Clinical relevance of postoperative proteinuria for prediction of early renal outcomes after kidney transplantation

Proteinuria is associated with poor allograft and patient survival in kidney transplant recipients. However, the clinical relevance of spot urine protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) as predictors of renal outcomes during the early postoperative period following kidney transplantation (KT) has not been determined. Methods: This single-center retrospective cohort study included 353 kidney transplant recipients who underwent KT between 2014 and 2017 and were followed up for more than 3 years. Among them, 186 and 167 recipients underwent living donor KT and deceased donor KT, respectively. The PCR and ACR were measured during the immediate postoperative period (within 7 days postoperatively), before discharge (2–3 weeks postoperatively), and 3–6 months postoperatively. Results: The median age of the patients was 51 years (interquartile range, 43–59 years), and 62.9% were male. An immediate postoperative PCR of ≥1 mg/mg was associated with old age, diabetes mellitus, high systolic blood pressure, delayed graft function, and donor factors (deceased donor KT, old age, and high serum creatinine concentrations). The PCR and ACR 3 to 6 months posttransplant were inversely associated with the estimated glomerular filtration rate at 1 year posttransplant. Deceased donor KT recipients with immediate postoperative PCR of ≥3 mg/mg showed a greater incidence of delayed graft function and lower estimated glomerular filtration rate before discharge than those with immediate postoperative PCR of <3 mg/mg. Conclusion: Early postoperative proteinuria is a useful biomarker to predict early renal outcomes after KT.

Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by SA-β-gal staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.

Role of Micronutrients in Skin Health and Function

Skin is the first line of defense for protecting our bodies against external perturbations, including ultraviolet (UV) irradiation, mechanical/chemical stress, and bacterial infection. Nutrition is one of many factors required for the maintenance of overall skin health. An impaired nutritional status alters the structural integrity and biological function of skin, resulting in an abnormal skin barrier. In particular, the importance of micronutrients (such as certain vitamins and minerals) for skin health has been highlighted in cell culture, animal, and clinical studies. These micronutrients are employed not only as active compounds in therapeutic agents for treating certain skin diseases, but also as ingredients in cosmetic products. Here, the author describes the barrier function of the skin and the general nutritional requirements for skin health. The goal of this review is to discuss the potential roles and current knowledge of selected micronutrients in skin health and function.

Vitamin C Stimulates Epidermal Ceramide Production by Regulating Its Metabolic Enzymes

Ceramide is the most abundant lipid in the epidermis and plays a critical role in maintaining epidermal barrier function. Overall ceramide content in keratinocyte increases in parallel with differentiation, which is initiated by supplementation of calcium and/or vitamin C. However, the role of metabolic enzymes responsible for ceramide generation in response to vitamin C is still unclear. Here, we investigated whether vitamin C alters epidermal ceramide content by regulating the expression and/or activity of its metabolic enzymes. When human keratinocytes were grown in 1.2 mM calcium with vitamin C (50 mug/ml) for 11 days, bulk ceramide content significantly increased in conjunction with terminal differentiation of keratinocytes as compared to vehicle controls (1.2 mM calcium alone). Synthesis of the ceramide fractions was enhanced by increased de novo ceramide synthesis pathway via serine palmitoyltransferase and ceramide synthase activations. Moreover, sphingosine-1-phosphate (S1P) hydrolysis pathway by action of S1P phosphatase was also stimulated by vitamin C supplementation, contributing, in part, to enhanced ceramide production. However, activity of sphingomyelinase, a hydrolase enzyme that converts sphingomyelin to ceramide, remained unaltered. Taken together, we demonstrate that vitamin C stimulates ceramide production in keratinocytes by modulating ceramide metabolic-related enzymes, and as a result, could improve overall epidermal barrier function.

Sphingolipids and Antimicrobial Peptides: Function and Roles in Atopic Dermatitis

Inflammatory skin diseases such as atopic dermatitis (AD) and rosacea were complicated by barrier abrogation and deficiency in innate immunity. The first defender of epidermal innate immune response is the antimicrobial peptides (AMPs) that exhibit a broad-spectrum antimicrobial activity against multiple pathogens, including Gram-positive and Gram-negative bacteria, viruses, and fungi. The deficiency of these AMPs in the skin of AD fails to protect our body against virulent pathogen infections. In contrast to AD where there is a suppression of AMPs, rosacea is characterized by overexpression of cathelicidin antimicrobial peptide (CAMP), the products of which result in chronic epidermal inflammation. In this regard, AMP generation that is controlled by a key ceramide metabolite S1P-dependent mechanism could be considered as alternate therapeutic approaches to treat these skin disorders, i.e., Increased S1P levels strongly stimulated the CAMP expression which elevated the antimicrobial activity against multiple pathogens resulting the improved AD patient skin.

Chronic Granulomatous Infection of Soft Tissue Complicated by Trauma of a Lower Leg / 대한정형외과학회잡지

Chronic granulomatous infection of the skin and soft tissue by nontuberculous mycobacteria in patients with normal immune system is rarely reported. This case was about a child patient, with normal immune system, whose lower leg was lacerated after a slip down in the Philippines and it was previously treated at a hospital in the Philippines. After a couple of surgical debridement of the wound, the cause of the soft tissue infection was found to be a combined infection of nontuberculous mycobacteria and mycobacterium tuberculosis. We present a case that has been rare in Korea, but common overseas.

Polymerase Chain Reaction and Heteroduplex Analysis Based Detection of Clonal T Cell Receptor Gamma Gene Rearrangements in Paraffin-embedded Tissues of Cutaneous T Cell Proliferative Diseases

BACKGROUND: Recently, the molecular pathologic investigation for clonality in lymphomas has been introduced and has gained a role in the diagnosis of lymphomas. In fact, the clonality test using TCRGR phenomenon has been done by Southern blot analysis (SBA) and polymerase chain reaction (PCR) for molecular pathologic diagnosis of T cell lymphomas. However, it is difficult to perform SBA with paraffin embedded specimens or with samples of small skin biopsies. OBJECTIVE: We investigated the efficacy of PCR amplification of TCR gene in paraffin em-bedded cutaneous T cell lymphomas. METHODS: Iii this study, the clonality was assessed by polymerase chain reaction (PCR) analysis of T cell receptor gamma (TCR) gene from the DNA extracts obtained from paraffin em-bedded tissues (PET) of malignant T cells, B cell lymphomas, and benign cutaneous T cell proliferative disorders. Heteroduple-x-analyses were also performed to rule out the false positives. RESULTS: Among the total of 62 cases analyzed, monoclonality was observed in 4 out of 10 mycosis fungoides, 7 out of 9 cutaneous T cell lymphomas excluding mycosis fungoides, 1 out of 3 angiocentric lymphomas, 2 out of 2 lymphomatosis papulosis, 1 out of 7 large plaque parapsoriasis, and 1 out of 2 T cell lymphomas in other organs. No monoclonality was observed in 9 inflammatory cutaneous diseases, 5 small plaque parapsoriasis, 4 cutaneous B cell lymphomas, and 11 B cell lymphomas in lymph nodes. CONCLUSION: The results suggest that the PCR method and heteroduplex analysis used in this study were not only practical but also efficacious for the diagnosis of cutaneous T cell lymphomas using tissues embedded in paraffins.