Effects of resistance training on cardiovascular health in non-obese active adolescents.

AIM: To determine the benefits of a 10-wk resistance training programme on cardiovascular health in non-obese and active adolescents. METHODS: This is a pragmatic randomised controlled intervention. The study was carried out in a Hong Kong Government secondary school. Thirty-eight lean and active boys and girls were randomised to either the resistance training group or the control group. Students in the resistance training group received in-school 10-wk supervised resistance training twice per week, with each session lasting 70 min. Main outcome measures taken before and after training included brachial endothelial dependent flow-mediated dilation, body composition, fasting serum lipids, fasting glucose and insulin, high sensitive C-reactive protein, 24-h ambulatory blood pressure and aerobic fitness. RESULTS: The only training related change was in endothelial dependent flow-mediated dilation which increased from 8.5% to 9.8%. A main effect of time and an interaction (P < 0.005) indicated that this improvement was a result of the 10-wk resistance training. Main effects for time (P < 0.05) in a number of anthropometric, metabolic and vascular variables were noted; however, there were no significant interactions indicating the change was more likely an outcome of normal growth and development as opposed to a training effect. CONCLUSION: Ten weeks of resistance training in school appears to have some vascular benefit in active, lean children.

Association between waist circumference and childhood-masked hypertension: A community-based study.

AIM: The aim of this study is to determine the association between waist circumference (WC) and childhood-masked hypertension. METHODS: A territory-wide, school-based cohort of 1385 Hong Kong students (672 boys and 713 girls) aged 8-17 years was analysed. The ambulatory blood pressure-monitoring assessment was performed using validated oscillometric recorders (A&D TM-2430 (A&D Inc., Tokyo, Japan)) following American Heart Association's recommendations. Subjects were considered normotensive if their casual blood pressure, 24-h daytime and night-time average systolic blood pressure and diastolic blood pressure (DBP) were <95th percentile. If one or more of the ambulatory blood pressure parameters was ≥95th percentile, subjects would be considered suffering from masked hypertension (MH). Subjects who had three successive casual blood pressure measurements above the 95th percentile were excluded. RESULTS: By body mass index, 148 (10.7%) subjects were obese, 182 (13.1%) overweight and 359 (25.9%) having larger WC (≥85th percentiles). MH was diagnosed in 217 subjects (15.7%). Subjects with larger WC or obesity were significantly associated with higher 24-h daytime and night-time systolic blood pressure (≥95th percentile) (odds ratios from 1.84 to 2.09 and from 2.07 to 3.54 for larger WC and obese respectively, all P < 0.05) as well as 24-h DBP for larger WC (odds ratio = 2, P = 0.015) than normal subjects adjusted by sex, age and height. CONCLUSION: Waist circumference and body mass index are independent risk factors of childhood and adolescent MH. WC appears a significant associated factor of elevated 24-h DBP in children aged 8-17 years.

Thrombopoietin improved ventricular function and regulated remodeling genes in a rat model of myocardial infarction.

BACKGROUND: Thrombopoietin (TPO) protects against heart damages by doxorubicin-induced cardiomyopathy in animal models. We aimed to investigate the therapeutic efficacy of TPO for treatment of myocardial infarction (MI) in a rat model and explored the mechanisms in terms of the genome-wide transcriptional profile, TPO downstream protein signals, and bone marrow endothelial progenitor cells (EPCs). METHODS: Sprague-Dawley rats were divided into 3 groups: Sham-operated, MI (permanent ligation of the left coronary artery) and MI+TPO. Three doses of TPO were administered weekly for 2 weeks, and outcomes were assessed at 4 or 8 weeks post-injury. RESULTS AND CONCLUSIONS: TPO treatment significantly improved left ventricular function, hemodynamic parameters, myocardium morphology, neovascularization and infarct size. MI damage upregulated a large cohort of gene expressions in the infarct border zone, including those functioned in cytoskeleton organization, vascular and matrix remodeling, muscle development, cell cycling and ion transport. TPO treatment significantly reversed these modulations. While phosphorylation of janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) was modified in MI animals, TPO treatment regulated phosphorylation of STAT3 and extracellular signal-regulated kinases (ERK), and bone morphogenetic protein 1 (BMP1) protein level. TPO also increased EPC colonies in the bone marrow of MI animals. Our data showed that TPO alleviated damages of heart tissues from MI insults, possibly mediated by multi-factorial mechanisms including suppression of over-reacted ventricular remodeling, regulation of TPO downstream signals and mobilization of endothelial progenitor cells. TPO could be developed for treatment of cardiac damages.

Validation of A&D TM-2430 upper-arm blood pressure monitor for ambulatory blood pressure monitoring in children and adolescents, according to the British Hypertension Society protocol.

OBJECTIVE: The A&D TM-2430 ambulatory blood pressure (BP) monitor has been validated in adults but not in a young population. We sought to validate the device monitoring in children and adolescents, according to the British Hypertension Society (BHS) protocol. METHODS: The A&D TM-2430 is an automated oscillometric upper-arm device for ambulatory BP monitoring. Nine consecutive measurements were taken in 61 children (mean age, 9.8 years; range, 5-15 years) according to the BHS criteria. Overseen by an independent supervisor, measurements were recorded by two observers blinded from each other's readings and from the device readings. RESULTS: The mean difference ± SD between the observers and device measurements was 0.73 ± 1.64 mmHg for systolic blood pressure (SBP) and -1.23 ± 1.65 mmHg for diastolic blood pressure (DBP), respectively, with an interobserver difference of 4 mmHg. The cumulative percentages of differences within 5, 10, and 15 mmHg were 89, 95, and 98% for SBP and 67, 88, and 98% for DBP. The device achieved a grade A rating for SBP and a B grade for DBP. CONCLUSION: The A&D TM-2430 upper-arm BP monitor has fulfilled the required BHS standards and can be recommended for measuring ambulatory BP in children and adolescent populations.

Thrombopoietin protects against doxorubicin-induced cardiomyopathy, improves cardiac function, and reversely alters specific signalling networks.

AIMS: We investigated the therapeutic efficacy of thrombopoietin (TPO) in acute and chronic rat models of heart damage and explored the mechanisms in terms of genome-wide transcriptional changes, phosphorylation signals, and bone marrow endothelial progenitor cell (EPC) levels. METHODS AND RESULTS: Cardiac damage was induced in rat models of (i) acute-doxorubicin (DOX) treatment: single high-dose DOX, four doses TPO, followed up for 5 days; and (ii) chronic-DOX treatment: one low-dose DOX and three doses TPO weekly for 6 weeks, followed up for 11 weeks. Our results demonstrated that TPO treatment led to significant improvements of fractional shortening, cardiac output, and morphologic parameters in both models. In the acute-DOX model, microarray and network analyses showed that DOX damage was associated with changes in a large cohort of gene expressions, of which many were inversely regulated by TPO, including modulators of signal transduction, ion transport, anti-apoptosis, protein kinase B/ p42/p44 extracellular signal-regulated kinase (AKT/ERK) pathways, cell division, and contractile protein/matrix remodelling. Many of these regulations also occurred in chronic-DOX animals, in which TPO treatment reduced morphological damage and cardiomyopathy score, and increased AKT phosphorylation of heart tissues. Thrombopoietin also increased EPC colonies in their bone marrow. CONCLUSION: Our overall data suggest that TPO promotes cardiac protection from acute- and chronic-DOX insults, possibly mediated by multi-factorial mechanisms including AKT- and ERK-associated restoration of regulatory gene activities critical for normal heart function.

Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: anti-apoptosis and promoting angiogenesis.

OBJECTIVES: Dexrazoxane (DZR) is a clinically approved agent for preventive treatment of doxorubicin-induced cardiotoxicity. The objective of this study was to investigate the cardioprotective effects of DZR in a rat model of myocardial infarction (MI). METHODS: Sprague-Dawley rats were randomly divided into four groups: MI (n = 16), MI + DZR (n = 16), SHAM-operated (n = 14) and DZR-only (n = 9). MI animals were subjected to left anterior descending coronary artery ligation. DZR was administered as a single dose at 125 mg/kg intraperitoneally. Four weeks after treatment, cardiac function by echocardiography, infarct size, capillary density in the infarct border zone, bone marrow-derived endothelial progenitor cells (EPCs), and cardiac expression of Bax were measured. RESULTS: Our results demonstrated that MI animals had compromised heart parameters. DZR treatment in MI animals resulted in reduction in infarct size (P = 0.013) and improved cardiac functions in terms of fractional shortening (P = 0.004) and ejection fraction (P = 0.004). The capillary density (P = 0.008) and bone marrow-derived EPCs (P < 0.05) were higher in the MI + DZR group than those in the untreated MI group. Bax expression was down-regulated in heart tissues of MI + DZR animals (P = 0.043). CONCLUSIONS: Our study demonstrated that DZR exerted a cardioprotective effect in the rat model of MI, and the mechanism might be associated with anti-apoptosis and increased neovascularization.

Randomized, double-blind, placebo-controlled trial of herbal therapy for children with asthma.

OBJECTIVES: The purpose of this trial was to evaluate whether the herbal formula of CUF2 used as complementary therapy improves the clinical symptoms and biochemical markers in children with asthma using inhaled corticosteroids. PATIENTS AND METHODS: In a double-blind, placebo-controlled prospective trial, 85 children with asthma aged 7-15 years were randomly assigned to receive either a daily oral herbal formula of 0.619-g CUF2 capsule of dried aqueous extract with an equal weight of five herbs (Astragalus mongholius Bunge, Cordyceps sinensis Sacc., Radix stemonae, Bulbus fritillariae cirrhosae, and Radix scutellariae) or placebo for 6 months. RESULTS: The primary endpoint was the change in steroids dosage; the secondary outcomes included the disease severity score, lung function test, and biochemical markers in blood. Eighty-five (85) children (42 on active treatment and 43 on placebo) completed the 6-month clinical trial. Children randomized to the herbal formula of CUF2 and the placebo showed a similar improvement in clinical symptoms and biomedical markers. The comparison between the CUF2 group and the placebo group showed no significant difference on the dosage of steroids (-2.3 versus -3.1 mg, p = 0.915), disease severity score (-2.3 versus -3.1, p = 0.215), and lung function test of forced expiratory volume in 1 second/forced vital capacity percent (0.1 versus 0.6%, p = 0.809) and peak expiratory flow rate (-7.3 versus -0.6 l/minutes, p = 0.118). No significant difference was found between the two study groups in the biochemical outcomes measured. The intervention effect of CUF2 was smaller than the placebo effect. CONCLUSIONS: This study provides no evidence to support the use of the herbal formula of CUF2 in children with asthma. Parents are thus advised to discuss with health professionals before choosing an herbal formula in preference to conventional treatment modes.

Dexrazoxane protects against doxorubicin-induced cardiomyopathy: upregulation of Akt and Erk phosphorylation in a rat model.

PURPOSE: Dexrazoxane (DZR), a clinically approved cation chelator, is effective in reducing doxorubicin (DOX)-induced heart damage, yet its cardioprotective mechanism is not fully understood. We aimed to investigate the effects of DZR on the activation of Akt and Erk 1/2 signals in a rat model of DOX-induced cardiomyopathy. METHODS: Male Sprague-Dawley rats received weekly DOX injection (2.5 mg/kg) for 6 weeks, with or without DZR pretreatment at a dose ratio of 20:1. The ventricular functions of these animals were monitored at week 6, 9 and 11 by echocardiography. At week 11, their heart morphology was studied by light and electron microscopy. Phosphorylation of Akt and Erk in heart tissues was measured by Western blot analysis. RESULTS: DOX caused myocardial damage with compromised left ventricular function, increased myocardium injury and reduced phosphorylation of Akt and Erk. DZR exerted a significant cardioprotective effect in terms of improved fractional shortening, cardiac output and cardiomyopathy score at one or more time points. We also provided the first evidence that dexarazoxane-treated animals had increased levels of Akt and Erk activation, whilst total Akt and Erk remained unchanged. CONCLUSIONS: Our results showed that the cardioprotective effect of dexarazoxane has been sustained beyond the treatment period. The data also suggested that activation of the Akt and Erk signaling pathways was regulated in the course of DOX-induced cardiomyopathy and protection by DZR.

Thrombopoietin protects against in vitro and in vivo cardiotoxicity induced by doxorubicin.

BACKGROUND: Doxorubicin (DOX) is an important antineoplastic agent. However, the associated cardiotoxicity, possibly mediated by the production of reactive oxygen species, has remained a significant and dose-limiting clinical problem. Our hypothesis is that the hematopoietic/megakaryocytopoietic growth factor thrombopoietin (TPO) protects against DOX-induced cardiotoxicity and might involve antiapoptotic mechanism exerted on cardiomyocytes. METHODS AND RESULTS: In vitro investigations on H9C2 cell line and spontaneously beating cells of primary, neonatal rat ventricle, as well as an in vivo study in a mouse model of DOX-induced acute cardiomyopathy, were performed. Our results showed that pretreatment with TPO significantly increased viability of DOX-injured H9C2 cells and beating rates of neonatal myocytes, with effects similar to those of dexrazoxane, a clinically approved cardiac protective agent. TPO ameliorated DOX-induced apoptosis of H9C2 cells as demonstrated by assays of annexin V, active caspase-3, and mitochondrial membrane potential. In the mouse model, administration of TPO (12.5 microg/kg IP for 3 alternate days) significantly reduced DOX-induced (20 mg/kg) cardiotoxicity, including low blood cell count, cardiomyocyte lesions (apoptosis, vacuolization, and myofibrillar loss), and animal mortality. Using Doppler echocardiography, we observed increased heart rate, fractional shortening, and cardiac output in animals pretreated with TPO compared with those receiving DOX alone. CONCLUSIONS: These data have provided the first evidence that TPO is a protective agent against DOX-induced cardiac injury. We propose to further explore an integrated program, incorporating TPO with other protocols, for treatment of DOX-induced cardiotoxicity and other forms of cardiomyopathy.

Unexplained subdural hematoma in young children: is it always child abuse?

BACKGROUND: In the published reports of the developed society, subdural hematoma and/or retinal hemorrhages, in the absence of documented history of major trauma, should be considered diagnostic of child abuse. Many people used the above criteria for diagnosis, but subsequently found that retinal hemorrhages were more common in non-accidental injuries (NAI). To what extent is the proposed pathognomonic association between unexplained subdural hematoma/retinal hemorrhages and child abuse a self-fulfilling prophecy? METHODS: Clinical details of nine children under 2 years with unexplained subdural hematoma admitted to Prince of Wales Hospital between 1995 and 1998 were reviewed. RESULTS: Four had no other physical signs of injury, five had retinal hemorrhages and one had multiple bruises over the body. Following multidisciplinary case conferences for seven children, a diagnosis of NAI was concluded in four cases, but in no case could the abuser be definitely identified. Clinical outcome was poor with seven children showing either profound disability (n = 5) or evidence of developmental delay (n = 2). CONCLUSION: In this series, NAI were not established in three of the seven cases. Did we underdiagnose child abuse in these cases? Despite a magnitude of opinion to the contrary, the issue of whether "trivial" head injury can cause subdural hemorrhages and/or retinal hemorrhages is yet unresolved. Clearly much more information on this very sensitive and serious issue is required and these data should be collected with an open mind.