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Biomedical subjects

Ken Okumura

Publications and source records attributed to Ken Okumura.

At least 19 recordsLinked to original sources
PubMed2007

Efficacy of amiodarone for preventing the recurrence of symptomatic paroxysmal and persistent atrial fibrillation after cardioversion.

BACKGROUND: It has been previously reported that the efficacy of class I antiarrhythmics in preventing the recurrence of symptomatic paroxysmal and persistent atrial fibrillation (AF) is limited when AF lasts for 48 h or more. However, it is unclear whether the efficacy of amiodarone, a class III drug, is superior to class I antiarrhythmics in patients with long-lasting AF. METHOD AND RESULTS: The relationship between the duration of tachycardia and the efficacy of amiodarone in preventing recurrence of tachycardia was examined in 55 patients (37 men, 18 women, mean age 68+/-9 years) to whom amiodarone was administered after electrical or pharmacological cardioversion for paroxysmal and persistent AF. In 26 patients, paroxysmal and persistent AF ceased within 48 h after onset (Group A), and in the other 29 patients, it ceased after 48 h (Group B). Patient characteristics and actuarial recurrence-free rates were compared between the 2 groups. The mean follow-up period was 30+/-11 months. No statistically significant difference between the groups was found in patient characteristics. Actuarial recurrence-free rates in Group A and B at 1, 3, 6, 9, and 12 months were 100%, 81%, 69%, 62%, and 54%, and 93%, 79%, 66%, 52%, and 48%, respectively (p=NS at 12 months). The period of maintenance of sinus rhythm was 14.7+/-3.2 months in group A and 13.3+/-3.3 months in group B (mean+/-SE, p=NS). CONCLUSION: In the case of amiodarone, efficacy for maintaining sinus rhythm after cardioversion of AF was not biased by the duration of arrhythmia. This observation suggests amiodarone is effective in maintaining normal sinus rhythm after cardioversion, even in patients with long-lasting AF and electrical atrial remodeling.

Aged↗
PubMed2006

Increased level of pericardial insulin-like growth factor-1 in patients with left ventricular dysfunction and advanced heart failure.

OBJECTIVES: To test the hypothesis that the cardiac insulin-like growth factor-1 (IGF-1) system is up-regulated in the failing heart, we measured the pericardial (cardiac) and plasma (circulating) IGF-1 levels in coronary artery disease patients. BACKGROUND: Local IGF-1 systems are regulated differently from the systemic IGF-1 system. The cardiac IGF-1 system is up-regulated by the increased left ventricular (LV) wall stress. However, it remains unknown how this system is affected in LV dysfunction and heart failure. METHODS: We measured the plasma and pericardial fluid levels of IGF-1 and brain natriuretic peptide (BNP) in 87 coronary artery disease patients undergoing cardiac surgery, and examined their relationships with LV function and heart failure severity. The expressions of IGF-1 and IGF-1 receptor proteins were examined in endomyocardial biopsies obtained from other patients with normal or impaired LV function. RESULTS: The pericardial IGF-1 and BNP levels were positively correlated with the plasma BNP level (both p < 0.001). The pericardial IGF-1 level was increased in heart failure patients, whereas the plasma IGF-1 level was rather decreased. The pericardial IGF-1 level was inversely correlated with the LV ejection fraction (p < 0.001), whereas the plasma IGF-1 level was not. Positive immunostaining for IGF-1 and IGF-1 receptor proteins was enhanced in myocardial biopsies from failing hearts compared with those from nonfailing hearts. CONCLUSIONS: The pericardial IGF-1 level was increased in patients with LV dysfunction and heart failure, whereas the plasma IGF-1 level was decreased. These results may indicate that up-regulation of the cardiac IGF-1 system serves as a compensatory mechanism for LV dysfunction.

Aged↗
PubMed2006

Level of antibodies against mycobacterial glycolipid in the effusion for diagnosis of tuberculous pleural effusion.

BACKGROUND: Diagnosing tuberculous pleural effusion (pTB) is often difficult because the culturing of tubercle bacilli results in a negative test in the majority of cases. Serological tests for the detection of antibodies to tuberculous glycolipid (TBGL) and lipoarabinomannan (LAM) have been introduced for the diagnosis of pulmonary tuberculosis. We examined the levels of these antibodies, adenosine deaminase (ADA) and interferon-gamma (IFN-gamma) in the pleural effusion and compared their diagnostic values in pTB. METHODS: We studied 65 patients with pleural effusion. Of those, 19 patients were diagnosed as having pTB according to our broad case definition. The etiologies in the other 46 patients were malignant effusion, transdative effusion and miscellaneous diseases. Determiner TBGL antibody (D-TBGL-Ab) and MycoDot were used for the detection of anti-LAM and anti-TBGL antibodies, respectively, in the pleural effusion. RESULTS: The sensitivity of ADA was 78.9% (15/19) and the specificity 97.8% (45/46). The sensitivity of IFN-gamma was 84.2% (16/19) and the specificity 93.5% (43/46). The sensitivities of D-TBGL-Ab and MycoDot were both 52.6% (10/19) and their specificities were 95.7% (44/46) and 97.8% (45/46), respectively. When DTBGL-Ab (cutoff point: 2.0 U/ml) and ADA activity (cutoff point: 57 IU/l) were combined, the sensitivity was 94.7% (18/19) and the specificity 93.5% (43/46). CONCLUSIONS: In the diagnosis of pTB, D-TBGL-Ab and MycoDot each have low sensitivity but high specificity. When D-TBGL-Ab is used in combination with ADA, the sensitivity and specificity are both >90%. We conclude that D-TBGL-Ab and ADA in combination are useful in the diagnosis of pTB.

Adenosine Deaminase↗
PubMed2006

Effects of amiodarone on electrical and structural remodeling induced in a canine rapid pacing-induced persistent atrial fibrillation model.

Structural in addition to electrical remodeling may be induced by persistent atrial fibrillation per se and make atrial fibrillation refractory to antiarrhythmic drug therapy. Matrix metalloproteinases (MMPs) contribute to structural remodeling in the interstitial space. Amiodarone is effective in treating persistent atrial fibrillation compared with other antiarrhythmic drugs. In mongrel dogs, right atrial pacing at 540 beats/min (bpm) was performed along with ventricular pacing at 100 bpm for 6 weeks after atrioventricular node ablation. Right atrial pacing at 400 bpm was continued for 4 weeks with (n=5) or without (n=5) oral amiodarone (30 mg/kg/day). In sham dogs, only ventricular pacing was done with (n=4) or without (n=6) amiodarone. In atrial pacing without amiodarone group, electrical remodeling characterized by monophasic action potential duration shortening, loss of action potential duration-rate adaptation and depressed conduction velocity and structural remodeling characterized by slightly but significantly increased interstitial fibrosis and enhanced MMP-2 activity compared with sham group were observed, and sustained atrial fibrillation was easily induced. In atrial pacing with amiodarone group, both electrical and structural remodeling were reversed and sustained atrial fibrillation was not induced. In sham group with amiodarone, action potential duration prolongation and depressed conduction velocity compared with sham without amiodarone were observed, but either increased fibrosis or enhanced MMP-2 activity was not observed. Not only electrical but structural remodeling were induced in a canine persistent atrial fibrillation model. Amiodarone reversed both of them, which may be related to its high efficacy in preventing recurrence of persistent atrial fibrillation.

Action Potentials↗
PubMed2006

Hypoxic conditions stimulate the production of angiogenin and vascular endothelial growth factor by human renal proximal tubular epithelial cells in culture.

BACKGROUND: Chronic low oxygen in the tubulointerstitial area is a crucial cause of renal degradation and tubulointerstitial damage. Previous reports have suggested that the maintenance of renal blood flow plays a role in the suppression of progressive renal damage. Neovascularization is important for the maintenance of blood flow. We studied the production of angiogenic factors by culturing renal proximal tubular epithelial cells (PTEC) under hypoxic conditions. METHODS: Cultured PTEC were exposed to normal and low-oxygen conditions. The levels of angiogenin (ANG) and vascular endothelial growth factor (VEGF) in the cell supernatants were measured by enzyme-linked immunosorbent assay. The messenger RNAs (mRNAs) of ANG and VEGF in the PTEC were examined by real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR). The presence of ANG, VEGF and hypoxia-inducible factor-1 (HIF-1) was studied by immunofluorescence techniques. The effect of cobalt chloride (CoCl(2)), which is an HIF-1 inducer, on the production of ANG and VEGF was also examined in order to elucidate the contribution of the HIF-1 pathway to the production of these cytokines. RESULTS: ANG and VEGF were demonstrated to exist in the cell supernatants, and ANG and VEGF mRNAs were detected in the PTEC. Hypoxic conditions stimulated the secretion of ANG (2.5-fold vs normoxia, P<0.001) and VEGF (3.2-fold vs normoxia, P<0.001) by PTEC. Hypoxic conditions increased the mRNA expression of ANG for 6 h (1.38-fold vs normoxia, P<0.05) and VEGF for 24 h (2.04-fold vs normoxia, P<0.01). Hypoxic conditions also enhanced ANG, VEGF and HIF-1 protein expression in PTEC. The CoCl(2) increased the secretion of ANG (5.2-fold vs control, P<0.0001) and VEGF (2.3-fold vs control, P<0.0001) by PTEC. CONCLUSION: Under hypoxic conditions, the ANG and VEGF secreted by PTEC may modulate angiogenesis and vascular remodeling in the renal interstitium via an increase in the production of HIF-1.

Cell Hypoxia↗
PubMed2006

Expression of IP-10/CXCL10 is upregulated by double-stranded RNA in BEAS-2B bronchial epithelial cells.

BACKGROUND: Interferon (IFN)-gamma-inducible protein of 10 kDa (IP-10/CXCL10) is a potent chemoattractant for activated T and NK cells, and elevated levels of IP-10 are identified in bronchoalveolar lavage fluids from patients with pulmonary disorders related to Th-1-type immunity, which is a prerequisite for elimination of viral pathogens. Bronchial epithelial cells play an important role in respiratory infections as the initiator of airway inflammation by releasing chemokines and expressing cell surface membrane molecules involved in leukocyte adhesion. Polyinosinic-polycytidylic acid (poly IC) is a synthetic double-stranded RNA (dsRNA) and induces antiviral reactions in cells. OBJECTIVES: We investigated the regulation of IP-10 in BEAS-2B bronchial epithelial cells in response to poly IC, and also addressed the possible role of retinoic-acid-inducible gene-I (RIG-I) and IFN-regulatory factor 3 (IRF-3), two genes involved in the signaling induced by viral infection. METHODS: The expressions of IP-10 mRNA and protein were analyzed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. The overexpression of RIG-I or IRF-3 was performed by transfection of BEAS-2B cells with each cDNA. RESULTS: Poly IC enhanced the expression of IP-10 mRNA and protein in concentration- and time-dependent manners. Overexpression of RIG-I or IRF-3 potentiated the poly-IC-induced upregulation of IP-10. CONCLUSIONS: IP-10 may contribute to antiviral activity through the activation of Th-1-type immunity, and RIG-I and IRF-3 may be involved in this reaction.

Bronchi↗
PubMed2006

Feasibility and safety of thrombectomy with TVAC aspiration catheter system for patients with acute myocardial infarction.

Early reperfusion with angioplasty and stenting is established as a central, effective treatment for acute myocardial infarction (AMI). The role of thrombectomy prior to angioplasty remains to be elucidated. To evaluate its feasibility, safety, and efficacy, thrombectomy using a TVAC aspiration catheter system was attempted prior to angioplasty and stenting in 40 consecutive patients with AMI. Fifty consecutive patients with AMI in whom angioplasty and stenting were performed without prior thrombectomy served as controls. Neither distribution of Killip classification nor culprit lesion was different between the two groups. In patients treated with the TVAC system, the procedure was successful in 39/40 patients (98%) and there were no procedure-related complications. In the final coronary angiogram, TIMI-3 (Thrombolysis in Myocardial Infarction) flow was obtained in 37/40 (93%) in patients treated with the TVAC system and 43/50 (86%) in control patients. Electrocardiograms before and after coronary intervention were analyzed in patients with ST elevation AMI (35 patients treated with the TVAC system and 41 control patients). ST elevation recovery >50% of the initial value was observed after coronary intervention in 26/35 (74%) in patients treated with the TVAC system and 26/41 (63%) in control patients (P = 0.33). In the case of anterior AMI, ST elevation recovery >50% of the initial value was observed in 13/17 (76%) in patients treated with the TVAC system and 8/20 (40%) in control patients (P = 0.045). Thus, thrombectomy using a TVAC system is feasible, safe, and may have the potential to enhance ST-segment resolution in patients with anterior AMI.

Aged↗
PubMed2006

Nephrotic syndrome associated with interferon-beta-1b therapy for multiple sclerosis.

A 43-year-old woman with multiple sclerosis (MS) had nephrotic syndrome 21 months after starting treatment with interferon (IFN)-beta-1b (subcutaneous administration). She had taken no drug except for the IFN-beta-1b. Because nephrotic syndrome may be induced by IFN therapy, the IFN was stopped. Percutaneous renal biopsy revealed that she had minimal change nephrotic syndrome. As nephrotic-range proteinuria, hypoalbuminemia, and general edema were worsening even 2 weeks after cessation of the drug, oral corticosteroid therapy (prednisolone 40 mg/day) was started. The nephrotic syndrome was treated successfully with prednisolone. The dosage of prednisolone was tapered, without a relapse, and then the corticosteroid therapy was stopped. IFN-beta-1b therapy was then resumed, and the patient is in remission for both nephrotic syndrome and MS. Though proteinuria and nephrotic syndrome is a rare adverse effect of IFN-beta-1b therapy, physicians treating MS patients with this agent should pay careful attention to new clinical symptoms and laboratory findings.

Adjuvants, Immunologic↗
PubMed2006

Effect of vasoconstrictor coupling factor 6 on gene expression profile in human vascular endothelial cells: enhanced release of asymmetric dimethylarginine.

BACKGROUND: Coupling factor 6 (CF6), a component of ATP synthase, inhibits phospholipase A2 and induces vasoconstriction. However, because arachidonic acid acts in the widespread fields of vascular biology, CF6 might exert profound effects in addition to vasoconstriction. We investigated the effect of CF6 on the gene expression profile in human umbilical vein endothelial cells. METHODS AND RESULTS: The increased gene expression after 24-h exposure to CF6 at 10 mol/l, assessed by cDNA microarray (n = 3), included neuregulin-1 (1.84 +/- 0.07 fold compared with control, P < 0.05) and relaxin-1 (1.74 +/- 0.20, P < 0.05), both relating to congestive heart failure, urokinase type plasminogen activator receptor (1.77 +/- 0.24, P = 0.06) and estrogen receptor beta (1.74 +/- 0.36, P = 0.08), both relating to vascular inflammation and cell infiltration, and protein arginine methyltransferase (PRMT-1; 1.73 +/- 0.20, P < 0.05). Out of these genes, the enzyme relating to the synthesis (PRMT-1) of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), was further examined concomitantly with the degradation enzyme, dimethylarginine dimethylaminohydrolase 2 (DDAH-2). The ratio of PRMT-1 to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA, measured by real-time quantitative reverse transcription-polymerase chain reaction, was increased by 9 +/- 2% (n = 10, P < 0.01) at 48 h after CF6 at 10 mol/l, whereas the ratio of DDAH-2 to GAPDH was decreased by 12 +/- 2% (n = 8, P < 0.01). DDAH-2 protein and activity were decreased by 28 +/- 5% (n = 5, P < 0.01) and 19 +/- 2% (n = 6, P < 0.01) by CF6, respectively. ADMA release was enhanced by 20 +/- 8% and NOS activity was decreased by 13 +/- 1% (both n = 8, P < 0.05) by CF6. CONCLUSIONS: CF6 changes the gene expression profile to be proatherogenic and functions as a novel stimulator for ADMA release by enhancing its synthesis and suppressing its degradation.

Amidohydrolases↗
PubMed2006

Roxithromycin inhibits transforming growth factor-beta production by cultured human mesangial cells.

BACKGROUND: Transforming growth factor-beta (TGF-beta) plays an important role in progression of renal injury. However, few materials which inhibit TGF-beta have been known. Roxithromycin (ROX), macrolide antibiotics, is known to have anti-inflammatory, immunomodulatory and tissue reparative effects besides its bacteriostatic activity, although the exact mechanism of its anti-inflammatory and immunomodulatory effects was not defined. We examined the effect of ROX on production of TGF-beta and type IV collagen by cultured human mesangial cells (HMC). METHODS: Human mesangial cells were incubated with several concentrations of ROX and TGF-beta and type IV collagen levels in the culture supernatants were measured by enzyme-linked immunoassay. Amount of TGF-beta mRNA was also quantified by using a colourimetric mRNA quantification kit and semiquantitative reverse transcriptase polymerase chain reaction. We also examined the effect of ROX on tyrosine kinase, MAP kinase and NF-kappaB stimulated by thrombin. RESULTS: Roxithromycin (0.1-10.0 microg/mL) inhibited TGF-beta production by HMC in a dose- and time-dependent manner without inducing cell injury. ROX (10.0 microg/mL) also inhibited mRNA expression of TGF-beta in HMC. Thrombin (5 U/mL) stimulated TGF-beta production by HMC and ROX significantly inhibited the stimulating effect of thrombin on TGF-beta production. ROX also inhibited the increment of type IV collagen production stimulated by thrombin. ROX (10.0 microg/mL) suppressed the thrombin-induced NF-kappaB activation, although ROX did not inhibit the activation of tyrosine kinase and MAP kinase by thrombin. CONCLUSION: Roxithromycin has an inhibitory effect on TGF-beta production by HMC possibly via inhibition of NF-kappaB. ROX may be a potential agent for the treatment of glomerulosclerosis.

Anti-Bacterial Agents↗
PubMed2006

Small adenocarcinoma of the lung: prognostic significance of central fibrosis chiefly because of its association with angiogenesis and lymphangiogenesis.

To clarify the reason why central fibrosis (CF) is an important histological prognostic factor in small adenocarcinoma (SA) of the lung, tumor tissues from 50 patients with SA < or = 2 cm in diameter were investigated using immunohistochemical and in situ hybridization analysis for factors relating to extracellular matrix and vessels. CF was observed in 33/50 cases (66%). In adenocarcinoma areas, positive activity was observed with both primary antibodies and probes for matrix metalloproteinase-2 (MMP-2) in 11/50 patients (22%), membrane-type 1 matrix metalloproteinase (MT1-MMP) in 39/50 patients (78%) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in 49/50 patients (98%). In CF areas, the positive activity of fibroblastic cells was seen for only TIMP-2 in 32/33 patients (97%). In CF areas, both CD34-positive (blood and lymphatic) vessels and D2-40-positive lymphatic vessels were semiquantitatively increased in 16/33 patients (48.5%) by immunohistochemistry. Tumors with increased vessel density were associated with statistically lower disease-free survival curves compared with tumors without increased vessels. Lymphatic vessels in some CF showed intravasation by carcinoma cells. In conclusion, CF could be an important histological prognostic factor in SA chiefly because of its association with angiogenesis and lymphangiogenesis.

Adult↗
PubMed2006

Randomized study of angiotensin II type 1 receptor blocker vs dihydropiridine calcium antagonist for the treatment of paroxysmal atrial fibrillation in patients with hypertension.

BACKGROUND: Mega trials of rhythm vs rate control could not demonstrate the usefulness of available antiarrhythmic drugs, so a more effective and safer therapy for atrial fibrillation (AF) is now required. One candidate is the so-called "upstream therapy", which refers to the blockade of upstream modifying elements (renin - angiotensin system, cathecholamines, oxidative stress etc) that contribute to the arrhythmogenic substrate. METHODS AND RESULTS: The Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) is a randomized comparative evaluation of an angiotensin II type 1 blocker (candesartan) and a dihydropiridine calcium blocker (amlodipine), both combined with antithrombotic therapy, as an antiarrhythmic therapy for the treatment of paroxysmal AF (PAF) associated with hypertension. To test the usefulness of this therapy, this study will reveal the recurrence rate of asymptomatic as well as symptomatic PAF during 1-year of treatment with candesartan or amlodipine, using daily transtelephonic monitoring. CONCLUSIONS: The J-RHYTHM II study will follow 400 patients with PAF and hypertension who were treated at approximately 50 sites throughout Japan, and will provide clinically important information.

Amlodipine↗
PubMed2006

Accumulation of risk factors increases risk of thromboembolic events in patients with nonvalvular atrial fibrillation.

BACKGROUND: Accumulation of risk factors could increase thromboembolic event rates in patients with nonvalvular atrial fibrillation (NVAF). To validate this hypothesis, a post hoc analysis was performed to determine the relationship of risk levels and thromboembolic events in patients with NVAF from our previous prospective study. METHODS AND RESULTS: Risk levels were quantified using the CHADS2 index in 509 patients with NVAF (66.3+/-10.3 years old). One point each was given for patients with advanced age (>or=75 years), hypertension, congestive heart failure, and diabetes mellitus, and 2 points, to those with prior ischemic stroke or transient ischemic attack. Patients with a CHADS2 score of 0 were classified as low risk, 1 to 2 a moderate risk and 3 or more were high risk. Because hypertrophic cardiomyopathy had emerged as an independent risk factor for thromboembolism, the original CHADS2 score was modified by adding 1 point to patients with hypertrophic cardiomyopathy. Warfarin was given to 263 patients (mean international normalized ratio (INR) at enrollment, 1.86), antiplatelets (aspirin or ticlopidine) to 163 patients and no antithrombotic therapy to 83. During a mean follow-up period of 2 years, 31 thromboembolic events occurred. As the risk level (modified CHADS2 score) increased, the event rate increased for both the patient groups receiving warfarin (p=0.035) and those not receiving warfarin (p=0.048). When a thromboembolic event occurred in patients who had been treated with warfarin, the mean INR level was 1.41. Twelve (75%) of 16 patients complicated with thromboembolism during warfarin treatment had INR levels below the optimal levels (1.6-2.6) for Japanese patients. CONCLUSION: Accumulation of risk factors could increase risk of thromboembolic events in patients with NVAF. Adherence to the guidelines for anticoagulation therapy is recommended.

Aged↗
PubMed2006

Randomized crossover study of the long-term effects of pilsicainide and cibenzoline in preventing recurrence of symptomatic paroxysmal atrial fibrillation: influence of the duration of arrhythmia before therapy.

BACKGROUND: There is little information on the selection of antiarrhythmic agents for long-term prevention of paroxysmal atrial fibrillation (PAF). In the present study the preventive effects of pilsicainide (Pil) and cibenzoline (Cib) were compared in patients with PAF that was defibrillated at <48 h or >or=48 h after onset. METHODS AND RESULTS: A total of 60 patients (45 men, 15 women, mean age 66+/-10 years) were divided into 2 groups: Group I consisted of 22 patients in whom atrial fibrillation (AF) lasted for <48 h before cardioversion and Group II consisted of 38 patients in whom AF lasted for >or=48 h. A randomized, crossover protocol of treatment with Pil (150 mg/day) and Cib (300 mg/day) was used. Mean follow-up was 35+/-18 months. In Group I, the mean duration of maintenance of sinus rhythm was 12.3+/-2.9 months in patients treated with Pil, compared with 12.9+/-2.5 months in those givem Cib (p=NS between 2 groups). Actuarial event-free rates at 1, 3, 6, 12 months were 82%, 68%, 59% and 41%, respectively, in patients treated with Pil, and 91%, 77%, 68% and 50%, respectively, in those givenh Cib (p=NS between 2 groups). In Group II, the mean duration of maintenance of sinus rhythm was 1.6+/-0.5 months in patients treated with Pil, compared with 5.9+/-1.7 months in those given Cib (p<0.01). Actuarial event-free rates at 1, 3, 6, 12 months were 45%, 18%, 8% and 3%, respectively, in patients treated with Pil, and 63%, 45%, 29% and 16%, respectively, in those given Cib (p<0.05, at 12 months). CONCLUSIONS: Prolonged tachycardia (>or=48 h) in patients with PAF seems to cause electrical remodeling. Cib, a multichannel blocker, is considered to be more effective in preventing the recurrence of PAF in the electrically remodeled atria than Pil, a pure sodium-channel blocker.

Adult↗
PubMed2006

Increased pericardial fluid level of matrix metalloproteinase-9 activity in patients with acute myocardial infarction: possible role in the development of cardiac rupture.

BACKGROUND: In an animal model of acute myocardial infarction (AMI), deletion of matrix metalloproteinase (MMP)-9 results in suppression of the development of cardiac rupture. The present study sought to clarify how myocardial MMP-9 activity is related to the pathophysiologies of AMI and cardiac rupture in humans. METHODS AND RESULTS: Levels of interleukin-8 (IL-8), polymorphonuclear leukocyte (PMN) elastase, monocyte chemotactic protein-1 (MCP-1) and MMP activity were measured in the pericardial fluid obtained from 28 patients with angina pectoris (AP group) and 16 patients with AMI (AMI group) undergoing cardiac surgery. In the AMI group, 5 were complicated with ventricular septal perforation (VSP) and the remaining 11 were not (non-VSP). Levels of IL-8, PMN elastase, MMP-2 and MMP-9 activity were all higher in the AMI group than in the AP group. In the AMI group, all levels other than MMP-2 activity were further elevated in cases with VSP compared with those in the non-VSP group. There was no significant difference in MCP-1 among the groups CONCLUSIONS: Markers of neutrophil activation in the infarcted cardiac tissue seem to be elevated in AMI. Highly elevated levels of MMP-9 activity, which may be derived from neutrophils, and PMN elastase may be related to the pathophysiology of VSP or cardiac rupture in AMI.

Acute Disease↗
PubMed2006

Rate control and quality of life in patients with permanent atrial fibrillation: the Quality of Life and Atrial Fibrillation (QOLAF) Study.

BACKGROUND: The present study aimed to determine whether quality of life (QOL) in permanent atrial fibrillation (AF) patients would be improved by monotherapy with beta-blocker (BB) or calcium antagonist (CAA) as compared with digitalis. METHODS AND RESULTS: Twenty-nine patients with permanent AF under digitalis were randomized into BB (bisoprolol, atenolol or metoprolol) or CAA (verapamil) monotherapy treatment group. Twenty-five were men and the mean age was 67+/-8 years. After the assigned monotherapy, 12 patients received the other monotherapy in a cross-over fashion. Under each treatment, efficacy of rate control was determined by Holter electrocardiogram (ECG), treadmill testing and QOL questionnaire (Short Form-36 (SF-36) and Quality of Life of Atrial Fibrillation (AFQLQ)), and compared with the baseline digitalis treatment. CAA significantly increased mean and minimum heart rate (HR) in Holter ECG as compared with digitalis, whereas BB increased only minimum HR. Exercise duration in treadmill testing was significantly prolonged by CAA treatment, although it only tended to be prolonged by BB treatment. CAA but not BB improved role function-physical score of SF-36, and frequency and severity of symptoms of AFQLQ. CONCLUSION: These results indicate that CAA is preferable to digitalis when monotherapy is selected for short-term improvement of QOL and exercise tolerance in patients with permanent AF.

Adrenergic beta-Antagonists↗
PubMed2006

Losartan, an angiotensin-II receptor antagonist, retards the progression of advanced renal insufficiency.

Chronic renal disease with elevated level of serum creatinine (Cr) often progresses to end-stage renal disease. Although blockade of the renin-angiotensin system has been shown to slow the progression of chronic renal disease, it remains uncertain whether one could expect such a renoprotective effect even when the treatment is initiated late in the course of renal disease. The purpose of the present study was to examine the effect of losartan, an angiotensin-II receptor antagonist, on the progression of advanced renal insufficiency. We retrospectively analyzed eight hypertensive patients, whose baseline Cr levels exceeded 2.0 mg/dl (2.2-5.5); the subjects included 6 non-diabetic glomerular diseases, 1 diabetic nephropathy and 1 polycystic kidney disease. Losartan was given at the dosage of 25-50 mg/day. Changes in mean blood pressure (MBP) and serum levels of Cr, potassium (K) and uric acid were evaluated after treatment for 24 weeks. Slopes of reciprocal of serum Cr plotted against time (1/sCr slope), which indicate the rate of renal function loss before and after the treatment period, were compared. There was a significant reduction of 1/sCr slope after losartan (-0.004 +/- 0.002 dl/mg/week before and -0.001 +/- 0.002 dl/mg/week after the treatment, p < 0.05). MBP and serum levels of Cr, K and uric acid were not changed significantly by losartan treatment. However, improvement of 1/sCr slope was correlated to the degree of MBP changes. Based on the available data from 4 patients, proteinuria was decreased in 3 patients. These results suggest that losartan may retard the progression of advanced renal insufficiency.

Adult↗