Comparing Axillary and Rectal Temperature Measurements in Very Preterm Infants: A Prospective Observational Study.

PURPOSE: The agreement between axillary temperature (AT) and rectal temperature (RT) measurements has not been well established in preterm infants. Therefore, our study aimed to evaluate the agreement between AT and RT measurements in very preterm infants. METHODS: Preterm infants <32 weeks of gestational age were prospectively included. The infants' body temperature (BT) was measured twice a day from day 1 to day 6. A paired t-test and the Bland-Altman method were used to analyze the difference between the AT and RT. A linear regression model was used to explore the effects of environmental factors on the differences of BT between the axillary and rectal measurements and to calibrate the RT according to the AT. RESULTS: Eighty infants each underwent 6 paired axillary and rectal measurements. The gestational age varied from 22 to 31 weeks (mean 28 weeks). The birth weight varied from 302 to 1,770 g (mean 1,025 g). The AT was significantly lower than the RT. The difference between the RT and AT significantly increased with increasing RT. The AT and RT demonstrated poor agreement overall; however, the RT can be estimated using the AT with the following equation: RT = -4.033 + 1.116 × AT. Environmental factors, including the incubator temperature, incubator humidity, phototherapy, and application of invasive mechanical ventilation did not affect the differences between the AT and RT measurements. CONCLUSION: AT measurements cannot be interchangeably used with RT measurements in very preterm infants.

Brassinin, a phytoalexin in cruciferous vegetables, suppresses obesity-induced inflammatory responses through the Nrf2-HO-1 signaling pathway in an adipocyte-macrophage co-culture system.

The aim of this study was to investigate the effect of brassinin (BR), a phytoalexin found in plants belonging to the Brassicaceae family, on the obesity-induced inflammatory response and its molecular mechanism in co-culture of 3T3-L1 adipocytes and RAW264.7 macrophages. BR effectively suppressed lipid accumulation by down-regulating the expression of adipogenic factors, which in turn, were regulated by early adipogenic factors such as CCAAT-enhancer-binding protein-ß and Kruppel-like factor 2. Production of inflammatory cytokines and reactive oxygen species, induced by adipocyte-conditioned medium, was significantly decreased in BR-treated cells. This effect of BR was more prominent in contact co-culture of adipocytes and macrophages with a 90% and 34% reduction in IL-6 and MCP-1 levels, respectively. BR also restored adiponectin expression, which was significantly reduced by culturing adipocytes in macrophage-conditioned medium. In the transwell system, BR increased the protein levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its target molecule, hemoxygenase-1 (HO-1), by 55%-93% and 45%-48%, respectively, and also increased Nrf2 translocation into the nucleus. However, knockdown of Nrf2 or HO-1 in RAW264.7 cells restored this BR-mediated inhibition of IL-6 and MCP-1 production. These results indicated that BR inhibited obesity-induced inflammation via the Nrf2-HO-1 pathway.

Red ginseng-derived saponin fraction suppresses the obesity-induced inflammatory responses via Nrf2-HO-1 pathway in adipocyte-macrophage co-culture system.

The aim of this study was to investigate the effect of saponin fraction (SF) from red ginseng on obesity-induced inflammatory response in a co-culture system of 3T3-L1 and RAW264.7 cells. HPLC analysis showed that SF contains more than 50% ginsenosides, and Rb1 was the most abundant ginsenoside [135.31 µg/mg (extract)]. The production of nitric oxide and cytokines, induced by adipocyte-conditioned medium (3T3-CM), was significantly decreased by SF. SF (100 µg/mL) suppressed the abundance of tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) by 78%, 40%, and 22%, respectively. This SF-mediated reduction in inflammatory cytokines was due to the suppression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation, and translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) into the nucleus. SF also regulated adipokine expression in adipocytes, which were stimulated by macrophage-conditioned medium (RAW-CM); adiponectin expression was upregulated (> 2-fold), while resistin was downregulated (40%). In the contact system of adipocytes and macrophages, SF significantly decreases MCP-1 (37%) and IL-6 (25%) production. In the transwell system, SF (100 µg/mL) significantly increased the abundance of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its target protein, hemoxygenase-1 (HO-1) by 1.5∼3.5-fold and 2.8∼3.6-fold, respectively, thus increasing Nrf2 translocation into nucleus. However, SF-mediated inhibitory effect on the release of IL-6 and MCP-1 cytokines was reversed in the Nrf2 or HO-1 knockdown condition. This result indicated that SF-mediated inhibition of obesity-induced inflammation was dependent on Nrf2 activation.

Safety and immunogenicity of therapeutic DNA vaccine with antiviral drug in chronic HBV patients and its immunogenicity in mice.

BACKGROUND & AIMS: Here, we evaluated the safety and immunogenicity of hepatitis B virus (HBV) DNA vaccine, HB-110, in mice and Korean patients with chronic hepatitis B (CHB) undergoing adefovir dipivoxil (ADV) treatment. METHODS: For animal study, mice (BALB/c or HBV transgenic) were immunized with mHB-110, and T-cell and antibody responses were evaluated. For clinical study, 27 patients randomly received either ADV alone or ADV in combination with HB-110. Liver function tests, serum HBV DNA levels and the presence of HBeAg/anti-HBe were analysed. T-cell responses were estimated by ELISPOT and FACS analysis. RESULTS: mHB-110 induced higher T-cell and antibody responses than mHB-100 in mice. No adverse effects were observed by HB-110 cotreated with ADV. HBV-specific T-cell responses were induced in a portion of patients in medium to high dose of HB-110. Interestingly, HB-110 exhibited positive effects on ALT normalization and maintenance of HBeAg seroconversion. One patient, who received high dose of HB-110 exhibited HBeAg seroconversion during vaccination, which correlated with vaccine-induced T-cell responses without ALT elevation. CONCLUSIONS: HB-110 was safe and tolerable in CHB patients. In contrast to results in animal models, HB-110 in Korean patients exhibited weaker capability of inducing HBV-specific T-cell responses and HBeAg seroconversion than HB-100 in Caucasian patients. As Asian patients, who are generally infected via vertical transmission, appeared to have higher level of immune tolerance than Caucasian, novel approaches for breaking immune tolerance rather than enhancing immunogenicity may be more urgently demanded to develop effective therapeutic HBV DNA vaccines.

Preclinical studies for pharmacokinetics and biodistribution of Ad-stTRAIL, an adenovirus delivering secretable trimeric TRAIL for gene therapy.

Malignant glioma is the most frequent type in brain tumors. The prognosis of this tumor has not been significantly improved for the past decades and the average survival of patients is less than one year. Thus, an effective novel therapy is urgently needed. TNF-related apoptosis inducing ligand (TRAIL), known to have tumor cell-specific killing activity, has been investigated as a novel therapeutic for cancers. We have developed Ad-stTRAIL, an adenovirus delivering secretable trimeric TRAIL for gene therapy and demonstrated the potential to treat malignant gliomas. Currently, this Ad-stTRAIL gene therapy is under phase I clinical trial for malignant gliomas. Here, we report preclinical studies for Ad-stTRAIL carried out using rats. We delivered Ad-stTRAIL intracranially and determined its pharmacokinetics and biodistribution. Most Ad-stTRAIL remained in the delivered site and the relatively low number of viral genomes was detected in the opposite site of brain and cerebrospinal fluid. Similarly, only small portion of the viral particles injected was found in the blood plasma and major organs and tissues, probably due to the brain-blood barrier. Multiple administrations did not lead to accumulation of Ad-stTRAIL at the injection site and organs. Repeated delivery of Ad-stTRAIL did not show any serious side effects. Our data indicate that intracranially delivered Ad-stTRAIL is a safe approach, demonstrating the potential as a novel therapy for treating gliomas.