Lactobacillus gasseri requires peptides, not proteins or free amino acids, for growth in milk.

Lactobacillus gasseri is a widespread commensal lactic acid bacterium inhabiting human mucosal niches and has many beneficial effects as a probiotic. However, L. gasseri is difficult to grow in milk, which hurts usability for the food industry. It had been previously reported that supplementation with yeast extract or proteose peptone, including peptides, enables L. gasseri to grow well in milk. In this study, our objective was to confirm peptide requirement of L. gasseri and evaluate efficacy of peptide release by enzymatic proteolysis on growth of L. gassei in milk. Three strains of L. gasseri did not grow well in modified DeMan, Rogosa, Sharpe broth without any nitrogen sources (MRS-N), but addition of a casein-derived peptide mixture, tryptone, promoted growth. In contrast, little effect was observed after adding casein or a casein-derived amino acid mixture, casamino acids. These results indicate that L. gasseri requires peptides, not proteins or free amino acids, among milk-derived nitrogen sources for growth. Lactobacillus gasseri JCM 1131T hardly had growth capacity in 6 kinds of milk-based media: bovine milk, human milk, skim milk, cheese whey, modified MRS-N (MRSL-N) supplemented with acid whey, and MRSL-N supplemented with casein. Moreover, treatment with digestive proteases, particularly pepsin, to release peptides made it grow well in each milk-based medium. The pepsin treatment was the most effective for growth of strain JCM 1131T in skim milk among the tested food-grade proteases such as trypsin, α-chymotrypsin, calf rennet, ficin, bromelain, and papain. As well as strain JCM 1131T, pepsinolysis of milk improved growth of other L. gasseri strains and some strains of enteric lactobacilli such as Lactobacillus crispatus, Lactobacillus gallinarum, Lactobacillus johnsonii, and Lactobacillus reuteri. These results suggest that some relatives of L. gasseri also use peptides as desirable nitrogen sources, and that milk may be a good supplier of nutritious peptides to enteric lactobacilli including L. gasseri after peptic digestion in the gastrointestinal tract. This is the first report showing peptide requirement of L. gasseri and efficacy of pepsinolysis on the growth of L. gasseri and its relatives in milk. This study would contribute to increasing usability of L. gasseri and its relatives as probiotics in dairy foods.

Improvement of accessory symptoms of hypertension by TSUMURA Orengedokuto Extract, a four herbal drugs containing Kampo-Medicine Granules for ethical use: a double-blind, placebo-controlled study.

A double-blind, placebo-controlled study was conducted to evaluate the efficacy, safety, and utility of TSUMURA Orengedokuto Extract Granules for Ethical Use (TJ-15) as a treatment for the accessory symptoms of hypertension. Two capsules of the study drug were administered orally 3 times daily (i.e., before meals) for 8 weeks. Among 265 patients enrolled in the study, 134 were assigned to the TJ-15 group and 131 were assigned to the placebo group, of whom 204 patients (103 in the TJ-15 group and 101 in the placebo group) were included in the efficacy and utility analyze and 251 patients (128 in the TJ-15 group and 123 in the placebo group) were included in the safety analysis. Efficacy was significantly higher in the TJ-15 group based on the total score for the accessory symptoms of hypertensions which was the primary efficacy endpoint (Wilcoxon's rank sum test, p=0.013). When each accessory symptom of hypertension was assessed separately, efficacy was higher for hot flushes and facial suffusion in the TJ-15 group (Wilcoxon's rank sum test, p=0.034, and 0.022, respectively). There were no significant differences between the TJ-15 and the placebo groups with respect to the decrease of blood pressure or the antihypertensive effect. There was also no significant difference between the two groups with regard to the overall safety rating. The utility rating was significantly higher in the TJ-15 group than in the placebo group (Wilcoxon's rank sum test, p=0.016). In conclusion, TJ-15 was superior to placebo with respect to efficacy, safety, and utility for the treatment of accessory symptoms of hypertension.

Relation between green tea consumption and the severity of coronary atherosclerosis among Japanese men and women.

PURPOSE: To examine the relation between green tea consumption and arteriographically determined coronary atherosclerosis. METHODS: Study subjects were 512 patients (302 men and 210 women) aged 30 years or older who underwent coronary arteriography for the first time at four hospitals in Fukuoka City or one hospital in an adjacent city between September 1996 and August 1997. Lifestyle characteristics including green tea consumption were ascertained before arteriography by a questionnaire supported with interview. RESULTS: 117 men (38.7%) and 50 women (23.8%) had significant stenosis of one or more coronary arteries. Green tea consumption tended to be inversely associated with coronary atherosclerosis in men, but not in women. An evident, protective association between green tea and coronary atherosclerosis was observed in a subgroup of 262 men excluding those under dietary or drug treatment for diabetes mellitus. In this subgroup, after adjustment for traditional coronary risk factors and coffee, odds ratios of significant stenosis for consumption of 2-3 cups and 4 or more cups per day were 0.5 (95% confidence interval 0.2-1.2) and 0.4 (0.2-0.9), respectively, as compared with a consumption of one cup per day or less. CONCLUSIONS: The results indicate that green tea may be protective against coronary atherosclerosis at least in men.

[Summating potential evoked by long-tone burst stimuli in Menière's disease].

It is now well documented that in cases of Menière's disease/endolymphatic hydrops, the electrocochleography (ECochG) evoked by a broad-band click is often characterized by an enlarged summating potential (enlarged-SP) and a large negative summating potential to action potential ratio (large -SP/AP) but these mechanism have not been clarified. The aim of this study was to find clues to the mechanism of enhanced -SP and large -SP/AP in Menière's disease, by using long-tone burst stimuli. We also sought to determine the significance of SP measurement for evaluating the cochlear function in Menière's disease/endolymphatic hydrops. ECochG was performed on 29 ears of patients with Menière's disease and 12 ears of adults with normal hearing as a control group. Extratympanic ECochG was carried out using an HN-7 electrode. The sound intensity used for measuring the SP and SP/AP was 90dBnHL. Both SP and AP were elicited by clicks and long-tone bursts of 50 ms duration with a 1-ms rise-fall time. The clicks and long-tone bursts with frequencies of 0.5, 1, 2, and 4 kHz were delivered by the tubal transducer (NC-3). In most of the patients with Menière's disease, SP evoked by the long tone burst stimuli showed negative polarity (-SP) at each frequency. Analysis of variance (X2test) indicated a significant difference in -SP at 0.5 and 1 kHz between Menière's disease and the control group (0.5 kHz: p < 0.001, 1 kHz: p < 0.02). When setting the normal upper limit of the -SP/AP to 0.4, we found that the number of cases over 0.4 which showed -SP at 0.5 and 1 kHz was much larger than those below 0.4 in the 29 ears of patients with Menière's disease. There was no difference between the types of Menière's disease or glycerol test and SP polarity elicited by long-tone burst stimuli. The enhanced -SP and large -SP/AP obtained by the broad band clicks seem to reflect a component of negative SP polarity in the low and middle frequency ranges. It was assumed that the reverse phenomena of SP polarity in the low and middle frequency ranges were related to changes in hydrodynamic characteristics in the upper cochlear turns due to abnormal endolymphatic pressure. Our findings suggest that SP recording by long-tone burst stimuli is useful in detecting changes in cochlear partition due to abnormal intracochlear pressure, most likely in the early phase of Menière's disease based on the wide frequency information of SP.

Two cases of MND/ALS developing the syndrome of inappropriate secretion of antidiuretic hormone.

We report 2 autopsy-proven cases of motor neuron disease/amyotrophic lateral sclerosis (MND/ALS), who developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) prior to the respiratory failure. With respect to the underlying mechanisms of SIADH in the cases, we considered two factors; 1) dysfunction of the feedback system in ADH secretion via intrathoracic volume receptors caused by changes in intrathoracic circulation, and 2) primarily functional abnormalities in the limbic system which could influence hypothalamic osmoreceptors. It appears that SIADH can be followed by an exacerbation of respiratory dysfunction in MND/ALS.

Jansen-type metaphyseal chondrodysplasia: analysis of PTH/PTH-related protein receptor messenger RNA by the reverse transcriptase-polymerase chain method.

Jansen-type metaphyseal chondrodysplasia (JMC) has both delayed ossification in long bones and usually hypercalcemia. We report a Japanese male patient with JMC who presented with rachitic signs on radiographs, hypercalcemia (13 mg/dl) and low %TRP at age 3 months (mo). Hypercalcemia was treated from age 3 mo to 11 yr. Progressive widening, splaying and fragmentation of the metaphyses have been recognized on radiographs which resulted in shortened tubular bones and consequent short stature [107 cm (-6.5 SD)] at age 13 yr. Hypercalcemia tended to normalize, and %TRP became normal at age 13 yr. Repeated measurements of serum PTH and PTH-related protein (PTHrP) levels showed that they were low or normal in the face of hypercalcemia and high urine cAMP excretion, which led us to suspect constitutive activation of the PTH/PTHrP receptor. Direct sequencing of PTH/PTHrP receptor complementary DNA from skin fibroblast cells revealed a CAC to CGC transversion yielding a strictly conserved His223 to Arg substitution found in 90% of DNA fragment in the second transmembrane domain of the receptor. This mutation created a restriction site Sphl (G/CATG/C). Direct sequencing of genomic DNA and also restriction enzyme digestion revealed heterozygous transition. The mutation was absent in the parents with normal phenotype. We conclude that both dysplastic bone lesions and calcium homeostasis are age-dependent in JMC, and that the His223-Arg substitution is the same as that found in four Caucasian patients with a similar phenotype irrespective of the ethnic difference, and that the preferential expression of an abnormal allele of the PTH/PTHrP receptor mRNA in skin fibroblast despite heterogygotic transversion in the genomic DNA suggests the importance of allele expression.

Medium-term effects of betaxolol monotherapy and combination therapy with nitrendipine on lipoprotein and apolipoprotein metabolism in patients with mild to moderate essential hypertension.

The objective of this study was to assess the medium-term effects of betaxolol, a long-acting, lipid-soluble, cardioselective, beta-adrenergic antagonist, alone and in combination with nitrendipine on blood pressure (BP) and metabolism of lipid, lipoprotein and apolipoprotein in patients with mild to moderate hypertension. Forty-seven patients (21 men, 26 women, average age 54 years) participated in an open controlled clinical trial. After a 4-week washout period, all of the patients received betaxolol monotherapy at a dose of 5-10 mg daily for 6 months (Phase I). From month 7 through month 12 (Phase II), half of the total patients (Group B, n = 23) with diastolic blood pressure (DBP) of 95 mm Hg or more at the end of Phase I were also given nitrendipine (10-20 mg, once daily), while the remaining patients (Group A, n = 24) continued to receive only betaxolol. Systolic blood pressure (SBP), DBP, and heart rate (HR) were monitored once monthly. Serum lipid profiles were measured at study entry and after 6 and 12 months of therapy. Betaxolol significantly reduced SBP, DBP, and HR in both groups during Phase I, and the reductions in SBP and DBP were markedly less in Group B than in Group A. During Phase II, the additional reduction of SBP and DBP to levels similar to those in Group A was achieved by betaxolol in combination with nitrendipine, and HR was slightly but significantly increased. Betaxolol monotherapy reduced serum levels of high density lipoprotein cholesterol (HDL-C) and increased levels of triglyceride, apolipoprotein (apo) C-II and apo C-III. Combination therapy with betaxolol and nitrendipine increased serum apo A-I but did not affect other lipid profiles. Our results indicate that betaxolol is an effective antihypertensive drug which has a preferable effect on HR and HDL profiles when combined with nitrendipine.

Comparative effects of monatepil, a novel calcium antagonist with alpha 1-adrenergic-blocking activity, and nitrendipine on lipoprotein and carbohydrate metabolism in patients with hypertension.

The effects of monatepil, a new calcium antagonist with alpha 1-blocking activity, and nitrendipine on lipoprotein and carbohydrate metabolism in 86 patients with mild-to-moderate hypertension were examined in a randomized, open-label, multicenter (32 hospitals) study. Thirty-nine patients treated with monatepil and 33 patients treated with nitrendipine completed the 12-week study. Monatepil and nitrendipine each significantly decreased both systolic and diastolic blood pressure. Changes in heart rate were not seen in either group. Monatepil administration significantly decreased total cholesterol, low density lipoprotein (LDL) cholesterol, the LDL cholesterol to high density lipoprotein (HDL) cholesterol ratio, apolipoprotein (Apo) B levels, and HbA1c levels, whereas no changes in these measurements were observed in nitrendipine-treated patients. Monatepil also significantly decreased lipoprotein(a) levels, but there were no significant changes in HDL cholesterol, Apo-AI, or Apo-E levels. After nitrendipine treatment, the C peptide concentration decreased significantly, although no significant changes were observed in fasting blood glucose or immunoreactive insulin levels. On the basis of these results, it can be concluded that monatepil belongs to a new class of antihypertensive calcium antagonist with favorable carbohydrate metabolism and lipid-lowering activity, although the clinical importance of these findings has not been established.

Combined therapy with arbekacin and fosfomycin for methicillin-resistant Staphylococcus aureus infections.

We examined the clinical efficacy of a combination of arbekacin and fosfomycin in the treatment of various methicillin-resistant Staphylococcus aureus (MRSA) infections. The combination of arbekacin plus fosfomycin displayed 65.4% (17/26) clinical efficacy and 65.4% (17/26) bacteriological efficacy. This combination thus appeared to be an effective regimen for the treatment of MRSA infections. However, its bacteriological efficacy against concomitant Pseudomonas aeruginosa strains was only 16.7% (1/6). In addition, in 4 episodes of superinfection involving P. aeruginosa strains developed during the combination therapy.

Characteristics of reactive electropermeable points on the auricles of coronary heart disease patients.

In oriental medicine there is a hypothesis related to acupuncture that the auricle is a projection of the functional anatomy of the whole human body. In this study reactive electropermeable points (REPP), that is, points on the skin with low electrical resistance, on the auricle were measured on patients with coronary heart disease using a neurometer LC-M. Our findings correlated positively with the particular points--heart I (shin) and heart II (shinzo)*--named by the Chinese group as being related to the functional anatomy of the heart. The incidence of positive REPP test results at the shin and shinzo points for subjects with acute myocardial infarction (AMI) were extremely high, and positive test results for patients with old myocardial infarction (OMI) and angina pectoris (AP) were also significant. There was no significant difference in the incidence rates of REPP at the shin and shinzo points between the OMI and AP groups. High incidence of positive REPP test results at the lung and heart III (shinyu) points occurred only in the AMI group, and this was significantly high when compared with the control group.

Effects of Chinese herbal drugs on serum lipids, lipoproteins and apolipoproteins in mild to moderate essential hypertensive patients.

We investigated the effects of the traditional Chinese herbal drugs, Dai-saiko-to (D) and Saiko-ka-ryukotsuboreito (S) on blood pressure, pulse rates, serum lipids, lipoproteins and apolipoproteins in 30 patients with mild to moderate hypertension in an open, randomised trial. After the drug treatment, BP remained unchanged, but pulse rates declined significantly after 3 months in the S treated group. Serum total cholesterol and triglyceride values did not change, but high density lipoprotein-cholesterol increased significantly (P < 0.05) in both groups. Apo-AI (P < 0.1 in S group) and apo-AII (P < 0.05 in D group, P < 0.1 in S group) tended to increase 3 months after treatment. These data indicate that both of these traditional Chinese medicines have a preferential effect on lipid metabolism with little antihypertensive action.

Effects of Chinese herbal drug, dai-saiko-to on plasma lipids, lipoproteins and liver lipid contents in guinea pig.

Effects of Chinese herbal drug, Dai-saiko-to, on plasma lipids, lipoproteins and liver lipid contents were investigated in guinea pig with/without cholesterol feeding. Guinea pigs were divided into 4 groups (Group 1: normal chow (N) diet, Group 2: N + 1% Dai-saiko-to (D) diet, Group 3: 1% cholesterol (C) diet, Group 4: 1% C+ 1% D diet), and were treated for 5 weeks. Significant body weight reductions were observed in Groups 3 and 4 compared to Groups 1 and 2. Significant reductions of plasma triglyceride (TG) and very low and low density lipoproteins [(V) LDL]-TG were found in Group 3 compared to Groups 1, 2, and 4. (HDL)-TG significantly decreased in Groups 3 and 4 compared to Groups 1 and 2, but no significant difference was noted between Groups 1 and 2, and Groups 3 and 4. Liver lipid contents analysis showed no significant changes between Groups 1 and 2, and Groups 3 and 4, respectively, but the distribution of lipid droplets as pathologically determined using a computer program showed Group 4 had less lipid deposition compared to Group 3. These data suggest that Dai-saiko-to acts on triglyceride metabolism in hypercholesterolemic guinea pigs.

Non-pharmacologic measures for lowering blood pressure.

Nondrug measures have proven effective, to some extent, in lowering blood pressure, especially in mild hypertensives, in many well-controlled studies. The proven measures are reduction of a) salt (less than 5 g/day), b) alcohol (less than 30 ml/day) intake, and c) obesity, and d) regular physical exercise (30-60 minutes/day) and e) mental relaxation. The reported effectiveness of each of these measures ranges from one third to two thirds in mild hypertensives. Should all these nondrug measures, together with cessation of smoking, be applied in all mild hypertensives, it might help prevent their progression to moderate or even severe hypertension with complications, such as coronary heart disease in particular, thereby solving most of the problems that antihypertensive drugs have left behind.

Anti-Bacteroides fragilis substance from rhubarb.

Extracts of 178 Chinese herbs were screened for their antibacterial activity against Bacteroides fragilis a major anaerobic microorganism in the intestinal flora of humans. Only rhubarb root (Rheum officinale) was found to have significant activity and the purified active substance was identified as rhein.

Alterations of immunoreactive substance P and enkephalins in rat spinal cord after electroacupuncture.

A form of electrically-induced analgesia known as electroacupuncture was administered to rats bilaterally at the point "Huan-tiao." Compared with untreated rats, treated rats showed altered pain thresholds characterized as low, intermediate, and high. From immunocytochemical studies, the spinal cords taken from the treated rats exhibited differences in immunoreactivity for substance P (SP), methionine- and leucine-enkephalins (ME and LE respectively). By densitometry, the altered levels of immunoreactive (IR) peptides correlated with the pain thresholds in specific ways. That is, high pain threshold correlated with the visualization of increased IR-SP adn IR-LE within neuronal processes throughout the dorsal horn substantia gelatinosa. In the same specimens, decreased IR-ME could be seen. In contrast, low pain threshold correlated with decreased IR-SP and IR-ME. IR-LE showed a concomitant decrease in the medial substantia gelatinosa region, and slight, insignificant changes laterally. The data suggest that different degrees of analgesia induced by electroacupuncture result from the variable release of SP, ME, and LE in spinal regions associated with nociception. In terms of current models of pain processing, the data do not entirely support an axo-axonic interaction between enkephalin interneurons and SP terminals. Some modifications and an alternative model are considered.

A case of pseudoaldosteronism due to addiction of Jintan, a mouth refresher popular among Japanese.

A 50-year-old man with hypertension showed hypokalemia, hyporesponsive low reninemia, and low levels of aldosterone in the plasma and urine. Plasma DOC and corticosterone level, adrenal scintigram, and phlebogram were within normal limits. Hypertension and hypokalemia were correctable by spironolactone. It was revealed that he had been ingesting Jintan granules in large doses, corresponding to 150-220 mg of glycyrrhizic acid per day for 10 years. Upon cessation of Jintan ingestion, blood pressure and serum potassium level were normalized after 40 days. Metabolic alkalosis, hypervolemia, hyporesponsive low reninemia, and the low levels of plasma and urine aldosterone were also improved. Thus, the present case of pseudoaldosteronism was attributed to Jintan, and raises a caution to excessive Jintan ingestion.

Duration of bupivacaine intradermal anesthesia when the bupivacaine is mixed with chloroprocaine.

In a double-blind trial in 20 human volunteers, the duration of intradermal anesthesia with a mixture of bupivacaine, 0.5 mg, and chloroprocaine, 3 mg, was compared with the duration of intradermal anesthesia obtained with either bupivacaine, 0.5 mg, or chloroprocaine, 3 mg, alone. The duration of intradermal anesthesia produced by the bupivacaine mixed with chloroprocaine, 36 +/- 16 (mean +/- 1 SD) minutes, was significantly less than the duration of the same amount of bupivacaine alone, 139 +/- 78 minutes. Duration of anesthesia with chloroprocaine alone, 24 +/- 11 minutes, was similar to the duration of anesthesia with chloroprocaine plus bupivacaine. A possible explanation for these results is that bupivacaine competes with chloroprocaine for nonspecific receptors at the biophase and in the surrounding nerve tissue.

An accelerated hypertension with neither malignant nephrosclerosis nor elevation of plasma renin activity.

A case of accelerated hypertension, which was unique in a resistance to an angiotensin antagonist, and a lack of the elevation of plasma renin activity (PRA) is reported. Non-elevated PRA was coincided with non-malignant nephrosclerosis in renal histology. The acceleration was attributed to the neurological cause i.e., cerebral hemorrhage in the right hypothalamus which extended to the ventricle and subarachnoid space. The case therefore clinically seemed malignant-like, but it was not malignant hypertension in the sense of Volhard's classical definition. This does not conflict with the usefulness of the determination of PRA in the diagnosis of malignant hypertension with nephrosclerosis.