Exosomal HMGB1 Promoted Cancer Malignancy

Reciprocal crosstalk between platelets and malignancies underscores the potential of antiplatelet therapy in cancer treatment. In this study, we found that human chronic myeloid leukemia K562 cell-differentiated megakaryocytes and murine platelets produced bioactive substances and these are released into the extracellular space, partly in their exosomal form. High-mobility group box 1 (HMGB1) is a type of exosomal cargo, and the antiplatelet drugs aspirin and dipyridamole interfered with its incorporation into the exosomes. Those released substances and exosomes, along with exogenous HMGB1, promoted cancer cell survival and protected cells from doxorubicin cytotoxicity. In a tumor-bearing model established using murine Lewis lung carcinoma (LLC) cells and C57BL/6 mice, the tumor suppressive effect of dipyridamole correlated well with decreased circulating white blood cells, soluble P-selectin, TGF-β1 (Transforming Growth Factor-β1), exosomes, and exosomal HMGB1, as well as tumor platelet infiltration. Exosome release inhibitor GW4869 exhibited suppressive effects as well. The suppressive effect of dipyridamole on cancer cell survival was paralleled by a reduction of HMGB1/receptor for advanced glycation end-products axis, and proliferation- and migration-related β-catenin, Yes-associated protein 1, Runt-related transcription factor 2, and TGF- β1/Smad signals. Therefore, exosomes and exosomal HMGB1 appear to have roles in platelet-driven cancer malignancy and represent targets of antiplatelet drugs in anticancer treatment

Factors Determining Bone Mineral Density in Patients with Biliary Atresia after a Successful Kasai Operation

Hepatic osteodystrophy is a common complication in patients with chronic liver disease, however, bone mineral status in patients with biliary atresia has rarely been investigated. Methods: Twenty-nine children with biliary atresia were enrolled in our study and their demographic data, bone mineral density (BMD) of lumbar spine and bilateral femoral neck, and biochemical parameters were measured and analyzed. Results: The majority of our patients had osteopenia or osteoporosis over at least one part of the skeleton although none had jaundice. Instead of T helper 1 cell cytokine, interleukin (IL)-4 had a significant negative correlation with BMD of the right femoral neck (β = −0.251, p = 0.027) and left femoral neck (β = −0.299, p = 0.012) independently by multiple linear regression analysis. Conclusion: We conclude that chronic inflammation with increased expression of IL-4 may be an important factor for compromised bone health in patients with biliary atresia

Clinical Features and Therapeutic Response in Taiwanese Children With Wilson's Disease: 12 Years of Experience in a Single Center

Wilson's disease (WD) is an autosomal recessive defect of cellular copper export. Early diagnosis in children is difficult due to its obscure clinical presentations. The efficacy of zinc salts is well documented, although there are limited data concerning zinc use in pediatric patients with WD. Methods: We performed a retrospective analysis of clinical features, laboratory results and treatment responses in children with WD diagnosed at Taichung Veterans General Hospital between 1996 and 2008. Diagnosis was established by low serum ceruloplasmin, high 24-hour urinary copper excretion, presence of Kayser-Fleischer rings, and mutation analysis. Results: Eleven children were included in this study. The main initial presentations were impaired liver function tests (6/11) and hemolytic anemia (2/11). Gene studies in seven children showed six different mutations (G934D, R778Q, C490X, 304insC, IVS4-1 G > C, P992I) and one possible novel mutation (L1181P). All patients had improved liver function tests and hemoglobin levels after treatment with D-penicillamine, trientine and zinc supplement therapy. During a mean period of 3.4 ± 2.1 years with zinc therapy, six patients had serum zinc levels above the normal limit, and seven patients had serum copper levels below the normal range. Conclusion: Serum ceruloplasmin and 24-hour urinary copper examinations could be used to rule out WD in children with chronic hepatitis and hemolytic anemia. Gene analysis is helpful for prompt diagnosis of asymptomatic siblings and patients with atypical features. Zinc treatment is generally safe in pediatric patients with WD. However, its adverse effects should be monitored

Wound infections secondary to snakebite in central Taiwan

There are very few microbiological data on wound infections following snakebites. The objective of this study was to investigate the treatment of secondary infection following snakebites in central Taiwan. Microbiological data and antibiotic sensitivity of wound cultures were retrospectively analyzed from December 2005 to October 2007 in a medical center in central Taiwan. A total of 121 snakebite patients participated in the study. Forty-nine (40.5%) subjects were bitten by cobra (Naja atra); 34 of them had secondary infection, and 24 of them (70.6%) needed surgical intervention. Cobra bites caused more severe bacterial infection than other snakebites. Morganella morganii was the most common pathogen, followed by Aeromonas hydrophila and Enterococcus. Gram-negative bacteria were susceptible to amikacin, trimethoprim/sulfamethoxazole, cefotaxime, cefepime, ciprofloxacin, and piperacillin/tazobactam. Enterococcus were susceptible to ampicillin, gentamicin, penicillin and vancomycin. It is reasonable to choose piperacillin/tazobactam, quinolone, second- or third-generation cephalosporin for empirical therapy following snakebite. Surgical intervention should be considered for invasive soft tissue infections

Treatment With Propranolol for Infantile Hemangioma in 13 Taiwanese Newborns and Young Infants

Hemangioma in infants has a benign self-limited course, but the 10% of cases with complications need further treatment. Successful treatment with propranolol in western countries has been reported over the past few years. We evaluated the efficacy of propranolol for treating infantile hemangioma in Taiwanese newborns and young infants. Methods: Patients below 1 year of age treated with propanolol between November 2009 and March 2011 were enrolled. Demographic data, clinical features, imaging findings, treatment regimens of propranolol, and outcome were investigated. Results: Thirteen patients were treated with propranolol at a dose of 2–3 mg/kg/day. Seven (53.8%) patients had solitary hemangioma and six had multiple ones. The indications for treatment were risk of local event in nine patients, functional risk in four, local complication in one, and life-threatening complication in one. The median age for starting propranolol was 4 months (range: 1–11 months). Responses to propranolol, such as decolorization, regression in tumor size, or improvement of hemangioma-associated complications were observed in all patients within 1–2 weeks after treatment. Propranolol-associated adverse effects occurred in two patients. One infant had occasional tachypnea, and the other had occasional pale-looking appearance. The symptoms resolved after dosage tapering. Conclusion: Propranolol may be a promising therapeutic modality for infantile hemangioma. Therapeutic strategies are needed to evaluate the optimal treatment protocol and long-term adverse effects