An in vivo model of postinflammatory hyperpigmentation and erythema: clinical, colorimetric and molecular characteristics.

BACKGROUND: Postinflammatory hyperpigmentation (PIH) is a common, acquired pigmentary disorder of the skin associated with significant quality-of-life impairment, especially in individuals with skin of colour. Current treatment for PIH is limited, largely due to a poor understanding of disease pathogenesis and the lack of a representative disease model. OBJECTIVES: This study is intended to further develop, update and validate our previously designed in vivo model of acne-induced PIH/postinflammatory erythema (PIE) using different concentrations of trichloroacetic acid (TCA), a medium-depth chemical peel. METHODS: Twenty-nine patients with skin types II-VI and clinician-confirmed presence of two or more truncal acne pustules and PIH/PIE were included. On the basis of Investigator's Global Assessment (IGA), clinical polarized photography (CPP), colorimetry and Skindex, we experimentally determined an optimum TCA concentration and assessed our model's ability to exhibit a dose-response relationship between degree of inciting insult and severity of resulting pigmentation. We also performed differential microRNA profiling and pathway analysis to explore the potential of microRNAs as molecular adjuncts to our model. RESULTS: Application of TCA 30% produced lesions indistinguishable from acne-induced PIH and PIE lesions on the basis of colorimetry data without causing epidermal necrosis. Application of progressively increasing TCA doses from 20% to 30% resulted in concentration-dependent increases in CPP, IGA and colorimetry scores at all timepoints during the study. miRNA-31 and miRNA-23b may play a role in PIH pathogenesis, although further validation is required. CONCLUSIONS: Our TCA-based in vivo model, using TCA concentrations between 20% and 30% with an optimum of 30%, enables the quantitative assessment of the pigmentary response to varying degrees of cutaneous inflammation in a fashion that mirrors natural acne-induced PIH and PIE.

Renal arteriolar hyalinosis, not intimal thickening in large arteries, is associated with cardiovascular events in people with biopsy-proven diabetic nephropathy.

AIMS: Diabetic nephropathy, a pathologically diagnosed microvascular complication of diabetes, is a strong risk factor for cardiovascular events, which mainly involve arteries larger than those affected in diabetic nephropathy. However, the association between diabetic nephropathy pathological findings and cardiovascular events has not been well studied. We aimed to investigate whether the pathological findings in diabetic nephropathy are closely associated with cardiovascular event development. METHODS: This retrospective cohort study analysed 377 people with type 2 diabetes and biopsy-proven diabetic nephropathy, with a median follow-up of 5.9 years (interquartile range 2.0 to 13.5). We investigated how cardiovascular events were impacted by two vascular diabetic nephropathy lesions, namely arteriolar hyalinosis and arterial intimal thickening, and by glomerular and interstitial lesions. RESULTS: Of the 377 people with diabetic nephropathy, 331 (88%) and 295 (78%) had arteriolar hyalinosis and arterial intimal thickening, respectively. During the entire follow-up period, those with arteriolar hyalinosis had higher cardiovascular event rates in the crude Kaplan-Meier analysis than those without these lesions (P = 0.005, log-rank test). When fully adjusted for clinically relevant confounders, arteriolar hyalinosis independently predicted cardiovascular events [hazard ratio (HR) 1.99; 95% confidence interval (CI) 1.12, 3.86], but we did not find any relationship between arterial intimal thickening and cardiovascular events (HR 0.89; 95% CI 0.60, 1.37). Additionally, neither glomerular nor interstitial lesions were independently associated with cardiovascular events in the fully adjusted model. CONCLUSIONS: Arteriolar hyalinosis, but not intimal thickening of large arteries, was strongly associated with cardiovascular events in people with diabetic nephropathy.

RORγt antagonist suppresses M3 muscarinic acetylcholine receptor-induced Sjögren's syndrome-like sialadenitis.

We showed recently that M3 muscarinic acetylcholine receptor (M3R)-reactive CD3+ T cells play a pathogenic role in the development of murine autoimmune sialadenitis (MIS), which mimics Sjögren's syndrome (SS). The aim of this study was to determine the effectiveness and mechanism of action of retinoic acid-related orphan receptor-gamma t (RORγt) antagonist (A213) in MIS. Splenocytes from M3R knockout (M3R-/- ) mice immunized with murine M3R peptide mixture were inoculated into recombination-activating gene 1 knockout (Rag-1-/- ) mice (M3R-/- →Rag-1-/- ) with MIS. Immunized M3R-/- mice (pretransfer treatment) and M3R-/- →Rag-1-/- mice (post-transfer treatment) were treated with A213 every 3 days. Salivary volume, severity of sialadenitis and cytokine production from M3R peptide-stimulated splenocytes and lymph node cells were examined. Effects of A213 on cytokine production were analysed by enzyme-linked immunosorbent assay (ELISA) and on T helper type 1 (Th1), Th17 and Th2 differentiation from CD4+ T cells by flow cytometry. Pretransfer A213 treatment maintained salivary volume, improved MIS and reduced interferon (IFN)-γ and interleukin (IL)-17 production significantly compared with phosphate-buffered saline (PBS) (P < 0·05). These suppressive effects involved CD4+ T cells rather than CD11c+ cells. Post-transfer treatment with A213 increased salivary volume (P < 0·05), suppressed MIS (P < 0·005) and reduced IFN-γ and IL-17 production (P < 0·05). In vitro, A213 suppressed IFN-γ and IL-17 production from M3R-stimulated splenocytes and CD4+ T cells of immunized M3R-/- mice (P < 0·05). In contrast with M3R specific responses, A213 suppressed only IL-17 production from Th17 differentiated CD4+ T cells without any effect on Th1 and Th2 differentiation in vitro. Our findings suggested that RORγt antagonism is potentially suitable treatment strategy for SS-like sialadenitis through suppression of IL-17 and IFN-γ production by M3R-specific T cells.

Emergence of New Delhi metallo-beta-lactamase 1 and other carbapenemase-producing Acinetobacter calcoaceticus-baumannii complex among patients in hospitals in Ha Noi, Viet Nam.

Acinetobacter baumannii is an important cause of multidrug-resistant hospital acquired infections in the world. Here, we investigate the presence of NDM-1 and other carbapenemases among carbapenem-resistant A. baumannii isolated between August 2010 and December 2014 from three large hospitals in Hanoi, Vietnam. We identified 23/582 isolates (4 %) (11 from hospital A, five from hospital B, and seven from hospital C) that were NDM-1 positive, and among them 18 carried additional carbapenemase genes, including seven isolates carrying NDM-1, IMP-1, and OXA-58 with high MICs for carbapenems. Genotyping indicated that NDM-1 carrying A. baumannii have expanded clonally in these hospitals. Five new STs (ST1135, ST1136, ST1137, ST1138, and ST1139) were identified. One isolate carried NDM-1 on a plasmid belonging to the N-repA replicon type; no NDM-1-positive plasmids were identified in the other isolates. We have shown the extent of the carbapenem resistance and the local clonal spread of A. baumannii carrying NDM-1 in these hospitals; coexistence of NDM-1 and IMP-1 is reported for the first time from Vietnam here, and this will further seriously limit future therapeutic options.

Biodegradable gelatin/beta-tricalcium phosphate sponges incorporating recombinant human fibroblast growth factor-2 for treatment of recession-type defects: A split-mouth study in dogs.

BACKGROUND AND OBJECTIVE: Tissue engineering by using recombinant human (rh) growth factor technology may offer a promising therapeutic approach for treatment of gingival recession. Fibroblast growth factor-2 (FGF-2) has shown the ability to promote periodontal regeneration. Gelatin/beta-tricalcium phosphate (gelatin/ß-TCP) sponges have been developed to control the release of growth factors. The present study evaluated the periodontal regenerative efficacy of rhFGF-2 by comparing gelatin/ß-TCP sponges incorporated with rhFGF-2 to the scaffolds alone in artificially created recession-type defects in dogs. MATERIAL AND METHODS: Critically sized buccal gingival recession defects were surgically created on maxillary canine teeth of five dogs. In each animal, defects were randomized to receive either a gelatin/ß-TCP sponge soaked with rhFGF-2 (gelatin/ß-TCP/rhFGF-2) or phosphate-buffered saline (gelatin/ß-TCP). Eight weeks after surgery, biopsy specimens were obtained and subjected to microcomputed tomography and histological analyses. RESULTS: Complete root coverage was achieved in both groups. Microcomputed tomography revealed significantly greater new bone volume in the gelatin/ß-TCP/rhFGF-2 group. Histologically, both groups achieved periodontal regeneration; however, gelatin/ß-TCP/rhFGF-2 sites exhibited more tissue regeneration, characterized by significantly larger amounts of new cementum and new bone. Gelatin/ß-TCP sites featured increased long junctional epithelium and connective tissue attachment. In the gelatin/ß-TCP/rhFGF-2 sites, new bone exhibited many haversian canals and circumferential lamellae as well as remarkably thick periosteum with blood vascularization and hypercellularity. CONCLUSION: Within the limitations of this study, rhFGF-2 in gelatin/ß-TCP sponges exhibits an increased potential to support periodontal wound healing/regeneration in canine recession-type defects.

An in vivo model for postinflammatory hyperpigmentation: an analysis of histological, spectroscopic, colorimetric and clinical traits.

BACKGROUND: Acne vulgaris is a common condition that occurs in all skin types. Postinflammatory hyperpigmentation (PIH) is often associated with acne in patients of darker skin types, making it a common complaint in dermatology offices. Despite this, there is limited understanding of and effective treatment options for PIH. OBJECTIVES: The study objective was to validate an in vivo model for PIH and to compare the clinical, histological and spectroscopic characteristics of artificially induced PIH and acne-induced PIH. METHODS: A nonblinded, nonrandomized pilot study was performed. Thirty subjects served as their own control in which four sites treated with 35% trichloroacetic acid (TCA) solution and four truncal acne pustules were followed for 8 weeks and were evaluated clinically and histologically, and by colorimetry and spectroscopy. RESULTS: The initial phases of inflammation between TCA- and acne-induced PIH differ. However, clinical evaluations were similar on and after day 14. Acne- and TCA-induced lesions were clinically, histologically and spectroscopically indistinguishable at day 28. CONCLUSIONS: Clinical, spectroscopic and histological similarities of acne-induced and TCA-induced PIH at day 28 suggest that TCA-induced PIH can be a reproducible model for the study of acne-induced PIH.

Ridge augmentation using recombinant human fibroblast growth factor-2 with biodegradable gelatin sponges incorporating ß-tricalcium phosphate: a preclinical study in dogs.

BACKGROUND AND OBJECTIVE: Fibroblast growth factor-2 (FGF-2) regulates the proliferation and differentiation of osteogenic cells, resulting in the promotion of bone formation. Biodegradable gelatin sponges incorporating ß-tricalcium phosphate (ß-TCP) have been reported as a scaffold, which has the ability to control growth factor release, offering sufficient mechanical strength and efficient migration of mesenchymal cells. In this study, we evaluated the effects of the combined use of recombinant human FGF-2 (rhFGF-2) and gelatin/ß-TCP sponge on ridge augmentation in dogs. MATERIAL AND METHODS: Six male beagle dogs were used in this study. Twelve wk after tooth extraction, bilateral 10 × 5 mm (width × depth) saddle-type defects were created 3 mm apart from the mesial side of the maxillary canine. At the experimental sites, the defects were filled with gelatin/ß-TCP sponge infiltrated with 0.3% rhFGF-2, whereas gelatin/ß-TCP sponge infiltrated with saline was applied to the control sites. Eight wk after surgery, qualitative and quantitative analyses were performed. RESULTS: There were no signs of clinical inflammation at 8 wk after surgery. Histometric measurements revealed that new bone height at the experimental sites (2.98 ± 0.65 mm) was significantly greater than that at the control sites (1.56 ± 0.66 mm; p = 0.004). The total tissue height was greater at the experimental sites (6.62 ± 0.66 mm) than that at the control sites (5.95 ± 0.74 mm), although there was no statistical significant difference (p = 0.051). Cast model measurements revealed that the residual defect height at the experimental sites (2.31 ± 0.50 mm) was significantly smaller than that at the control sites (3.51 ± 0.78 mm; p = 0.012). CONCLUSION: The combined use of rhFGF-2 and gelatin/ß-TCP sponge promotes ridge augmentation in canine saddle-type bone defects.

Polymorphism in promoter region of growth hormone receptor is associated with potential production capacity of insulin-like growth factor-1 in pre-pubertal Holstein heifers.

Insulin-like growth factor-1 (IGF-1) is one of the important factors for growth, milk production and reproductive functions and mainly released from the liver in response to growth hormone (GH) via GH receptor (GHR) in cattle. Recently, some single nucleotide polymorphisms (SNPs) were identified in the bovine GHR gene. Some GHR-SNPs were shown to be related to plasma IGF-1 concentration in cattle. Hence, the capacity to IGF-1 production in the liver might be affected by GHR-SNP and associated with performance in the future. This study examined whether GHR-SNP is associated with IGF-1 production in the liver of pre-pubertal heifers. In 71 Holstein calves, blood samples for genomic DNA extraction were obtained immediately after birth. To genotype the GHR-SNPs in the promoter region, polymerase chain reaction (PCR) products were digested with restriction enzyme NsiI (cutting sites: AA, AG and GG). All heifers at 4 months of age were intramuscularly injected with 0.4 mg oestradiol benzoate. Blood samples were obtained from the jugular vein just before (0 h) and 24 h after injection. The number of AA, AG and GG at the NsiI site was 0, 17 and 54 respectively. In AG and GG, plasma GH concentrations were higher pre-injection than 24 h post-injection (p < 0.01). Moreover, plasma GH concentrations in AG post-injection were higher than in GG (p < 0.05). In contrast, the GG genotype exhibited higher plasma IGF-1 concentrations in pre-injection than post-injection (p < 0.01), although oestradiol did not change IGF-1 concentration in the AG genotype. We conclude that the GG polymorphism in the promoter region of GHR is associated with a higher potential capacity of IGF-1 production in the liver of cattle.

Positive association of free triiodothyronine with pancreatic ß-cell function in people with prediabetes.

AIM: To analyse the effects of thyroid hormones on ß-cell function and glucose metabolism in people with prediabetes who are euthyroid. METHODS: A total of 111 people who were euthyroid underwent 75-g oral glucose tolerance tests, of whom 52 were assigned to the normal glucose tolerance and 59 to the prediabetes groups. Homeostatic model assessment of ß-cell function, insulinogenic index and areas under the curve for insulin and glucose were evaluated as indices of pancreatic ß-cell function. RESULTS: In both groups, BMI, fasting insulin, homeostasis model assessment ratio and HDL cholesterol correlated significantly with all indices of pancreatic ß-cell function. Free triiodothyronine correlated positively with all insulin secretion indices in the prediabetes group. Multiple linear regression analysis showed that free triiodothyronine was an independent variable that had a positive correlation with all indices of ß-cell function in the prediabetes group. By contrast, no such correlation was found in the normal glucose tolerance group. CONCLUSIONS: Free triiodothyronine is associated with both basal and glucose-stimulated insulin secretion in people with prediabetes who are euthyroid; therefore, the regulation of insulin secretion by thyroid hormones is a potentially novel therapeutic target for the treatment of diabetes.

Severity markers in severe leptospirosis: a cohort study.

We aimed to evaluate parameters for their value as severity markers in hospitalized leptospirosis patients. We recruited 47 informed adult consenting patients and assessed a number of clinical, hematological, biochemical, and biological variables. Patients were sorted according to severity based on fatality or the requirement of mechanical ventilation or dialysis; the parameters studied were compared between groups on inclusion and the next day. Beside septic shock presentation or a high severity score (Simplified Acute Physiology Score; SAPS II), increased lactate, total bilirubin, lipase, and AST/ALT ratio or a decreased cytokines IL-10/TNF-α ratio were all significantly associated with severity. The gene expression of the IL-1 receptor antagonist IL-1ra, IL-1α, and the long pentraxin PTX-3 were also transcribed at higher levels in most severe cases. Patients could rapidly improve or deteriorate, highlighting the need for a new assessment the next day. Our results add to the limited body of knowledge about severity markers in leptospirosis. They also suggest that patients should be reassessed the next day before being possibly discharged from the hospital. Further studies are needed in order to confirm relevant and reliable prognostic parameters in leptospirosis that would be helpful for the purpose of triage.

Common isolation of New Delhi metallo-beta-lactamase 1-producing Enterobacteriaceae in a large surgical hospital in Vietnam.

This study sought to monitor the presence of carbapenem-resistant Enterobacteriaceae (CRE) and the proportion New Delhi metallo-beta-lactamase 1 (NDM-1)-producing bacteria between August 2010 and December 2012 in a surgical hospital in Vietnam. We identified 47 CRE strains from a total of 4,096 Enterobacteriaceae isolates (1.1 %) that were NDM-1-positive from 45 patients admitted to 11 different departments, with the majority being from the urology department. The NDM-1 gene was found in seven different species. Genotyping revealed limited clonality of NDM-1-positive isolates. Most of the isolates carried the NDM-1 gene on a plasmid and 17.8 % (8/45) of those were readily transferable. We found five patients at admission and one patient at discharge with NDM-1-positive bacteria in their stool. From 200 screening environmental hospital samples, five were confirmed to be NDM-1-positive and included Acinetobacter species (n = 3) and Enterobacter aerogenes (n = 2). The results reveal that NDM-1-producing Enterobacteriaceae are commonly isolated in patients admitted to a Vietnamese surgical hospital and are also detected in the hospital environment.

Does poor sleep quality affect skin ageing?

BACKGROUND: Sleep is important for growth and renewal of multiple physiological systems. The effects of chronic poor sleep quality on human skin function and visible signs of ageing have not been elucidated. AIM: To evaluate the effect of chronic poor sleep quality on measures of skin health and ageing. Self-perceived satisfaction with appearance was also assessed. METHODS: 60 healthy caucasian women, who were categorized as poor quality sleepers [Pittsburg Sleep Quality Index (PSQI) > 5, sleep duration ≤ 5 h] or good quality sleepers (PSQI ≤ 5, sleep duration 7-9 h). A validated clinical tool, SCINEXA(TM) , was used to assess intrinsic and extrinsic skin ageing. Dark under-eye circles were evaluated using standardized photos. Measurement of in vivo transepidermal water loss (TEWL) was used to assess recovery of the skin barrier after tape stripping. Subjects were exposed to simulated solar ultraviolet light, and recovery from erythema was monitored. Subjects also completed a questionnaire evaluating self-perception of attractiveness. RESULTS: Good sleepers had significantly lower intrinsic skin ageing scores by SCINEXA(TM) . At baseline, poor sleepers had significantly higher levels of TEWL. At 72 h after tape stripping, good sleepers had 30% greater barrier recovery compared with poor sleepers. At 24 h after exposure to ultraviolet light, good sleepers had significantly better recovery from erythema. Good sleepers also reported a significantly better perception of their appearance and physical attractiveness compared with poor sleepers. CONCLUSIONS: This study indicates that chronic poor sleep quality is associated with increased signs of intrinsic ageing, diminished skin barrier function and lower satisfaction with appearance.

Short communication: Development of the first follicular wave dominant follicle on the ovary ipsilateral to the corpus luteum is associated with decreased conception rate in dairy cattle.

In this study, we examined the effect of the locations of the first-wave dominant follicle (DF) and corpus luteum (CL) on fertility. In total, 350 artificial insemination (AI) procedures were conducted (lactating dairy cows: n=238, dairy heifers: n=112). Ovulation was confirmed 24 h after AI. The locations of the first-wave DF and CL were examined 5 to 9d after AI using rectal palpation or transrectal ultrasonography. Lactating dairy cows and dairy heifers were divided into 2 groups: (1) the ipsilateral group (IG), in which the DF was ipsilateral to the CL; and (2) the contralateral group (CG), in which the DF was contralateral to the CL. Pregnancy was diagnosed using transrectal ultrasonography 40d after AI. Conception rates were 54.0% in all cattle: 48.9% in lactating dairy cows, and 58.9% in dairy heifers. The incidence of the first-wave DF location did not differ between IG and CG (all cattle: 184 vs. 166; lactating cows: 129 vs. 109; heifers: 55 vs. 57 for IG vs. CG). Conception rates were lower in IG than in CG (all cattle: 40.2 vs. 69.3%; lactating dairy cows: 38.0 vs. 67.0%; dairy heifers: 45.5 vs. 73.7%, for IG vs. CG). Conception rate was not affected by season or live weight in heifers and lactating cows. In addition, days in milk at AI, milk production, body condition score, and parity did not affect conception in lactating cows. In summary, development of the first-wave DF in the ovary ipsilateral to the CL was associated with reduced conception rates in both lactating cows and heifers.

Evaluation of PAH contamination in soil treated with solid by-products from shale pyrolysis.

The aim of this work was to evaluate the concentrations of polycyclic aromatic hydrocarbons (PAHs) in soils to which solid shale materials (SSMs) were added as soil conditioners. The SSMs were derived from the Petrosix pyrolysis process developed by Petrobras (Brazil). An improved ultrasonic agitation method was used to extract the PAHs from the solid samples (soils amended with SSMs), and the concentrations of the compounds were determined by gas chromatography coupled to mass spectrometry (GC-MS). The procedure provided satisfactory recoveries, detection limits, and quantification limits. The two-, three-, and four-ring PAHs were most prevalent, and the highest concentration was obtained for phenanthrene (978 ± 19 µg kg(-1) in a pyrolyzed shale sample). The use of phenanthrene/anthracene and fluoranthene/pyrene ratios revealed that the PAHs were derived from petrogenic rather than pyrogenic sources. The measured PAH concentrations did not exceed national or international limit values, suggesting that the use of SSMs as soil conditioners should not cause environmental damage.

Resveratrate protects human skin from damage due to repetitive ultraviolet irradiation.

BACKGROUND: Ultraviolet (UV) exposure results in the production reactive oxygen species. Resveratrol has attracted considerable attentions owing to its natural abundance and multiple biological effects. OBJECTIVE: To investigate the protective effects of resveratrate against damage to human skin induced by repetitive solar simulator ultraviolet radiation (ssUVR). MATERIALS AND METHODS: Fifteen healthy volunteers were enrolled, and six sites on the non-exposed dorsal skin of each volunteer were marked for study. Sites 1-4 were exposed to ssUVR at a dosage of 1.5 minimal erythema dose for consecutive 4 days. Immediately after each exposure, one test material (resveratrate + antioxidant, antioxidant, resveratrate, vehicle) was applied to one of the four sites. Site 5 and site 6 were marked as positive control site (UVR only) and baseline control site (no treatment, no UVR). L*a*b values were assessed preprocedure and postprocedure. Skin biopsies were taken 24 h after the last irradiation. The specimens were stained to determine the number of sunburn cells and melanin content melanin. RESULTS: On resveratrate treated sites, erythema was barely seen with only slight decrease of L value and insignificant increase of *a value. Furthermore, resveratrate significantly inhibited sunburn cell formation, and decreased Fontana-Masson staining in skin samples. CONCLUSIONS: Resveratrate exerts protective effects against repetitive ssUVR-induced sunburn and suntan.

Persistent spontaneous pneumothorax for four years: a case report.

Pneumothorax, defined as the presence of air in the pleural space, is usually classified as spontaneous or traumatic; it is unusual for pneumothorax to be categorized as being acute or chronic. Even if conservative treatment is chosen, the pneumothorax is cured when air in the pleural space dissolves into the venous blood. A 50-years-old Japanese man with no prior medical history was referred to our department with a right pneumothorax and two rightsided pulmonary nodules on chest X-ray and CT. The chest radiographs of past mass screening which was taken four years ago showed right pneumothorax and right-sided pulmonary nodules. From then, all chest radiograph and chest computed tomography showed right pneumothorax and pulmonary nodules. But he underwent no medical interventions. We designed to perform an operation for a treatment of right pneumothorax and the diagnosis of pulmonary tumors. We underwent right upper lobectomy and pleural decortication under video assisted thoracic surgery. We obtained pathological diagnosis of inflammatory pseudotumor and surrounding atelectasis. He was cured from pneumothorax and pulmonary tumors. A unique case of spontaneous pneumothorax presenting with a pleural air space that was confirmed by chest radiographs and computed tomography examinations over a 4-year period is reported.

Field test of quantum key distribution in the Tokyo QKD Network.

A secure communication network with quantum key distribution in a metropolitan area is reported. Six different QKD systems are integrated into a mesh-type network. GHz-clocked QKD links enable us to demonstrate the world-first secure TV conferencing over a distance of 45km. The network includes a commercial QKD product for long-term stable operation, and application interface to secure mobile phones. Detection of an eavesdropper, rerouting into a secure path, and key relay via trusted nodes are demonstrated in this network.