[Show abstract][Hide abstract] ABSTRACT: Background:
Persistent patent ductus arteriosus (PDA) during hospitalization is thought to be associated with adverse pulmonary outcomes in very preterm infants. This observational study aimed to compare the lung function in very preterm infants with and without PDA at discharge.
Very preterm infants, admitted to our neonatal intensive unit, who required respiratory support soon after birth and had undergone a lung function test at discharge, were enrolled. Infants with a need for positive-pressure support (either an invasive ventilator, or nasal continuous positive airway pressure without oxygen) or supplemental oxygen at a postmenstrual age of 36 weeks were defined as having bronchopulmonary dysplasia (BPD). Echocardiography was performed weekly for each of the very preterm infants with PDA to confirm closure of the PDA. The data were collected retrospectively.
Fifty-two very preterm infants received lung function tests before discharge during the study period, 28 of whom had PDA and received conservative management, and 20 who did not. The other 4 infants who were given active treatment for PDA were excluded. Gestational age was significantly smaller in the PDA group than in the no-PDA group (27.1 ± 2.0 vs. 28.6 ± 1.6 weeks, p = 0.009). Birth weight did not differ significantly in those with and those without PDA (0.98 ± 0.26 vs. 1.12 ± 0.26 kg, p = 0.074). Significantly more infants with PDA had BPD (p = 0.002) and required respiratory support for a longer period (p = 0.001) than those without PDA. However, functional residual capacity (ml/kg) at discharge was comparable between the two groups after adjusting for gestational age and postmenstrual age at testing (21.6 ± 8.4 vs. 21.5 ± 6.7 ml/kg, p = 0.894). Other lung function test parameters were also comparable.
Under a definition of BPD (including infants needing CPAP but without oxygen) other than the conventional definition, the very preterm infants in our study who received conservative management for PDA had a higher percentage of BPD than the infants without PDA. The parameters of the lung function test and lung clearance index were comparable between these two groups at discharge.
[Show abstract][Hide abstract] ABSTRACT: The signaling cascades of the mitogen activated protein kinase (MAPK) family, calcineurin/NFATc4, and PI3K/Akt/GSK3, are believed to participate in endothelin-1 (ET-1)-induced cardiac hypertrophy. The aim of this study was to investigate whether KMUP-1, a synthetic xanthine-based derivative, prevents cardiomyocyte hypertrophy induced by ET-1 and to elucidate the underlying mechanisms. We found that in H9c2 cardiomyocytes, stimulation with ET-1 (100 nM) for 4 days induced cell hypertrophy and enhanced expressions of hypertrophic markers, including atrial natriuretic peptide and brain natriuretic peptide, which were all inhibited by KMUP-1 in a dose-dependent manner. In addition, KMUP-1 prevented ET-1-induced intracellular reactive oxygen species generation determined by the DCFH-DA assay in cardiomyocytes. KMUP-1 also attenuated phosphorylation of ERK1/2 and Akt/GSK-3β, and activation of calcineurin/NFATc4 and RhoA/ROCK pathways induced by ET-1. Furthermore, we found that the expression of heme oxygenase-1 (HO-1), a stress-response enzyme implicated in cardio-protection, was up-regulated by KMUP-1. Finally, KMUP-1 attenuated ET-1-stimulated activator protein-1 DNA binding activity. In conclusion, KMUP-1 attenuates cardiomyocyte hypertrophy induced by ET-1 through inhibiting ERK1/2, calcineurin/NFATc4 and RhoA/ROCK pathways, with associated cardioprotective effects via HO-1 activation. Therefore, KMUP-1 may have a role in pharmacological therapy of cardiac hypertrophy.
[Show abstract][Hide abstract] ABSTRACT: Serotonin (5-hydroxytryptamine, 5-HT) is a potent pulmonary vasoconstrictor that promotes pulmonary artery smooth muscle cell (PASMC) proliferation. 5-HT-induced K(+) channel inhibition increases [Ca(2+)]i in PASMCs, which is a major trigger for pulmonary vasoconstriction and development of pulmonary arterial hypertension (PAH). This study investigated whether KMUP-1 reduces pulmonary vasoconstriction in isolated pulmonary arteries (PAs) and attenuates 5-HT-inhibited K(+) channel activities in PASMCs. In endothelium-denuded PA rings, KMUP-1 (1 μM) dose-dependently reduced 5-HT (100 μM) mediated contractile responses. Responses to KMUP-1 were reversed by K(+) channel inhibitors (TEA, 10 mM, 4-aminopyridine, 5 mM, and paxilline, 10 μM). In primary PASMCs, KMUP-1 also dose-dependently restored 5-HT-inhibited voltage-gated K(+)-channel (Kv1.5 and Kv2.1) and large-conductance Ca(2+)-activated K(+)-channel (BKCa) proteins, as confirmed by immunofluorescent staining. Furthermore, 5-HT (10 μM)-inhibited Kv1.5 protein was unaffected by the PKA inhibitor KT5720 (1 μM) and the PKC activator PMA (1 μM), but these effects were reversed by KMUP-1 (1 μM), 8-Br-cAMP (100 μM), chelerythrine (1 μM), and KMUP-1 combined with a PKA/PKC activator or inhibitor. Notably, KMUP-1 reversed 5-HT-inhibited Kv1.5 protein and this response was significantly attenuated by co-incubation with the PKC activator PMA, suggesting that 5-HT-mediated PKC signaling can be modulated by KMUP-1. In conclusion, KMUP-1 ameliorates 5-HT-induced vasoconstriction and K(+)-channel inhibition through the PKC pathway, which could be valuable to prevent the development of PAH.
International journal of biological sciences 04/2015; 11(6):633-642. DOI:10.7150/ijbs.11127 · 4.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been recently demonstrated that intracellular heat shock cognate protein 70 (HSC70) can be released into extracellular space with physiologic effects. However, its extracellular function in sepsis is not clear. In this study, we hypothesize that extracellular HSC70 can protect against lipopolysaccharide (LPS)-induced myocardial and hepatic dysfunction due to its anti-inflammatory actions. In Wistar rats, septic shock developed with hypotension, tachycardia, myocardial and hepatic dysfunction at 4 h following LPS administration (10 mg/kg, i.v.). Pretreatment with recombinant bovine HSC70 (20 μg/kg, iv) attenuated LPS-induced hypotension and tachycardia by 21% and 23 %, respectively (p<0.05), improved myocardial dysfunction (LVSP: 33%; Max dp/dt: 20%; Min dp/dt: 33%, p<0.05), and prevented hepatic dysfunction (GOT: 81 vs. 593 IU/L; GPT: 15 vs. 136 IU/L, p<0.05) compared with LPS-treated rats at 4 h. HSC70 also prevented LPS-induced hypoglycemia (217 vs. 59 mg/dL, p<0.05) and elevated LDH (1312 vs. 6301 IU/L, p<0.05). Furthermore, HSC70 decreased LPS-induced elevation of circulating TNF-α and NOx, and tissue expression of iNOS, COX-2, MMP-9 in the heart and liver. To investigate underlying mechanisms, we found that HSC70 attenuated LPS-induced nuclear translocation of NF-κB subunit p65 by blocking the phosphorylation of IκBα. Finally, we showed that HSC70 repressed the activation of MAPKs caused by LPS. These results demonstrate that in LPS-induced septic shock, extracellular HSC70 conveys pleiotropic protection on myocardial, hepatic and systemic derangements, with associated inhibition of pro-inflammatory mediators including TNF-α, NO, COX-2, MMP-9, through MAPK/NF-κB signaling pathways. Therefore, extracellular HSC70 may have a promising role in the prophylactic treatment of sepsis.
[Show abstract][Hide abstract] ABSTRACT: Background
Lysophosphatidylcholine (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.
Cell 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.
We 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.
Baicalein protects cardiomyocytes from lysoPC-induced apoptosis by reducing ROS production, inhibition of calcium overload, and deactivations of MAPK signaling pathways.
BMC Complementary and Alternative Medicine 07/2014; 14(1):233. DOI:10.1186/1472-6882-14-233 · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
The American Journal of Chinese Medicine 07/2014; 42(4):785-97. DOI:10.1142/S0192415X14500505 · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Pneumonia is a life-threatening disease in children. With the current lack of universal diagnostic criteria, the diagnosis is usually made on clinical manifestations and findings from chest radiographs. Ultrasonography has recently been applied to the detection of pulmonary diseases. However, few data have been published showing its effectiveness in detecting pneumonia in children. The objective of this study was to determine the power of lung ultrasonography (LUS) for the diagnosis of pneumonia in children.
Materials and methods
This retrospective study was carried out by reviewing medical records. Patients admitted to a pediatric ward with a diagnosis of pneumonia from June 1, 2010 to December 31, 2012 were enrolled in this study. Personal information, laboratory data, characteristics on LUS scan, and the results of chest radiography and LUS were collected. We compared the detection rate of pneumonia by chest radiography and LUS. LUS scans were followed up in 23 patients during the progression of their disease.
A total of 163 patients was enrolled. Chest radiography was able to detect pneumonia in 152 patients, whereas LUS detected pneumonia in 159 patients. In LUS, the positive rates of the comet-tail sign, air bronchograms, fluid bronchograms, vascular pattern within the consolidation, and pleural effusion were 50.9%, 93.7%, 20.1%, and 28.9%, respectively. During follow up, the average size of the pneumonia patch in 23 patients decreased from 10.9 ± 8.7 cm2 to 5.5 ± 8.2 cm2, and finally to 2 ± 1.9 cm2 on Day 1, Days 3–5 and Days 7–14, respectively.
LUS is a sensitive diagnostic tool with which to identify pneumonia in children. It is also useful in following up the progress of pneumonia. We suggest that LUS is a complementary tool to chest radiography in the diagnosis of pneumonia in children and that the follow up of pneumonia by LUS can reduce the exposure of children to ionizing radiation.
[Show abstract][Hide abstract] ABSTRACT: Objectives
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). MethodsA prospective study was conducted in the pediatric intensive care unit. Children with NMD and ARF treated by combined NIV and MIE were included. Treatment success was defined as freedom from tracheal intubation during the hospital stay. Physiologic indices including PaO2, PaCO2, pH, and PaO2/FiO(2) were recorded before and 12, 24hr after the use of NIV/MIE. ResultsCombined NIV/MIE was used in 15 NMD children (mean: 8.1 years, range: 3 months to 18 years) with 16 cases of ARF. There was no mortality in this cohort. Treatment success was achieved in 12 cases (75%), including six cases (38%) demanding Do Not Intubate. ARF was due to pneumonia, with a mean baseline PaCO2 of 73.219.0mmHg. In the success group, hypercarbia and acidosis improved after use of NIV/MIE for 24hr (PaCO2: 71.7 +/- 18.6mmHg vs. 55.8 +/- 11.6mmHg, P<0.01; pH: 7.29 +/- 0.07 vs. 7.38 +/- 0.05, P<0.01). All patients tolerated NIV/MIE well despite transient skin pressure sores in five cases. Conclusions
Combined NIV/MIE is a safe and effective approach to rapidly improve physiologic indices and decrease the need for intubation in NMD children with ARF. NIV/MIE provides a good alternative for those refusing intubation. Pediatr Pulmonol. 2014; 49:589-596. (c) 2013 Wiley Periodicals, Inc.
[Show abstract][Hide abstract] ABSTRACT: The study objective was to determine the association between preoperative B-type natriuretic peptide levels and outcome after total cavopulmonary connection. Surgical palliation of univentricular cardiac defects requires a series of staged operations, ending in a total cavopulmonary connection. Although outcomes have improved, there remains an unpredictable risk of early total cavopulmonary connection takedown. The prediction of adverse postoperative outcomes is imprecise, despite an extensive preoperative evaluation.
We prospectively enrolled 50 patients undergoing total cavopulmonary connection. We collected preoperative clinical data, preoperative plasma B-type natriuretic peptide levels, and postoperative outcomes, including the incidence of an adverse outcome within 1 year of surgery (defined as death, total cavopulmonary connection takedown, or the need for cardiac transplantation).
The mean age of patients was 4.7 years (standard deviation, 2.1 years). The median (interquartile range) preoperative B-type natriuretic peptide levels were higher in patients who required total cavopulmonary connection takedown and early postoperative mechanical cardiac support (n = 3; median, 55; interquartile range, 42-121) compared with those with a good outcome (n = 47; median, 11; interquartile range, 5-17) (P < .05). A preoperative B-type natriuretic peptide level of 40 pg/mL or greater was highly associated with the need for total cavopulmonary connection takedown (sensitivity, 100%; specificity, 93%; P < .05), yielding a positive predictive value of 50% and a negative predictive value of 100%. Higher preoperative B-type natriuretic peptide levels also were associated with longer intensive care unit length of stay, longer hospital length of stay, and increased incidence of low cardiac output syndrome (P < .05).
Preoperative B-type natriuretic peptide blood levels are uniquely associated with the need for mechanical support early after total cavopulmonary connection and total cavopulmonary connection takedown, and thus may provide important information in addition to the standard preoperative assessment.
The Journal of thoracic and cardiovascular surgery 09/2013; 148(1). DOI:10.1016/j.jtcvs.2013.08.009 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
PLoS ONE 07/2013; 8(7):e69468. DOI:10.1371/journal.pone.0069468 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Botulism is a severe neuroparalytic illness which is difficult to diagnose accurately, especially in children. We report a child with type A botulism intoxication, with very rapid progression to coma-like consciousness and respiratory failure. Careful physical examinations led to the suspicion of botulism, and electrophysiologic examinations, including electroencephalogram and repetitive nerve stimulation tests, further supported the diagnosis. Hospitalization due to botulism had a great emotional impact on the patient and psychological support was crucial.
[Show abstract][Hide abstract] ABSTRACT: Contrary to the classical form, infantile facioscapulohumeral muscular dystrophy (FSHD) usually denotes a severe phenotype and is frequently associated with extramuscular involvements. To elucidate the genotype–phenotype correlation in this severe subgroup, we identified a cohort of nine patients with infantile FSHD who also carried a very short (10–13 kb) EcoRI fragment. Their current age ranged from 8 to 33 years and age of onset ranged from 0.4 to 5 years. One patient even manifested his first FSHD-related symptoms at as early as 5 months of age, including inability to smile, poor response to call, and infantile spasms. To date, four patients were wheelchair-bound and six patients had asymmetric weakness. Sensorineural hearing loss and abnormal fundoscopic findings were observed in eight and all of patients respectively. Three with the smallest EcoRI fragments (10–11 kb, with normal length being 50–300 kb) had mental retardation. Two of these had epilepsy. Cardiac arrhythmias were found in five patients. Restrictive ventilatory defects were observed in seven patients, with one progressing to chronic respiratory failure. Two had swallowing difficulties; one of these required gastrostomy. We identified several rarely reported phenotypes in infantile FSHD, including cardiac arrhythmia, respiratory insufficiency, and swallowing difficulties. There seems to be a correlation between the severity of phenotype and the very short EcoRI fragment in the chromosome 4q35 region. We conclude that the high frequency of multi-organ involvements in this severe FSHD variant suggests the need for an early and multidisciplinary intervention.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Inflammation is an important molecular basis of atherosclerosis. Recent studies have shown that dihydropyridine calcium channel blockers (CCBs) can exert potent anti-inflammatory effects in models of vascular dysfunction. The purpose of the present study was to evaluate anti-inflammatory effects and mechanisms of lercanidipine and labedipinedilol-A, new generation dihydropyridine CCBs, in rat vascular smooth muscle cells (VSMCs) exposed to lipopolysaccharide (LPS) and interferon-γ (IFN-γ).
Methods and results:
MTT, Griess reagent, RT-PCR, ELISA, gelatin zymography, immunocytochemistry and Western blotting were employed. We found that lercanidipine and labedipinedilol-A attenuated production of NO, ROS and TNF-α from LPS/IFN-γ-stimulated VSMCs. In addition, they both diminished the LPS/IFN-γ-induced expression of iNOS protein and mRNA, with attenuation of HMGB1 cytosolic translocation and subsequent extracellular release. Furthermore, they down-regulated MMP-2/MMP-9 activities, whereas expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), an inhibitor of MMP-9, was up-regulated. Finally, we found that lercanidipine and labedipinedilol-A inhibited the nuclear translocation of NF-κB and suppressed the phosphorylation of JNK, p38 MAPK and Akt.
Lercanidipine and labedipinedilol-A can exert their anti-inflammatory effects through suppression of NO, ROS and TNF-α through down-regulation of iNOS, MMP-2/MMP-9, and HMGB1, with inhibition of signaling transduction of MAPKs, Akt/IkB-α and NF-κB pathways. These findings implicate a valuable role of new generation dihydropyridine CCBs lercanidipine and labedipinedilol-A for the treatment of inflammatory vascular diseases.
[Show abstract][Hide abstract] ABSTRACT: Background
Pulmonary vascular function is impaired with increased pulmonary blood flow (PBF). We hypothesized that a peroxisome proliferator-activated receptor-gamma (PPARγ) agonist would mitigate this effect.
An aorta to pulmonary artery shunt was placed in 11 fetal lambs. Lambs received the PPARγ agonist rosiglitazone (RG, 3 mg/kg/day, n=6) or vehicle (n=5) for 4-weeks. Lung tissue from 5 normal 4-week lambs was used for comparisons.
At 4-weeks, pulmonary artery pressure (PAP) and vascular resistance (PVR) decreased with inhaled NO in RG and vehicle-treated shunt lambs. PAP and PVR decreased with acetylcholine in RG-treated, not vehicle-treated shunt lambs. In vehicle-treated shunt lambs, NADPH oxidase activity, rac1, superoxide, and 3-nitrotyrosine (3-NT) levels were increased and Ser1177 endothelial NO synthase (eNOS) protein was decreased compared to normal lambs. In RG-treated shunt lambs, NOX, Ser1177 eNOS protein and eNOS activity were increased, and NADPH activity, rac1, superoxide levels and 3-NT levels were decreased, compared to vehicle-treated shunt lambs. PPARγ protein expression was lower in vehicle-treated shunt lambs than normal and RG-treated shunt lambs.
The PPARγ agonist, RG, prevents the loss of agonist induced endothelium-dependent pulmonary vascular relaxation in lambs with increased PBF, in part, due to decreased oxidative stress and/or increased NO production.
Pediatric Research 11/2012; 73(1). DOI:10.1038/pr.2012.149 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypertension can induce left ventricular hypertrophy (LVH), and the nitric oxide (NO) pathway plays an important role in the pathogenesis of cardiac hypertrophy. This study aimed to examine whether KMUP-1, a novel xanthine-based derivative, could inhibit LVH in spontaneously hypertensive rats (SHRs) and to investigate potential mechanisms underlying its antihypertrophic effects. Two groups of animals with chronic or subacute LVH were treated. In the chronic LVH group, KMUP-1 (10 or 30 mg/kg/d orally) was administered for 28 days to both normotensive rats and SHRs. In the subacute LVH group, KMUP-1 (0.5 mg/kg/d intraperitoneally) or sildenafil (0.7 mg/kg/d intraperitoneally) was administered for 10 days with or without co-treatment with the nitric oxide synthase (NOS) inhibitor N-omega-nitro-l-arginine (L-NNA; 20 mg/L orally). After treatment, the effects of KMUP-1 or sildenafil on hypertension, cardiac hypertrophy, survival, expression of the NO/soluble guanylate cyclase (sGC)/protein kinase G (NO/sGC/PKG) pathway in the aorta andleft ventricle, and calcineurin A/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in the left ventricle were examined. In the chronic LVH group, the SHRs developed hypertension with LVH over the 28 days. KMUP-1 attenuated the hypertension and LVH, increased survival rate, enhanced endothelial NOS/cyclic guanosine monophosphate/PKG (eNOS/cGMP/PKG) and decreased inducible NOS (iNOS) expression in the aorta and left ventricle of the SHRs. In the subacute LVH group, both KMUP-1 and sildenafil administered for 10 days attenuated the LVH in SHRs, with enhanced eNOS/cGMP/PKG and suppressed iNOS/calcineurin A/ERK1/2 expression in the left ventricle. In addition, both KMUP-1 and sildenafil attenuated L-NNA-induced LVH. KMUP-1 inhibition of hypertension-induced LVH with associated upregulation of eNOS, downregulation of iNOS in both the aorta and left ventricle, and attenuation of calcineurin A and ERK1/2 signaling in the left ventricle.
The Kaohsiung journal of medical sciences 11/2012; 28(11):567-76. DOI:10.1016/j.kjms.2012.04.022 · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Posterior reversible encephalopathy syndrome (PRES), first reported by Hinchey et al. in 1996, is an emerging neurological illness. It is characterized by headache, altered consciousness, visual disturbance, and seizures, with typical radiographic findings of vasogenic edema involving the posterior cerebral region. With widespread utilization of magnetic resonance imaging (MRI), PRES is becoming more familiar to adult phy-sicians. However, because of the relatively sparse number and relatively recent appearance of reports on PRES in the pediatric literature compared to the adult literature, this condition is less well addressed in field of pediatric critical care. Between 2005 and 2011, seven children (age 7–17 years) admitted to our pediatric intensive care unit (PICU) with a confirmed diagnosis of PRES were retrospectively investi-gated. Their initial and follow-up data, including underlying diseases, precipitating factors, clinical mani-festations, neuroimaging characteristics, and outcomes, were analyzed. The underlying diseases included collagen diseases, glomerulonephritis, renovascular hypertension, and malignancies. Hypertensive crisis occurred in five patients. The initial MRI scans of all patients showed typical vasogenic edema dis-tributed in the subcortical white matter of the parieto-temporo-occipi-tal regions. Moreover, six patients also had atypical MRI lesions, such as atypical distribution, cytotoxic edema, and abnormal contrast enhancement. After meticulous treatment with antihypertensive agents, anti-epileptics, and the with-holding of potential offending medications, all patients achieved complete clinical recovery with sub-sequent radiological resolution. To our knowledge, this is the first case series to describe PRES in the set-ting of PICU.
Intensive Care Medicine 09/2012; 39(1-Publish on-line). DOI:10.1007/s00134-012-2705-y · 7.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
B-type natriuretic peptide is used in the diagnosis, risk stratification, and management of adult patients with cardiac disease. However, its use in infants with congenital heart disease has been limited, particularly in the perioperative period. Our objective was to determine the alterations in perioperative B-type natriuretic peptide levels and their predictive value on postoperative outcomes, in infants undergoing congenital heart surgery.
We prospectively enrolled 115 patients: 24 with univentricular heart disease undergoing a modified Norwood procedure, 11 with d-transposition of the great arteries, 55 with hemodynamically important left-to-right shunt, and 25 with tetralogy of Fallot undergoing primary repair. Clinical data and B-type natriuretic peptide samples were collected before and 2, 12, and 24 hours after cardiopulmonary bypass. Univariate analysis and multivariate linear regression analysis were performed.
The perioperative B-type natriuretic peptide levels were lesion specific. Patients with d-transposition of the great arteries and univentricular heart disease had high preoperative B-type natriuretic peptide levels that decreased postoperatively, and those with hemodynamically important left-to-right shunts and tetralogy of Fallot had lower preoperative levels that increased during the first 12 hours postoperatively. The patients with univentricular heart disease with an adverse outcome had a significantly greater 24-hour B-type natriuretic peptide level than those without (P < .05). Those with hemodynamically important left to right shunts and an adverse outcome had a greater 12-hour B-type natriuretic peptide level than those without (P < .05). A 12-hour postoperative/preoperative ratio greater than 45 was 100% sensitive and 82% specific for an adverse outcome in the patients with tetralogy of Fallot.
The perioperative changes in B-type natriuretic peptide levels and their ability to predict outcomes are lesion-specific. Characterization of these changes might be useful in caring for infants after congenital heart surgery.
The Journal of thoracic and cardiovascular surgery 08/2012; 145(5). DOI:10.1016/j.jtcvs.2012.07.067 · 4.17 Impact Factor