Evaluation of LPS-Induced Acute Lung Injury Attenuation in Rats by Aminothiazole-Paeonol Derivatives.

Paeonol is a key phenolic compound in the root bark of Moutan Cortex Radicis that has been used in traditional Chinese Medicine to ameliorate inflammation. A series of aminothiazole-paeonol derivatives (APDs) were synthesized in this work and subjected to preliminary evaluation in cells followed by verification in animals. Quantification of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in culture media of LPS-activated A549 cells, a lung epithelial adenocarcinoma cell line, were used to investigate the anti-inflammatory capability of APDs. ALI-bearing rats were employed to verify therapeutic efficacy of APDs according to observations of total cells, protein amounts, MCP-1 and IL-6 in bronchoalveolar lavage fluid (BALF). Histopathological examinations of lung tissues were consequently applied for validation of APDs. Among these compounds, 2-(2-aminothiazol-4-yl)-5-methoxyphenol (4) had the most potent activity, showing comparable inhibition of MCP-1/IL-6 and superior elimination of neutrophil infiltration and protein exudation in lungs compared to others as well as dexamethasone. This study demonstrated a comprehensive strategy to evaluate APDs through integration of cell-based screening and animal-based verification. In order to fulfill unmet needs of treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), APDs introduced in this work could be promising lead compounds to develop high potent anti-inflammation agents.

Protective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1, 4-diol on ischemic and hypoxic neuronal injury.

BACKGROUND: Stroke is one of the leading causes of neuronal death. Sesamin is known for neuroprotection by its antioxidant and anti-inflammatory properties but it lacks blood-brain barrier (BBB) activity. A panel of sesamin derivatives was screened and 3-bis (3-methoxybenzyl) butane-1,4-diol (BBD) was selected for high BBB activity and tested for its neuroprotective effect. METHODS: The focal cerebral ischemia of Sprague-Dawley rats and hypoxia models of murine BV-2 microglia or PC12 cells under oxygen/glucose deprivation were used for in vivo and in vitro test, respectively. Lipid peroxidation and superoxide dismutase (SOD) activity from the ischemic brain were tested and reactive oxygen species (ROS), cytokine production, prostaglandin (PGE2) and related signaling pathways from hypoxic cells were examined by ELISA or Western blot assay, respectively. RESULTS: BBD showed a protective effect when given 90 min after the focal cerebral ischemia. It also reduced lipid peroxidation and preserved SOD activity from the ischemic brain. The mechanism of BBD was further confirmed by attenuating ROS, cytokine production, and PGE2 release from hypoxic BV-2 or PC12 cells. BBD significantly reduced hypoxia-induced c-Jun N-terminal kinases (JNK) and modulated AKT-1 and caspase-3 (survival and apoptotic pathways) in BV-2 cells, and inhibited hypoxia-induced JNK and cyclooxygenase-2 activation in PC12 cells. CONCLUSIONS: The neuroprotective effect of BBD on ischemia/hypoxia models was involved with antioxidant and anti-inflammatory effects. The result would help the development of new CNS drug for protection of ischemia/hypoxia injury.

Energetic studies on DNA-peptide interaction in relation to the enthalpy-entropy compensation paradox.

This study aims to interpret the energetic basis of complex DNA-peptide interactions according to a novel allosteric interaction network approach. In common with other designed peptides, five new conjugates incorporating the XPRK or XHypRK motif (Hyp = hydroxyproline) attached to a N-methylpyrrole (Py) tract with a basic tail have been found to display cooperative binding to DNA involving multiple monodentate as well as interstrand bidentate interactions. Using quantitative DNase I footprinting it appears that allosteric communication via cooperative binding to multiple sites on complementary DNA strands corresponds to two different types of DNA-peptide interaction network. Temperature variation experiments using a dodecapeptide RY-12 show that lower temperature (25 °C) favor a circuit type of allosteric interaction network, whereas higher temperatures (31 and 37 °C) afford only a partial-circuit type of network. Circular dichroism studies show that our five peptides induce significant local conformational changes in DNA via the minor groove, with apparently dimeric binding stoichiometry. Isothermal titration calorimetry reveals that these peptides, together with another seven for comparison, are strongly exothermic upon binding to a model 13-mer DNA duplex, characterized by ΔH ranging from -14.7 to -74.4 kcal mol(-1), and also high TΔS ranging from -6.5 to -65.9 kcal mol(-1). Multiple monodentate and bidentate interactions, as well as ionic forces that mediate positive cooperativity in sequence recognition, are consistent with a dramatic decrease in entropy and a 'tightening' effect of DNA conformation. Distinctive enthalpy-entropy compensation (EEC) relationships are demonstrated for the interaction of all twelve designed peptides with DNA, affording a straight line of slope close to unity when ΔH is plotted versus TΔS, with a y-axis intercept (average ΔG) corresponding to -8.5 kcal mol(-1), while the observed ΔG ranges from -8.2 to -9.1 kcal mol(-1) for the peptides. The EEC seen with peptide RY-12 binding to the model duplex persists throughout various incubation temperatures. The net compensation of energy between the favorable negative ΔH and unfavorable negative ΔS components thus constrains the value of net binding free energy ΔG within a remarkably constant range, as is clearly visible in a 3-dimensional energetic plot. We conclude that the preservation of a rather narrowly-defined ΔG value is central to the EEC in DNA-peptide interactions, illuminating the universal EEC paradox commonly found in diverse biochemical reactions.

Synthesis and evaluation of [18F]Fluorobutyl ethacrynic amide: a potential PET tracer for studying glutathione transferase.

[(18)F]Flurobutyl ethacrynic amide ([(18)F]FBuEA) was prepared from the precursor tosylate N-Boc-N-[4-(toluenesulfonyloxy)butyl]ethacrynic amide with a radiochemical yield of 3%, a specific activity of 48 GBq/µmol and radiochemical purity of 98%. Chemical conjugation of [(18)F]FBuEA with glutathione (GSH) via a self-coupling reaction and enzymatic conjugation under catalysis of glutathiontransferase alpha (GST-α) and π provided about 41% yields of radiochemical conjugated product [(18)F]FBuEA-GSH, 85% and 5-16%, respectively. The catalytic selectivity of this tracer toward GST-alpha was addressed. Positron emission tomography (PET) imaging of [(18)F]FBuEA in normal rats showed that a homogeneous pattern of radioactivity was distributed in the liver, suggesting a catalytic role of GST. By contrast, PET images of [(18)F]FBuEA in rats with thioacetamide-induced cholangiocarcinoma displayed a heterogeneous pattern of radioactive accumulation with cold spots in tumor lesions. PET imaging with [(18)F]FBuEA could be used for early diagnosis of hepatic tumor with a low GST activity as well as liver function.

Neuroprotective effects of carnosic acid on neuronal cells under ischemic and hypoxic stress.

Ischemia/hypoxia induces oxidative stress which is associated with neurodegenerative diseases. The present study investigated protective mechanism of carnosic acid (CA) on ischemia/reperfusion and hypoxia-induced neuronal cell injury. The results showed that CA reduced 52% of the infarct volume from brains under ischemia/reperfusion in vivo and protected the PC12 cells from hypoxic injury in vitro. CA (1.0 µM) enhanced cell viability, prevented lactic dehydrogenase (LDH) release, scavenged reactive oxygen species (ROS), increased superoxide dismutase activity, and attenuated Ca(2+) release, lipid peroxidation, and prostaglandin E2 production in hypoxic PC12 cells. In addition, CA also reduced nitric oxide (NO) and interleukine (IL)-1 and IL-6 production from activated BV-2 microglia. Furthermore, its effect on hypoxia-induced mitogen-activated protein kinases (MAPKs) signaling pathway and caspase-3 was examined. Extracellular signal-regulated protein kinases, c-jun NH2-terminal kinase, and p38 MAPK were activated during hypoxia. CA inhibited MAPKs, caspase-3, and COX-2 activation and correlated well with the diminished LDH release and apoptosis (TUNEL) in PC12 cells under hypoxia. Taken together, CA protected neuronal cells under ischemia/hypoxia through scavenging or reducing of ROS and NO, inhibiting COX-2 and MAPK pathways by anti-inflammatory and anti-oxidative properties.

Synthesis of amino core compounds of galactosyl phytosyl ceramide analogs for developing iNKT-cell inducers.

1-Aminophytosphingosine and 6-aminogalactosyl phytosphingosine were prepared in 61% and 40% yield libraries with 44 carboxylic acids showed that a 4-butylbenzoic acid-derived product exe, respectively. Glycosylation using benzoyl-protected lipid resulted in better a-selectivity for ceramide analogs, but the yield was less than that obtained with benzyl moieties. Screening the amide rted less cytotoxicity. These analogs were purified for validation of immunological potencies and the a-GalCer analog but not the sphingosine analog stimulated human iNKT cell population.

Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation.

BACKGROUND: Kainic acid (KA)-induced status epilepticus (SE) was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. METHODS: Rodents (male FVB mice and Sprague-Dawley rats) were fed with sesamin extract (90% of sesamin and 10% sesamolin), 15 mg/kg or 30 mg/kg, for 3 days before KA subcutaneous injection. The effect of sesamin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA), neurodegeneration (Caspase-3), and inflammation (COX-2) in PC12 cells and microglial BV-2 cells. RESULTS: Treatment with sesamin extract (30 mg/kg) significantly increased plasma α-tocopherol level 50% and 55.8% from rats without and with KA treatment, respectively. It also decreased malondialdehyde (MDA) from 145% to 117% (p=0.017) and preserved superoxide dismutase from 55% of the vehicle control mice to 81% of sesamin-treated mice, respectively to the normal levels (p=0.013). The treatment significantly decreased the mortality from 22% to 0% in rats. Sesamin was effective to protect PC12 cells and BV-2 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca2+, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that sesamin significantly reduced ERK1/2, p38 mitogen-activated protein kinases, Caspase-3, and COX-2 expression in both cells and RhoA expression in BV-2 cells. Furthermore, Sesamin was able to reduce PGE2 production from both cells under KA-stimulation. CONCLUSIONS: Taken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory and partially antioxidative mechanisms.

Solution-phase parallel synthesis and screening of anti-tumor activities from fenbufen and ethacrynic acid libraries.

The derivatives with fenbufen and ethacrynic acid core compounds was synthesized through a facial preparation of 1-amino-4-azidobutane. The subsequent coupling with 102 members of carboxylic acids afforded amide products. The in situ screening using colorimetric assay with 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide showed that fenbufen but not ethacrynic acid butyl amide members displayed the cytotoxicities to tumor cells substantially, including two human cell lines (MCF7 and A549) and two murine cell lines (C26 and TRAMP-C1). Three fenbufen analogs were found to have a good anti-tumor activity comparable to cisplatin.

Detection of multiple network-based allosteric interactions between peptides and arrays of DNA binding sites.

Quantitative DNase I footprinting shows that three designed peptides containing N-methylpyrrole (Py) moieties display different types of network-based allosteric communication in binding to DNA: circuit type, incomplete-circuit type, and non-circuit type characterized by interstrand bidentate interactions. Positive cooperative binding of all three peptides to individual DNA binding sites is commonly observed. CD spectral characterization of the interaction between peptides and model undecanucleotide duplexes is consistent with the footprinting results and supports the allosteric model. This study provides insights relating to the interaction network nature of allostery in complex DNA-small molecule interactions.

Novel DNA-peptide interaction networks.

Allostery in the binding of peptides to DNA has been studied by quantitative DNase I footprinting using four newly designed peptides containing the XP(Hyp)RK motif and N-methylpyrrole (Py) moieties. Apparent binding constants in the micromolar range as well as Hill coefficients were determined for each peptide. The results, together with previous studies on five other peptides support the proposal that interaction network cooperativity is highly preferred in DNA-peptide interactions that involve multiple recognition sites. It is envisaged that interstrand bidentate interactions participate in the relay of conformational changes between recognition sites on the complementary strands. Models for interpreting DNA allostery based upon interaction networks are outlined. Circular dichroism experiments involving the titration of peptides against a short oligonucleotide duplex indicate that some of these peptides bind in a dimeric manner to DNA via the minor groove, inducing characteristic conformational changes. These insights should prompt the design of new DNA-binding peptides for investigating allosteric interactions between peptides and DNA, as well as novel interaction networks, and ultimately may shed light upon the fundamental chemical rules that govern allostery in more complex biological process such as DNA-protein interaction networks.

Effect of naloxone on the induction of immediately early genes following oxygen- and glucose-deprivation in PC12 cells.

Cerebral ischemia/reperfusion involves inflammatory process and naloxone is able to reduce infarct volume and has been used as a therapeutic agent for brain injury. Hypoxia induces the immediate early genes (IEGs) rapidly and transiently that may initiate a cascade of cellular responses that are necessary for survival and normal function. However, the protective effect of naloxone on ischemic/hypoxic neuronal cells was only partly studied. Thus, the effects of naloxone on oxygen- and glucose-deprivation (OGD) and OGD followed by reoxygenation (OGD/R) on the expression of IEGs were examined in PC12 cells. The result showed that lactate dehydrogenase (LDH) released in the media was reduced by naloxone. The temporal response of IEG mRNA encoding c-fos, c-jun, nur77, and zif268 was induced with different degree of intensity following hypoxia, whereas the level of GAPDH mRNA was relatively constant. However, these signals of c-fos, c-jun, and nur77 by hypoxia were reduced significantly by naloxone. Treatment with OGD also activated mitogen-activated protein kinase (MAPK) pathway. The induction of c-fos, c-jun, nur77, and zif268 by hypoxia was inhibited by naloxone (0.1 microM) and MAPK inhibitors (10 microM of U0126, D98059, SB203580). However, naloxone increased the expression of ERK1/2 by OGD concomitantly diminished the LDH release. Thus, the present studies demonstrated that OGD induced IEGs including c-fos, c-jun, nur77, and zif268 and MAPK signaling pathways were regulated differently by naloxone.

Bromelain inhibits lipopolysaccharide-induced cytokine production in human THP-1 monocytes via the removal of CD14.

Bromelain has been reported to have anti-inflammatory and immunomodulatory effects. However, the anti-inflammatory mechanism of bromelain is unclear. Therefore, we investigated the effect of bromelain on cytokine production from lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMC) and monocytic leukemia THP-1 cells. The result showed that bromelain (50-100 microg/ml) significantly and reversibly reduced tumor necrosis factor (TNF)-alpha interleukin- (IL)-1beta and IL-6 from LPS-induced PBMC and THP-1 cells. This effect was correlated with reduced LPS-induced TNF-alpha mRNA and NF-kappaB activity in THP-1 cells. In addition, bromelain dose-dependently inhibited LPS-induced prostaglandin E(2), thromboxane B(2) and COX-2 mRNA but not COX-1 mRNA. Importantly, bromelain degraded TNF-alpha and IL-1beta molecules, reduced the expression of surface marker CD14 but not Toll-like receptor 4 from THP-1 cells. Taken together, the results suggest that the suppression of signaling pathways by bromelain's proteolytic activity may contribute to the anti-inflammatory activity of bromelain.

Effect of Cordyceps militaris supplementation on sperm production, sperm motility and hormones in Sprague-Dawley rats.

Cordyceps species have been traditionally used as for the enhancement of sexual function, but its direct evidence is lacking. We investigated the spermatogenic effect of Cordyceps militaris (CM) as supplementation with CM mycelium to 7-week-old male Sprague-Dawley (SD) rats. Ninety rats (30 for each group) were selected to regular diet or diet supplemented with CM mycelium (1% and 5%) for 6 weeks. Epididymal sperm were collected from 6 animals per group at each interval of observation. They were allowed to recover for one week. The quality and quantity of sperm were compared in these rats. The CM supplementation resulted in an increase of serum cordycepin concentration (n = 6, each group) that correlated with treatment time and the cordycepin level was significantly higher (p < 0.05) in 5% group as compared to 1% group at the 5th and 6th week. Epididymal sperm count was enhanced significantly from the control, at the 5th week and peaked at the 6th week in both groups supplemented with CM (each time point, n = 6; p < 0.05) and maintained for 2 weeks after stopping the treatment. Increased serum testosterone and estradiol-17 (E2) concentrations were found in rats with the CM supplementation (p < 0.05), but not other hormones such as follicle stimulating hormone (FSH), luteinizing hormone (LH) or prolactin. Importantly, percentages of motile sperm cells were also enhanced significantly (p < 0.05) paralleled the serum testosterone pattern from the supplement groups as compared to the control group. Taken together, these results indicate that supplementation with CM improves sperm quality and quantity in rats.

Dispensing errors from look-alike drug trade names.

OBJECTIVES: To improve patient safety, we investigated near-miss dispensing errors in our hospital and evaluated the effectiveness of specific preventive strategies. METHODS: The incidence and type of near-miss dispensing errors in a single hospital in Taiwan were identified in 2013. The causes of dispensing errors were analysed by consensus of an expert panel comprising a senior pharmacist on duty, a group leader in the pharmacy and an author. Because alphabetical trade names were routinely used in our pharmacy, they were used for similarity analysis. Trigram-2b and normalised edit distance (NED) were used to calculate orthographic similarity and distance measure, respectively. The correlation between drug-name confusion and dispensing errors was then studied. Preventive strategies, including the introduction of tall man letters, were completed at the end of 2013, and error data were then recollected in 2014. Differences between before and after the interventions were examined by t-test. RESULTS: Before the intervention, look-alike alphabetical names were the main cause of dispensing wrong medicine (134/202, 66.3%). The frequency of near-miss dispensing errors correlated significantly with drug-name similarity (p<0.01). After implementation of preventive strategies, dispensing errors due to drug-name confusion were reduced significantly (77/140, 55.0%, p=0.004). CONCLUSIONS: The frequency of near-miss drug dispensing errors correlated with greater similarity or lower NED scores, and dispensing errors related to drug-name confusion were significantly reduced by our interventions. However, other dispensing errors might need to be investigated in order to prevent them.

Carrageenan polysaccharides and oligosaccharides with distinct immunomodulatory activities in murine microglia BV-2 cells.

This study was to investigate the anti-inflammatory activities in vitro of various carrageenans (Car) fractions (κ-, ι-, and λ-types) with well characterized molecular properties, using murine microglia BV-2 cell line treated with lipopolysaccharide (LPS) as model. It is indicated that pretreatments with the oligosaccharide fractions from κ- or ι-carrageenan acid hydrolysates (κ- and ι-CarAOS, respectively) at 125-500 µg/mL significantly and dose-dependently decreased the levels of tumor necrosis factor α (TNF-α) secreted from LPS-treated BV-2 cells, showing promisingly anti-inflammatory effects. Differently, pretreatments of most of polymeric carrageenans at 250-500 µg/mL significantly increased the TNF-α level, implying the co-inflammatory effects with LPS. The co-inflammatory effectiveness of pure carrageenans at 125 µg/mL was notable for λ-Car, followed by ι-Car, and insignificantly for κ-Car. Generally, cytokine TNF-α was a more sensitive biomarker to the presence of carrageenans than was the IL-6. The TNF-α level varied greatly at a low carrageenan concentration (125 µg/mL) and high polymer percentage (e.g. purified κ- and ι-Car). Conclusively, the anti-inflammatory effects on LPS-treated BV-2 cells could be attenuated by pretreatments with κ- and ι-CarAOS at 125-500 µg/mL.

Effect of microbial fermentation on content of statin, GABA, and polyphenols in Pu-Erh tea.

Besides cancer prevention, the hypolipidemic effects of tea have been well studied in animals and humans. Recently, statin has been identified in Pu-erh tea extract. Clinical trials have confirmed that statin decreases the incidence of major coronary and cerebrovascular events and this may be due to its hypolipidemic and antiinflammatory effects. Since a good Pu-erh tea needs longer storage (10 years or more) of fermentation to enhance the flavor and fragrance, we screened microorganisms from two Pu-erh teas, 20 and 25 years old. Species of fungi and bacteria strains that contributed to a good taste of Pu-erh tea were isolated. The effect of fermentation was investigated by inoculating fresh tea leaves with individual strains of isolated microorganisms. Results showed that statin, total polyphenol content, and the scavenging activities of alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radicals increased during fermentation. Tea leaves inoculated with Streptomyces bacillaris strain R9 had the highest polyphenol content (3.3 mg/100 g) and scavenging ability to DPPH radicals (92%). Streptomyces cinereus strain Y11 was equally good for polyphenol content but yielded the highest amount of statin (1012 ng/g) after 42 days of fermentation. Interestingly, the statin content of fresh tea leaves fermented with strain R9 or Y11 after 180 days was much higher (4- and 8-fold, respectively) than that of the 25-year-old Pu-erh tea (513 ng/g) as measured by the HPLC method. Similarly, these two strains also increased the content of gamma-aminobutyric acid (GABA) 5.7- and 4.7-fold in tea fermented for 180 days as compared with the fresh leaves (1270 microg/g) and that were higher than that of the Pu-erh tea (4900 microg/g). Taken together, the present results indicate that tea short-term fermented with S. bacillaris or S. cinereus enhances the color and content of statin, GABA, and polyphenols.

Improvement of sperm production in subfertile boars by Cordyceps militaris supplement.

Cordyceps species have been traditionally used for the enhancement of sexual function, however, there is few direct evidence to prove this. We investigated the spermatogenic effect of Cordyceps militaris (CM) by supplementation with CM mycelium to subfertile boars. Seventeen Duroc and 12 Landrace boars (29 to 40 months old) were selected to feed with regular diet (control groups, n = 8 and 6, respectively) or diet supplemented with CM mycelium (treatment groups, n = 9 and 6, respectively) for 2 months. Semen was collected once a week. The quality of fertile sperm (normally greater than 62% of motility and 70% of normal morphology) and the quantity (semen volume, and total sperm number) were compared in these boars. The result showed that sperm production was enhanced significantly at the end of first month (p < 0.05), peaked at the second month (p < 0.01) of supplementation with CM and was maintained for 2 weeks after stopping the treatment (p < 0.01). Plasma cordycepin concentration was detected in boars supplemented with CM but not in the controls. More importantly, the percentages of motile sperm cells and sperm morphology were also improved significantly in most of treated boars during the second month of supplementation (p < 0.01) and 2 weeks after the treatment (p < 0.05) as compared to their initial values. These results indicate that supplementation with CM mycelium improves sperm quality and quantity in subfertile boars and may partly support the role of Cordyceps in sexual enhancement.

Cross-linked bromelain inhibits lipopolysaccharide-induced cytokine production involving cellular signaling suppression in rats.

Bromelain has been reported to have anti-inflammatory and immunomodulatory effects. It has been cross-linked with organic acids and polysaccharides by gamma irradiation. The cross-linked (CL)-bromelain preparation resisted an acidic environment of pH 3 for 2 h and preserved 80% of its enzyme activity. Pretreatment of rats with CL-bromelain intragastrically for 7 days significantly reduced serum cytokine production induced by injected i.p. with 2.5 mg/kg of lipopolysaccharide (LPS). Bromelain significantly reduced serum glutamate-oxalacetate transaminase induced by LPS. The anti-inflammatory effect of CL-bromelain was correlated with reduced LPS-induced NF-kappaB activity and cyclooxygenase 2 (COX-2) mRNA expression in rat livers. In addition, CL-bromelain dose-dependently inhibited LPS-induced COX-2 mRNA and prostaglandin E2 (PGE2) in BV-2 microglial cells. CL-Bromelain also suppressed the LPS-activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK). In conclusion, the anti-inflammatory effects of the CL-bromelain preparation in vivo and in vitro suggest its therapeutic potentials.

Morbidity, mortality, associated injuries, and management of traumatic rib fractures.

BACKGROUND: Thoracic trauma is responsible for approximately 25% of trauma deaths, and rib fractures are present in as many as 40-80% of patients, and intensive care and/or ventilator support are frequently required for these patients. To identify their risk factors would improve treatment strategies for these patients. METHODS: Between March 2005 and December 2013, consecutive patients with blunt thoracic trauma, who were admitted to the Department of Thoracic Surgery at Tungs' Taichung Metro Harbor Hospital (Taichung, Taiwan), were reviewed in this retrospective cohort study with the approval of the Institutional Review Board. The duration of hospital stay, ventilator support, injury severity score (ISS), type of injury, associated injuries, treatments, and mortality were analyzed statistically. RESULTS: A total of 1621 thoracic trauma patients were included in this study, with a male majority and an age range of 18-95 years (mean age, 51.2 years). Approximately 11.7% of these patients had an ISS ≥ 16 and a mortality rate of 6.9%. Among them, 78.5% had rib fractures; 31.8%, traumatic hemothorax; 15.6%, pneumothorax; 9.6%, hemopneumothorax; and 4.6%, lung contusion. The most common associated injury was extremity fracture, followed by head injury and clavicle fracture. Surgery on the extremities (20.6% of patients) and chest tube placement (22.7% of patients) were the most common treatments. The number of rib fractures was associated with prolonged hospital and intensive care unit (ICU) stays (≥7 days), an ISS ≥ 16, and pulmonary complications of hemothorax, pneumothorax, and hemopneumothorax, but not with mechanical ventilator use. Furthermore, old age was significantly associated with rib fractures in patients with thoracic trauma. CONCLUSION: The severity of traumatic rib fractures was identified in this study. Therefore, a trauma team needs better preparation to provide effective treatment strategies when encountering thoracic trauma patients, especially patients who are older and have rib fractures.

Anti-inflammatory effect of longan seed extract in carrageenan stimulated Sprague-Dawley rats.

OBJECTIVES: Longan seeds have been used as a folk medicine in China. Longan seed extract (LSE) is known for antioxidative, antiproliferative, hypoglycemic, and hypouremic effects. However, its anti-inflammatory effect has not been shown. MATERIALS AND METHODS: In this study, Sprague-Dawley (SD) rats were given LSE orally (vehicle, 10, and 30 mg/kg) for 3 days to its test anti-inflammatory effect by injecting λ-carrageenan (CARR) in the right hind paw or lipopolysaccharide (LPS), IP. For the positive control, animals were given aspirin (20 mg/kg) orally and treated likewise. Serum or tissue samples from treated rats were collected after 3 hr of stimulation. Regarding the in vitro study, BV2 microglial cells were stimulated with LPS in the presence of LSE or normal saline for 10 min or 24 hr for Western blot and ELISA assay, respectively. RESULTS: LSE reduced CARR-induced edema in the experimental animals. LSE also reduced LPS/CARR-induced nitric oxide (NO), interleukin-1ß (IL1ß), IL6, and COX2 productions. These inflammatory factors were also reduced dose dependently by LSE in LPS-stimulated BV2 cells. Furthermore, Western blot analysis revealed that LSE inhibited LPS activated c-Jun NH2-terminal protein kinase (JNK), extracellular signal-regulated kinases (ERKs), and p38 MAP kinases signaling pathways, caspase-3, inducible NO synthase, and COX2 expressions. CONCLUSION: LSE pretreatment suppressed CARR- and LPS-induced inflammations and these effects might be through the inhibition of MAP kinases signaling pathways and inflammatory factors.