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Diabetic peripheral neuropathy (DPN) may lead to several changes in the skin, and some of these may influence the skin impedance spectrum. In the present study we have developed a prototype solution for skin impedance spectroscopy at selected skin sites (big toe pulp, heel and toe ball) that was tested in a pilot study on five patients with DPN and five healthy controls. At the big toe, most of the controls had markedly lower impedance than the DPN group, especially in the range of 1-100 kHz. The separation between the groups seems to be weaker at the heel and weakest at the toeball. The results may indicate that monitoring of the skin impedance spectrum may be a method for detection of skin changes associated with DPN, encouraging further studies with the big toe sensor in particular.

Introduction: Cytomegalovirus (CMV) infection remains a challenge following kidney transplantation (KTx). Currently, CMV-IgG serostatus at transplantation is used to individualize CMV preventive strategies. We assessed the clinical utility of CMV-IGRA for predicting CMV infection following KTx. Methods: We performed a nationwide prospective cohort study from August 2016 until December 2022. Data from all adult KTx recipients in Norway, n=1,546 (R+; n=1,157, D+/R-; n=260, D-/R-; 129), were included with a total of 3,556 CMV-IGRA analyses (1,375 at KTx, 1,188 at eight weeks, 993 one-year after KTx) and 35,782 CMV DNAemia analyses. Results: In R+ recipients CMV-IGRA status, measured at any of the time-points, could not identify any differential risk of later CMV infection. D+/R- recipients remaining CMV-IGRA negative 1-year after transplantation (regardless of positive CMV DNAemia and/or CMV IgG status at that time) had increased risk of developing later CMV infection compared to D+/R- recipients who had become CMV-IGRA positive (14% vs. 2%, p=0.01). Conclusion: Knowledge of pre-transplant CMV-IGRA status did not provide additional information to CMV-IgG serostatus that could improve current post-transplant CMV treatment algorithms. However, D+/R- recipients with a persisting negative CMV-IGRA one-year after transplantation remained at increased risk of experiencing later CMV infection. Therefore we advocate post-transplant CMV-IGRA monitoring in these patients. [ABSTRACT FROM AUTHOR]

Uric acid is a purine degradation product but also an important antioxidant and reactive oxygen species (ROS) scavenger. Experimental settings that mimic myocardial ischemia-reperfusion have not included uric acid despite that it is always present in human extracellular fluid and plasma. We hypothesized that uric acid has an important role in myocardial ROS scavenging. Here, we tested the cardiac response to uric acid on infarct size following ischemia-reperfusion with and without exacerbated oxidative stress due to acute pressure overload and during preconditioning. We also examined mitochondrial respiration and ROS-induced mitochondrial permeability transition pore opening. Under exacerbated ROS stress induced by high-pressure perfusion, uric acid lowered oxidative stress and reduced infarct size. In contrast, uric acid blocked cardioprotection induced by ischemic preconditioning. However, this effect was reversed by probenecid, an inhibitor of cellular uptake of uric acid. In accordance, in intact cardiomyocytes, extracellular uric acid reduced the susceptibility of mitochondria towards opening of the permeability transition pore, suggesting that uric acid may prevent ischemia-reperfusion injury due to scavenging of maladaptive ROS. Moreover, as uric acid also scavenges adaptive ROS, this may interfere with preconditioning. Altogether, uric acid might be a confounder when translating preclinical experimental results into clinical treatment. Key words: uric acid, ROS, cardioprotection, ischemic preconditioning, pressure overload/high pressure. En plus d'etre un produit de degradation des purines, l'acide urique est un important antioxydant et piegeur des derives reactifs de l'oxygene. En depit du fait qu'il soit toujours present dans le liquide extracellulaire et le plasma chez l'humain, l'acide urique n'a pas ete inclus dans les strategies experimentales qui miment l'ischemie-reperfusion myocardique. Nous avons formule une hypothese selon laquelle l'acide urique joue un role important dans le piegeage des derives reactifs de l'oxygene. Ici, nous avons evalue la reaction du creur a l'acide urique quant a la taille de l'infarctus a la suite d'une ischemie-reperfusion avec ou sans stress oxydatif cause par une surcharge de pression aigue et pendant le preconditionnement. Nous avons aussi etudie la respiration mitochondriale et l'ouverture des pores de transition de permeabilite mitochondriale provoquee par les derives reactifs de l'oxygene. Sous un stress exacerbe par les derives reactifs de l'oxygene produits l'aide d'une pression de perfusion elevee, l'acide urique entrainait un abaissement du stress oxydatif avec une diminution de la taille de l'infarctus. En revanche, l'acide urique entrainait une inhibition de la cardioprotection obtenue avec le preconditionnement ischemique. Cependant, cet effet etait inverse en presence du probenecide, un inhibiteur de la recapture de l'acide urique par les cellules. Dans ce contexte, dans les cardiomyocytes intacts, l'acide urique intracellulaire entrainait une diminution de la susceptibilite des mitochondries envers l'ouverture des pores de transition de permeabilite, ce qui laisse entendre que l'acide urique pourrait permettre de prevenir les lesions d'ischemie-reperfusion obtenues avec le piegeage de produits reactifs de l'oxygene inappropries. De plus, l'acide urique piege aussi des derives reactifs de l'oxygene appropries, ce qui pourrait interferer avec le preconditionnement. Dans l'ensemble, l'acide urique pourrait etre un facteur confondant quand on tente de faire le saut entre des resultats experimentaux precliniques et le traitement clinique. [Traduit par la Redaction] Mots-cles: acide urique, derives reactifs de l'oxygene, cardioprotection, preconditionnement ischemique, surcharge de pression/ pression elevee., Introduction In humans and other higher primates, uric acid (UA) is the end-product of purine metabolism whereas in other mammals, the presence of uricase ensures its further degradation (Sautin and [...]

Diabetic peripheral neuropathy (DPN) leads to several changes in the skin, and some of these may influence the skin impedance spectrum. In the present study we have developed a prototype solution for skin impedance spectroscopy at selected skin sites (big toe pulp, heel and toe ball) that was tested in a pilot study on five patients with DPN and five healthy controls. At the big toe, most of the controls had markedly lower impedance than the DPN group, especially in the range of 1-100 kHz. The separation between the groups seemed to be weaker at the heel and weakest at the toeball. The results may indicate that monitoring of the skin impedance spectrum may be a method for detection of skin changes associated with DPN, encouraging further studies with the big toe sensor in particular. [ABSTRACT FROM AUTHOR]

Among the variety of signals stimulating pancreatic secretion, cholecystokinin (CCK) and related hormones are assumed to be responsible for modulating proteinase output. in some species, intra-duodenal tryptic activity has to be abolished to demonstrate feedback-induced CCK release. The aim of this study was to investigate in vivo effects of modest inhibition of intraduodenal proteolytic enzymes on the secretion patterns of pancreatic enzymes and plasma CCK concentrations. Two inhibitors (Kunitz trypsin inhibitor and Bowman-Birk inhibitor) were applied. Intermittent sampling of plasma and duodenal juice was performed during intraduodenal saline and inhibitor instillations in six healthy volunteers. Enzyme activities and concentrations were determined in the duodenal samples and expressed as percentages of basal values. Instillation of Kunitz trypsin inhibitor caused an increase in trypsin and the pancreatic secretory trypsin inhibitor (PSTI), without changes in plasma CCK. This result demonstrates, for the first time, that pancreatic exocrine secretion of trypsin and chymotrypsin is regulated by different mechanisms. Bowman-Birk inhibitor additionally stimulated the secretion of chymotrypsin and carboxypeptidase A and B and increased plasma CCK. Elastase 1 and amylase secretions were not increased by either instillations. Although the inhibitors have similar in vitro inhibition patterns, their in vivo effects are different. The nonparallel secretion of proteinases (trypsin, chymotrypsin and elastase 1) supports the view of a complex system involved in feedback regulation of human pancreatic exocrine secretion, including signals other than CCK. INDEXING KEY WORDS: * cholecystokinin release * feed-back regulation * pancreatic secretion * proteinases * soybean inhibitors * humans