Organic light emitting diode improves diabetic cutaneous wound healing in rats

A major complication for diabetic patients is chronic wounds due to impaired wound healing. It is well documented that visible red wavelengths can accelerate wound healing in diabetic animal models and patients. In vitro and in vivo diabetic models were used to investigate the effects of organic light emitting diode (OLED) irradiation on cellular function and cutaneous wound healing. Human dermal fibroblasts were cultured in hyperglycemic medium (glucose concentration 180 mM) and irradiated with an OLED (623 nm wavelength peak, range from 560 to 770 nm, power density 7 or 10 mW/cm² at 0.2, 1, or 5 J/cm²). The OLED significantly increased total adenosine triphosphate concentration, metabolic activity, and cell proliferation compared with untreated controls in most parameters tested. For the in vivo experiment, OLED and laser (635 ± 5 nm wavelength) treatments (10 mW/cm², 5 J/cm² daily for a total of seven consecutive days) for cutaneous wound healing were compared using a genetic, diabetic rat model. Both treatments had significantly higher percentage of wound closure on day 6 postinjury and higher total histological scores on day 13 postinjury compared with control. No statistical difference was found between the two treatments. OLED irradiation significantly increased fibroblast growth factor‐2 expression at 36‐hour postinjury and enhanced macrophage activation during initial stages of wound healing. In conclusion, the OLED and laser had comparative effects on enhancing diabetic wound healing.     

Imaging findings of mimickers of hepatocellular carcinoma

Radiological imaging plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC) as the noninvasive diagnosis of HCC in high-risk patients by typical imaging findings alone is widely adopted in major practice guidelines for HCC. While imaging techniques have markedly improved in detecting small liver lesions, they often detect incidental benign liver lesions and non-hepatocellular malignancy that can be misdiagnosed as HCC. The most common mimicker of HCC in cirrhotic liver is nontumorous arterioportal shunts that are seen as focal hypervascular liver lesions on dynamic contrast-enhanced cross-sectional imaging. Rapidly enhancing hemangiomas can be easily misdiagnosed as HCC especially on MR imaging with liver-specific contrast agent. Focal inflammatory liver lesions mimic HCC by demonstrating arterial-phase hypervascularity and subsequent washout on dynamic contrast-enhanced imaging. It is important to recognize the suggestive imaging findings for intrahepatic cholangiocarcinoma (CC) as the management of CC is largely different from that of HCC. There are other benign mimickers of HCC such as angiomyolipomas and focal nodular hyperplasia-like nodules. Recognition of their typical imaging findings can reduce false-positive HCC diagnosis.     

Aberrant actin depolymerization triggers the pyrin inflammasome and autoinflammatory disease that is dependent on IL-18, not IL-1β

Gain-of-function mutations that activate the innate immune system can cause systemic autoinflammatory diseases associated with increased IL-1β production. This cytokine is activated identically to IL-18 by an intracellular protein complex known as the inflammasome; however, IL-18 has not yet been specifically implicated in the pathogenesis of hereditary autoinflammatory disorders. We have now identified an autoinflammatory disease in mice driven by IL-18, but not IL-1β, resulting from an inactivating mutation of the actin-depolymerizing cofactor Wdr1. This perturbation of actin polymerization leads to systemic autoinflammation that is reduced when IL-18 is deleted but not when IL-1 signaling is removed. Remarkably, inflammasome activation in mature macrophages is unaltered, but IL-18 production from monocytes is greatly exaggerated, and depletion of monocytes in vivo prevents the disease. Small-molecule inhibition of actin polymerization can remove potential danger signals from the system and prevents monocyte IL-18 production. Finally, we show that the inflammasome sensor of actin dynamics in this system requires caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain, and the innate immune receptor pyrin. Previously, perturbation of actin polymerization by pathogens was shown to activate the pyrin inflammasome, so our data now extend this guard hypothesis to host-regulated actin-dependent processes and autoinflammatory disease.Autoinflammatory syndromes are caused by dysregulation of the innate immune system, frequently affecting the inflammasome or other pathogen recognition pathways and leading to the overproduction of active IL-1β and IL-18 (Masters et al., 2009). To date, there are at least 12 known genetic causes of autoinflammatory disease, including familial Mediterranean fever (FMF), hyper-IgD syndrome, and cryopyrin-associated periodic syndrome. Therapeutic options for these diseases include nonsteroidal antiinflammatory drugs, corticosteroids, colchicine (for FMF), anti-TNF, and direct blockade of IL-1, which can be highly efficacious (Masters et al., 2009; Caso et al., 2013). IL-18 and IL-1β are produced in many cells, including monocytes and macrophages (Okamura et al., 1995; Ushio et al., 1996). IL-18 and IL-1β are produced as precursors and do not have a signal peptide to facilitate their secretion; instead, they are activated and released extracellularly as mature proteins after cleavage by caspase-1 (Li et al., 1995; Ghayur et al., 1997; Gu et al., 1997). Despite these similarities, there is no known hereditary autoinflammatory disease where the pathology is caused exclusively by IL-18.The inflammasome is an intracellular molecular platform that forms in response to pathogen- or danger-associated molecular patterns (DAMPs), leading to recruitment and activation of caspase-1 (Martinon et al., 2002; Schroder and Tschopp, 2010). A growing number of inflammasomes have been reported, each nucleated by a different innate immune receptor, such as NLRP1 (Martinon et al., 2000; Boyden and Dietrich, 2006), NLRP3 (Agostini et al., 2004), NLRC4 (Franchi et al., 2006), pyrin (Chae et al., 2011), and AIM2 (Hornung et al., 2009). Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is a key adaptor used by most of these innate immune receptors to interact with and recruit caspase-1 (Srinivasula et al., 2002). Activating mutations in NLRP3 result in increased IL-1β and IL-18 production, which can be prevented in mice by deleting caspase-1 or ASC. Furthermore, deleting either the IL-18R or the IL-1R can both independently protect mice from this NLRP3-mediated autoinflammatory disease (Brydges et al., 2013). For the FMF protein, pyrin, activating mutations induce ASC-dependent but NLRP3-independent IL-1β activation and cause severe autoinflammation in mice (Chae et al., 2011). Interestingly, pyrin interacts with ASC, microtubules, and actin filaments (Mansfield et al., 2001; Richards et al., 2001; Waite et al., 2009), and it has recently been shown that modification of RhoGTPases by bacterial toxins can trigger the pyrin inflammasome, perhaps via modulation of actin dynamics (Xu et al., 2014). This raises the fascinating prospect of a link between perturbations in the actin cytoskeleton and autoinflammatory disease.Wdr1 is required for disassembly of actin filaments in conjunction with the actin-depolymerizing factor/cofilin family of proteins. Mice homozygous for a hypomorphic allele of Wdr1 (Wdr1^rd/rd) exhibit spontaneous autoinflammatory disease and thrombocytopenia (Kile et al., 2007). Both defects have been suggested to result from a disruption in actin dynamics. Thrombocytopenia results from defects in megakaryocytes, a cell type that is entirely dependent on a functional cytoskeleton to shed platelets (Patel et al., 2005). Wdr1 mutant mice also exhibit neutrophilia; however, the critical inflammatory mediators and cell types important for the development of inflammation in this genetic condition are unclear (Kile et al., 2007). Intriguingly, Wdr1 was found to be secreted after caspase-1 activation (Keller et al., 2008).We examined the role of key inflammatory mediators that drive autoinflammation in Wdr1^rd/rd mice and demonstrated that this disease is IL-18 dependent, but IL-1 independent. As expected, this IL-18 is produced by the inflammasome; however, it is not produced from neutrophils or macrophages, but instead only from monocytes. Finally, we found that the autoinflammatory disease was mediated by pyrin, providing evidence that this innate immune receptor recognizes alterations in the actin polymerization pathway.     

Endometriosis coexisting with mature cystic teratoma in the same ovary and ectopic pregnancy of left fallopian tube: a rare coexistence

A coexistence of endometriosis and mature cystic teratoma in the same ovary is a rare occurrence although such tumors of ovaries are said to be common in the reproductive age group. We report a case of fimbrial ectopic pregnancy combined with simultaneous ipsilateral ovarian presentation of endometriosis and mature teratoma.     

Prognostic Indicators for Acute Liver Failure Development and Mortality in Patients with Hepatitis A: Consecutive Case Analysis

Purpose

Due to the seroepidemiological shift in hepatitis A (HA), its severity, mortality, and complications have increased in recent years. Thus, the aim of this study was to identify predictive factors associated with poor prognosis among patients with HA.

Materials and Methods

A total of 304 patients with HA admitted to our institution between July 2009 and June 2011 were enrolled consecutively. Patients with complications defined as acute liver failure (ALF) were evaluated, and mortality was defined as death or liver transplantation.

Results

The mean age of patients (204 males, 100 females) was 32 years. Eighteen (5.9%) patients had progressed to ALF. Of the patients with ALF, 10 patients (3.3%) showed spontaneous survival while 8 (2.6%) died or underwent liver transplantation. Multivariate regression analysis showed that Model for End-Stage Liver Disease (MELD) and systemic inflammatory response syndrome (SIRS) scores were significant predictive factors of ALF. Based on receiver operating characteristics (ROC) analysis, a MELD ≥23.5 was significantly more predictive than a SIRS score ≥3 (area under the ROC: 0.940 vs. 0.742, respectively). In addition, of patients with a MELD score ≥23.5, King''s College Hospital criteria (KCC) and SIRS scores were predictive factors associated with death/transplantation in multivariate analysis.

Conclusion

MELD and SIRS scores ≥23.5 and ≥3, respectively, appeared to be related to ALF development. In addition, KCC and SIRS scores ≥3 were valuable in predicting mortality of patients with a MELD ≥23.5.     

Development of a radiopaque,long-term drug eluting bioresorbable stent for the femoral-iliac artery

Tubular tissues exist in various forms purported for blood supply, waste secretion, etc. to aid proper function and maintenance of the human body. Under pathological conditions, however, these tissues may undergo stenosis. A major surgical treatment for stenosis is to implant a medical device called a stent which aims to expand the narrowed tissue and maintain its patency. Most stents are currently made from metals; despite their high mechanical strength, however, interactions with the host tissue often results in restenosis and stent fracture. To solve these problems, a bioresorbable stent (BRS) is proposed as a next generation stent. In this study, a rotating rod combined 3D printing system was developed to fabricate various types of BRSs. In addition, we confirmed that a 1.5 year long-term release of paclitaxel is possible using polymeric materials. Moreover, a stent loaded with contrast powder was fabricated and was successfully viewed under fluoroscopy. The stent was then implanted in the iliac arteries of pigs and no adverse events were observed for up to 8 weeks.

A radiopaque, long-term drug eluting bioresorbable stent is developed for the treatment of femoral-iliac artery. The prepared materials are printed on a pre-designed rotating rod. The fabricated stent can be adapted for various clinical cases.