Antiobesity effect of Pediococcus pentosaceus LP28 on overweight subjects: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND/OBJECTIVES: The population of the obese is increasing worldwide. Prevention and improvement of obesity are indispensable for decreasing the risk of metabolic disorders. We have recently shown that obesity and fatty liver are reduced by a plant-derived lactic acid bacterium, Pediococcus pentosaceus LP28 (LP28), in high-fat diet-induced obese mice. The aim of the present clinical study is to prove that LP28 is effective for reducing body fat and body weight, as shown in the experiment using mice. SUBJECTS/METHODS: The clinical trial was carried out as a double-blind, randomized, placebo-controlled study comprising 62 subjects (20-70 years of age, BMI 25-30 kg/m(2)). These subjects were randomly assigned to three groups that received living LP28, heat-killed LP28 or a placebo powder, administered orally once a day for 12 weeks. RESULTS: Heat-killed LP28 reduced BMI (0.45 kg/m(2), 95% CI (0.04, 0.86), P=0.035), body fat percentage (1.11%, (0.39, 1.82), P=0.002), body fat mass (1.17 kg (0.43, 1.92), P=0.004) and waist circumference (2.84 cm (0.74, 4.93), P=0.009) when compared with a placebo group. Fasting plasma glucose, HbA1c, fasting insulin, HOMA-IR and serum lipids levels did not change by either living LP28 or heat-killed LP28 intake. CONCLUSIONS: Heat-killed LP28 displays an antiobesity effect that reduces BMI, body fat and waist circumference, suggesting that the plant-derived lactic acid bacterium LP28 would be a promising preventive of metabolic syndrome.

Cefoselis, a beta-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release.

Cefoselis is a widely used beta-lactam antibiotic, but occasionally induces seizures and convulsion in elder and renal failure patients. However, beta-lactams are known not to pass through the blood-brain barrier (BBB). In this study, we examined the BBB penetration of cefoselis in normal and renal failure rats by means of brain microdialysis. Cefoselis was dose-dependently appeared in brain extracellular fluid in proportion to its blood level. The elimination constant from brain extracellular fluid (apparent) was slightly lower than that from blood. These results indicated that cefoselis might penetrate the BBB or be discharged by a certain transport system. In contrast to the result of cefoselis, cefazolin, a leading drug of cephalosporins, could not be detected in the brain extracellular fluid after an intravenous injection. In renal dysfunction rats, the elimination half-lives of cefoselis from both blood and brain were extensively prolonged. This would be one of responsible factors inducing seizures seen in patients. However, the additional factor, such as decrease in brain function related to aging, would be involved in seizures in patient received cefoselis, because an extremely high dose was required to induce seizures even in renal failure rats. A local administration of cefoselis into the hippocampus through the microdialysis probe caused a striking elevation of extracellular glutamate, with a minimum increase in gamma-aminobutyric acid (GABA). However, a systematic cefoselis administration via the tail vein did not elevate extracellular glutamate and GABA concentrations in the hippocampus of renal failure rats that exhibited marked seizures. These results suggested that not the stimulation of glutamate release, but the blockade of GABA receptors might be responsible for the seizure induced by cefoselis.

L-Deprenyl prevents the cell hypoxia induced by dopaminergic neurotoxins, MPP(+) and beta-carbolinium: a microdialysis study in rats.

N-Methyl-4-phenylpyridinium (MPP(+)) and 2,9-di-methyl-norharmanium (2,9-Me2NH(+)), which is a beta-carbolinium proposed as an endogenous MPP(+)-like toxin underlying Parkinson's disease, are strong mitochondrial toxins. We have measured the extracellular lactate levels as a marker for the in vivo cell hypoxia in the striatum of freely moving rats. The perfusions with MPP(+) and 2,9-Me2NH(+) increased extracellular lactate levels in a dose-dependent manner. These increases in lactate levels were significantly prevented by the co-perfusion with 10 microM L-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, but not by pargyline, a non-specific MAO inhibitor. The increase in extracellular lactate levels was considered to be the reflection of the cell damage resulted from the impairment of mitochondrial function. The present results suggested that L-deprenyl would rescue nerve cells from these toxins through the direct influence on the mitochondrial electron transport.

Effects of prolonged strenuous exercise on plasma levels of atrial natriuretic peptide and brain natriuretic peptide in healthy men.

BACKGROUND: Now that marathon racing is growing in popularity, many thousands of enthusiastic athletes are participating in various ultramarathons all over the world each year. However, it remains controversial whether such a sport contributes to the promotion of health. The occurrence of transient cardiac dysfunction and irreversible myocardial injury has been reported in association with such exercise in healthy individuals. Brain natriuretic peptide (BNP) is a cardiac hormone, as is atrial natriuretic peptide (ANP), and its measurement has been widely used for clinical evaluation of cardiac dysfunction. However, little is known about the response of plasma BNP to prolonged strenuous exercise. We hypothesized that confirmation of minimal cardiac dysfunction or myocardial injury may be made by measurements of plasma BNP. METHODS: Levels of plasma ANP, BNP, catecholamines, blood lactate, and serum cardiac troponin T (cTnT) were determined before and after a 100-km ultramarathon in 10 healthy men to examine the effects of the exercise on levels of ANP and BNP and correlations between the natriuretic peptides and cTnT as a marker for myocardial damage. RESULTS: Whereas all variables significantly increased after the race, increased levels of ANP and BNP were most strongly correlated with increases in cTnT levels. The cTnT level after the race was greater than the upper reference limit in 9 of 10 men. CONCLUSIONS: Such exercise significantly increased ANP and BNP levels in healthy men, and the increases could be partially attributed to myocardial damage during the race.

Influence of angiotensin-converting enzyme gene polymorphism on development of athlete's heart.

BACKGROUND AND HYPOTHESIS: Genetic influence on development of athlete's heart is uncertain. This study investigated whether angiotensin-converting enzyme (ACE) gene polymorphism influenced development of athlete's heart. METHODS: Forty-three participants in a 100-km ultramarathon were classified on the basis of ACE gene polymorphism into a deletion group (n = 26) and an insertion group (n = 17). Echocardiograms were recorded to determine left ventricular end-diastolic and end-systolic diameters, interventricular septal thickness, left ventricular posterior wall thickness, left ventricular mass, and ejection fraction. RESULTS: Left ventricular end-diastolic diameter (65.5 +/- 4.0 mm) and left ventricular mass (369.5 +/- 73.9 g) were significantly larger in the subjects with deletion than in those with insertion (57.4 +/- 4.2 mm, 306.5 +/- 93.7 g). However, no significant differences in the other parameters were noted. CONCLUSIONS: In long-distance runners, ACE gene polymorphism of the D/D and D/I genotypes has a stronger influence on left ventricular hypertrophy than polymorphism of the I/I genotype.

Efficacy of primary percutaneous transluminal coronary angioplasty for acute myocardial infarction in patients aged > or = 80 years.

The therapeutic result of primary percutaneous transluminal coronary angioplasty (PTCA) in the elderly was assessed in 20 of 44 patients > or = 80 years old (range 81-92 years, mean age 84 +/- 3 years) with acute myocardial infarction who underwent primary PTCA and the results compared with 194 younger patients (< 80 years) who underwent primary PTCA during the same period. In-hospital prognosis, and long-term outcomes were investigated. Emergency coronary angiography was performed in 47.7% of the patients with acute myocardial infarction in the elderly group with 45.5% receiving primary PTCA. Primary PTCA was successful in 95.0% of the elderly group, showing no significant difference from the younger group. In-hospital mortality showed no significant difference between the elderly group and the younger group (5.0% vs 4.1%). However, the incidences of pump failure of the heart and bleeding complication requiring blood transfusion were higher in the elderly group during hospitalization. The 2-year survival rate for the elderly group was 82.5 +/- 9.3%, which was better than previous studies. These results suggest that primary PTCA has a good success rate in the elderly patients with acute myocardial infarction, and decreases the in-hospital mortality and improves the long-term outcome. However, this study was conducted retrospectively in a small group of patients. The efficacy of primary PTCA for the elderly remains to be clarified in a larger prospective trial.

[A case of an advanced aged Eisenmenger's syndrome].

We report a 70-year-old women with Eisenmenger's syndrome. Eisenmenger's syndrome with ventricular septal defect was diagnosed at another hospital when she was 32 years old. Then, she was referred to our hospital at age 60 old and she now is according to the out patient in over clinic. She have mild cardiac function, NYHA classification, was II-M, polycythemia cell blood count 535 x 10(4) and 17.2 g/dl in hemoglobin. Echocardiography suggested serious Eisenmenger's syndrome. The left ventricle was compressed, the blood pressure of the right ventricle exceeded 105 mmHg, and the onset of the right to left shunt flow was thought to be 250 msec bored on the electrocardiogram Q wave. The reason why the progression of complicated obstructive pulmonary artery disease was slow may have been become of the mildness of her polycythemia, and this is presumed to be the reason for her long survival to age 70.

The tissue distribution of lidocaine in acute death due to overdosing.

A 78-year-old woman committed double suicide with a bolus injection of 1 g of lidocaine hydrochloride. The tissue distribution of lidocaine in this fatal poisoning was investigated using an improved gas chromatographic method. The blood level was 42 microg/ml and the brain concentration was 70 miccro/g. Thus, the cause of death in this case was clearly diagnosed as lidocaine overdosing. The blood level of 42 microg/ml was higher than that calculated using the standard pharmacokinetic parameters. Lower blood/tissue ratios were also detected compared with the data described in the literature. These results indicated that the cardiac failure should have occurred immediately after the lidocaine injection. The present data show the distribution of lidocaine after acute death due to overdosing.

Acute myocardial infarction induced by alternating exposure to heat in a sauna and rapid cooling in cold water.

We describe a patient with acute myocardial infarction, which was thought to result from plaque rupture or thrombosis because of coronary artery spasm. The vasospasm was most likely induced by stimulation of the alpha-adrenergic receptors during alternating heat exposure during sauna bathing and rapid cooling during cold water bathing. This report emphasizes the dangers of rapid cooling after sauna bathing in patients with coronary risk factors.

[Outcomes of primary angioplasty in patients aged 85 years old and older who have acute myocardial infarction].

Outcomes of primary angioplasty in 6 elderly patients with acute myocardial infarction who were admitted to the hospital between July of 1994 and June of 1997 were reviewed retrospectively. Emergency coronary angiography was done in 7 of 16 patients (44%) who were at least 85 years old and primary angioplasty was done in 6 patients (38%). Dilatation was successful in all 6 patients. Congestive heart failure occurred in 4 patients and cardiogenic shock occurred in 1 patient, but no patient died during hospitalization. Blood transfusion and surgical resection were done in 1 patient because of a giant hematoma and pseudoaneurysm at the puncture site. Although the creatinine level increased after angioplasty in all 6 patients, dialysis therapy was not needed. All patients were alive and none had angina at follow-up (mean follow-up period = 16.5 months). Primary angioplasty was successful in patients at least 85 years old; both short-term and long-term outcomes were good. Primary angioplasty should be considered to be an effective treatment for acute myocardial infarction in people 85 years old and older.

Influence of exercise on QT dispersion in ischemic heart disease.

UNLABELLED: QT dispersion (QTd: maximum QT interval-minimum QT interval) is associated with severe cardiac arrhythmia and with abnormal ventricular repolarization. We investigated the influence of exercise on QTd in patients with ischemic heart disease. On standard 12-lead electrocardiograms, QTd was measured before and after treadmill exercise in 7 normal subjects, 17 patients with effort angina pectoris (and > or = 75% stenosis on coronary arteriography), and 33 patients with old myocardial infarction. Bazett's formula was used to obtain the corrected QTd (QTcd). The pre-exercise resting QTcd was 45.9 +/- 10.6, 44.3 +/- 15.2, and 74.8 +/- 28.1 msec in the respective groups, being significantly greater in the infarct group (p < 0.05). The QTcd at 5 min after exercise was respectively 49.3 +/- 9.0, 58.8 +/- 19.9, and 75.4 +/- 30.9 msec (p = 0.0347, infarct vs. controls). The difference in QTcd was significant for the angina group before and after physical exercise (p = 0.0003). There was a significant increase of QTcd after exercise in the angina group whether or not the patients were receiving beta-blockers. The infarct patients without beta-blocker therapy showed an increase of QTcd after exercise, while those receiving beta-blockers showed a decrease. The post-exercise difference between these subgroups was significant (p = 0.0351). CONCLUSIONS: QTcd was significantly increased by exercise in the angina group, possibly reflecting impaired repolarization due to ischemia. Inhibition of the increase in QTd by beta-blockers suggested a possible preventive effect on severe arrhythmias due to nonhomogeneous ventricular repolarization.

Nucleotide sequence of the Syrian hamster intracisternal A-particle gene: close evolutionary relationship of type A particle gene to types B and D oncovirus genes.

We determined the complete nucleotide sequence of the intracisternal A-particle gene, IAP-H18, cloned from the normal Syrian hamster liver DNA. IAP-H18 was 7,951 base pairs in length with two identical long terminal repeats of 376 base pairs at both ends. On the coding strand, imperfect open reading frames corresponding to gag and pol of the retrovirus genome were observed, whereas many stop codons were present in the region corresponding to env. The putative H18 gag gene (809 amino acids) had a sequence homologous to the N-terminal half of the mouse mammary tumor virus gag gene and locally to the Rous sarcoma virus gag gene. The putative H18 pol gene (900 residues) was homologous to the Rous sarcoma virus pol gene almost throughout the entire region. Two conserved regions among the retrovirus pol genes have been reported. One presumably corresponds to the DNA polymerase and the RNase H domain, and the other corresponds to the DNA endonuclease domain of the multifunctional protein pol. By the comparison of the deduced amino acid sequences of the putative endonuclease domain of six representative oncovirus genomes, a phylogenetic tree of the oncovirus genomes was constructed, and the intracisternal A-particle (type A) genome was found to be more closely related to the mouse mammary tumor virus (type B) and squirrel monkey retrovirus (type D) genomes.