The microstructures of two poly(propylene)s with matched molar masses and overall defect concentrations are inferred from the crystallization behavior of their narrow molar mass fractions. One poly(propylene) was produced with a MgCl2-supported Ziegler-Natta catalyst and the other with a metallocene catalyst. The fractions obtained from the metallocene isotactic poly(propylene) display a range in molar masses but each has the same defect concentration indicating a uniform intermolecular concentration of defects in the parent metallocene isotactic poly(propylene). These fractions provide direct evidence of the "single site" character of the metallocene catalyst. The variations of crystallization rates with molar mass reflect different chain diffusion/transport phenomena that are governed by the remnant entanglement state of the melt during crystallization. The molar mass fractions obtained from the ZN-iPP confirm that the interchain distribution of the nonisotactic content is broad in this polymer. The stereodefects are more concentrated in the low molar mass fractions. Furthermore, the invariance of the linear growth rates among the ZN fractions and the lack of formation of any significant content of the γ polymorph, even in the most defected fraction, is consistent with a nonrandom, blocky intramolecular distribution of defects in the ZN-iPP molecules. In contrast to the growth rates, the overall crystallization rates are a direct function of the primary nucleation density, which varies among the fractions and the unfractionated iPPs. Hence, the measured overall crystallization rates would be correlated with nucleation density and not necessarily with the microstructure of the iPP molecules. The crystallization data are also interpreted in light of results from pentad/heptad distributions predicted by two-state and threestate statistical models. Parameters from the models allow the prediction of sequence distribution curves that could be used to evaluate each of the models as to their consistency with the crystallization rate data.

Recent studies from our laboratory have shown that the mineralocorticoid receptor (MR) blockade with spironolactone (Sp) prevented renal dysfunction and reduced renal injury in both acute and chronic cyclosporine (CsA) nephrotoxicity. This study was designed to evaluate whether Sp administration reduces functional and structural renal damage associated in the setting of preexisting chronic CsA nephrotoxicity. Twenty eight male Wistar rats were fed a low-sodium diet. Fourteen received vehicle (V) and the others were treated with CsA (15 mg/kg sc). After 18 days one half of each group received Sp (20 mg/kg po) for the subsequent 18 days. Creatinine clearance, arteriolopathy, tubulointerstitial fibrosis, arteriolar thickening, glomerular diameter, apoptosis index and TGF-beta, procaspase-3, and kidney injury molecule 1 (Kim-1) mRNA levels as well as Kim-1 shedding in urine were evaluated. Sp reduced the progression of renal dysfunction and tubulointerstitial fibrosis in preexisting chronic CsA nephrotoxicity. There was a significant reduction of arteriolar thickening in the CsA+Sp group that was associated with greater glomerular diameter and reduction of apoptosis index. These renoprotective effects were associated with reduction of TGF-beta, procaspase-3, and Kim-1 mRNA levels as well as Kim-1 shedding into the urine. In conclusion, MR blockade with Sp prevented the progression of renal injury in preexisting chronic CsA nephropathy. These results suggest that Sp may reduce CsA-induced established nephrotoxicity in patients.

We showed that spironolactone reduced structural damage and prevented renal dysfunction in chronic cyclosporine (CsA) nephrotoxicity. These findings evidenced an aldosterone renal vascular effect under this condition. To investigate aldosterone's role in modulating renal vascular tone, renocortical vasoactive pathways mRNA levels in chronic CsA nephrotoxicity as well as spironolactone's effect on renal function in acute CsA nephrotoxicity were evaluated. Two experimental sets were designed. For chronic nephrotoxicity, rats fed with low-sodium diet were divided into groups receiving vehicle, spironolactone (Sp), CsA, and CsA+Sp, for 21 days. Creatinine clearance, survival percentage, and renocortical mRNA levels of pro-renin, angiotensinogen (Ang), angiotensin receptors (AT(1A), AT(1B), and AT(2)), preproendothelin, endothelin receptors (ET(A), ET(B)), cyclooxygenase-2 (COX-2), and adenosine receptors (Ad(1), Ad(2A), Ad(2B), and Ad(3)) were analyzed. For acute nephrotoxicity, similar groups fed with a standard chow diet for 7 days were included. Serum potassium and sodium, glomerular filtration rate (GFR), and renal blood flow (RBF) were determined. In chronic model, CsA produced pro-renin and ET upregulation, altered adenosine receptors expression, and reduced Ang, AT(1A), AT(1B), ET(B), and COX-2 mRNA levels. Spironolactone protective effect in chronic nephrotoxicity was associated with prevention of pro-renin upregulation and increased AT(2), together with ET(B) reduction. In acute nephrotoxicity, spironolactone completely prevented GFR and RBF reduction induced by CsA. Our results suggest that aldosterone contributes to renal vasoconstriction observed in CsA nephrotoxicity and that renoprotection conferred by spironolactone was related to modification of renocortical vasoactive pathways expression, in which pro-renin normalization was the most evident change in chronic nephropathy. Finally, our data point to spironolactone as a potential treatment to reduce CsA nephrotoxicity in transplant patients.

Donation after the circulatory determination of death (DCDD) has emerged as a valuable strategy to increase the availability of organs for transplantation. 1 In 2018, 23% of the 39 357 deceased organ donors reported to the Global Observatory on Donation and Transplantation had been declared dead by circulatory criteria. 2,3 DCDD also provides the opportunity of posthumous donation when patients die following an unsuccessfully-resuscitated cardiac arrest (uncontrolled DCDD [uDCDD]) or the decision to withdraw of life-sustaining therapies (WLSTs) that are no longer deemed beneficial to the patient (controlled DCDD [cDCDD]). 4cDCDD programs already exist in 17 countries throughout the world. 2,3,5 In cDCDD, the effects of warm ischemia during the agonal period after the WLST and following the cessation of circulation are further exacerbated during the later phase of cold