Postmortem diagnosis of gestational psittacosis: A case report.

Background: Gestational psittacosis is one of the causes of unanticipated maternal death but has been difficult to diagnose early in clinical practice. Case Presentation: A 28-year-old woman who was 7 months pregnant experienced flu-like symptoms, which deteriorated. She was brought to our hospital in shock, and the fetus was nonviable. The patient was diagnosed with pneumonia and septic shock and administered meropenem. Despite aggressive resuscitation, she died 7 h after symptom onset. After obtaining consent from the patient's family, the autopsy was done to identify the cause of death. Microscopically, there was intervillous neutrophil accumulation in the placenta. Genetic analysis detected the Chlamydia psittaci gene in several organs, including placenta. Conclusion: Gestational psittacosis should be considered for a pregnant woman with flu-like symptoms. Moreover, unanticipated death of a pregnant woman might warrant a detailed autopsy to reveal the cause of death.

Association between increased nonaerated lung weight and treatment failure in patients with de novo acute respiratory failure: Difference between high-flow nasal oxygen therapy and noninvasive ventilation in a multicentre retrospective study.

PURPOSE: To determine the association between lung collapse and treatment failure in high-flow nasal cannula oxygen therapy (HFNC) or noninvasive ventilation (NIV). METHODS: We performed a quantitative analysis of chest computed tomography in patients with de novo acute respiratory failure who received HFNC (HFNC group) or NIV (NIV group) between January 2012 and December 2017. In the HFNC and NIV group, the nonaerated lung weight were compared between patients in whom respiratory treatment succeeded or failed, respectively. We used logistic regression to examine the association between the nonaerated lung weight and treatment failure. RESULTS: Treatment failed in 70/118 (59%) patients in the HFNC group and 66/101 (65%) patients in the NIV group. The nonaerated lung weight was significantly greater in unsuccessfully treated patients than in successfully treated patients in the HFNC group (p = 0.005), but not in the NIV group (p = 0.535). Logistic regression revealed that greater nonaerated lung weight was associated with increased risk of HFNC failure (adjusted odds ratio 1.30 per 5% increase, 95% confidence interval 1.09-1.55, p = 0.003) but not of NIV failure. CONCLUSIONS: Patients with a greater nonaerated lung weight had a higher risk of HFNC failure, but not of NIV failure.

Comparison of high-flow nasal cannula oxygen therapy and non-invasive ventilation as first-line therapy in respiratory failure: a multicenter retrospective study.

AIM: To identify which subgroups of respiratory failure could benefit more from high-flow nasal cannula oxygen therapy (HFNC) or non-invasive ventilation (NIV). METHODS: We undertook a multicenter retrospective study of patients with acute respiratory failure (ARF) who received HFNC or NIV as first-line respiratory support between January 2012 and December 2017. The adjusted odds ratios (OR) with 95% confidence intervals (CI) for HFNC versus NIV were calculated for treatment failure and 30-day mortality in the overall cohort and in patient subgroups. RESULTS: High-flow nasal cannula oxygen therapy and NIV were used in 200 and 378 patients, and the treatment failure and 30-day mortality rates were 56% and 34% in the HFNC group and 41% and 39% in the NIV group, respectively. The risks of treatment failure and 30-day mortality were not significantly different between the two groups. In subgroup analyses, HFNC was associated with increased risk of treatment failure in patients with cardiogenic pulmonary edema (adjusted OR 6.26; 95% CI, 2.19-17.87; P < 0.01) and hypercapnia (adjusted OR 3.70; 95% CI, 1.34-10.25; P = 0.01), but the 30-day mortality was not significantly different in these subgroups. High-flow nasal cannula oxygen therapy was associated with lower risk of 30-day mortality in patients with pneumonia (adjusted OR 0.43; 95% CI, 0.19-0.94; P = 0.03) and in patients without hypercapnia (adjusted OR 0.51; 95% CI, 0.30-0.88; P = 0.02). CONCLUSION: High-flow nasal cannula oxygen therapy could be more beneficial than NIV in patients with pneumonia or non-hypercapnia, but not in patients with cardiogenic pulmonary edema or hypercapnia.

Endothelin and the heart in health and diseases.

Endothelin-1 (ET-1), a 21-amino acid peptide, was initially identified in 1988 as a potent vasoconstrictor and pressor substance isolated from the culture supernatant of porcine aortic endothelial cells. From human genomic DNA analysis, two other family peptides, ET-2 and ET-3, were found. They showed different effects and distribution, suggesting that each peptide may play separate roles in different organs. In the heart, ET-1 also causes positive inotropic and chronotropic responses and hypertrophic activity of the cardiomyocytes. ETs act via activation of two receptor subtypes, ETA and ETB receptors, both of which are coupled to various GTP-binding proteins depending on cell types. Endogenous ET-1 may be involved in progression of various cardiovascular diseases. ET antagonists are currently used clinically in the treatment for patients with pulmonary hypertension, and are considered to have further target diseases as heart failure, cardiac hypertrophy and other cardiac diseases, renal diseases, systemic hypertension, and cerebral vasospasm.

The number of microvascular complications is associated with an increased risk for severity of periodontitis in type 2 diabetes patients: Results of a multicenter hospital-based cross-sectional study.

AIMS/INTRODUCTION: To explore the relationships between periodontitis and microvascular complications as well as glycemic control in type 2 diabetes patients. MATERIALS AND METHODS: This multicenter, hospital-based, cross-sectional study included 620 patients with type 2 diabetes. We compared the prevalence and severity of periodontitis between patients with ≥1 microvascular complication and those without microvascular complications. We also compared the prevalence and severity of periodontitis among patients with different degrees of glycemic control. RESULTS: After adjusting for confounding factors, multiple logistic regression analysis showed that the severity of periodontitis was significantly associated with the number of microvascular complications (odds ratio 1.3, 95% confidence interval 1.1-1.6), glycated hemoglobin ≥8.0% (64 mmol/mol; odds ratio 1.6; 95% confidence interval 1.1-2.3), and older age (≥50 years; odds ratio 1.7; 95% confidence interval 1.1-2.6). However, the prevalence of periodontitis was not significantly associated with the number of microvascular complications, but was associated with male sex, high glycated hemoglobin (≥8.0% [64 mmol/mol]), older age (≥40 years), longer duration of diabetes (≥15 years) and fewer teeth (≤25). Furthermore, propensity score matching for age, sex, diabetes duration and glycated hemoglobin showed that the incidence of severe periodontitis was significantly higher among patients with microvascular complications than among those without microvascular complications (P < 0.05). CONCLUSIONS: The number of microvascular complications is a risk factor for more severe periodontitis in patients with type 2 diabetes, whereas poor glycemic control is a risk factor for increased prevalence and severity of periodontitis.

Risk factors for late defecation and its association with the outcomes of critically ill patients: a retrospective observational study.

BACKGROUND: Late defecation was recently reported to be associated with worse clinical outcomes in critically ill patients. However, more research is needed to examine the causes and clinical significance of late defecation. The objectives of this study were to investigate the risk factors for late defecation and its association with the outcomes of intensive care unit (ICU) patients. METHODS: Patients in an ICU for ≥7 days between January and December 2011 were retrospectively assessed. Based on the time between admission and the first defecation, they were assigned to early (<6 days; n = 186) or late (≥6 days; n = 96) defecation groups. Changes in clinical variables between admission and ICU day 7 were assessed to investigate the effects of late defecation. The clinical outcomes were ICU mortality, length of ICU stay, and length of mechanical ventilation. RESULTS: Late enteral nutrition (odds ratio (OR) 3.42; 95 % confidence interval (CI) 1.88-6.22; P < 0.001), sedatives (OR 3.07; 95 % CI 1.71-5.52; P < 0.001), and surgery (OR 1.86; 95 % CI 1.01-3.42; P = 0.047) were the independent risk factors for late defecation. The median (interquartile) changes in body temperature (0.3 [-0.4 to 1.0] vs 0.7 [0.1 to 1.5] °C; P = 0.004), serum C-reactive protein concentration (1.6 [-0.5 to 6.6] vs 3.5 [0.7 to 8.5] mg/dL; P = 0.035), and Sequential Organ Failure Assessment score (-1 [-2 to 1] vs 0 [-1 to 2]; P = 0.008) between admission and ICU day 7 were significantly greater in the late defecation group than in the early defecation group. ICU stay was significantly longer in the late defecation group (12 [9 to 19] vs 16 [10 to 23] days; P = 0.021), whereas ICU mortality and the length of mechanical ventilation were similar in both groups. CONCLUSIONS: Late enteral nutrition, sedatives, and surgery were independent the risk factors for late defecation in critically ill patients. Late defecation was associated with prolonged ICU stay.

Antagonists to endothelin receptor type B promote apoptosis in human pulmonary arterial smooth muscle cells.

AIMS: Vascular remodeling results from aberrations in the balance between cell proliferation and death, which is seen in the obstructive vasculature of pulmonary arterial hypertension (PAH). Endothelin (ET)-1 has a potent proliferative activity on vascular smooth muscle cells, and ET receptor inhibitors are used to treat PAH; however, it remains unclear whether ET receptor inhibition contributes to the apoptosis of pulmonary arterial smooth muscle cells (PASMCs), another cause of pulmonary vascular remodeling. MAIN METHODS: Cultured human PASMCs were treated with the ETA receptor antagonist BQ-123 (100µM), or the ETB antagonist A-192621 (1-100µM) or BQ-788 (1-100µM) for 48h. The cells were then incubated for another 24h with or without doxorubicin (DOX, 1µM), an anthracyclin antitumor antibiotic that promotes p53-mediated apoptosis. Cell viability and apoptosis were evaluated by MTT assays, caspase-3/7 activity assays, and Western blots for cleaved caspase-3 expression. KEY FINDINGS: The viability of PASMCs was significantly decreased by A-192621 and BQ-788, in a dose-dependent manner. A-192621 and BQ-788 significantly increased the caspase-3/7 activity and cleaved caspase-3 expression in PASMCs. The PASMCs' susceptibility to DOX-induced apoptosis was significantly higher in the presence of A-192621 and BQ-788 than with vehicle. However, BQ-123 did not affect these parameters. SIGNIFICANCE: Blockade of the ETB receptor increases the extent of apoptosis and susceptibility to DOX-induced apoptosis in PASMCs. Apoptosis caused by ETB receptor blockade in PASMCs may be one of the mechanisms by which vascular remodeling is reduced in ET receptor inhibitor-based PAH treatments.

Extent of pleural effusion on chest radiograph is associated with failure of high-flow nasal cannula oxygen therapy.

PURPOSE: The purpose of the study was to determine whether pleural effusion (PE) is associated with a failure of high-flow nasal cannula (HFNC) therapy. MATERIALS AND METHODS: We conducted a single-center retrospective study. Seventy-three patients with acute respiratory failure given HFNC therapy between January 2012 and December 2014 were reviewed. HFNC failure was defined as intubation or noninvasive positive pressure ventilation following HFNC therapy. The numbers of quadrants with consolidation or ground glass opacity were counted on chest radiographs performed within 24 hours before starting HFNC therapy, and the PE score was calculated. PE score was the original score, verified by the computed tomographic images of some of the study patients. RESULTS: Overall, 29 of 73 experienced HFNC failure. PE score was significantly greater in the HFNC failure group, but the number of quadrants with opacity was not significantly different. Age and Sequential Organ Failure Assessment (SOFA) score were significantly greater in the HFNC failure group. The PE (odds ratio, 1.49; 95% confidence interval, 1.10-2.02; P = .01) and SOFA (odds ratio, 1.33; 95% confidence interval, 1.05-1.68; P = .02) scores were independently associated with HFNC failure in multivariate analysis. CONCLUSIONS: The extent of PE on chest radiograph and SOFA score were associated with HFNC failure.

Splenic volume in severe sepsis is associated with disease severity and pneumococcal infection.

Aim: A small spleen, which is occasionally found in patients with pneumococcal sepsis, may increase pneumococcal susceptibility because of splenic malfunction. However, a small spleen may also originate from severe disease. We carried out a retrospective study to evaluate the association between splenic volume and severe pneumococcal sepsis or disease severity. Methods: We reviewed the medical records of 23 patients with severe pneumococcal sepsis treated at our institution between January 2004 and September 2015 (pneumococcal group) and 61 patients with severe non-pneumococcal bacteremia treated between April 2011 and September 2015 (control group). Splenic volume measured by abdominal computed tomography on admission was compared between the two groups. Correlations between Acute Physiology and Chronic Health Evaluation (APACHE) II scores and splenic volume on admission and the change in splenic volume from the non-septic state to admission were also determined. Results: Splenic volume on admission was significantly smaller (P = 0.001) and a small spleen was more frequent (P < 0.001) in the pneumococcal group. The APACHE II score was negatively correlated with splenic volume on admission (r = -0.46, P < 0.001) and the change in splenic volume (r = -0.44, P = 0.004). Pneumococcal infection (odds ratio 13.1, 95% confidence interval 2.6-65.7; P = 0.002) and APACHE II score (odds ratio 1.2, 95% confidence interval 1.1-1.3; P = 0.002) were independently associated with small spleen. Conclusion: Splenic volume decreased with increasing severity of severe sepsis. A small spleen was also associated with severe pneumococcal infection.

Cardiac arrest due to massive hemorrhage from uterine adenomyosis with leiomyoma successfully treated with damage control resuscitation.

Case: A 57-year-old woman was transferred to our emergency department by ambulance with cardiopulmonary arrest caused by massive genital bleeding. Cardiopulmonary resuscitation, including massive transfusion, was carried out and the return of spontaneous circulation was achieved. A giant uterine tumor was considered the source of the bleeding. Although hysterectomy was necessary to achieve definitive hemostasis, the patient was unable to tolerate the operation because of hemodynamic instability, acidosis, and coagulopathy. Therefore, we undertook vaginal gauze packing and uterine artery embolization to attain temporary hemostasis, which resulted in hemodynamic stabilization. Abdominal hysterectomy for definitive hemostasis was carried out 10 h after the embolization. Outcome: The patient made a good post-surgical recovery without any complications. Conclusion: In treating hemorrhagic shock due to uterine leiomyoma, damage-control resuscitation may be useful as a bridge prior to definitive hemostasis through hysterectomy.

Effects of mechanical chest compression device with a load-distributing band on post-resuscitation injuries identified by post-mortem computed tomography.

OBJECTIVE: To determine the effects of cardiopulmonary resuscitation (CPR) with AutoPulse™ (LDB-CPR) on post-resuscitation injuries identified by post-mortem computed tomography (PMCT). AutoPulse™ is a novel mechanical chest-compression device with a load-distributing band (LDB) that may affect post-resuscitation injury identified by PMCT. METHODS: We conducted a retrospective cohort study of non-traumatic adult out-of-hospital cardiac arrest patients whose death was confirmed in our emergency department between October 2009 and September 2014. Patients were divided according to whether LDB-CPR (LDB-CPR group) or manual CPR only (manual CPR only group) was performed. The background characteristics and post-resuscitation injuries identified by PMCT were compared between both groups. Logistic regression was used to identify risk factors for posterior rib fracture and abdominal injury. RESULTS: Overall, 323 patients were evaluated, with 241 (74.6%) in the LDB-CPR group. The total duration of CPR was significantly longer in the LDB-CPR group than in the manual CPR only group. Posterior rib fracture, hemoperitoneum, and retroperitoneal hemorrhage were significantly more frequent in the LDB-CPR group. The frequencies of anterior/lateral rib and sternum fracture were similar in both groups. Pneumothorax tended to be more frequent in the LDB-CPR group, although not significantly. LDB-CPR was an independent risk factor for posterior rib fracture (odds ratio 30.57, 95% confidence interval 4.15-225.49, P=0.001) and abdominal injury (odds ratio 4.93, 95% confidence interval 1.88-12.95, P=0.001). CONCLUSIONS: LDB-CPR was associated with higher frequencies of posterior rib fracture and abdominal injury identified by PMCT. PMCT findings should be carefully examined after LDB-CPR.

Predictive Factors for Hospitalization of Patients with Heat Illness in Yamaguchi, Japan.

The objective of the study was to investigate the predictive factors for the hospitalization of patients who presented with mild to moderate heat illness at an emergency department. We conducted a retrospective survey of hospitals with an emergency department in Yamaguchi Prefecture, Japan. The survey questionnaire entries included patient age, sex, use of an ambulance, vital signs, blood examination conducted at the emergency department, the length of hospitalization, and outcome. We analyzed the predictive factors for hospitalization in patients with heat illness. A total of 127 patients were analyzed. Of these, 49 (37%) were admitted, with 59% discharged on the day following admission. In univariate analysis, the following inpatient characteristics were predictive for hospitalization: old age, low Glasgow Coma Scale score, elevated body temperature, increased serum C-reactive protein, and increased blood urea nitrogen. In logistic regression multivariate analysis, the following were predictive factors for hospitalization: age of ≥ 65 years (odds ratio (OR) 4.91; 95% confidence interval (CI) 1.42-17.00), body temperature (OR 1.97; 95% CI 1.14-3.41), Glasgow Coma Scale (OR 0.40; 95% CI 0.16-0.98), and creatinine (OR 2.92; 95% CI 1.23-6.94). The results suggest that the elderly with hyperthermia, disturbance of consciousness, and elevated serum creatinine have an increased risk for hospitalization with heat illness.

Higher circulatory level of endothelin-1 in hypertensive subjects screened through a cross-sectional study of rural Bangladeshi women.

Endothelin-1 (ET-1) is a potential marker of the endothelial dysfunction, which has been shown to be elevated in hypertensive subjects. No previous study has investigated the circulatory level of ET-1 and hypertension in a South Asian country. The present study assessed the circulating levels of ET-1 in subjects with or without hypertension and further examined the association of ET-1 with clinical and metabolic parameters. A total of 2543 rural Bangladeshi women with a mean age of 44.5 years were studied using a cross-sectional survey. Multiple regressions were used to examine the association between the circulatory ET-1 levels and hypertension. The prevalence of hypertension was 29.3%. The ET-1 levels were significantly higher in the hypertensive (mean 3.08 pg ml(-1), s.e. (0.19)) than in the non-hypertensive subjects (mean 2.01 pg ml(-1), s.e. (0.03)) (P = 0.001). After adjusting for age, the ET-1 level had significant positive associations with the diastolic blood pressure (P = 0.002), systolic blood pressure (P = 0.001), mean arterial pressure (P = 0.002) and fasting blood glucose (P = 0.002). In a tertile analysis, we found that hypertension in the subjects was significantly increased as the levels of ET-1 increased (P for the trend = 0.001). In a stepwise multiple regression analysis, after adjusting for age and all other potential variables, we found that the mean arterial pressure and the fasting plasma levels have significant associations with the ET-1 level. The present study demonstrates that there is a higher concentration of ET-1 among the hypertensive subjects in an apparently healthy population of Bangladeshi rural women. The relationship between ET-1 and hypertension requires further investigation to define the clinical utility and predictive value of serum ET-1 levels for hypertension for a South Asian population.

Effects of selective endothelin (ET)-A receptor antagonist versus dual ET-A/B receptor antagonist on hearts of streptozotocin-treated diabetic rats.

AIMS: The aim was to study the differences in the effectiveness of two types of endothelin (ET) receptor antagonists (selective ET-A or dual ET-A/B antagonists) on the hearts of streptozotocin (STZ)-induced diabetic rats (type I diabetes) at functional and biochemical/molecular levels. MAIN METHODS: Citrate saline (vehicle) or STZ was injected into rats. The ET-A/B dual receptor antagonist (SB209670, 1mg/kg/day) and the ET-A receptor antagonist (TA-0201, 1mg/kg/day) were then administered to these rats. One week after injection, the animals were separated into those receiving SB209670, TA-0201 or vehicle by 4-week osmotic mini-pump. KEY FINDINGS: The VEGF level and percent fractional shortening in the diabetic heart were significantly decreased compared to the non-diabetic heart, whereas SB209670 and TA-0201 treatments greatly and comparably prevented this decrease. SB209670 treatment was more effective in reversing decreased expressions of KDR and phosphorylated AKT, downstream of VEGF angiogenic signaling, than TA-0201 treatment. The eNOS levels in hearts were significantly higher in diabetic rats than in healthy rats, and this increase was significantly reduced by TA-0210 but not by SB209670 treatment. SIGNIFICANCE: Improvement of KDR mRNA and pAKT levels by SB209670 but not TA-0201 suggests that dual ET-A/-B blockade may be effective in improving intracellular systems of these components in the diabetic rat heart. However, the present study also showed that TA-0201 or SB209670 improved percent fractional shortening and VEGF levels of the diabetic hearts to a similar extent, suggesting that ET-A blockade and dual ET-A/-B blockade are similarly effective in improving cardiac dysfunction in the diabetic rats.

Effects of uninterrupted chest compressions on the rescuer's physical condition.

STUDY OBJECTIVE: Recent guidelines have emphasized the need for uninterrupted chest compressions. The purpose of this study was to evaluate the rescuer's tolerability of uninterrupted chest compressions. METHODS: Twenty-five healthy subjects performed uninterrupted chest compressions for 7 minutes at a rate of 100 compressions per minute using a training manikin. The quality of chest compressions was assessed in terms of the total number and percentage of chest compressions, compression depth, recoil distance, and duty cycle. Correct chest compression was defined as a depth of 38 to 51 mm. Physiological and laboratory parameters were measured before and after the procedure. Fatigue was measured using a numerical rating scale. Data were compared before and after the procedure. RESULTS: The participants were 10 emergency physicians and 15 medical students. The compression rate was nearly 100 compressions per minute. The number and percentage of correct compressions decreased gradually after 3 minutes. The compression depth decreased significantly after 2 minutes. The recoil distance and duty cycle were unchanged over 7 minutes. Systolic blood pressure, pulse rate, respiratory rate, numerical rating scale, serum lactate, adrenalin, and noradrenalin increased significantly after the procedure. Noradrenalin levels measured before the procedure were significantly and negatively correlated with the total number and percentage of correct compressions (r = -0.587, P = .004; r = -0.549, P = .008, respectively). CONCLUSIONS: Performing uninterrupted chest compressions for 7 minutes is an arduous procedure. Higher noradrenalin levels before the procedure might be associated with incorrect chest compressions.

Plasma ADMA concentrations associate with aerobic fitness in postmenopausal women.

AIMS: Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase, an enzyme responsible for the generation of NO. Plasma concentrations of ADMA increase in the elderly and in postmenopausal women. In fact, an elevated ADMA level is a risk factor of cardiovascular disease. Aerobic exercise has a beneficial effect on cardiovascular disease. However, the relationship between ADMA and aerobic fitness is unknown. The aim of this study was to determine whether plasma ADMA concentrations correlate with aerobic fitness levels in postmenopausal women. MAIN METHODS: Thirty healthy postmenopausal women aged 50-76 years participated in this study. We measured plasma concentrations of ADMA and oxygen consumption at the ventilatory threshold (VO2VT) as an index of aerobic fitness. Subjects were divided into the low aerobic fitness (Low fitness) and high aerobic fitness (High fitness) groups, and the dividing line was set at the median VO2VT value. KEY FINDINGS: VO2VT was significantly higher in the High fitness group than in the Low fitness group (P<0.01). The plasma ADMA concentrations in the High fitness group were significantly lower than those in the Low fitness group (P<0.05). There was a negative correlation between plasma ADMA concentrations and VO2VT (r=-0.532, P<0.01). SIGNIFICANCE: We found that plasma ADMA concentrations were associated with aerobic fitness in postmenopausal women. The results of this study suggest that habitual aerobic exercise may decrease plasma ADMA concentrations.

Fish oil constituent eicosapentaenoic acid inhibits endothelin-induced cardiomyocyte hypertrophy via PPAR-α.

AIMS: A growing body of evidence shows the cardiovascular benefits of fish oil ingredients, including eicosapentaenoic acid (EPA), in humans and experimental animals. However, the effects of EPA on endothelin (ET)-1-induced cardiomyocyte hypertrophy and the involved signaling cascade are largely unknown. A previous study has demonstrated that peroxisomal proliferator-activated receptor (PPAR)-α ligand (fenofibrate) prevents ET-1-induced cardiomyocyte hypertrophy. Although EPA is a ligand of PPAR-α, to date, no study has examined a relationship between EPA and PPAR-α in cardiomyocyte hypertrophy. Here, we investigated whether EPA can block ET-1-induced cardiomyocyte hypertrophy and the possible underlying mechanisms. MAIN METHODS: At day 4 of culture, neonatal rat cardiomyocytes were divided into four groups: control, control cells treated with EPA (10 µM), ET-1 (0.1 nM) administered only and EPA-pre-treated ET-1 administered groups. Also, the cardiomyocytes were treated with PPAR-α siRNA in order to elucidate the mechanisms that may underlie suppression of hypertrophy via the EPA-PPAR system. KEY FINDINGS: Following ET-1 treatment, 2.12- and 1.92-fold increases in surface area and total protein synthesis rate in cardiomyocytes, respectively, were observed and these changes were greatly blocked by EPA pre-treatment. Further, the expression of PPAR-α increased in EPA-treated groups. PPAR-PPRE binding activity was suppressed in ET-1 administered cardiomyocyte and this suppression was improved by EPA treatment. Lastly, pre-treatment of cardiomyocytes with PPAR-α siRNA prior to EPA treatment attenuated the suppressing effects of EPA on cardiomyocyte hypertrophy. SIGNIFICANCE: In conclusion, the present study shows that EPA attenuates ET-1 induced cardiomyocyte hypertrophy by up regulating levels of PPAR-α pathway.

Diabetes and obesity are significant risk factors for morning hypertension: from Ibaraki Hypertension Assessment Trial (I-HAT).

AIMS: Although morning hypertension (HT) has been identified as a major cardiovascular risk, susceptible populations remain unknown. This study aimed to clarify the relationship between morning HT and diabetes or obesity in a large-scale population. MAIN METHODS: Clinic blood pressure (BP) and BP upon awakening were recorded in 2554 outpatients with HT who attended 101 clinics or hospitals for two weeks. Mean clinic and awakening BP>140/90 and >135/85 mmHg, respectively, were considered as HT. The patients were classified according to values for clinic and home BP, into normal BP, white coat HT, masked HT, and sustained HT. KEY FINDINGS: Morning BP (mmHg) significantly and progressively elevated in the order of normal glucose tolerance, impaired glucose tolerance and diabetes (134.1 ± 12.2, 135.4 ± 13.1 and 137.5 ± 11.5; p<0.0001). The incidence of morning HT significantly increased and progressively in the same order (53.4%, 55.6%, 66.4%, p<0.0001). Morning BP was significantly higher among obese patients with diabetes than among non-obese and non-diabetic patients (138.8 ± 10.5, 133.1 ± 11.9, p<0.0001). In addition, the incidence of morning HT was significantly higher in obese diabetic patients than in non-obese and non-diabetic patients (73.0% vs. 49.9%, p<0.0001). SIGNIFICANCE: Diabetic or obese patients frequently have morning HT.

Calcitonin gene-related peptide protects the myocardium from ischemia induced by endothelin-1: intravital microscopic observation and (31)P-MR spectroscopic studies.

AIMS: Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide. We investigated the ameliorating effect of CGRP in myocardial ischemia induced by endothelin-1 (ET-1), with special emphasis on myocardial microvascular hemodynamics and levels of energy-related metabolites. MAIN METHODS: The Langendorff preparations of rat isolated heart were perfused at a constant flow rate. Microvascular blood flow was also visualized in the anterior epicardium of the left ventricle by means of an intravital fluorescence microscope system. Energy-related metabolite contents in the myocardium were measured by means of (31)P-magnetic resonance spectroscopy ((31)P-MRS). KEY FINDINGS: Intracoronary bolus injections of CGRP caused dose-dependent decreases in coronary perfusion pressure (CPP) in the hearts exposed to ET-1 (30 pmol). The vasodilator potency of CGRP was about 10,000-fold greater than that of nitroglycerin and 1,000-fold greater than that of isobutylmethylxanthine. Vasodilation of the small-sized arterioles (10-40 µm in diameter) in response to CGRP (100 pmol) was confirmed by direct microscopic observation. After ET-1 (30 pmol) plus vehicle administration, high energy phosphates (phosphocreatine (PCr), ATP) were markedly reduced (p<0.05). CGRP administration significantly (p<0.05) attenuated the anaerobic changes in the myocardium (decrease in PCr) and macrohemodynamic alterations (increase in CPP, decrease in dP/dt etc.) induced by ET-1. SIGNIFICANCE: We conclude that CGRP effectively confers hemodynamic and metabolic protections to isolated beating hearts against ET-1-induced myocardial ischemia.

Effects of protease activated receptor (PAR)2 blocking peptide on endothelin-1 levels in kidney tissues in endotoxemic rat mode.

AIMS: Septic shock, the severe form of sepsis, is associated with development of progressive damage in multiple organs. Kidney can be injured and its functions altered by activation of coagulation, vasoactive-peptide and inflammatory processes in sepsis. Endothelin (ET)-1, a potent vasoconstrictor, is implicated in the pathogenesis of sepsis and its complications. Protease-activated receptors (PARs) are shown to play an important role in the interplay between inflammation and coagulation. We examined the time-dependent alterations of ET-1 and inflammatory cytokine, such as tumor necrosis factor (TNF)-α in kidney tissue in lipopolysaccharide (LPS)-induced septic rat model and the effects of PAR2 blocking peptide on the LPS-induced elevations of renal ET-1 and TNF-α levels. MAIN METHODS: Male Wistar rats at 8 weeks of age were administered with either saline solution or LPS at different time points (1, 3, 6 and 10h). Additionally, we treated LPS-administered rats with PAR2 blocking peptide for 3h to assess whether blockade of PAR2 has a regulatory role on the ET-1 level in septic kidney. KEY FINDINGS: An increase in ET-1 peptide level was observed in kidney tissue after LPS administration time-dependently. Levels of renal TNF-α peaked (around 12-fold) at 1h of sepsis. Interestingly, PAR2 blocking peptide normalized the LPS-induced elevations of renal ET-1 and TNF-α levels. SIGNIFICANCE: The present study reveals a distinct chronological expression of ET-1 and TNF-α in LPS-administered renal tissues and that blockade of PAR2 may play a crucial role in treating renal injury, via normalization of inflammation, coagulation and vaso-active peptide.