The role of Na+/H+ exchanger in Ca2+ overload and ischemic myocardial damage in hearts from type 2 diabetic db/db mice.

BACKGROUND: A higher increase in intracellular Na(+) via Na(+)/H(+) exchanger (NHE) during ischemia has been reported in type 2 diabetic mouse hearts. We investigated the role of NHE in inducing changes in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) and alterations in ventricular function during ischemia-reperfusion in type 2 diabetic mouse hearts. METHODS: Hearts from male type 2 diabetic db/db (12-15 weeks old) and age-matched control db/+ mice were subjected to Langendorff perfusion and loaded with 4 µM of the Ca(2+) indicator fura-2. The hearts were exposed to no-flow ischemia for 15 minutes and then reperfused. [Ca(2+)](i) was measured by monitoring fura-2 fluorescence at 500 nm (excitation wavelengths of 340 and 380 nm), while left ventricular (LV) pressure was simultaneously measured. RESULTS: db/db hearts exhibited a lower recovery of LV developed pressure than db/+ hearts during reperfusion following ischemia. Diastolic [Ca(2+)](i) was increased to a greater level in diabetic hearts than in the control hearts during ischemia and reperfusion. Such an increase in cytoplasmic Ca(2+) overload during ischemia-reperfusion in diabetic hearts was markedly reduced in the presence of the NHE inhibitor cariporide. This was accompanied by a significantly improved recovery of ventricular function on reperfusion, as shown by a lower increase in diastolic pressure and increased recovery of developed pressure. CONCLUSION: NHE plays a key role in enhancing cytoplasmic Ca(2+) overload during ischemia-reperfusion and severely impairing post-ischemic cardiac function in hearts from type 2 diabetic db/db mice.

Effect of rosuvastatin on systemic blood pressure in patients with hypercholesterolemia.

OBJECTIVE: To investigate whether rosuvastatin reduces blood pressure (BP) in patients with hypercholesterolemia. METHODS: The present study investigated the effect of rosuvastatin on lipids and clinical parameters in 25 patients with a mean (± SD) age of 58.4±10.6 years over a three-month period. RESULTS: Rosuvastatin (2.5 mg/day to 5.0 mg/day) reduced systolic BP from 136.3±13.1 mmHg to 130.8±10.7 mmHg (P<0.01), along with a significant reduction in serum low-density lipoprotein cholesterol level (P<0.01). The patients were divided into two groups: 13 responders whose BP decreased by >5 mmHg with rosuvastatin treatment and 12 nonresponders who showed a BP reduction of ≤5 mmHg. Baseline systolic BP was significantly higher in responders than nonresponders (143.6±9.6 mmHg versus 128.4±11.9 mmHg, respectively; P<0.01). Responders also had a lower serum concentration of high-sensitivity C-reactive protein compared with nonresponders (0.11±0.07 mg/dL versus 0.40±0.28 mg/dL; P<0.01). The extent of BP reduction was positively correlated with baseline systolic BP (r=0.585; P=0.0021) but not with the reduction of low-density lipoprotein cholesterol level. Among the patients with baseline systolic BP >130 mmHg, all 11 responders (138.3 mmHg) were nonsmokers, while five of six nonresponders (145.7 mmHg) were smokers. CONCLUSION: Rosuvastatin had an additive antihypertensive effect in patients with poorly controlled hypertension that was independent of its lipid-lowering effect, which may be related to an inflammatory mechanism.

Association of uric acid with risk factors for chronic kidney disease and metabolic syndrome in patients with essential hypertension.

Hyperuricemia has recently been recognized to not only be a predictor of cardiovascular disease but also a marker of metabolic syndrome. We examined the association between uric acid levels and various clinical parameters, including the components of metabolic syndrome, in essential hypertension. One hundred forty-six untreated Japanese hypertensive patients (mean 58.3 years) without overt cardiovascular disease were divided into low and high uric acid groups by the median uric acid value (cut-off: 6.3 for men and 4.4 mg/dL for women). The high uric acid group had higher serum creatinine (0.74 vs. 0.67 mg/dL, p = 0.019) and a larger body mass index (BMI) (25.2 vs. 23.6 kg/m(2), p = 0.018) compared to the low group. Men from the high uric acid group were younger and had higher blood pressure (BP) than men from the low group. Uric acid levels were correlated with creatinine in both genders, with blood pressure, triglycerides in men only, and with BMI, fasting glucose in women only. Multiple regression analysis also indicated a significant correlation of uric acid with creatinine in both genders, with triglycerides in men, and with glucose in women. Metabolic syndrome (modified NCEP-ATPIII definition) was found in 37.0% of the high uric acid group (men 45.0, women 27.3%) and 20.8% of the low group. Results suggest that an increase of uric acid is associated with impaired renal function and constitutes a risk factor for metabolic syndrome. Uric acid may also be a useful index for initial risk stratification of untreated patients with essential hypertension.

Myocardial Ca2+ handling and cell-to-cell coupling, key factors in prevention of sudden cardiac death.

Using whole-heart preparations, we tested our hypothesis that Ca(2+) handling is closely related to cell-to-cell coupling at the gap junctions and that both are critical for the development and particularly the termination of ventricular fibrillation (VF) and hence the prevention of sudden arrhythmic death. Intracellular free calcium concentration ([Ca(2+)](i)), ECG, and left ventricular pressure were continuously monitored in isolated guinea pig hearts before and during development of low K(+)-induced sustained VF and during its conversion into sinus rhythm facilitated by stobadine. We also examined myocardial ultrastructure to detect cell-to-cell coupling alterations. We demonstrated that VF occurrence was preceded by a 55.9% +/- 6.2% increase in diastolic [Ca(2+)](i), which was associated with subcellular alterations indicating Ca(2+) overload of the cardiomyocytes and disorders in coupling among the cells. Moreover, VF itself further increased [Ca(2+)](i) by 58.2% +/- 3.4% and deteriorated subcellular and cell-to-cell coupling abnormalities that were heterogeneously distributed throughout the myocardium. In contrast, termination of VF and its conversion into sinus rhythm was marked by restoration of basal [Ca(2+)](i), resulting in recovery of intercellular coupling linked with synchronous contraction. Furthermore, we have shown that hearts exhibiting lower SERCA2a (sarcoplasmic reticulum Ca(2+)-ATPase) activity and abnormal intercellular coupling (as in older guinea pigs) are more prone to develop Ca(2+) overload associated with cell-to-cell uncoupling than hearts with higher SERCA2a activity (as in young guinea pigs). Consequently, young animals are better able to terminate VF spontaneously. These findings indicate the crucial role of Ca(2+) handling in relation to cell-to-cell coupling in both the occurrence and termination of malignant arrhythmia.

Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study.

BACKGROUND: Drugs that inhibit the renin-angiotensin-aldosterone system benefit patients at risk for or with existing cardiovascular disease. However, evidence for this effect in Asian populations is scarce. We aimed to investigate whether addition of an angiotensin receptor blocker, valsartan, to conventional cardiovascular treatment was effective in Japanese patients with cardiovascular disease. METHODS: We initiated a multicentre, prospective, randomised controlled trial of 3081 Japanese patients, aged 20-79 years, (mean 65 [SD 10] years) who were undergoing conventional treatment for hypertension, coronary heart disease, heart failure, or a combination of these disorders. In addition to conventional treatment, patients were assigned either to valsartan (40-160 mg per day) or to other treatment without angiotensin receptor blockers. Our primary endpoint was a composite of cardiovascular morbidity and mortality. Analysis was by intention to treat. The study was registered at clintrials.gov with the identifier NCT00133328. FINDINGS: After a median follow-up of 3.1 years (range 1-3.9) the primary endpoint was recorded in fewer individuals given valsartan than in controls (92 vs 149; absolute risk 21.3 vs 34.5 per 1000 patient years; hazard ratio 0.61, 95% CI 0.47-0.79, p=0.0002). This difference was mainly attributable to fewer incidences of stroke and transient ischaemic attack (29 vs 48; 0.60, 0.38-0.95, p=0.028), angina pectoris (19 vs 53; 0.35, 0.20-0.58, p<0.0001), and heart failure (19 vs 36; 0.53, 0.31-0.94, p=0.029) in those given valsartan than in the control group. Mortality or tolerability did not differ between groups. INTERPRETATION: The addition of valsartan to conventional treatment prevented more cardiovascular events than supplementary conventional treatment. These benefits cannot be entirely explained by a difference in blood pressure control.

Familial pulmonary thromboembolism with a prothrombin mutation and antithrombin resistance.

We describe the case of a 45-year-old man with congenital thrombophilia induced by antithrombin resistance. He had recurrent venous thrombosis without traditional risk factors or abnormal coagulation function and had a family history of venous thrombosis which included his mother, brother, and nephew. We suspected the association of hereditary antithrombin resistance, which has been reported in some cases of familial venous thromboses due to prothrombin mutations. Although prothrombin abnormality typically shows a bleeding tendency, variations of arginine at position 596 in the gene encoding prothrombin have been reported to conversely cause thrombosis. Therefore, we tested and detected antithrombin resistance in the patient's plasma. We also performed genetic analysis for his second filial generation, and found a missense mutation (c.1787G>A), resulting in a substitution of arginine for glutamine at position 596 (p.Arg596Gln) in the gene encoding prothrombin (called prothrombin Belgrade). The Gln596 substitution caused the susceptibility to thrombosis. This variation is the same as one previously reported in Serbia and India, and it is the third report in Japan. .

Exacerbation of acidosis during ischemia and reperfusion arrhythmia in hearts from type 2 Diabetic Otsuka Long-Evans Tokushima Fatty rats.

BACKGROUND: Sensitivity to ischemia and its underlying mechanisms in type 2 diabetic hearts are still largely unknown. Especially, correlation between reperfusion induced ventricular arrhythmia and changes in intracellular pH has not been elucidated. METHODS AND RESULTS: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats at 16 and 32 weeks of age were used along with age-matched nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. Hearts from rats in these 4 groups were perfused in the working heart mode, thus inducing whole heart ischemia. At 16 weeks of age, no differences in blood glucose levels or incidence and duration of reperfusion arrhythmia were found between the strains. At 32 weeks of age, both impaired glucose tolerance and obesity were observed in the OLETF rats. Further, the duration of reperfusion-induced ventricular fibrillation (VF) was significantly longer in the OLETF rats, while the pH level was significantly lower and proton contents were significantly higher in coronary effluent during ischemia in those rats. Following treatment with troglitazone, improvements in pH and proton level in coronary effluent during ischemia were observed, as was the duration of reperfusion-induced VF in OLETF rats at 32 weeks of age. CONCLUSION: The hearts of spontaneously diabetic OLETF rats were found to be more susceptible to ischemic insult. Troglitazone treatment improved ischemic tolerance by improving glucose metabolism in the myocardium of those rats.

Beneficial effect of combination therapy with antihypertensive drugs in patients with hypertension.

BACKGROUND: Cardiac hypertrophy and failure are major complications of hypertension. OBJECTIVES: The beneficial effect of treatment with antihypertensive drugs on serum levels of brain natriuretic peptide (BNP) was examined in patients with essential hypertension. METHODS: Antihypertensive drugs were administered to 88 hypertensive patients (44 diabetic and 44 nondiabetic) whose systolic blood pressure was greater than 140 mmHg and/or diastolic blood pressure was greater than 90 mmHg. Other antihypertensive drugs were added every two months until the blood pressure fell below 130/85 mmHg. Candesartan, benidipine, bisoprolol or celiprolol, and bunazosin were administered in this order. RESULTS: The mean systolic blood pressure was reduced from 163.7+/-11.6 mmHg to 121.8+/-7.5 mmHg after 12 months in patients with diabetes and from 167.6+/-12.3 mmHg to 122.8+/-7.5 mmHg in patients without diabetes. The mean diastolic blood pressure was also significantly reduced in patients with and without diabetes. Serum BNP levels were reduced from 52.2+/-38.8 pg/mL to 38.8+/-30.9 pg/mL in patients with diabetes and from 47.1+/-34.2 pg/mL to 35.8+/-22.5 pg/mL in patients without diabetes. In patients older than 70 years of age, serum BNP levels were reduced from 56.3+/-39.3 pg/mL to 40.2+/-23.0 pg/mL in those with diabetes and from 54.6+/-32.9 pg/mL to 38.0+/-16.0 pg/mL in those without diabetes. CONCLUSIONS: These results indicate that combination therapy with antihypertensive drugs is usually necessary to reduce blood pressure to below 130/85 mmHg and to improve serum BNP levels.

Impact of alcohol intake on the relationships of uric acid with blood pressure and cardiac hypertrophy in essential hypertension.

BACKGROUND: Hyperuricemia, which is frequently associated with hypertension, can be caused by alcohol intake. To date, limited data have shown the link between alcohol intake and hyperuricemic hypertension. METHODS: We retrospectively examined the influence of alcohol intake on the relationship between the uric acid level and blood pressure or cardio-metabolic parameters in 171 untreated non-failing hypertensive patients (mean 59.3±10.7 years). Cross-sectional analysis was separately performed in regular alcohol drinkers (more than 25g/day ethanol, n=74, 82.4% men) and non-drinkers (n=97, 33.0% men). RESULTS: Diastolic blood pressure was significantly higher in drinkers than in non-drinkers (101.6±11.5mmHg vs. 96.8±8.2mmHg, p<0.01). Estimated glomerular filtration rate (80.4±14.7mL/min/1.73m2 vs. 80.0±17.8mL/min/1.73m2) and body mass index (BMI, 24.7±4.4kg/m2 vs. 24.8±4.2kg/m2) were similar in the two groups. In the drinker group, the uric acid level (mean 6.3±1.7mg/dL) was positively correlated with both systolic and diastolic blood pressures (r=0.270/p=0.020 and r=0.354/p=0.0020, respectively), and with the markers of cardiac hypertrophy, including electrocardiographic voltage (V1S+V5R, r=0.244/p=0.042) and echocardiographic left ventricular mass index (r=0.270/p=0.026). These correlations were also observed in the male drinker sub-group. In the non-drinkers, the uric acid level (mean 5.0±1.4mg/dL) was positively correlated with BMI (r=0.369/p=0.0002) but not with blood pressure or the markers of cardiac hypertrophy. CONCLUSIONS: The results suggest that the role of uric acid in blood pressure might differ between hypertensive drinkers and non-drinkers. In regular alcohol drinkers, there was a positive association of uric acid level with blood pressure and the severity of cardiac hypertrophy. In non-regular drinkers, an increased uric acid level is likely to be closely associated with increased BMI.

Prevalence and characteristics of Cyprinid herpesvirus 3 (CyHV-3) infection in common carp (Cyprinus carpio L.) inhabiting three rivers in Kochi Prefecture, Japan.

Cyprinid herpesvirus 3 (CyHV-3) causes lethal disease in common and koi carp. Mortality by CyHV-3 disease has not been reported since 2011 in Kochi Prefecture, Japan. Here, we detected and quantified CyHV-3 in common carp inhabiting three rivers in the prefecture to examine if the carp are carriers of CyHV-3 as a source of infection. CyHV-3 DNA was detected in 16.7% (12/72) of brain samples in Kagami River, 3.9% (3/76) of brain and 3.9% (3/76) of gill samples in Monobe River, and 5.1% (4/79) of brain and 1.3% (1/79) of gill samples in Wajiki River. CyHV-3 genotypes identified in the 23 samples were classified as the J genotype A1 that has been found in Japan. The CyHV-3 DNA load did not differ statistically between sampling months, indicating that CyHV-3 has been silent in common carp, unlike Lake Biwa where the annual reactivation occurs in spring. Taken together, our results represented definitive evidence that seasonal changes in water temperature do not affect CyHV-3 activity in carp. Considering that infectious virus was not isolated from CyHV-3 DNA-positive samples, it was suggested that CyHV-3 establishes a latent infection in carp populations inhabiting Kagami River, Monobe River and Wajiki River. Further, the presence of circular or concatameric CyHV-3 DNA was detected in five of 23 CyHV-3 DNA-positive samples. Common carp inhabiting Lake Biwa were reported previously to harbor linear but not circular CyHV-3 DNA. This difference suggested that the CyHV-3 genome may be circularized for long-term maintenance without active viral replication.

Impaired Ca2+ handling in perfused hypertrophic hearts from Dahl salt-sensitive rats.

To clarify the correlation between intracellular Ca2+ dynamics and level of Ca2+-regulatory proteins, changes in Ca2+ handling and these proteins were investigated in a whole-heart experimental model of pressure-overload hypertrophy. We used 17-18-week-old male Dahl salt-sensitive rats (DS) and Dahl salt-resistant rats (DR) fed a high-salt diet. We monitored the fura-2 fluorescence ratio, an index of cytoplasmic Ca2+ concentration ([Ca2+]i), using a Ca2+ analyzer in a retrograde perfused heart. Left ventricular pressure (LVP) and an electrocardiogram were simultaneously recorded. Ca2+ handling was assessed by exposing the hearts to 2 min of low-Na+ (70 mmol/l) perfusion to produce an increase in [Ca2+]i (n = 6), which was sensitive to Ni2+, a blocker of the Na+/Ca2+ exchanger (NCX). In another series, the hearts were stimulated at 2.5 to 5 Hz to determine the Ca2+-force-frequency relationship (n = 6). DS rats showed marked cardiac hypertrophy without any signs of failure. The time-to-peak Ca2+ transient was prolonged in DS compared with that in DR during normal beating. During low-Na+ exposure, the time-to-peak diastolic [Ca2+]i (TTP) and the decay-time from peak [Ca2+]i (DT) were prolonged in DS compared with DR (TTP, 43.3 +/- 4.0 vs. 32.5 +/- 2.5 s, p < 0.05; DT, 70.0 +/- 8.8 vs. 29.2 +/- 2.7 s, p < 0.005). Following pretreatment with 10 mmol/l caffeine to inhibit sarcoplasmic reticulum (SR) function, TTP and DT were still prolonged in DS compared with DR (TTP, 64.2 +/- 9.7 vs. 37.0 +/- 5.8 s, p < 0.05; DT, 55.8 +/- 12.6 vs. 26.0 +/- 5.7 s, p < 0.05). The force (LVP)-frequency relationship was initially positive in DR but was negative at all times in DS (%LVP/2.5 Hz: DS, 90.3 +/- 2.0%; DR, 112.2 +/- 4.5%; p < 0.05). Elevation of diastolic [Ca2+]i (percent increase of baseline) was greater in DS than in DR with increased stimulation (5 Hz: DS, 80.7 +/- 6.7%; DR, 52.1 +/- 5.9%; p < 0.05). In Western blot analysis, the protein level of NCX was equivalent, whereas that of SR Ca2+ ATPase (SERCA2) was significantly decreased in DS compared with DR. These results suggest that slowing of cellular Ca2+ mobilization and removal is related to impaired Ca2+ handling in late-phase cardiac hypertrophy. Both the activity of the NCX and that of the SR may be affected. The SR dysfunction may be associated with change in protein level of SERCA2.

Effects of bradykinin on cardiovascular remodeling in renovascular hypertensive rats.

Angiotensin converting enzyme (ACE) inhibitors inhibit both the formation of angiotensin II and the catabolism of bradykinin (BK). They prevent not only hypertension but also cardiac hypertrophy and fibrosis. An increase in BK level stimulates the expression of nitric oxide (NO) synthase (NOS) and induces prostaglandins, both of which are powerful vasodilator factors. The direct effect of BK against cardiac hypertrophy is still unclear. This study was performed to examine the cardioprotective effects of BK in hypertrophic models. Renovascular hypertensive (RHT) rats were treated with BK (1,000 ng/kg/day), BK+D-arginyl-[Hyp(3), Thi(5), D-Tic(7), Oic(8)]-bradykinin (HOE140) (a BK B(2) receptor antagonist), and BK+N(omega)-nitro-L-arginine methyl ester (L-NAME) (a NOS inhibitor) for 3 weeks. Blood pressure was measured and echocardiographic analysis performed during the treatment. Histological data were analyzed to confirm the hypotrophic effect of BK. Treatment with BK improved cardiac remodeling, reducing both the heart weight/body weight ratio and the left ventricular wall thickness. However, co-treatment with HOE140 or L-NAME reversed the anti-hypertrophic action of BK. In particular, cardiac fibrosis or perivascular fibrosis, along with collagen accumulation, were inhibited by treatment with BK, while HOE140 and L-NAME counteracted these changes. In addition, expressions of atrial natriuretic peptides (ANP) and brain natriuretic peptides (BNP), which are markers of cardiac abnormalities, were down-regulated by treatment with BK. These effects were reversed by co-treatment with HOE140 and L-NAME. Together, these results indicate that BK directly inhibits the progression of cardiac hypertrophy and cardiac fibrosis due to NO release via the BK B(2) receptor. The BK-NO pathway may play an important role in the progression of cardiac remodeling.

Perindopril reverses myocyte remodeling in the hypertensive heart.

Studies have shown that the renin-angiotensin system (RAS) plays an important role in cardiac remodeling induced by hypertension. However, the role of this system on myocyte remodeling remains unclear. In the present study, we have assessed the effect of perindopril, an angiotensin converting enzyme (ACE) inhibitor, in spontaneously hypertensive rats (SHRs) as a means to evaluate the role of RAS in myocyte remodeling. We also investigated the effect of beta blockade on myocyte remodeling. We used female SHRs at 12 weeks of age. They were divided into four experimental groups: a control group, group C; low dose perindopril group (0.3 mg/kg/day, p.o.), group PL; high dose perindopril group (3 mg/kg/day, p.o.), group PH; and bisoprolol group (60 mg/kg/day, p.o.), group B. We isolated myocytes from these rats after 4 weeks. LV myocyte volume and cross-sectional area decreased in groups PL and PH compared to group C. LV myocyte length decreased in group PH compared to group C. However, there was no morphological change in LV myocytes in group B compared to group C. In summary, ACE inhibitors reversed cardiac hypertrophy mainly by a reduction in LV myocyte volume; however, beta blockade did not reverse myocyte remodeling. These results suggest that RAS plays an important role in myocyte remodeling in the hypertensive heart.

Preliminary study on linkage mapping based on microsatellite DNA and AFLP markers using homozygous clonal fish in ayu (Plecoglossus altivelis).

A mapping referential family (F(1)) of ayu was produced by crossing a normal diploid male with a homozygous clonal female. A genetic linkage map was constructed using 191 amplified fragment length polymorphism (AFLP) and 4 microsatellite DNA markers. A total of 178 loci were mapped in 36 linkage groups comprising 1659.6 cM, which includes approximately 77.3% to 81.8% of the total genome. As the markers were randomly distributed over the genome, they showed high efficiency for the construction of a wide linkage map.

Thyroid hormones and cardiac arrhythmias.

Thyroid hormone plays an important role in cardiac electrophysiology and Ca2+ handling through both genomic and nongenomic mechanisms of action, while both actions can interfere. Chronic changes in the amount of circulating thyroid hormone due to thyroid dysfunction or systemic disease result in structural, electrophysiological and Ca2+ handling remodeling, while acute changes may affect basal activity of cardiac cells membrane systems. Consequently, long-term or rapid modulation of sarcolemmal ion channels, Ca2+ cycling proteins and intercellular communicating channels by thyroid hormone may affect heart function as well as susceptibility of the heart to arrhythmias. This aspect including pro- and anti-arrhythmic potential of thyroid hormone is highlighted in this review.

Telmisartan predominantly suppresses cardiac fibrosis, rather than hypertrophy, in renovascular hypertensive rats.

Angiotensin II receptor blockers have beneficial effects in patients with cardiac diseases. We examined the effects of an angiotensin II receptor blocker, telmisartan, on cardiac remodeling in renovascular hypertensive rats. Telmisartan was administered to renovascular hypertensive rats at either a high dose (5 mg per kg per day; high-T group) or a low dose (0.5 mg per kg per day; low-T group). After 4 weeks, histomorphological studies, including an evaluation of cardiac fibrosis, hypertrophy, vascular changes and measurement of the serum aldosterone concentration, were performed. A significant reduction in systolic blood pressure was obtained in the high-T group, and the heart weight to body weight ratio in the high-T and low-T groups was significantly lower than that in the control renovascular hypertensive group. Cardiac and perivascular fibrosis and the accumulation of collagen were significantly suppressed in the high-T and low-T groups. An increase in the cross-sectional area of the myocytes and vessel hypertrophy were significantly prevented in the high-T group, but not in the low-T group. The dependence of myocyte lengthening on the blood pressure was also prevented in the high-T group, but not to a significant degree. The elevation of the serum aldosterone level observed in the renovascular hypertensive group was prevented in both the high-T and low-T groups.Treatment with telmisartan strongly suppresses the progression of cardiac fibrosis, rather than cardiac hypertrophy, in a manner that is independent of the blood pressure.

Clinical significance of B-type natriuretic Peptide in the assessment of untreated hypertension.

BACKGROUND: Recent studies suggest that B-type natriuretic peptide (BNP) is an important predictor of cardiac events in hypertensive patients. METHODS AND RESULTS: The relationship between the plasma BNP level and various clinical parameters was examined in 154 untreated hypertensive patients without heart failure or atrial fibrillation (mean age: 58.0+/-10.7; mean blood pressure: 164.5+/-15.2/99.1+/-9.7 mmHg; mean BNP: 32.7+/-36.7 pg/ml). First, the patients were divided into 2 groups based on BNP: normal (<18.5 pg/ml, mean 9.7+/-5.7, n=69); or elevated (>18.5 pg/ml, mean 51.4+/-40.4, n=85). The elevated BNP group had a significantly greater electrocardiographic voltage index (SV1+RV5; 3.7+/-1.2 vs 3.2+/-0.8 mV, p=0.0029), cardiothoracic ratio/chest radiography (CTR; 49.1 vs 46.9%, p=0.0037), left ventricular mass index (LVMI; 122.2+/-31.7 vs 103.1+/-26.4 g/m2, p=0.0005) and deceleration time (DT; 241+/-39 vs 208+/-30 ms, p=0.0001), as well as a smaller E-wave to A-wave (E/A ratio) (0.80+/-0.22 vs 0.96+/-0.28, p=0.0003), compared with the normal BNP group. There were no significant differences in casual blood pressure, body mass index, serum creatinine and ejection fraction between the 2 groups. Next, the patients were divided into 3 groups based on BNP: normal (<18.5, n=69), moderate (18.5 to 40, mean 27.0+/-5.7, n=43) and high (40<, mean 76.3+/-45.3, n=42). In the high BNP group, most clinical parameters indicated the most severe organ damage compared with other groups, including SV1+RV5, DT and LVMI. In all patients, logarithmic BNP was positively correlated with the age, pulse pressure, SV1+RV5, CTR, ventricular wall thickness, DT, LVMI and negatively correlated with hemoglobin, renin and E/A ratio. Using multiple regression analysis, renin and DT were significantly associated with BNP. No gender differences in the relationship between BNP and clinical parameters were found. CONCLUSIONS: Results suggest that BNP is a useful indicator for the initial assessment of the severity of essential hypertension, detecting both cardiac hypertrophy and diastolic dysfunction, and may also be valuable for risk stratification.

Pericarditis causing congestive heart failure as an initial manifestation of systemic lupus erythematosus.

Pericarditis is a common complication in systemic lupus erythematosus (SLE) patients, however, that causing congestive heart failure (CHF) is a rare initial manifestation of SLE. We treated a patient whose initial manifestation of SLE was pericardial effusion causing CHF, which improved following prednisolone therapy that led to a dramatic decrease in pericardial effusion and improvement in left ventricular diastolic dysfunction as shown in Doppler echocardiography findings. Further, the plasma brain natriuretic peptide level became normalized.

Nuclear markers reveal that inter-lake cichlids' similar morphologies do not reflect similar genealogy.

The apparent inter-lake morphological similarity among East African Great Lakes' cichlid species/genera has left evolutionary biologists asking whether such similarity is due to sharing of common ancestor or mere convergent evolution. In order to answer such question, we first used Geometric Morphometrics, GM, to quantify morphological similarity and then subsequently used Amplified Fragment Length Polymorphism, AFLP, to determine if similar morphologies imply shared ancestry or convergent evolution. GM revealed that not all presumed morphological similar pairs were indeed similar, and the dendrogram generated from AFLP data indicated distinct clusters corresponding to each lake and not inter-lake morphological similar pairs. Such results imply that the morphological similarity is due to convergent evolution and not shared ancestry. The congruency of GM and AFLP generated dendrograms imply that GM is capable of picking up phylogenetic signal, and thus GM can be potential tool in phylogenetic systematics.