Assessment of the (Pro)renin Receptor Protein Expression in Organs.

The (pro)renin receptor ((P)RR) is an essential component of the renin-angiotensin system (RAS) as a specific single-pass transmembrane receptor for prorenin and renin and has now emerged as a multifunctional protein implicated in a wide variety of developmental and physio-pathological processes and pathways. The (P)RR may be of pathological significance in metabolic syndrome. The (P)RR has received much consideration; substantial efforts have been made to understand the localization, regulation, and function of the (P)RR at both a molecular and system level. (P)RR regulation of cell function depends on whether it is intact or cleaved into its constituent forms. Therefore, the present chapter describes immunohistochemical approaches to examine the expression of (P)RR in various organs. It was shown that different molecular forms of (P)RR could be present in different tissue compartments in almost all organs. Among them, the liver has high PRR activity. Our findings could elucidate more detailed distribution of different (P)RR molecular forms in different organs, which could provide useful information to further investigate the pathophysiological mechanisms of the development of various diseases in the future.

Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma.

PURPOSE: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR-TKI-induced skin toxicities. EXPERIMENTAL DESIGN: This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR-TKI-treated cancer patients were analysed and compared with those of 43 non-EGFR-TKI-treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib-induced skin eruptions was established in a 14-day-murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR-TKI-treated cancer patients. RESULTS: EGFR-TKI-treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR-TKI-induced skin toxicities showed a significant negative correlation (r = -0.29; p < 0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR-TKI treatment. Zinc supplementation to the EGFR-TKI-treated cancer patients showed a significant decrease in the CTCEA grading (p < 0.0005 for mucositis and p < 0.0.0001 for all other cases) after 8 weeks. CONCLUSIONS: Skin impairment following EGFR-TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR-TKI therapy.

Inhibition of Advanced Glycation End Products Formation Attenuates Cardiac Electrical and Mechanical Remodeling and Vulnerability to Tachyarrhythmias in Diabetic Rats.

Diabetic patients with cardiomyopathy show a higher incidence of arrhythmias and sudden death. Chronic hyperglycemia induces the formation of advanced glycation end products (AGEs), which contribute to the pathogenesis of diabetic cardiomyopathy. This study investigated whether inhibition of AGEs formation by aminoguanidine (AG) could prevent cardiac electromechanical and arrhythmogenic remodeling in diabetes mellitus. Streptozotocin-induced diabetic rats received AG (100 mg/kg daily, i.p.) or vehicle (normal saline, i.p.) for 5 weeks. The rats underwent hemodynamic recording to evaluate cardiac function, and heart preparations were used to determine the electrical, mechanical, and biochemical functions. In vitro high glucose-induced AGEs formation, reactive oxygen species (ROS) generation, and action potential changes were examined in HL-1 atrial cells. AG treatment improved the diabetes-induced depression in left ventricular pressure and the relaxation rate, and normalized the prolongation of QTc intervals in anesthetized rats. AG reduced the vulnerabilities to atrial and ventricular tachyarrhythmias in perfused diabetic hearts. AG normalized the prolonged action potential duration in diabetic atrial and ventricular muscles, which was correlated with the restoration of both transient outward (I to) and steady-state outward (I SS) K+ current densities in cardiomyocytes. The abnormal kinetics of Ca2+ transients and contraction were reversed in cardiomyocytes from AG-treated diabetic rats, along with parallel preservation of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) expression. Furthermore, ex vivo and in vitro studies showed AG attenuated AGEs and ROS formation. Thus, long-term administration of AG ameliorated cardiac electromechanical remodeling and arrhythmogenicity in diabetic rats and may present an effective strategy for the prevention of diabetes-associated arrhythmias.

A Novel DES L115F Mutation Identified by Whole Exome Sequencing is Associated with Inherited Cardiac Conduction Disease.

Inherited cardiac conduction disease (CCD) is rare; it is caused by a large number of mutations in genes encoding cardiac ion channels and cytoskeletal proteins. Recently, whole-exome sequencing has been successfully used to identify causal mutations for rare monogenic Mendelian diseases. We used trio-based whole-exome sequencing to study a Chinese family with multiple family members affected by CCD, and identified a heterozygous missense mutation (c.343C>T, p.Leu115Phe) in the desmin (DES) gene as the most likely candidate causal mutation for the development of CCD in this family. The mutation is novel and is predicted to affect the conformation of the coiled-coil rod domain of DES according to structural model prediction. Its pathogenicity in desmin protein aggregation was further confirmed by expressing the mutation, both in a cellular model and a CRISPR/CAS9 knock-in mouse model. In conclusion, our results suggest that whole-exome sequencing is a feasible approach to identify candidate genes underlying inherited conduction diseases.

Crusade Microcatheter-Facilitated Reverse Wire Technique for Revascularization of Bifurcation Lesions of Coronary Arteries.

BACKGROUND: This study aims to analyze the lesion characteristics of bifurcations that required reverse wire technique and the efficacy and safety of this technique in approaching branches with a highly angulated take-off. METHODS: We enrolled patients in whom reverse wire technique was used after failed conventional antegrade wiring with the support of a Crusade catheter. The study endpoints were the technical success defined as succeeding in sending the reversely bent wire to the targeted branches without complications and the procedural success defined as succeeding in revascularization of the bifurcation lesions without complications. RESULTS: Among 158 patients with bifurcation lesions undergoing percutaneous coronary intervention using a Crusade catheter to facilitate wiring, 23 (14.6%) requiring the reverse wire technique in an attempt to access branches of the bifurcation lesions with an acutely angulated take-off were enrolled for analysis. The obtainable angle of take-off was 162.9 ± 4.7 degrees. For the parent vessel, the ostium of the targeted branch, and nontargeted branch, the minimal luminal diameters were 0.3 ± 0.5 mm, 0.4 ± 0.2 mm, and 1.8 ± 0.5 mm, respectively; the diameter stenosis were 88.8 ± 18.5%, 83.0 ± 7.3%, and 32.0 ± 14.5%, respectively. Technical and procedural success was achieved in 22 cases (96% for both). CONCLUSIONS: We showed in the present study that the reverse wire technique is effective and safe for approaching highly angulated branches of bifurcation lesions and consequently for complete revascularization of difficult bifurcation lesions.

Perceptions about eating experiences of low-literate older adults with heart disease: a qualitative study.

AIMS: To explore perceptions of low-literate older adults with heart disease about their eating experiences. BACKGROUND: Heart disease has been closely linked with nutrition, and nutritional status is poor in patients with limited education, but no studies have explored the eating experiences of low-literate adults with heart disease. DESIGN: Qualitative descriptive study. METHODS: Data were collected in tape-recorded semi-structured interviews from March-June 2012. A convenience sample of 13 low-literate older adults with heart disease was recruited from a cardiovascular ward of a medical centre in northern Taiwan. Participants were recruited until findings reached saturation and data were analysed using qualitative content analysis. FINDINGS: Analysis of participants' interview data on eating experiences identified three main categories: (1) eating-related hardships because of low literacy; (2) eating adjustments due to low literacy; and (3) misinformation about dietary modifications for heart disease. CONCLUSION: Because of their low literacy, these older adults had difficult life experiences, gained inappropriate or inadequate eating information and held a passive, fatalistic perspective about eating with heart disease. Healthcare practitioners caring for this population need to appreciate their unique eating challenges and respect their eating customs. Nurses could play a greater role in educating and supporting low-literate older adults in selecting appropriate foods and preparing meals. Strategies to help this population learn to select, prepare and cook their food should be easy and practical, using specific symbols, concrete signs and simple labels.

Clinicopathologic analysis of coxsackievirus a6 new variant induced widespread mucocutaneous bullous reactions mimicking severe cutaneous adverse reactions.

BACKGROUND: The cutaneous manifestations of human enterovirus (HEV) infection are usually limited, such as hand-foot-mouth disease. By comparison, Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction (SCAR), mainly caused by drugs. During the HEV outbreaks in 2010-2012 in Taiwan, we identified 21 patients who developed widespread blistering mucocutaneous reactions without any suspected drug causality. METHODS: We screened possible pathogen(s) for detecting human herpes virus (HHV1-HHV7), HEV, or Mycoplasma pneumoniae infections using throat swab virus cultures, real-time PCR, DNA sequencing, immunochemistry and electron microscopy analyses. RESULTS: Coxsackievirus A6 (CVA6) DNA was identified in the blistering skin lesions in 6 of 21 patients. Cytotoxic T lymphocytes and natural killer cells expressing granulysin predominantly infiltrated into the skin lesions, sharing the histopathological features with SJS. Intact CVA6 viral particles were identified in the blister fluids and skin lesions by electron microscopy. The phylogenetic analysis of the viral genome showed the CVA6 DNA sequence sharing higher similarity (97.6%-98.1%) to CVA6 strains reported from Finland at 2008. CONCLUSIONS: This study identifies a new variant of CVA6 as the causative agent for severe mucocutaneous blistering reactions mimicking SCAR. An awareness of this unusual presentation of HEV infection is needed in the epidemic area.

Risk of myocardial infarction among patients with gout: a nationwide population-based study.

OBJECTIVE: To investigate the association between gout and myocardial infarction (MI) in a representative cohort in Taiwan. METHODS: Data were collected from the Taiwan National Health Insurance database. Adults >20 years of age without history of MI were included. Patients were considered to have gout if they received a diagnosis of gout requiring medical treatment. Multivariate Cox proportional hazards models were used to evaluate the risk of MI in gout patients. RESULTS: Of the 704 503 patients included, 26 556 (3.8%) had gout. In total, 3718 (with gout, n = 463; without gout, n = 3255) patients had an MI, 299 (with gout, n = 35; without gout, n = 264) of whom died. The incidence of MI was 2.20 and 0.60 per 1000 patient-years in individuals with and without gout, respectively (log-rank test, P < 0.001). After adjustment for age, sex and history of diabetes mellitus, hypertension, coronary heart disease (CHD), stroke and end-stage renal disease, gout was associated with MIs [hazard ratio (HR), 1.23] and non-fatal MIs (HR, 1.26). In individuals without cardiovascular risk factors, gout was associated with MIs (HR 1.84; 95% CI 1.51, 2.24) and non-fatal MIs (HR 1.80; 95% CI 1.49, 3.95), after adjustment for age and sex. Moreover, in our study population, the HRs for MI decreased as age increased. CONCLUSION: Gout is an independent risk factor for MI, and the increased risk of MI is present even in young people and those without cardiovascular risk factors.

Transdermal delivery of three vitamin C derivatives by Er:YAG and carbon dioxide laser pretreatment.

The objective of this study was to investigate the effects of two lasers (Er:YAG and CO2) in enhancing skin permeation of three vitamin C derivatives, L-ascorbic acid 2-phosphate sesquimagnesium salt (MAP-1), magnesium L-ascorbic acid-2-phosphate (MAP-2), and 2-phospho-L-ascorbic acid trisodium salt (SAP). Dorsal skin of 1-week-old pathogen-free pigs was used for this in vitro study. Changes in permeation in laser-treated skin treated by the lasers were examined by confocal scanning electron microscopy. Transdermal flux of vitamin C derivatives was examined with a Franz diffusion cell. Fluxes of MAP-1, MAP-2, and SAP across Er:YAG laser-treated skin were 15-27-fold, 48-123-fold, and 22-56-fold higher, respectively, than their fluxes across intact skin. The fluxes of MAP-1, MAP-2, and SAP across CO2 laser-treated skin were 28-36-fold, 116-156-fold, and 79-102-fold higher, respectively, than their fluxes across intact skin. Optimal fluency for the Er:YAG laser was 3.8 J/cm(2) for MAP-1 and 5 J/cm(2) for MAP-2 and SAP. Optimal fluency for the CO2 laser was 5 W for all three derivatives. In conclusion, optimal fluency for all derivatives was 5 W for the CO2 laser and 3.8 to 5 J/cm(2) for the Er:YAG laser.

Fractional carbon dioxide laser treatment to enhance skin permeation of ascorbic acid 2-glucoside with minimal skin disruption.

BACKGROUND: Topical treatment with vitamin C has been used to treat photoaged skin and as a skin whitener, but no standard procedure exists for percutaneous delivery. OBJECTIVE: To compare skin histology and the permeation of ascorbic acid 2-glucoside (AA2G) after fractional and conventional carbon dioxide (CO(2) ) laser pretreatment. METHODS: The effect on porcine skin of treatment with different strengths of fractional and conventional CO(2) laser treatment was examined using scanning electron microscopy and transmission electron microscopy. Permeation of AA2G through porcine skin was tested in vitro using a Franz diffusion chamber. In vivo changes in fluorescein thiocyanate permeability in nude mice were examined using confocal laser scanning microscopy. RESULTS: Fractional CO(2) laser treatment with four or fewer passes caused less disruption than conventional laser treatment at the same fluence. AA2G permeation using four passes of fractional laser treatment was similar to that seen with conventional CO(2) laser treatment of the same fluence. Changes in permeability and in depth of permeation were higher with conventional than fractional laser treatment. CONCLUSION: Fractional CO(2) laser treatment can cause similar transdermal delivery of AA2G to conventional laser treatment with less skin disruption and a different pattern of histologic change.

Candesartan Cilexetil Attenuates Arrhythmogenicity Following Pressure Overload in Rats via the Modulation of Cardiac Electrical and Structural Remodeling and Calcium Handling Dysfunction.

Background Cardiac hypertrophy is associated with abnormal electrophysiology and increased arrhythmia risk. This study assessed whether candesartan cilexetil, an angiotensin II type 1 receptor blocker, could suppress arrhythmogenecity by attenuating cardiac electrical remodeling and calcium mishandling in rats with pressure-overload hypertrophy. Methods and Results Male Sprague-Dawley rats were randomly subjected to abdominal aorta banding or sham procedure and received either candesartan cilexetil (3.0 mg/kg per day) or vehicle by gavage for 5 weeks. Pressure overload was characterized by compensated left ventricular (LV) hypertrophy and fibrosis, increased LV pressure and its decay time, and prolonged corrected QT interval, all of which were attenuated by candesartan cilexetil treatment. Candesartan cilexetil-treated banded rat hearts displayed shorter QT intervals and lower vulnerability to atrial and ventricular tachyarrhythmias than vehicle-treated banded hearts. Candesartan cilexetil prevented banding-induced prolonged action potential duration and reduced the occurrence of triggered activity in LV papillary muscles. In addition, the prolonged time to 50% cell relengthening and calcium transient decay time were normalized in LV myocytes from candesartan cilexetil-treated banded rats, along with a normalization of decreased SERCA2a (sarco[endo]plasmic reticulum calcium-ATPase) expression in LV tissues. Furthermore, candesartan cilexetil normalized depressed transient outward potassium current densities and protein and mRNA levels of both voltage-gated potassium 4.2 and 4.3 channel subunits (Kv4.2 and Kv4.3) in banded rats. Conclusions Candesartan cilexetil protects the heart from pressure overload-induced adverse electrical remodeling by preserving potassium channel densities. In addition, calcium handling and its molecular regulation also improved after treatment. These beneficial effects may contribute to a lower susceptibility to arrhythmias in hearts from candesartan cilexetil-treated pressure-overloaded rats.

Added Value of Computed Tomography Virtual Intravascular Endoscopy in the Evaluation of Coronary Arteries with Stents or Plaques.

Coronary computed tomography angiography (CCTA) is a widely used imaging modality for diagnosing coronary artery disease (CAD) but is limited by a high false positive rate when evaluating coronary arteries with stents and heavy calcifications. Virtual intravascular endoscopy (VIE) images generated from CCTA can be used to qualitatively assess the vascular lumen and might be helpful for overcoming this challenge. In this study, one hundred subjects with coronary stents underwent both CCTA and invasive coronary angiography (ICA). A total of 902 vessel segments were analyzed using CCTA and VIE. The vessel segments were first analyzed on CCTA alone. Then, using VIE, the segments were classified qualitatively as either negative or positive for in-stent restenosis (ISR) or CAD. These results were compared, using ICA as the reference, to determine the added diagnostic value of VIE. Of the 902 analyzed vessel segments, CCTA/VIE had sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (shown in %) of 93.9/90.2, 96.2/98.2, 96.0/97.7, 70.0/83.1, and 99.4/99.0, respectively, in diagnosing ISR or CAD, with significantly improved specificity (p = 0.025), accuracy (p = 0.046), and positive predictive value (p = 0.047). VIE can be a helpful addition to CCTA when evaluating coronary arteries.

Slow conduction and gap junction remodeling in murine ventricle after chronic alcohol ingestion.

BACKGROUND: Long-term heavy alcohol drinkers are prone to the development of cardiac arrhythmia. To understand the mechanisms, we evaluated the cardiac structural and electrophysiological changes in mice chronically drinking excessive alcohol. RESULTS: Male C57BL/6J mice were given 36% alcohol in the drinking water. Those given blank water were used as control. Twelve weeks later, the phenotypic characteristics of the heart, including gap junctions and electrical properties were examined. In the alcohol group the ventricles contained a smaller size of cardiomyocytes and a higher density of capillary networks, compared to the control. Western blots showed that, after drinking alcohol, the content of connexin43 (Cx43) protein in the left ventricle was increased by 18% (p < 0.05). Consistently, immunoconfocal microscopy demonstrated that Cx43 gap junctions were up-regulated in the alcohol group with a disorganized distribution, compared to the control. Optical mapping showed that the alcohol group had a reduced conduction velocity (40 ± 18 vs 60 ± 7 cm/sec, p < 0.05) and a higher incidence of ventricular tachyarrhythmia (62% vs 30%, p < 0.05). CONCLUSION: Long-term excessive alcohol intake resulted in extensive cardiac remodeling, including changes in expression and distribution of gap junctions, growth of capillary network, reduction of cardiomyocyte size, and decrease of myocardial conduction.

Skin pretreatment with lasers promotes the transdermal delivery of vitamin C derivatives.

The objective of this study is to investigate the effects of two lasers (erbium:YAG and CO(2)) on the ability to enhance skin permeation of two vitamin C derivatives, 3-O-ethyl ascorbic acid (EAC) and ascorbic acid 2-glucoside (AA2G). The study was taken in the skin of a female nude mouse (Balb/c-nu strain, 8 weeks old) in vitro. The histologic and ultrastructural changes of the nude mouse skin treated by the lasers were examined under light microscopy and transmission electron microscopy, respectively. The in vitro permeation of vitamin C derivatives was performed in Franz cell. The stratum corneum (SC) layer in the skin was partly ablated by erbium:YAG laser treatment, resulting in greater permeation of both vitamin C derivatives. The flux of EAC and AA2G across erbium:YAG laser-treated skin was 105 to 189-fold and 35 to 78-fold higher, respectively, than their flux across intact skin. The increase in enhancement ratio with increase in fluency decreases markedly for both compounds at the last dose escalation (from 5.0 to 6.3 J/cm(2)). Both SC ablation and a thermal effect may contribute to the effect of the CO(2) laser on skin structure. The flux of EAC and AA2G across CO(2) laser-treated skin was 181 to 277-fold and 82 to 117-fold higher, respectively, than their flux across intact skin. We concluded that both erbium:YAG and CO(2) laser pretreatment increased the transdermal flux of two stable vitamin C derivatives, EAC and AA2G. The optimal fluency for the Er:YAG laser was 5 J/cm(2).

Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat.

BACKGROUND: Intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is the standard treatment for acute ischemic stroke. Standard-dose rt-PA (0.9 mg/kg) is known to achieve good recanalization but carries a high bleeding risk. Lower dose of rt-PA has less bleeding risk but carries a high re-occlusion rate. We investigate if induced pluripotent stem cells (iPSCs) can improve the thrombolytic effect of low-dose rt-PA (0.45 mg/kg). METHODS: Single irradiation with 6 mW/cm2 light-emitting diode (LED) for 4 h at rat common carotid artery was used as thrombosis model according to our previous report. Endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), and interleukin 1 beta (IL-1 beta) were used as the inflammatory markers for artery endothelial injury. Angiopoietin-2 (AP-2), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were examined in artery wall and iPSCs culture. Animal ultrasound was used to evaluate the stenosis degree of common carotid artery before and at 2 h, 24 h, 4 days and 7 days after LED irradiation. RESULTS: After LED irradiation alone, there was a persistent occlusion from 2 h to 7 days. Standard-dose rt-PA alone could recanalize the occluded artery from 24 h to 7 days to stenotic degree ≤ 50%. Low-dose rt-PA or 1 × 106 mouse iPSCs alone could not recanalize the occluded arteries from 2 h to 7 days. Combination use of low-dose rt-PA plus 1 × 106 mouse iPSCs caused better recanalization from 24 h to 7 days. ET-1, ICAM-1 and IL-1 beta were strongly expressed after LED irradiation but reduced after iPSCs treatment. AP-2, BDNF and VEGF were rarely induced after LED irradiation but strongly expressed after iPSCs treatment. In vitro study showed iPSCs could express AP-2, BDNF and VEGF. CONCLUSION: The adjuvant use of iPSCs may help improving the thrombolytic effect of low-dose rt-PA by suppressing inflammatory factors and inducing angiogenic trophic factors. Stem cells could be a potential regimen in acute thrombolytic therapy to improve recanalization and reduce complications.

Using betaxolol for the prevention of paronychia induced by epidermal growth factor receptor inhibitors: a case-control cohort study.

BACKGROUND: High rates of posttreatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion resulting from epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)-induced paronychia, which may even interrupt the course of treatment for EGFR-TKI therapy. Thus, we conducted this study to determine how effectively a topical ß-blocker, betaxolol, prevents EGFR-TKI-induced paronychia. METHODS: This case-control cohort study included a total of 131 non-small-cell lung cancer patients. The prevention group comprised 40 patients treated with topical betaxolol 0.25% solution to prevent paronychia while they received EGFR-TKI therapy. The control group comprised 91 patients who did not preventively use topical betaxolol 0.25% solution while receiving EGFR-TKI therapy. The patients' age, gender, antineoplastic regimen, duration of antineoplastic treatment before the appearance of lesions, number of involved digits (fingernails or toenails) with lesions, grading of paronychia, and pain score were recorded. RESULTS: In terms of the cumulative incidence of paronychia, significant differences (P < 0.01) were noted at both the 2nd and 3rd months after starting EGFR-TKIs. Furthermore, the average visual analogue scale scores were 3.125 and 6.29 in the prevention group and control group, respectively (P < 0.01). The average grades of paronychia were 1.5 and 2.12 in the prevention group and control group, respectively (P < 0.01). The average numbers of involved digits were 2.25 (range: 1-5 digits) in the prevention group and 3.03 (range: 1-7) in the control group (P = 0.07). CONCLUSIONS: Preventively using topical betaxolol can significantly decrease the incidence, VAS score, and grading of EGFR-TKI-induced paronychia.

Gout: an independent risk factor for all-cause and cardiovascular mortality.

OBJECTIVE: The relation of gout and hyperuricaemia to cardiovascular diseases has been well documented. This study investigates the survival impact of both gout and hyperuricaemia. METHODS: The subjects of this study comprised participants of a health screening programme conducted by the Chang Gung Memorial Hospital in Taiwan from 2000 to 2006. The status and causes of death were ascertained by the Taiwan National Death Registry 2000-07. Cox proportional hazard model was performed to examine the association. RESULTS: Among 61 527 subjects, 1383 deaths (198 cardiovascular deaths) were identified, corresponding to a crude mortality rate of 4.86 deaths per 1000 person-years. Crude mortality rates were 4.50, 5.61 and 10.46 deaths per 1000 person-years for subjects with normouricaemia, hyperuricaemia and gout, respectively. Compared with subjects with normouricaemia, the hazard ratios (HRs) of all-cause mortality were 1.46 (95% CI 1.12, 1.91) for individuals with gout and 1.07 (95% CI 0.94, 1.22) for those with hyperuricaemia, respectively, after adjustments were made for age, sex, component number of metabolic syndrome and proteinuria. The adjusted HRs of cardiovascular mortality were 1.97 (95% CI 1.08, 3.59) for individuals with gout and 1.08 (95% CI 0.78, 1.51) for those with hyperuricaemia. Moreover, the risk of all-cause or cardiovascular mortality for gout remained unchanged when limiting the data to those with an estimated glomerular filtration of >60 ml/min/1.73 m(2). CONCLUSION: This study demonstrates a link of gout, not hyperuricaemia, with a higher risk of death from all causes and cardiovascular diseases.

Role of uric acid in the link between arterial stiffness and cardiac hypertrophy: a cross-sectional study.

OBJECTIVES: Hyperuricaemia has been linked to atherosclerosis; however, there is limited evidence about its association with arterial stiffness and cardiac hypertrophy, which are associated with adverse cardiovascular outcomes. We studied the association of hyperuricaemia with an increased risk of arterial stiffness and cardiac hypertrophy in a population participating in a health-screening programme. METHODS: In subjects who underwent health screening from 2005 to 2007, arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV), whereas cardiac hypertrophy was determined by plain chest radiography and electrocardiography. Polychotomous logistic regression was used to identify associations of hyperuricaemia with arterial stiffness and cardiac hypertrophy, after adjusting for the presence of metabolic syndrome. RESULTS: Of the total 9375 subjects enrolled, 1324 (14.5%) had hyperuricaemia. Subjects with hyperuricaemia had a significantly higher baPWV [1618.8 (379.3) cm/s] than those without it [1501.8 (334.9) cm/s]. Cardiac hypertropy was observed in 1047 (11.2%) subjects. Hyperuricaemia was associated with cardiac hypertrophy with an odds ratio (OR) of 1.53 (95% CI 1.32, 1.77). Polychotomous logistic regression showed that hyperuricaemia was associated with ORs (95% CI) for coexisting abnormal baPWV and cardiac hypertrophy of 1.75 (95% CI 1.24, 2.47) and 1.41 (95% CI 1.04, 1.91) in men and women, respectively, after adjusting for age, proteinuria, high high-sensitive CRP, abnormal ankle-brachial index or a number of metabolic syndrome components present. CONCLUSION: Hyperuricaemia was associated with arterial stiffness and cardiac hypertrophy. Hyperuricaemia, along with other risk factors related to atherosclerosis, could play a role in the development of cardiac hypertrophy by increasing arterial stiffness.

Expression of nerve growth factor immunoreactivity and messenger RNA in ischemic urinary bladder.

AIMS: The bladder contractile dysfunction resulting from acute ischemia may be attributed to nerve growth factor (NGF) overexpression. This study was conducted to evaluate the acute and mid-term effects of bladder ischemia on the temporal expression of NGF immunoreactivity and mRNA. MATERIALS AND METHODS: Bladder ischemia was induced by ligation of bilateral vesical arteries in female rats. We examined the NGF content of bladder detrusor muscle at 1 day, 1 week and 4 weeks after artery ligation. Immunoreactivity of NGF was studied by immunofluorescent staining and Western blot. The NGF mRNA was analyzed by real-time polymerase chain reaction. RESULTS: The immunofluorescence of NGF at 1 week and 4 weeks was significantly reduced when compared to sham-operated group (P < 0.05). This decreased tendency was also found in Western blot test. An increased expression of NGF mRNA was noted at 1 day, 1 week and 4 weeks, but had no significant change when compared to sham-operated group (P > 0.05). CONCLUSIONS: Our study showed bilateral vesical artery ligation may cause damage of detrusor muscle and there is decreased NGF immunofluorescence and elevated NGF mRNA in bladder suggesting an expression disparity following ischemia.

Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats.

The effects of human amniotic fluid stem cell (hAFSC) transplantation on bladder function and molecular changes in spinal cord-injured (SCI) rats were investigated. Four groups were studied: sham and SCI plus phosphate-buffered saline (SCI + PBS), human embryonic kidney 293 (HEK293) cells, and hAFSCs transplantation. In SCI + PBS rat bladders, cystometry showed increased peak voiding pressure, voiding volume, bladder capacity, residual volume, and number of non-voiding contractions, and the total elastin/collagen amount was increased but collagen concentration was decreased at days 7 and 28. Immunoreactivity and mRNA levels of IGF-1, TGF-ß1, and ß3-adrenoceptor were increased at days 7 and/or 28. M2 immunoreactivity and M3 mRNA levels of muscarinic receptor were increased at day 7. M2 immunoreactivity was increased, but M2/M3 mRNA and M3 immunoreactivity levels were decreased at day 28. Brain derived-neurotrophic factor mRNA was increased, but immunoreactivity was decreased at day 7. HEK293 cell transplantation caused no difference compared to SCI + PBS group. hAFSCs co-localized with neural cell markers and expressed BDNF, TGF-ß1, GFAP, and IL-6. The present results showed that SCI bladders released IGF-1 and TGF-ß1 to stimulate elastin and collagen for bladder wall remodelling, and hAFSC transplantation improved these changes, which involved the mechanisms of BDNF, muscarinic receptors, and ß3-adrenoceptor expression.