converted to sinus rhythm on the ECG by means of ECV. The building of ROC curves allowed us to establish that early measurements of global atrial strain could serve to predict both the risk of failure to recover the atrial mechanical function and the one of AF relapses over a 12 month follow-up. The values of 18% and 17% were also calculated to serve as cut off values, respectively, for the risk of atrial mechanical dysfunction and for the risk of AF relapses over a 12 month follow-up.Conclusions: Failure to recover the atrial reservoir function can accompany a restoration of sinus rhythm on the ECG in patients with long –standing persistent AF.In this case a serial STE evaluation could be useful to evaluate the atrial hypofunction over time

Cell based therapeutic approach in vascular surgery: application and review

Multipotent stem cells - such as mesenchymal stem/stromal cells and stem cells derived from different sources like vascular wall are intensely studied to try to rapidly translate their discovered features from bench to bedside. Vascular wall resident stem cells recruitment, differentiation, survival, proliferation, growth factor production, and signaling pathways transduced were analyzed. We studied biological properties of vascular resident stem cells and explored the relationship from several factors as Matrix Metalloproteinases (MMPs) and regulations of biological, translational and clinical features of these cells. In this review we described a translational and clinical approach to Adult Vascular Wall Resident Multipotent Vascular Stem Cells (VW-SCs) and reported their involvement in alternative clinical approach as cells based therapy in vascular disease like arterial aneurysms or peripheral arterial obstructive disease