Jong-Hau Hsu

Staging of gastric cancer with 16-channel MDCT

Early detection and accurate preoperative staging of gastric cancer are clinically important because the prognosis and choice of an optimal therapeutic approach are directly related to the stage of a neoplasm at time of presentation. Multidetector row computed tomography is a potentially powerful tool for noninvasive gastric evaluation. When thin collimation is used, near-isotropic imaging of the stomach is possible. Proper air distention of the stomach is used with virtual gastroscopic images; the technique is able to evaluate endoluminal lesions of the stomach and assist in early detection of gastric cancer. Adequate water-filled dynamic multiplanar reformatted images allow the radiologist to choose the optimal imaging plane to accurately evaluate depth of tumor invasion of the gastric wall and perigastric fat plane infiltration, identify a thin fat plane between a tumor and adjacent organs, avoid partial volume averaging effects, and better differentiate lymph nodes from small perigaskric vessels. Thus, the combination of air distention and hydrodistention of the stomach and dynamic contrast-enhanced multidetector row computed tomography with near-isotropic imaging offer improved diagnosis and staging of gastric cancers.

B-Type Natriuretic Peptide Predicts Responses to Indomethacin in Premature Neonates with Patent Ductus Arteriosus

OBJECTIVES To determine whether B-type natriuretic peptide (BNP) predicts indomethacin responsiveness in premature neonates with patent ductus arteriosus (PDA). STUDY DESIGN Premature neonates receiving indomethacin for an echocardiograhically large (diameter>1.5 mm) and clinically significant PDA were prospectively studied. All neonates underwent paired echocardiography and BNP measurements at baseline and 24 hours after each dose of indomethacin. After treatment, neonates who responded (with closed or insignificant PDA) and neonates who did not respond (with persistent significant PDA requiring surgical ligation) were compared. RESULTS Thirty-one premature neonates (mean gestational age, 30 weeks) underwent 119 paired echocardiography and BNP determinations. Mean BNP levels (1286+/-986 pg/mL) associated with significant PDA (n=96) were higher than those associated with closed or insignificant PDA (n=23; 118+/-124 pg/mL; P<.001). Twenty-three neonates responded and 8 neonates did not respond to indomethacin. Mean baseline BNP levels were higher in neonates who were non-responders (2234+/-991 pg/mL) than neonates who were responders (983+/-814 pg/mL; P=.001). A baseline BNP level>1805 pg/mL had a sensitivity rate of 88% and a specificity rate of 87% for predicting indomethacin non-responsiveness (P=.003). CONCLUSIONS High baseline BNP levels predict poor responses to indomethacin and the need for surgery in premature neonates with PDA.

KMUP‐1 attenuates isoprenaline‐induced cardiac hypertrophy in rats through NO/cGMP/PKG and ERK1/2/calcineurin A pathways

Background and purpose:  To determine whether KMUP‐1, a novel xanthine‐based derivative, attenuates isoprenaline (ISO)‐induced cardiac hypertrophy in rats, and if so, whether the anti‐hypertrophic effect is mediated by the nitric oxide (NO) pathway.

Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways.

BackgroundLysophosphatidylcholine (lysoPC), a metabolite from membrane phospholipids, accumulates in the ischemic myocardium and plays an important role in the development of myocardial dysfunction ventricular arrhythmia. In this study, we investigated if baicalein, a major component of Huang Qui, can protect against lysoPC-induced cytotoxicity in rat H9c2 embryonic cardiomyocytes.MethodsCell viability was detected by the MTT assay; ROS levels were assessed using DCFH-DA; and intracellular free calcium concentrations were assayed by spectrofluorophotometer. Cell apoptosis and necrosis were evaluated by the flow cytometry assay and Hoechst staining. Mitogen-Activated Protein Kinases (MAPKs), which included the ERK, JNK, and p38, and the apoptotic mechanisms including Bcl-2/Bax, caspase-3, caspase-9 and cytochrome c pathways were examined by Western blot analysis. The activation of MAPKs was examined by enzyme-linked immunosorbent assay.ResultsWe found that lysoPC induced death and apoptosis of H9c2 cells in a dose-dependent manner. Baicalein could prevent lysoPC-induced cell death, production of reactive oxygen species (ROS), and increase of intracellular calcium concentration in H9c2 cardiomyoctes. In addition, baicalein also inhibited lysoPC-induced apoptosis, with associated decreased pro-apoptotic Bax protein, increased anti-apoptotic Bcl-2 protein, resulting in an increase in the Bcl-2/Bax ratio. Finally, baicalein attenuated lysoPC-induced the expression of cytochrome c, casapase-3, casapase-9, and the phosphorylations of ERK1/2, JNK, and p38. LysoPC-induced ERK1/2, JNK, and p38 activations were inhibited by baicalein.ConclusionsBaicalein protects cardiomyocytes from lysoPC-induced apoptosis by reducing ROS production, inhibition of calcium overload, and deactivations of MAPK signaling pathways.

San-Huang-Xie-Xin-Tang Prevents Rat Hearts from Ischemia/Reperfusion-Induced Apoptosis through eNOS and MAPK Pathways

San-Huang-Xie-Xin-Tang (SHXT) is a traditional Chinese medication consisting of three herbs, namely Coptidis rhizome, Scutellariae radix and Rhei rhizome. This study aimed to examine the cardioprotective effects of SHXT in a rat model of acute myocardial apoptosis induced by ischemia/reperfusion (I/R). Vehicle (intravenous saline) or SHXT (intravenous or oral) was administered prior to I/R (occlusion of left coronary artery for 45 min followed by reperfusion for 2 h). In the vehicle group, myocardial I/R caused myocardial infarction with increased plasma cardiac enzymes, severe arrhythmia and mortality. Myocardial apoptosis was induced by I/R as evidenced by DNA ladder and Bcl-2/Bax ratio. In the SHXT group, we found that SHXT significantly reduced plasma levels of cardiac enzymes, arrhythmia scores (from 5 ± 1 to 2 ± 1, P < .01) and mortality rate (from 53 to 0%, P < .01). In addition, pretreatment with intravenous SHXT reduced the infarct size dose-dependently when compared with the vehicle group (10 mg kg−1: 14.0 ± 0.2 versus 44.5 ± 5.0%, and 30 mg kg−1: 6.2 ± 1.2% versus 44.5 ± 5.0%, both P < .01). Similarly, oral administration of SHXT reduced the infarct size dose-dependently. Furthermore, SHXT markedly decreased the apoptosis induced by I/R with increased Bcl-2/Bax ratio. Finally, we found that SHXT counteracted the I/R-induced downstream signaling, resulting in increased myocardial eNOS expression and plasma nitrite, and decreased activation of ERK1/2, p38 and JNK. These data suggest that SHXT has cardioprotective effects against I/R-induced apoptosis, and that these effects are mediated, at least in part, by eNOS and MAPK pathways.

Combined Noninvasive Ventilation and Mechanical In-Exsufflator in the Treatment of Pediatric Acute Neuromuscular Respiratory Failure

The present study aims to evaluate the efficacy and complications of combined noninvasive ventilation (NIV) and assisted coughing by mechanical in‐exsufflator (MIE) for acute respiratory failure (ARF) in children with neuromuscular disease (NMD).

Labedipinedilol-A prevents lysophosphatidylcholine-induced vascular smooth muscle cell death through reducing reactive oxygen species production and anti-apoptosis

OBJECTIVE Labedipinedilol-A, a novel calcium antagonist, has been previously demonstrated to have pleiotropic protective effects in the cardiovascular system. This study aimed to investigate its cytoprotective effects in rat vascular smooth muscle cells (VSMCs) treated with lysophosphatidylcholine (lysoPC), a key lipid component mediating atherogenesis. METHODS AND RESULTS VSMCs were incubated with lysoPC with or without labedipinedilol-A pretreatment to determine its effects on lysoPC-induced cell death, Ca(2+) influx, oxidative stress, MAPK signaling and apoptosis. Labedipinedilol-A attenuated lysoPC-induced cell death and Ca(2+) influx. It also reduced reactive oxygen species (ROS) production evoked by lysoPC and down-regulated expressions of NAD(P)H oxidase subunits, Nox1 and Rac1. Moreover, it inhibited lysoPC-induced phosphorylation of MAPK including ERK1/2, JNK, and p38. It mitigated the dissipation of mitochondrial transmembrane potential induced by lysoPC. Lastly, labedipinedilol-A inhibited lysoPC-induced apoptosis with attenuation of caspase-3/-9 activations and modulation of Bax/Bcl-2 protein expressions. CONCLUSION Labedipinedilol-A can suppress lysoPC-induced VSMCs death via reducing ROS production and anti-apoptosis. These protective effects are potentially mediated through the inhibition of Ca(2+) influx, down-regulation of the NAD(P)H oxidase subunits (Nox1/Rac1) and MAPK signaling, and attenuation of mitochondrial depolarization. Thus, labedipinedilol-A may have a valuable role in the preventing atherosclerosis associated with hyperlipidemia.

KMUP-1 Suppresses RANKL-Induced Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss: Roles of MAPKs, Akt, NF-κB and Calcium/Calcineurin/NFATc1 Pathways

Background KMUP-1 is a xanthine derivative with inhibitory activities on the phosphodiesterase (PDE) 3,4 and 5 isoenzymes to suppress the degradation of cyclic AMP and cyclic GMP. However, the effects of KMUP-1 on osteoclast differentiation are still unclear. In this study, we investigated whether KMUP-1 inhibits osteoclastogenesis induced by RANKL in RAW 264.7 cells and bone loss induced by ovariectomy in mice, and the underlying mechanisms. Principal Findings In vitro, KMUP-1 inhibited RANKL-induced TRAP activity, the formation of multinucleated osteoclasts and resorption-pit formation. It also inhibited key mediators of osteoclastogenesis including IL-1β, IL-6, TNF-α and HMGB1. In addition, KMUP-1 inhibited RANKL-induced activation of signaling molecules (Akt, MAPKs, calcium and NF-κB), mRNA expression of osteoclastogensis-associated genes (TRAP, MMP-9, Fra-1, and cathepsin K) and transcription factors (c-Fos and NFATc1). Furthermore, most inhibitory effects of KMUP-1 on RANKL-mediated signal activations were reversed by a protein kinase A inhibitor (H89) and a protein kinase G inhibitor (KT5823). In vivo, KMUP-1 prevented loss of bone mineral content, preserved serum alkaline phosphate and reduced serum osteocalcin in ovariectomized mice. Conclusions KMUP-1 inhibits RANKL-induced osteoclastogenesis in vitro and protects against ovariectomy-induced bone loss in vivo. These effects are mediated, at least in part, by cAMP and cGMP pathways. Therefore, KMUP-1 may have a role in pharmacologic therapy of osteoporosis.

Granulocyte-colony stimulating factor alleviates perinatal hypoxia-induced decreases in hippocampal synaptic efficacy and neurogenesis in the neonatal rat brain.

Using various animal models, studies have greatly expanded our understanding of perinatal hypoxia-induced neuronal injury in the newborn at the cellular/molecular levels. However, the synapse-basis pathogenesis and therapeutic strategy for such detrimental alterations in the neonatal brain remain to be addressed. We investigated whether the damaged synaptic efficacy and neurogenesis within hippocampal CA1 region (an essential integration area for mammalian learning and memory) of the neonatal rat brain after perinatal hypoxia were restored by granulocyte-colony stimulating factor (G-CSF) therapy. Ten-day-old (P10) rat pups were subjected to experimentally perinatal hypoxia. G-CSF (10, 30, or 50 μg/kg, single injection/d, P11–16) was s.c. administered to neonatal rats which were analyzed on P17. Perinatal hypoxia reduced the expression in pRaf-pERK1/2-pCREBSer-133 signaling, the synaptic complex of postsynaptic density protein-95 (PSD-95) with N-methyl-d-aspartate receptor (NMDAR) subunits (NR1, NR2A, and NR2B), synaptic efficacy, and neurogenesis. A representatively effective dosage of G-CSF (30 μg/kg) alleviated the perinatal hypoxia-induced detrimental changes and improved the performance in long-term cognitive function. In summary, our results suggest a novel concept that synaptic efficacy defects exist in the neonatal brain previously exposed to perinatal hypoxia and that G-CSF could be a clinical potential for the synapse-basis recovery in the perinatal hypoxia suffers.

Baicalein Inhibits HMGB1 Release and MMP-2/-9 Expression in Lipopolysaccharide-Induced Cardiac Hypertrophy

Myocardial dysfunction, a common complication after sepsis, significantly contributes to the death of patients with septic shock. In the search for potentially effective drugs to decrease mortality from sepsis, we investigated the cardioprotective effects of baicalein, a flavonoid present in the root of Scutellaria baicalensis, on lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and matrix metalloproteinase-2 and -9 (MMP-2/-9) expression. We found that baicalein significantly attenuated LPS-induced cardiac hypertrophy and counteracted reactive oxygen species (ROS) generation in neonatal rat cardiomyocytes. In addition, pretreatment with baicalein inhibited LPS-induced early (e.g., tumor necrosis factor-α (TNF-α) and interleukin-6) and late (e.g., high mobility group box 1 (HMGB1) pro-inflammatory cytokine release, inducible nitric oxide synthase (iNOS) expression and NO production. Finally, baicalein also significantly down-regulated the expression of MMP-2/-9 and attenuated HMGB1 translocation from the nucleus to the cytoplasm. These results suggest that baicalein can protect cardiomyocytes from LPS-induced cardiac injury via the inhibition of ROS and inflammatory cytokine production. These cardioprotective effects are possibly mediated through the inhibition of the HMGB1 and MMP-2/-9 signaling pathways.