Angiopoietin-like 4 Stimulates STAT3-mediated iNOS Expression and Enhances Angiogenesis to Accelerate Wound Healing in Diabetic Mice

Impaired wound healing is a major source of morbidity in diabetic patients. Poor outcome has, in part, been related to increased inflammation, poor angiogenesis, and deficiencies in extracellular matrix components. Despite the enormous impact of these chronic wounds, effective therapies are lacking. Here, we showed that the topical application of recombinant matricellular protein angiopoietin-like 4 (ANGPTL4) accelerated wound reepithelialization in diabetic mice, in part, by improving angiogenesis. ANGPTL4 expression is markedly elevated upon normal wound injury. In contrast, ANGPTL4 expression remains low throughout the healing period in diabetic wounds. Exogenous ANGPTL4 modulated several regulatory networks involved in cell migration, angiogenesis, and inflammation, as evidenced by an altered gene expression signature. ANGPTL4 influenced the expression profile of endothelial-specific CD31 in diabetic wounds, returning its profile to that observed in wild-type wounds. We showed ANGPTL4-induced nitric oxide production through an integrin/JAK/STAT3-mediated upregulation of inducible nitric oxide synthase (iNOS) expression in wound epithelia, thus revealing a hitherto unknown mechanism by which ANGPTL4 regulated angiogenesis via keratinocyte-to-endothelial-cell communication. These data show that the replacement of ANGPTL4 may be an effective adjunctive or new therapeutic avenue for treating poor healing wounds. The present finding also confirms that therapeutic angiogenesis remains an attractive treatment modality for diabetic wound healing.     

Usefulness in clinical practice of noninvasive measurement of colloids osmotic pressure-capillary pulmonary pressure gradient in the management of acute dyspnea

BACKGROUND: Increased pulmonary capillary pressure (PAWP) and decreased serum colloid osmotic pressure (COP) are important factors in pulmonary edema (PE) formation. The aim of this study was to evaluate the clinical usefulness of noninvasive determination of COP, PAWP and COP-PAWP gradient in patients with acute dyspnea. METHODS: Thirty four patients presenting with PE, 19 with preserved left ventricular systolic function (Ia) and 15 with depressed systolic function (Ib), and 26 patients presenting with acute pulmonary diseases (II) were enrolled. COP was estimated using Landis and Pappenheimer formula (COP = 2.1 x P + 0.16 x P2 + 0.009 x P3, P: serum total protein concentration). PAWP was measured by transthoracic Doppler echocardiography using E/Vp and 1000/(2 x IPT + Vp) Doppler indexes. RESULTS: The mean value of the gradient was 0.5 +/- 5, 1.7 +/- 3.4 and 10.4 +/- 4.7 mmHg in Ia, Ib and II respectively (P < 0.001 Ia and Ib vs II). PAWP was higher in Ia and Ib than in II (P < 0.001). However, hypoalbuminemia with COP < or = 18 mmHg was observed in 63% of patients in Ia as compared to those in Ib (7%) and II (8%). CONCLUSIONS: Severe hypoalbuminemia frequently contributes to PE formation in the presence of normal left ventricular systolic function. A COP-PAWP gradient value lower than 6 mmHg is highly predictive of the diagnosis of acute heart failure in these patients presenting with acute dyspnea.     

Altered response to inflammatory cytokines in hepatic energy metabolism in inducible nitric oxide synthase knockout mice

BACKGROUND/AIMS: Production of nitric oxide (NO) in the liver is believed to be a critical factor for carbohydrate and energy metabolism in endotoxin shock. The present study focuses on the involvement of NO produced by inducible nitric oxide synthase (iNOS) in glycogen synthesis and energy metabolism stimulated by insulin.METHODS: Primary hepatocytes prepared from wild-type and iNOS knockout (iNOS(-/-)) mice were employed.RESULTS: Incubation of wild-type hepatocytes with a combination of cytokines (interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma) and lipopolysaccharide (cytokines/LPS) inhibited insulin-stimulated glycogen synthesis and adenosine triphosphate (ATP) increase, and decreased the ketone body ratio (KBR) at 8-12 h, concomitant with expression of iNOS protein and NO production. While the glycogen synthesis was suppressed by cytokines/LPS, reduction of the ATP increase and a decrease in KBR by cytokines/LPS were not observed in iNOS(-/-) hepatocytes. Further, N(G)-monomethyl-L-arginine, a NOS inhibitor, reversed the inhibition of ATP increase and decrease in KBR by cytokines/LPS, but not the inhibition of glycogen synthesis. Conversely, addition of S-nitroso-N-acetylpenicillamine, a NO donor, inhibited the insulin-stimulated ATP increase synthesis in iNOS(-/-) hepatocytes, but not the insulin-stimulated glycogen synthesis.CONCLUSIONS: These results demonstrate that NO mediates the suppression of insulin-stimulated energy metabolism, but not glycogen synthesis, in cytokines/LPS-treated hepatocytes.     

Normalized peripheral transit time to monitor hypertensionin children

Studies have demonstrated that a notable increase in arterial stiffening can signify the presence of cardiovascular abnormalities, such as hypertension. Presently, the mercury sphygmomanometer continues to be the clinical gold standard to identify such abnormalities, but due to its measuring nature it cannot be used for continuous observation. Pulse transit time (PTT), which has an inverse relationship with blood pressure (BP), is proposed here as a simple and non-invasive technique to monitor hypertension in children. In order to minimize inter-subject PTT differences, all obtained PTT data were normalized to the study population. The results indicated that normalized mean PTT value is able to differentiate hypertensive from normal children in a significant (p < 0.01) manner in both upper and lower limbs. Preliminary findings herein suggest that PTT can be useful tool to monitor for hypertension in children especially during prolonged clinical observations.     

Intramuscular schwannoma: clinical and magnetic resonance imaging features

INTRODUCTION

Schwannomas that arise within the muscle plane are called intramuscular schwannomas. The low incidence of these tumours and the lack of specific clinical features make preoperative diagnosis difficult. Herein, we report our experience with intramuscular schwannomas. We present details of the clinical presentation, radiological diagnosis and management of these tumours.

METHODS

Between January 2011 and December 2013, 29 patients were diagnosed and treated for histologically proven schwannoma at the National University Hospital, Singapore. Among these 29 patients, eight (five male, three female) had intramuscular schwannomas.

RESULTS

The mean age of the eight patients was 40 (range 27–57) years. The most common presenting feature was a palpable mass. The mean interval between surgical treatment and the onset of clinical symptoms was 17.1 (range 4–72) months. Six of the eight tumours (75.0%) were located in the lower limb, while 2 (25.0%) were located in the upper limb. None of the patients had any preoperative neurological deficits. Tinel’s sign was present in one patient. Magnetic resonance (MR) imaging showed that the findings of split-fat sign, low signal margin and fascicular sign were present in all patients. The entry and exit sign was observed in 4 (50.0%) patients, a hyperintense rim was observed in 7 (87.5%) patients and the target sign was observed in 5 (62.5%) patients. All patients underwent microsurgical excision of the tumour and none developed any postoperative neurological deficits.

CONCLUSION

Intramuscular schwannomas demonstrate the findings of split-fat sign, low signal margin and fascicular sign on MR imaging. These findings are useful for the radiological diagnosis of intramuscular schwannoma.     

A Study on the Utilization of Coal Fly Ash Derived Grog in Clay Ceramics

Grog is an additive material that plays important roles in ceramic making. It improves the fabrication process of green bodies as well as the physical properties of fired bodies. Few low-cost materials and wastes have found their application as grog in recent years, thus encouraging the replacement of commercial grogs with cost-saving materials. Coal fly ash, a combustion waste produced by coal-fired power plant, has the potential to be converted into grog owing to its small particle sizes and high content of silica and alumina. In this study, grog was derived from coal fly ash and mixed with kaolin clay to produce ceramics. Effects of the grog addition on the resultant ceramics were investigated. It was found that, to a certain extent, the grog addition reduced the firing shrinkage and increased the total porosity of the ceramics. The dimensional stability of the ceramics at a firing temperature of 1200 °C was also not noticeably affected by the grog. However, the grog addition in general had negative effects on the biaxial flexural strength and refractoriness of the ceramics.     

Rapid Myopic Progression in Childhood Is Associated With Teenage High Myopia

PurposeThe purpose of this study was to evaluate the association of childhood progression of spherical equivalent (SE) with high myopia (HM) in teenagers in the Singapore Cohort of Risk factors for Myopia (SCORM).MethodsWe included 928 SCORM children followed over a mean follow-up of 6.9 ± 1.0 years from baseline (6–11 years old) until their teenage years (12–19 years old). Cycloplegic autorefraction and axial length (AL) measurements were performed yearly. The outcomes in teenagers were HM (SE ≤ −5 diopter [D)], AL ≥ 25 mm, SE and AL. Three-year SE and AL progression in childhood and baseline SE and AL with outcomes were evaluated using multivariable logistic or linear regression models, with predictive performance of risk factors assessed using the area under the curve (AUC).ResultsAt the last visit, 9.8% of teenagers developed HM and 22.7% developed AL ≥ 25 mm. In multivariate regression analyses, every −0.3 D/year increase in 3-year SE progression and every 0.2 mm/year increase in 3-year AL progression were associated with a −1.14 D greater teenage SE and 0.52 mm greater teenage AL (P values < 0.001). The AUC (95% confidence interval [CI]) of a combination of 3-year SE progression and baseline SE for teenage HM was 0.97 (95% CI = 0.95 – 0.98). The AUC of 3-year AL progression and baseline AL for teenage AL ≥ 25 mm was 0.91 (95% CI = 0.89 – 0.94).ConclusionsThree-year myopia progression in childhood combined with baseline SE or AL were good predictors of teenage HM. Clinicians may use this combination of factors to guide timing of interventions, potentially reducing the risk of HM later in life.     

Development of hydrophobic reduced graphene oxide as a new efficient approach for photochemotherapy

Nowadays, chemotherapy is one of the crucial and common therapies in the world. So far, it has been revealed to be highly promising, yet patients suffer from the consequences of severe negative medical dosages. In order to overcome these issues, the enhancement of photothermal chemotherapy with reduced graphene oxide (rGO) as a photothermal agent (PTA) is widely utilised in current medical technologies. This is due to its high near-infrared region (NIR) response, in vitro or in vivo organism biocompatibility, low risk of side effects, and effective positive results. Moreover, rGO not only has the ability to ensure that selective cancer cells have a higher mortality rate but can also improve the growth rate of recovering tissues that are untouched by necrosis and apoptosis. These two pathways are specific diverse modalities of cell death that are distinguished by cell membrane disruption and deoxyribonucleic acid (DNA) disintegration of the membrane via phosphatidylserine exposure in the absence of cell membrane damage. Therefore, this review aimed to demonstrate the recent achievements in the modification of rGO nanoparticles as a PTA as well as present a new approach for performing photochemotherapy in the clinical setting.

rGO of QD-rGO nanocomposite could absorb and convert into heat when harvested under NIR radiation, resulting cell death with reduction of fluorescence.