Hemolytic uremic syndrome associated with pneumococcal pneumonia in Taiwan

Abstract Streptococcus pneumoniae ( S. pneumoniae ) has been associated with hemolytic uremic syndrome (HUS), which is an unusual but serious disease in childhood. We conducted a retrospective review of children aged less than 18 years with S. pneumoniae -associated HUS in northern Taiwan from January 2000 to June 2005. The demographic characters, clinical courses, and outcomes were analyzed. Seven children (three girls, four boys) with S. pneumoniae -associated HUS were studied. The median age at onset of HUS was 40 months (range: 25–60 months). The median duration of hospital stay was 36 days (range: 15–50 days). The interval between the onset of illness attributable to S. pneumoniae and the development of HUS was around 1–2 weeks. The onset of oliguria developed within 2 weeks after illness. Six patients required dialysis with median duration of 16 days. Three patients had leukopenia as the initial presentation. All seven patients had pneumococcal pneumonia complicating with empyema, and two of them received decortication via video-assisted thoracoscopic surgery. Between patients who needed dialysis or not, there was no significant difference in age, sex, duration of thrombocytopenia, incidence of extra-renal complications, such as hepatitis, pancreatitis, and hypertension, and length of hospital stay. The seven patients survived with normal renal function. HUS is a potentially fatal complication of S. pneumoniae infection. Clinicians managing patients with pneumococcal pneumonia with empyema accompanied by leukopenia should beware of the development of HUS. The long-term prognosis for recovery of renal function appears to be good in these patients in northern Taiwan.     

Bacterial tracheitis in pediatrics: 12 year experience at a medical center in Taiwan

Background:  Bacterial tracheitis may cause life-threatening airway obstruction.
Methods:  Records of patients admitted to the pediatric wards of Mackay Memorial Hospital between 1994 and 2005 with a diagnosis of bacterial tracheitis made on bronchoscopic visualization of thick membranous tracheal secretions were retrospectively reviewed.
Results:  A total of 40 patients (aged 1 month–8 years, 29 [73%] under 3 years old) were included. Cough, fever, dyspnea, and hoarseness were the commonest symptoms. Fourteen patients (21%) required intubation. The most frequently isolated bacteriae were α-hemolytic streptococcus (in 11, 38%), pseudomonas (5, 17%), and Staphylococcus aureus (4, 14%). Intubation was more frequent in patients seen between 1994 and 1999 compared with those seen later (8/12 early vs 9/28 late). In the early period α-hemolytic streptococcus (55%) and pseudomonas (36%) were isolated. In the later period the most frequently isolated bacteria was α-hemolytic streptococcus (28%), followed by S. aureus (22%). No patients died, but those with pseudomonas infection had more severe complications, including tracheal stenosis. The average hospital stay in the early period was 26.2 ± 20.5 days versus 9.1 ± 4.8 days in the late period. The corresponding lengths of stay in the intensive care unit were 10.5 ± 11.5 days and 2.0 ± 2.2 days.
Conclusions:  Bacterial tracheitis requiring hospitalization of children appeared to be milder in the second half of the study period. Pseudomonas tracheitis tends to have a severe course.     

Transmission of cytomegalovirus from mothers to preterm infants by breast milk

OBJECTIVES: To assess the risk of transmission of cytomegalovirus (CMV) by breast milk from CMV-seropositive mothers to their breast-fed preterm infants and to evaluate their outcome. PATIENTS AND METHODS: The study population comprised breast-fed preterm infants with a birth weight of <1,500 g and gestational age of <35 weeks. Venous blood samples from the mothers and infants were tested for CMV IgG and IgM antibodies on the 5th and 30th day after birth. Breast milk was obtained for CMV DNA detection by polymerase chain reaction and viral culture on the 5th day and on the 3rd, 6th and 12th week. Urine samples of the babies were collected at the same time for CMV culture. Neurodevelopmental assessment was done at 6 months of age, corrected for preterm birth. RESULTS: Thirty-eight mothers and 42 infants (including 4 sets of twins) were enrolled in the study. A mother-infant pair was excluded because of inadequate breast milk collection. Thirty-six mothers (97.3%) were CMV-seropositive. CMV DNA of breast milk was detected in 35 seropositive mothers. Six infants of 5 mothers were infected (infected group) at a mean of 77 days after birth, and 34 infants of 31 mothers were not (noninfected group). In all the mothers of the infected group, CMV virus could be cultured from the milk whey. The average maternal CMV IgG on day 5 after delivery was higher in the infected than in the noninfected group. Sepsis-like symptoms and hyperbilirubinemia were more frequently noted in the infected infants than in the noninfected, but the difference was not statistically significant. Neurodevelopmental outcome did not significantly differ between the 2 groups. CONCLUSIONS: The risk of CMV infection in breast-fed premature infants was highest when the mothers shed viable virus in their breast milk. These mothers had high CMV IgG, which may help identify those mother-infant pairs at risk. Inactivation of the virus in milk by freezing may be a way of reducing the transmission of this virus via breast milk.     

Filamentous, mixed micelles of triblock copolymers enhance tumor localization of indocyanine green in a murine xenograft model

Polymeric micelles formed by the self-assembly of amphiphilic block copolymers can be used to encapsulate hydrophobic drugs for tumor-delivery applications. Filamentous carriers with high aspect ratios offer potential advantages over spherical carriers, including prolonged circulation times. In this work, mixed micelles composed of poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) (PEO-PHB-PEO) and Pluronic F-127 (PF-127) were used to encapsulate a near-infrared fluorophore. The micelle formulations were assessed for tumor accumulation after tail vein injection to xenograft tumor-bearing mice by noninvasive optical imaging. The mixed micelle formulation that facilitated the highest tumor accumulation was shown by cryo-electron microscopy to be filamentous in structure compared to spherical structures of pure PF-127 micelles. In addition, increased dye loading efficiency and dye stability were attained in this mixed micelle formulation compared to pure PEO-PHB-PEO micelles. Therefore, the optimized PEO-PHB-PEO/PF-127 mixed micelle formulation offers advantages for cancer delivery over micelles formed from the individual copolymer components.     

The association between availability of serotonin transporters and time to relapse in heroin users - A two-isotope SPECT small sample pilot study

Neuroimaging evidence supporting an association between either dopamine or serotonin and time to relapse of heroin users is limited. In this two-isotope SPECT small sample (N=9) pilot study, the relationship between the availability of serotonin transporter (SERT) and dopamine transporter (DAT) and the relapse of heroin users was investigated. A significant negative association between SERT availability and time to relapse among those who relapsed (N=7) was found.     

Prevention of human enterovirus 71 infection by kappa carrageenan

Enterovirus 71 (EV 71), the newest member of Enteroviridae, is notorious for its etiological role in epidemics of the hand-foot-and-mouth disease, particularly in association with fatal neurological complications in young children. Searching for new and more effective agents against EV 71 infections has never relented as corresponding vaccines or antiviral drugs remain unavailable. Sulfated polysaccharides from seaweed are known to possess a broad range of biological activities across anti-virus, anti-tumor, immunomodulation, anti-coagulation, etc. In this study, we report kappa carrageenan also has a strong and effective anti-EV 71 activity able to reduce plaque formation, prevent viral replication before or during viral adsorption, as well as inhibit EV 71-induced apoptosis. In virus binding assay, kappa carrageenan was shown able to bind EV 71 firmly, forming carrageenan-viruses complexes, whereby the virus-receptor interaction is likely disrupted. Added together, kappa carrageenan may be an ideal candidate worthwhile to develop into anti-EV 71 agents.     

Availability of dopamine and serotonin transporters in opioid-dependent users—a two-isotope SPECT study

Rationale and objective

The aims of this study were to examine the differences between 32 opioid-dependent users treated with a very low dose of methadone or undergoing methadone-free abstinence and 32 controls.

Methods

SPECT analysis using [^99mTc] TRODAT-1 to assess striatal dopamine transporter (DAT) availability and [¹²³I] ADAM to assess midbrain serotonin transporter (SERT) availability were performed.

Results

Lower striatal DAT and midbrain SERT availabilities were noted in low-dose methadone users. History of metamphatamine use was associated with the lower striatal DAT. The striatal DAT of methadone-free abstainers was also lower than controls. The midbrain SERT availability tended to be higher in the methadone-free abstainers than the low-dose methadone users. The severity of depressive symptoms was negatively correlated with midbrain SERT availability in the opioid users.

Conclusion

The availability of striatal DAT tended to be, and the availability of midbrain SERT was, lower in the opioid users. History of metamphatamine use may confound the difference in straital DAT between controls and opioid users, as midbrain SERT and depressive symptoms are also associated with opioid use and abstinence.     

AMPK‐dependent signaling modulates the suppression of invasion and migration by fenofibrate in CAL 27 oral cancer cells through NF‐κB pathway

Fenofibrate, a peroxisome proliferator‐activated receptor alpha (PPARα) agonist and lipid‐lowering agent, has been used worldwide for treatment of hyperlipidemia. The clinical trials demonstrate that fenofibrate possesses multiple pharmacological activities, including antitumor effects. However, the precise mechanisms in oral squamous cell carcinoma (OSCC) remain unclear. In this study, we investigated the anticancer effects of fenofibrate on the migration and invasion of human oral cancer CAL 27 cells. Fenofibrate inhibited the cell migration and invasion of CAL 27 cells by the wound healing and Boyden chamber transwell assays, respectively. In addition, fenofibrate reduced the protein expressions of MMP‐1, MMP‐2, MMP‐7, and MMP‐9 by Western blotting and inhibited enzyme activities of MMP‐2/‐9 using gelatin zymography assay. Results from immunoblotting analysis showed that the proteins of p‐LKB1 (Ser428), LKB1, p‐AMPKα (Thr172), p‐AMPKα1/α2 (Ser425/Ser491), p‐AMPKβ1 (Ser108), and AMPKγ1 were upregulated by fenofibrate; the levels of p‐IKKα/β (Ser176) and p‐IκBα were reduced in fenofibrate‐treated cells. Also, fenofibrate suppressed the expressions of nuclear NF‐κB p65 and p50 by immunoblotting and NF‐κB DNA binding activity by EMSA assay. The anti‐invasive effect of fenofibrate was attenuated by compound C [an adenosine 5′‐monophosphate‐activated protein kinase (AMPK) inhibitor] or dominant negative form of AMPK (DN‐AMPKα1). Thus, fenofibrate considerably inhibited metastatic behaviors of CAL 27 cells might be mediated through blocking NF‐κB signaling, resulting in the inhibition of MMPs; these effects were AMPK‐dependent rather than PPARα signaling. Our findings provide a molecular rationale, whereby fenofibrate exerts anticancer effects and additional beneficial effects for the treatment of cancer patients. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 866–876, 2016.     

OSU-A9, an indole-3-carbinol derivative,induces cytotoxicity in acute myeloid leukemia through reactive oxygen species-mediated apoptosis

Indole-3-carbinol (I3C) is a broadly targeted phytochemical shown to prevent carcinogenesis in animal studies and to suppress the proliferation of cancer cells of human breast, colon, prostate, and endometrium. Here we demonstrate that OSU-A9, an I3C derivative with improved anticancer potency, induces cytotoxicity in acute myeloid leukemia (AML) cell lines (HL-60 and THP-1) and primary leukemia cells from AML patients in a dose-responsive manner. Normal human bone marrow cells were less sensitive to OSU-A9 than leukemia cells. OSU-A9 induces caspase activation, PARP cleavage, and autophagy but not autophagic cell death. Interestingly, pretreatment of AML cell lines and primary AML cells with N-acetylcysteine or glutathione rescues them from apoptosis (and concomitant PARP cleavage) and Akt hypophosphorylation, implicating a key role of reactive oxygen species (ROS) in OSU-A9-related cytotoxicity. Importantly, the anticancer utility of OSU-A9 is extended in vivo as it, administered intraperitoneally, suppresses the growth of THP-1 xenograft tumors in athymic nude mice without obvious toxicity. This study shows that ROS-mediated apoptosis contributes to the anticancer activity of OSU-A9 in AML cell lines and primary AML cells, and thus should be considered in the future assessment of its translational value in AML therapy.