Microclimate and development of pressure ulcers and superficial skin changes

This study aims to evaluate the microclimate and development of pressure ulcers and superficial skin changes. A prospective cohort study was conducted in an acute care ward in Indonesia. Risk factors for pressure ulcers and superficial skin changes were identified based on the Bergstrom Braden conceptual model. Microclimate data were collected every 3 days for 15 days while the development of pressure ulcers and superficial skin changes was observed every day. Pressure ulcers and superficial skin changes were developed in 20 of the 71 participants. Total mean difference in skin temperature was higher for patients with pressure ulcers and superficial skin changes (0·9 ± 0·6°C) compared with controls (0·6 ± 0·8°C) (P = 0·071). Binary logistic regression predictor values for pressure ulcers and superficial skin changes were 0·111 for type of sheet and 0·347 for Braden Scale results. In conclusion, difference in skin temperature seems to be a predictor for pressure ulcer development and superficial skin changes, while synthetic fibre sheets are able to maintain a beneficial microclimate.     

Chronic active hepatitis with hepatitis B virus DNA and antibody against e antigen in the serum. Disturbed synthesis and secretion of e antigen from hepatocytes due to a point mutation in the precore region

Some patients with type B chronic active hepatitis have a high titer of hepatitis B virus DNA despite antibody against e antigen in the serum. Clones of hepatitis B virus were propagated from the sera of seven patients with this disease, and the precore region was sequenced. Essentially all clones (128/131 or 98%) showed a point mutation from guanine to adenine at nucleotide 83, converting codon 28 for tryptophan (TGG) to a stop codon (TAG); the second guanine-to-adenine point mutation at nucleotide 86 was identified in only 29 clones from two patients. In patients followed up since they had hepatitis B e antigen, a shift from guanine to adenine was observed at nucleotide 83 along with the seroconversion to the antibody to e antigen. The precore-region product is required for the synthesis and secretion of e antigen from hepatocytes. A point mutation from guanine to adenine at nucleotide 83 observed in the seven patients, therefore, would be responsible for disturbed secretion of e antigen.     

Short‐ and long‐term effect of sitagliptin after near normalization of glycemic control with insulin in poorly controlled Japanese type 2 diabetic patients

Aims/Introduction

The aim of the present study was to examine the short‐ and long‐term effect of sitagliptin on glucose tolerance after near normalization of glycemic control with insulin in poorly controlled type 2 diabetic patients.

Materials and Methods

We consecutively enrolled a total of 30 type 2 diabetic patients whose glycated hemoglobin levels (National Glycohemoglobin Standardization Program) were ≥7.4%, stopped all oral antidiabetic drugs and started insulin therapy. When fasting plasma glucose levels became <140 mg/dL, we carried out the first oral glucose tolerance test (OGTT). After 1‐week sitagliptin treatment (50 mg/day), the second OGTT was carried out. Furthermore, we evaluated the long‐term efficacy of sitagliptin on glucose tolerance after near normalization of glycemic control with insulin.

Results

After 1‐week sitagliptin treatment, the area under the curve of insulin was markedly increased, and the area under the curve of glucagon and glucose was markedly decreased. Duration of diabetes and insulin secretory capacity were correlated with the effect of sitagliptin. Furthermore, interestingly, near normalization of glycemic control with insulin therapy for 1–2 weeks brought out the long‐term effectiveness of sitagliptin on glucose tolerance for 24 weeks, which was not observed with other antidiabetic drugs.

Conclusions

These findings suggest that near normalization of glycemic control with insulin improves the clinical response to sitagliptin in poorly controlled type 2 diabetic patients.     

Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development

The immune system is influenced by the vital zinc (Zn) status, and Zn deficiency triggers lymphopenia; however, the mechanisms underlying Zn-mediated lymphocyte maintenance remain elusive. Here we investigated ZIP10, a Zn transporter expressed in the early B-cell developmental process. Genetic ablation of Zip10 in early B-cell stages resulted in significant reductions in B-cell populations, and the inducible deletion of Zip10 in pro-B cells increased the caspase activity in parallel with a decrease in intracellular Zn levels. Similarly, the depletion of intracellular Zn by a chemical chelator resulted in spontaneous caspase activation leading to cell death. Collectively, these findings indicated that ZIP10-mediated Zn homeostasis is essential for early B-cell survival. Moreover, we found that ZIP10 expression was regulated by JAK-STAT pathways, and its expression was correlated with STAT activation in human B-cell lymphoma, indicating that the JAK-STAT-ZIP10-Zn signaling axis influences the B-cell homeostasis. Our results establish a role of ZIP10 in cell survival during early B-cell development, and underscore the importance of Zn homeostasis in immune system maintenance.Zinc (Zn) has wide-ranging effects on immunity. Zn deficiency has uncovered the importance of Zn homeostasis in immune cell maintenance and function (1). Dramatic effects of Zn on immunity have been observed in several immune and allergy-related cells, including lymphocytes such as B cells (2–6). B cells develop in the bone marrow (BM); the initial commitment to pro-B cells is followed by their differentiation into pre-B cells, and subsequently into immature B cells, which express the B-cell receptor on their surface (7). The immature B cells reach the spleen as transitional B cells, further differentiating into follicular or marginal zone mature B cells (7). Although the perturbation of Zn homeostasis causes splenic atrophy associated with lymphocyte reduction, and compromises cellular and humoral immune responses (6), the mechanisms underlying how Zn controls immune cell function, and in particular, the impact on early B-cell development, have been largely unknown.Zn homeostasis is tightly controlled by Zn transporter family members, Zrt- and Irt-like proteins (ZIPs, Zn importers) and zinc transporters (ZnTs, Zn exporters) (8), and recent studies revealed that alterations in Zn homeostasis mediated by specific Zn transporters play indispensable roles in a variety of cellular events (9). The intestinal Zn transporter ZIP4 is important for the initial absorption of dietary Zn, and patients with mutations in the SLC39A4/ZIP4 gene suffer from the inherited disorder acrodermatitis enteropathica (10, 11). ZIP13 controls the formation of bone, teeth, and connective tissues by modulating BMP/TGF-β signaling (12), and its loss-of-function mutation causes spondylocheiro dysplastic Ehlers-Danlos syndrome in humans (12, 13). ZIP14 controls systemic growth by regulating G protein-coupled receptor (GPCR) signaling (14), and ZIP8 is involved in osteoarthritis (15) and negatively manipulates NF-κB activation (16). In addition, ZnT5 regulates cytokine production by controlling the activation of protein kinase C upon antigen exposure in mast cells (17). Thus, Zn homeostasis mediated by Zn transporters is linked to a wide variety of biological and regulatory functions, and the disruption of a Zn transporter-Zn axis can lead to various symptoms in the absence of redundant machinery (18).Here we demonstrate a definitive role of ZIP10 in early B-cell development. We found that a loss of ZIP10 during an early B-cell stage specifically abrogated cell survival, resulting in the absence of mature B cells, which led to splenoatrophy and reduced Ig levels. The inducible deletion of Zip10 in pro-B cells increased the caspase activity because of the reduced intracellular Zn level, leading to cell death. This phenomenon was mimicked by the intracellular chelation of Zn. These findings indicated that Zn homeostasis via ZIP10 plays an indispensable role in early B-cell survival. We also demonstrated that the ZIP10 expression levels were regulated by STAT3/STAT5 activation, and that ZIP10 was highly expressed in human B-cell lymphoma samples in which both STAT proteins were activated, indicating that the JAK-STAT-ZIP10-Zn signaling axis is important for B-cell maintenance. Our results establish a functional link between ZIP10 and the survival of early stages of B cells, revealing a molecular mechanism underlying the requirement of Zn for maintenance of the immune system.     

Exposure to intermittent hypoxia inhibits allergic airway inflammation in a murine model of asthma

Sleep and Breathing - Obesity increases the severity of asthma, and patients with severe asthma are often complicated with obstructive sleep apnea syndrome (OSAS), a concomitant disease of obesity....