Fragments of Nle3‐angiotensin(1–7) accelerate healing in dermal models

Abstract: The renin angiotensin system (RAS) has been shown to be present in dermal tissue and exogenous peptides from the RAS accelerates healing and reduces scarring. An analogue of Angiotensin(1–7) [A(1–7)], Norleucine³‐A(1–7) [Nle³‐A(1–7)], is the lead compound under development for treatment of dermal injuries. As proteases are prevalent in wounded tissue and at very high levels in chronic wounds, the ability of fragments of Nle³‐A(1–7) to accelerate healing and the effect of proteases on the peptide were determined. Daily application of fragments of Nle³‐A(1–7) of five or six amino acids accelerated healing in two models of dermal injury. In addition, the peptide was found to be stable (not substantially degraded) after incubation for 4 h in the presence of Cathepsin G, collagenases blend (from clostridium), matrix metalloprotease [MMP] 2, MMP 3, MMP 9, elastase (human leukocytic or porcine pancreatic) or plasmin. Only kallikrein, an enzyme known to cleave peptides of the RAS, cleaved the peptide into two major fragments one of which was identified as NorLeu³‐A(1–4). These data support the activity of Nle³‐A(1–7) on dermal wounds.     

S-allylcysteine scavenges singlet oxygen and hypochlorous acid and protects LLC-PK(1) cells of potassium dichromate-induced toxicity.

It has been found that S-allylcysteine (SAC), a garlic-derived compound, has in vivo and in vitro antioxidant properties. In addition, it is known that SAC is able to scavenge different reactive oxygen or nitrogen species including superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)), hydroxyl radical (OH()), and peroxynitrite anion (ONOO(-)) although the IC(5O) values for each reactive species has not been calculated and the potential ability of SAC to scavenge singlet oxygen ((1)O(2)) and hypochlorous acid (HOCl) has not been explored. The purposes of this work was (a) to explore the potential ability of SAC to scavenge (1)O(2) and HOCl, (b) to further characterize the O(2)(-), H(2)O(2), OH(), and ONOO(-) scavenging ability of SAC by measuring the IC(50) values using in vitro assays, and (c) to explore the potential ability of SAC to ameliorate the potassium dichromate (K(2)Cr(2)O(7))-induced cytotoxicity in LLC-PK1 cells in which oxidative stress is involved. The scavenging activity was compared against the following reference compounds: N-acetylcysteine for O(2)(-), sodium pyruvate for H(2)O(2), dimethylthiourea for OH(), lipoic acid and glutathione for (1)O(2), lipoic acid for HOCl, and penicillamine for ONOO(-). It was found that SAC was able to scavenge concentration-dependently all the species assayed with the following IC(5O) (mean+/-SEM, mM): O(2)(-) (14.49+/-1.67), H(2)O(2) (68+/-1.92), OH() (0.68+/-0.06), (1)O(2) (1.93+/-0.27), HOCl (2.86+/-0.15), and ONOO(-) (0.80+/-0.05). When the ability of SAC to scavenge these species was compared to those of the reference compounds it was found that the efficacy of SAC (a) to scavenge O(2)(-), H(2)O(2), OH(), and ONOO(-) was lower, (b) to scavenge HOCl was similar, and (c) to scavenge (1)O(2) was higher. In addition, it was found that SAC was able to prevent K(2)Cr(2)O(7)-induced toxicity in LLC-PK1 cells in culture. It was showed for the first time that SAC is able to scavenge (1)O(2) and HOCl and to ameliorate the K(2)Cr(2)O(7)-induced toxicity.     

Immune-mediated neurological syndromes in SARS-CoV-2-infected patients

Journal of Neurology - Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore...     

Natural orifice transluminal endoscopic surgery: The transvaginal route moving forward from cholecystectomy

The advent of minimally invasive surgery and the advances in endoluminal flexible endoscopy have converged to generate a new concept in digestive surgery, whose acronym natural orifice transluminal endoscopic surgery (NOTES), has become a familiar term in the surgical community. NOTES has been performed through the mouth, the bladder, the rectum and the vagina. Of these four approaches, the vagina has gained most popularity for several reasons. It is not only readily accessible and easy to decontaminate but it also provides safe entry and simple closure. The transvaginal approach has been described in the experimental and the clinical setting as an option for cholecystectomy, nephrectomy, splenectomy, segmental gastrectomy, retroperitoneal exploration and bariatric surgery. However, larger series are needed to delineate the exact risks of this approach, and to transcend cultural barriers that impede its wider introduction. Prospective randomized trials will shed light on the definitive role of the vaginal approach in minimal invasive surgery of the future.     

FCGR3A V(176) polymorphism for systemic lupus erythematosus susceptibility in Mexican population

The objective of this study is to establish whether there is an association between the presence of FCGR3A V(176) polymorphism with SLE or its manifestations. We included 94 patients according to the 1982 ACR criteria as well as 98 controls matched by age and gender. The 11 ACR diagnostic criteria were analyzed on the clinical files. The polymorphism FCGR3A V(176) was determined by direct sequencing. There was not an association between the polymorphism FCGR3A V(176) with SLE or its main manifestations. The allelic frequency for F(176) was: 0.80 and 0.72 in cases and controls, respectively (P?=?0.09, IC95%: 0.42?C1.07); and the genotypic frequency in the group of cases was: 0.65 for homozygotes F(176)/F(176), 0.30 for heterozygotes and 0.05 for the homozygotes V(176)/V(176), while for the control group it was 0.53, 0.39 and 0.08, respectively. The polymorphism FCGR3A V(176) is not associated with SLE or any of its manifestations in patients with SLE from the West of Mexico.     

Cover Image,Volume 20, Issue 4

The cover image, by Inmaculada Ruz‐Maldonado et al., is based on the Original Article LH‐21 and abnormal cannabidiol improve β‐cell function in isolated human and mouse islets through GPR55‐dependent and ‐independent signalling, DOI: 10.1111/dom.13180 .