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Depression-like behavior during lactation may relate to changes in the hypothalamic-pituitary-adrenal (HPA) axis, brain monoamines, and brain amino acid metabolism. This study investigated how the behavior, HPA axis activity, brain monoamines, and brain free amino acid metabolism of rats were changed by stress or lactation period. Rats were separated into four groups: (1) control lactating (n = 6), (2) stress lactating (n = 6), (3) control virgin (n = 7), and (4) stress virgin (n = 7) and restrained for 30 min a total of ten times (once every other day) from postnatal day (PND) 1. Depression-like behavior in the forced swimming test (FST) on PND 10 and concentration of corticosterone in plasma, as well as monoamines and L-amino acids including β-alanine, γ-aminobutyric acid, cystathionine, 3-methyl-histidine and taurine in the prefrontal cortex and hypothalamus on PND 19 were measured. The plasma corticosterone concentration, measured just after restraint stress, was significantly higher in the stress groups, versus the control groups, but there were no significant differences between control and stress lactating groups. Depression-like behavior (immobility) in the FST was significantly lower in the lactating groups, versus the virgin groups. Stress enhanced dopamine and glutamate, and decreased threonine and glycine concentrations in the hypothalamus. In addition, 3-methoxy-4-hydroxyphenylglycol (MHPG), threonine and ornithine concentrations in the prefrontal cortex were significantly higher in the lactating groups compared with the virgin groups. Changes in plasma corticosterone concentration, monoamine, and amino acid metabolism may relate to stress-induced depression-like behavior in lactating rats. Lay summary This study revealed that reduced depression-like behavior in lactating, relative to virgin rats, was associated with changes in monoamine and amino acid metabolism in the prefrontal cortex of the brain. In addition, the effect of stress on monoamine and amino acid metabolism is prominently observed in the hypothalamus and may be related to neuroendocrine stress axis activity and secretion of corticosterone. This study suggested that stress-induced depression-like behavior may be associated with several changes in the stress axis, brain monoamines, and brain amino acid metabolism. These parameters were associated with attenuated depression-like behavior in lactating rats.

A critical factor for preventing osteoporosis after menopause is attenuation of the accelerated turnover rate of bone metabolism. The present randomized controlled study was conducted to clarify the effects of a lemon beverage with calcium (Ca) supplementation that makes use of the chelating action of citric acid. Comprehensive evaluations of bone were performed by assessments of bone mineral density (BMD) and biomarkers related to bone turnover. Seventy-nine postmenopausal women were enrolled and asked to participate in an 11-month continuous intake of the test beverages. The subjects were divided into three groups: those who consumed a lemon beverage containing citric acid with Ca supplementation (LECA group), those who consumed a lemon beverage containing citric acid without Ca supplementation (LE group), and those who consumed no test beverage (control group). Using a double-blind protocol, subjects in the LECA and LE groups consumed one bottle containing 290 mL of the test beverage each day. The ratio of change in BMD after 11 months was significantly higher in the LECA group as compared to the control and LE groups. The LECA group also showed significant decreases in concentrations of tartrate-resistant acid phosphatase 5b (TRACP-5b), a bone resorption marker, and bone alkaline phosphatase (BAP) as compared to the other groups, as well as a significant decrease in concentration of osteocalcin (OC), a bone formation marker, as compared to the LE group. Based on our findings, we speculated that bone resorption and bone formation in postmenopausal women might be suppressed along with an increase in Ca resorption caused by chelation of citric acid in association with continuous ingestion of a Ca-supplemented lemon beverage containing citric acid, resulting in suppression of high bone metabolic turnover. In addition, the results provide information regarding BMD maintenance in the bones of the trunk, including the lumbar spine and proximal femur.

It is well known that maternal stress during the gestation and lactation periods induces abnormal behavior in the offspring and causes a lowering of the offspring’s body weight. Various causes of maternal stress during the lactation period, relating to, for example, maternal nutritional status and reduced maternal care, have been considered. However, little is known about the effects on milk of maternal stress during the lactation period. The current study aimed to determine whether free amino acids, with special reference to sulfur-containing amino acids in milk, are altered by restraint stress in lactating mice. The dams in the stress group were restrained for 30 min at postnatal days 2, 4, 6, 8, 10 and 12. Restraint stress caused a reduction in the body weight of lactating mice. The concentration of taurine and cystathionine in milk was significantly higher in the stress group, though stress did not alter their concentration in maternal plasma. The ratio of taurine concentration in milk to its concentration in maternal plasma was significantly higher in the stress group, suggesting that stress promoted taurine transportation into milk. Furthermore, taurine concentration in milk was positively correlated with corticosterone levels in plasma. In conclusion, restraint stress in lactating mice caused the changes in the metabolism and in the transportation of sulfur-containing amino acids and resulted in higher taurine concentration in milk. Taurine concentration in milk could also be a good parameter for determining stress status in dams.

The aim of the present study was to elucidate how bone metabolism and bone mineral density are affected by the consumption of a lemon juice-containing calcium (Ca)-enriched beverage. The efficacy of this investigational product was evaluated in postmenopausal women during five months of continuous intake (intervention). This was a randomized, controlled trial. Eighty-three subjects were assigned to three groups. Using a double-blind format, the first two groups received a Ca-supplemented lemon-juice (lemon) beverage (LECA) or a Ca-unsupplemented lemon-juice (lemon) beverage (LE). The third group (control) received no intervention. Each subject in the LECA and LE groups consumed one bottle (290 mL) of their assigned investigational product every day for five consecutive months. After five months of intervention, the gain in bone mineral density at the lumbar spine was significantly larger in the LECA and LE groups than in the control group. In the femur, subjects in the LECA group gained significantly more bone mineral density than the control subjects. The largest gain in bone mineral density at the lumbar spine was observed in the LECA group. As for the concentrations of the bone resorption marker tartrate-resistant acid phosphatase 5b (TRACP-5b), subjects in the LECA group had significantly lower values than those in the control group. Similarly, when compared with the LE and control groups, a significant decrease was detected in the LECA group in the concentrations of the bone formation markers, bone alkaline phosphatase (BAP) and osteocalcin (OC). In postmenopausal women, continuous consumption of Ca-supplemented lemon beverages improved the absorption of Ca and inhibited bone resorption. This likely blocked the function of osteoblasts and led to the suppression of bone formation, resulting in the attenuation of high-turnover bone metabolism.

Attention-deficit hyperactivity disorder (ADHD) is defined as attention deficiency, restlessness and distraction. The main characteristics of ADHD are hyperactivity, impulsiveness and carelessness. There is a possibility that these abnormal behaviors, in particular hyperactivity, are derived from abnormal dopamine (DA) neurotransmission. To elucidate the mechanism of high locomotor activity, the relationship between innate activity levels and brain monoamines and amino acids was investigated in this study. Differences in locomotor activity between ICR, C57BL/6J and CBA/N mice were determined using the open field test. Among the three strains, ICR mice showed the greatest amount of locomotor activity. The level of striatal and cerebellar DA was lower in ICR mice than in C57BL/6J mice, while the level of L-tyrosine (L-Tyr), a DA precursor, was higher in ICR mice. These results suggest that the metabolic conversion of L-Tyr to DA is lower in ICR mice than it is in C57BL/6J mice. Next, the effects of intraperitoneal injection of (6R)-5, 6, 7, 8-tetrahydro-l-biopterin dihydrochloride (BH4) (a co-enzyme for tyrosine hydroxylase) and L-3,4-dihydroxyphenylalanine (L-DOPA) on DA metabolism and behavior in ICR mice were investigated. The DA level in the brain was increased by BH4 administration, but the increased DA did not influence behavior. However, L-DOPA administration drastically lowered locomotor activity and increased DA concentration in several parts of the brain. The reduced locomotor activity may have been a consequence of the overproduction of DA. In conclusion, the high level of locomotor activity in ICR mice may be explained by a strain-specific DA metabolism.

Thermal manipulation (TM) of incubation temperature causes metabolic alterations and contributes to improving thermotolerance in chicks post hatching. However, there has been no report on amino acid metabolism during TM and the part it plays in thermotolerance. In this study, we therefore first analyzed free amino acid concentrations in the embryonic brain and liver during TM (38.6°C, 6h/d during embryonic day (ED) 10 to ED 18). It was found that leucine (Leu), phenylalanine and lysine were significantly decreased in the embryonic brain and liver. We then chose l-Leu and other branched-chain amino acids (l-isoleucine (L-Ile) and l-valine (l-Val)) for in ovo injection on ED 7 to reveal their roles in thermoregulation, growth, food intake and thermotolerance in chicks. It was found that in ovo injection of l-Leu, but not of l-Ileu or l-Val, caused a significant decline in body temperature at hatching and increased food intake and body weight gain in broiler chicks. Interestingly, in ovo injection of l-Leu resulted in the acquisition of thermotolerance under high ambient temperature (35±1°C for 180min) in comparison with the control thermoneutral temperature (28±1°C for 180min). These results indicate that the free amino acid concentrations during embryogenesis were altered by TM. l-Leu administration in eggs caused a reduction in body temperature at hatching, and afforded thermotolerance in heat-exposed young chicks, further suggesting that l-Leu may be one of the key metabolic factors involved in controlling body temperature in embryos, as well as in producing thermotolerance after hatching.

The Djungarian hamster and the Roborovskii hamster belong to the same genus of Phodopus. However, the Djungarian hamster is tame and shows sedative behavior, while Roborovskii hamster is not tame and shows high levels of locomotor activity. Hyperactivity occurs in animals with tameless behavior. Tameness or tamelessness behavior is very important because tameness helps for breeding and controlling as well as it enables a strong human-animal bond. In the present study, we examined the relationships between activity levels and cognitive function in Djungarian and Roborovskii hamsters. Three types of behavioral tests were performed to analyze their activity levels, memory and leaning ability. The levels of L- and D-amino acids and monoamines in the brain were then determined. Roborovskii hamsters showed significantly higher locomotor activity than Djungarian hamsters. Memory ability was not significantly different between the two hamsters, but Roborovskii hamsters showed lower learning ability. Brain levels of D-serine which is related to enhancement in memory and learning ability, were significantly higher in Djungarian hamsters, but the reverse was true for brain dopamine and serotonin levels. These results suggest that these differences in brain metabolism may be related to the behavioral differences between the two hamsters.

Exposure of chicks to a high ambient temperature (HT) has previously been shown to increase neuropeptide Y (NPY) mRNA expression in the brain. Furthermore, it was found that NPY has anti‐stress functions in heat‐exposed fasted chicks. The aim of the study was to reveal the role of central administration of NPY on thermotolerance ability and the induction of heat‐shock protein (HSP) and NPY sub‐receptors (NPYSRs) in fasted chicks with the contribution of plasma metabolite changes. Six‐ or seven‐day‐old chicks were centrally injected with 0 or 375 pmol of NPY and exposed to either HT (35 ± 1°C) or control thermoneutral temperature (CT: 30 ± 1°C) for 60 min while fasted. NPY reduced body temperature under both CT and HT. NPY enhanced the brain mRNA expression of HSP‐70 and ‐90, as well as of NPYSRs‐Y5, ‐Y6, and ‐Y7, but not ‐Y1, ‐Y2, and ‐Y4, under CT and HT. A coinjection of an NPYSR‐Y5 antagonist (CGP71683) and NPY (375 pmol) attenuated the NPY‐induced hypothermia. Furthermore, central NPY decreased plasma glucose and triacylglycerol under CT and HT and kept plasma corticosterone and epinephrine lower under HT. NPY increased plasma taurine and anserine concentrations. In conclusion, brain NPYSR‐Y5 partially afforded protective thermotolerance in heat‐exposed fasted chicks. The NPY‐mediated reduction in plasma glucose and stress hormone levels and the increase in free amino acids in plasma further suggest that NPY might potentially play a role in minimizing heat stress in fasted chicks.

Thermal manipulation declined embryonic brain and liver concentrations of leucine (Leu). L -Leu in ovo injection afforded thermotolerance in male broiler chicks. This study aimed to examine the role of in ovo injection of L -Leu in metabolic functions, and differences between male and female broiler chicks in thermotolerance. L -Leu injection was performed in ovo on embryonic day (ED) 7 to reveal its role in metabolic activity in embryos and in post-hatch male and female broiler chicks under heat stress. To examine the metabolic activity of embryos, oxygen (O2) consumption, carbon dioxide (CO2) production, heat production and plasma metabolites were analyzed. Rectal temperature, food intake and plasma metabolites were also analyzed in heat-exposed (35 ± 1 °C for 180 min) male and female broiler chicks. It was found that O2 consumption, heat production, and plasma triacylglycerol (TG) and non-esterified fatty acid (NEFA) concentrations in ED 14 embryos were significantly increased by in ovo injection of L -Leu in comparison with the controls. Plasma glucose concentration was significantly increased in both male and female chicks under heat stress, but in ovo injection of L -Leu attenuated the increase in male chicks. In contrast, plasma TG, NEFA, and ketone body concentrations were significantly higher in male chicks injected in ovo with L -Leu, but not in similarly injected female chicks, compared with control chicks, all under heat stress. Rectal temperature and food intake were significantly lower in male, but not female, chicks under heat stress injected in ovo with L -Leu. In conclusion, in ovo L -Leu administration enhanced the prenatal metabolic rate and lipid metabolisms, which possibly appeared as sex-dependent fashion to facilitate thermotolerance in males. A reduction in heat production through lowered food intake in heat-exposed male, but not female chicks injected in ovo with L -Leu may help to afford thermotolerance in male broiler chicks under heat stress.

Dried bonito dashi, a traditional Japanese fish stock, enhances palatability of various dishes because of its specific flavor. Daily intake of dashi has also been shown to improve mood status such as tension-anxiety in humans. This study aimed at investigating beneficial effects of dashi ingestion on anxiety/depression-like behaviors and changes in amino acid levels in the brain and plasma in rats. Male Wistar rats were given either dried bonito dashi or water for long-term (29 days; Experiment 1) or single oral administration (Experiment 2). Anxiety and depression-like behaviors were tested using the open field and forced swimming tests, respectively. Concentrations of amino acids were measured in the hippocampus, hypothalamus, cerebellum, and jugular vein. During the long-term (29 days) consumption, rats given 2% dashi frequently entered the center zone and spent more time compared with the water controls in the open field test. However, the dashi was ineffective on depression-like behavior. In the hippocampus, concentrations of hydroxyproline, anserine, and valine were increased by dashi while those of asparagine and phenylalanine were decreased. In the hypothalamus, the methionine concentration was decreased. In a single oral administration experiment, the dashi (1%, 2% or 10%) showed no effects on behaviors. Significance was observed only in the concentrations of α-aminoadipic acid, cystathionine, and ornithine in the hippocampus. Dried bonito dashi is a functional food having anxiolytic-like effects. Daily ingestion of the dashi, even at lower concentrations found in the cuisine, reduces anxiety and alters amino acid levels in the brain.

Objectives We examined the factors considered to change body composition and blood biochemistry indicators in menopausal middle-aged and elderly women. These changes result from exercise by walking as part of their daily activities and lemon consumption by women who live on the small islands of the Seto Inland Sea, Japan's largest citrus fruit (lemon)-producing region. Methods Between September 2011 and March 2012, we recorded the daily lemon consumption and the number of steps taken by 101 middle-aged and elderly female lemon farmers. We also measured their body dimensions, body compositions, and blood pressure pulse wave velocity and conducted blood tests before and after the survey period. The results before and after the survey period were compared by the t-test and associations were determined on the basis of Pearson's correlation coefficient. Covariance structural analysis was carried out to determine causal associations. Results From the results of covariance structure analysis, lemon intake did not have a direct impact on each item examined. The third item, i.e., "the factors related to arteriosclerosis," was affected indirectly via citric acid and fatigue, and anticoagulation was shown. The fourth item, i.e., "the factors related to maintenance of muscle mass," which is affected by menopausal years and the change in walking speed, was shown to be associated with the second item, i.e., "the factors related to lipid metabolism." Menopausal years affected the first, third and fourth items. Conclusions Lemon intake did not have a direct impact on each item. Lemon has been shown to indirectly affect the third item through citric acid. Walking affected the second item, the level of total cholesterol, such as HDL cholesterol, through the fourth item. The importance of providing services that lead to sustained physical activity and a well-balanced metabolism between lipids and carbohydrates has been shown.

Aging and stress affect quality of life, and proper nourishment is one of means of preventing this effect. Today, there is a focus on the amount of protein consumed by elderly people; however, changes in the amino acid metabolism of individuals have not been fully considered. In addition, the difference between average life span and healthy life years is larger in females than it is in males. To prolong the healthy life years of females, in the present study we evaluated the influence of stress and aging on metabolism and emotional behavior by comparing young and middle-aged female mice. After 28 consecutive days of immobilization stress, behavioral tests were conducted and tissue sampling was performed. The results showed that the body weight of middle-aged mice was severely lowered by stress, but emotional behaviors were hardly influenced by either aging or stress. Aging influenced changes in amino acid metabolism in the brain and increased various amino acid levels in the uterus and ovary. In conclusion, we found that aged mice were more susceptible to stress in terms of body-weight reduction, and that amino acid metabolisms in the brain and genital organs were largely influenced by aging rather than by stress.

Recently, we demonstrated that brain neuropeptide Y (NPY) mRNA expression was increased in heat exposed chicks. However, the functions of brain NPY during heat stress are unknown. This study was conducted to investigate whether centrally administered NPY affects food intake, rectal temperature, monoamines, stress hormones and plasma metabolites in chicks under high ambient temperatures (HT). Five or six-day-old chicks were centrally injected with 0, 188 or 375pmol of NPY and exposed to either HT (35±1°C) or a control thermoneutral temperature (CT; 30±1°C) for 3h whilst fed or fasted. NPY increased food intake under both CT and HT. NPY reduced rectal temperature 1 and 2h after central administration under CT, but not under HT. Interestingly, NPY decreased brain serotonin and norepinephrine concentrations in fed chicks, but increased concentrations of brain dopamine and its metabolites in fasted and fed chicks, respectively. Plasma epinephrine was decreased by NPY in fed chicks, but plasma concentrations of norepinephrine and epinephrine were increased significantly by NPY in fasted-heat exposed chicks. Furthermore, NPY significantly reduced plasma corticosterone concentrations in fasted chicks. Plasma glucose and triacylglycerol were increased by NPY in fed chicks, but triacylglycerol declined in fasted NPY-injected chicks. In conclusion, brain NPY may attenuate the reduction of food intake during heat stress and the increased brain NPY might be a potential regulator of the monoamines and corticosterone to modulate stress response in heat-exposed chicks.

Aim: Although neck circumference (NC) is thought to predict obesity-related metabolic abnormality, its causal role in cardiometabolic risk is unclear. The aim of this study was to clarify the impact of changes in NC on cardiometabolic risk in healthy postmenopausal women through a community-based longitudinal study. Methods: From a local community in Japan, 63 generally healthy postmenopausal women were recruited. All participants received an assessment of obesity-related anthropometric markers, biochemical parameters, and hemodynamic measures and were followed on average for 3 years. Results: At baseline analysis, larger NC was positively associated with atherosclerosis-related markers, brachial-ankle pulse wave velocity (baPWV) and blood pressure, as well as some lipid parameters. After the follow-up period, change in NC was associated with changes in body mass index (BMI), body fat percentage, and waist circumference (WC). Interestingly, significant correlations of change in NC with changes in baPWV and blood pressure were observed, whereas changes in WC and BMI were only associated with changes in low-density lipoprotein cholesterol and/or total cholesterol. In multivariate linear regression analysis, change in NC was significantly associated with changes in baPWV and systolic blood pressure, independent of changes in BMI, WC, and biochemical parameters. In addition, an increase in NC was associated with a 2.69-fold increased odds ratio of accelerated baPWV. Conclusions: Change in NC was independently associated with changes in atherosclerosis-related markers. These observations suggest that NC is an important predictor of the risk of developing obesity-related atherosclerosis in healthy postmenopausal women.

Acute liver damage induced by the administration of carbon tetrachloride is characterized by lipid accumulation in the liver and changes in the plasma free amino acid profile. The major objective of the present study was to clarify the relationships between liver lipid levels and plasma free amino acids, and to estimate liver lipid contents via the concentrations of plasma free amino acids. Mice were administered with carbon tetrachloride or olive oil. Liver and plasma samples were obtained before (initial value) and after 1, 3 and 7 days of administration. Liver triacylglycerol increased at 1 day and total cholesterol was raised at 1 and 3 days post injection of carbon tetrachloride, and thereafter both returned to their initial values. L-Phenylalanine, L-serine and L-alanine were significantly increased, but L-arginine was significantly decreased at 1 day. Liver triacylglycerol and total cholesterol levels were linearly, but weakly, correlated with several amino acids. Thus, stepwise regression analysis was applied and we found that the liver triacylglycerol level could be estimated by the levels of free plasma L-histidine, L-methionine and L-phenylalnine, and that the liver total cholesterol could be estimated by the levels of L-glutamine, L-valine and L-phenylalnine. In conclusion, the increase in plasma free L-phenylalanine plays an important factor in the accumulation of liver lipid induced by acute treatment with carbon tetrachloride in mice.

We previously reported that Wistar Kyoto rats, an animal model of depression, have a characteristically abnormal serine metabolism in the brain, i.e., lower serine and cystathionine, which is a metabolite of serine, concentrations in the brain. To explore the mechanism underlying this abnormality, the expression of cystathionine β-synthase and serine racemase, which are the enzymes involved in the serine metabolism, was investigated in the cerebellum and hippocampus of Wistar and Wistar Kyoto rats. Wistar Kyoto rats exhibited a significantly lower mRNA expression of cystathionine β-synthase in the cerebellum in comparison with Wistar rats, while expression levels in the hippocampus did not differ between strains. Previous study indicated that the reduction of cystathionine β-synthase in the brain induced cerebellar aplasia in mice. Therefore, the cerebellar size was compared between Wistar rats and Wistar Kyoto rats. Wistar Kyoto rats displayed a lower ratio of cerebellum weight to whole-brain weight compared with Wistar rats of the same generation or similar body weight, suggesting that Wistar Kyoto rats exhibit smaller cerebellum. These results suggest that the lower mRNA expression of cystathionine β-synthase in the cerebellum and the smaller size of cerebellum may be related to the depression-like behavior in Wistar Kyoto rats.

The purpose of this study was to investigate the relationship between daily physical activity and physical fitness in 10 type 2 diabetes mellitus (DM) patients without cardiovascular complications, aged 43-72 years (body mass index [BMI], 23.7 ± 2.2 kg/m2). The pedometric measurement was made using a calorie counter (CAL-D) in daily life at home, and was compared with oxygen uptake (VO2) and work load with gas analysis obtained using a bicycle ergometer. The mean number of gait steps recorded with CAL-D, and energy expenditure in exercise per day were 8,202 ± 1,966 steps/day and 231 ± 70 kcal/day respectively. The mean number of gait steps per day was positively correlated with VO2 (r=0.44, p

Djungarian hamster (P. sungorus) and Roborovskii hamster (P. roborovskii) belong to the same genus of phodopus. Roborovskii hamster shows high locomotor activity and low level of dopamine (DA) in the brain. Administration of L-tyrosine, a precursor of DA, decreases locomotor activity in Roborovskii hamsters. However, the amino acid metabolism in relation to the hyperactivity is not yet well known. In the present study, L- and D-amino acid concentrations in the brain, liver, and plasma in Djungarian and Roborovskii hamsters were investigated during day and night times to explain the possible difference in hyperactivity between them. Most of the examined amino acids were higher in the night time when hamsters are active compared to those in day time. L- and D-tyrosine concentrations were higher in the liver of Roborovskii hamsters than in Djungarian hamsters. Furthermore, brain concentration of D-tyrosine was higher in the Roborovskii than in Djungarian hamsters, but no significant difference was observed for L-tyrosine concentrations between the two species. These results suggest that the conversion of L-tyrosine to D-tyrosine in the brain of Roborovskii hamster may be higher than in Djungarian hamster, which may cause low DA concentration and hyperactivity in Roborovskii hamster. On the other hand, L- and D-serine, which are known as sedative factors, were lower in Roborovskii hamsters than Djungarian hamster. These results suggest that species-specific regulation in amino acid metabolism may contribute to hyperactivity in Roborovskii hamsters.

Background. Recent studies suggest that the daily intake of lemon (Citrus limon) has a good effect on health, but this has not been confirmed in humans. In our previous studies, it was observed that people who are conscious of their health performed more lemon intake and exercise. An analysis that took this into account was required.Methodology. For 101 middle-aged women in an island area in Hiroshima, Japan, a record of lemon ingestion efforts and the number of steps walked was carried out for five months. The change rates (Δ%) of the physical measurements, blood test, blood pressure, and pulse wave measured value during the observation period were calculated, and correlations with lemon intake and the number of steps walked were considered. As a result, it was suggested that daily lemon intake and walking are effective for high blood pressure because both showed significant negative correlation to systolic blood pressure Δ%.Conclusions. As a result of multiple linear regression analysis, it was possible that lemon ingestion is involved more greatly with the blood citric acid concentration Δ% and the number of steps with blood pressure Δ%, and it was surmised that the number of steps and lemon ingestion are related to blood pressure improvement by different action mechanisms.

サイクラー使用により腹腔気腫を起こし除水能が低下した例を経験した. 症例は62歳男性で1995年腹膜透析 (CAPD) を導入. その後1997年よりサイクラーを用い腹膜透析 (CCPD) を施行していた. 1999年3月1日サイクラーの準備中に注液バッグに穴があいたことに気づかずに透析を開始した. 初回注液中に腹腔内にairの注入が起こり呼吸困難と側腹部痛にて来院した. 約10日間で空気は自然吸収されたものの, その後除水量が低下し腹腔気腫の関与が示唆された.

目的: 近年透析人口増加に伴い, 高齢者の透析導入が増加している. そこで高齢者透析導入の特徴を把握するため, 当院における導入患者を比較検討した.対照と方法: 1989年から1998年までの間に, 血液透析に導入した719人を若年群 (65歳未満; 517名) と高齢群 (65歳以上; 202名) に分け, 導入時の臨床所見を比較した.結果: 1989年に19%であった高齢群の透析導入は, 1998年には41%に増加した. 若年群に比較し高齢群の特徴として以下の3点が挙げられた. (1) 慢性糸球体腎炎 (CGN) による導入が少なく, 腎硬化症による導入が多い. (2) 心胸比が大きく, 体液過剰を呈する率が高い. (3) クレアチニンが低く, 消化器症状を呈する率が低い. また1989, 90年に導入した145人と比較し, 1997, 98年の170人において, 高齢群で腎硬化症の割合が有意に減少し, 糖尿病性腎症 (DN) の増加がみられた. 若年群ではDNの割合が有意に増加しCGNが有意に減少した. 疾患の特徴としては若年群の中でDNはCGNに比べ心胸比, リン, 重炭酸イオンが有意に高く, 平均血圧, 尿毒窒素, クレアチニンが有意に低いという特徴があった. しかし高齢群でのDNの特徴はクレアチニンが低いことのみであった.考察: 近年高齢者の透析導入が増加し, その内訳にDNによる導入の増加が伴っていた. しかし, 若年群にみられたCGNとDNの違いは高齢になると薄らいでしまった. 高齢者の透析導入には高齢者そのものの特徴を理解し対処することが望ましいと考えられた.

維持透析患者のdry weight (DW) 設定に際し, 非侵襲的方法として, 超音波断層法による下大静脈径, ヒト心房性利尿ペプチド (hANP), 連続的ヘマトクリット測定 (クリットライン) を参考にし生児を得た症例を経験したので報告する.症例は28歳, 透析歴6年の女性. 近医産科にて妊娠7週と診断され, 妊娠8週時に透析および高血圧の管理目的で当科入院となった. 以後非侵襲的方法によりDW設定と透析管理を行い安定した状態が継続できた. しかし十分量な透析にもかかわらず, 妊娠中期より羊水過多を認めるようになり, また高血圧のコントロール不良となり, 妊娠28週帝王切開にて836gの女児を分娩した.妊娠透析患者のDW設定や透析管理に際し, 母体・胎児に影響が少ない非侵襲的方法で, かつそれぞれの方法の利点, 欠点を理解した上で総合的に判断することが有用であると思われた.

The influence of age and physique on dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) was investigated in young, middle-aged, and older women. The validity of the bilateral calcaneal QUS values was investigated regarding the bone mineral density (BMD) values on DXA of the lumbar spine, left femoral neck, and left femur as the optimal standards. The subjects were 55 young women (19.6 +/- 1.0 years), and 152 middle-aged and older women (62.9 +/- 7.2 years). The BMD on DXA was significantly correlated with the bone strength on QUS in both young and middle-aged or older women, but the positive likelihood ratios of the standard QUS values recommended by the manufacturer to the optimum standards on DXA were low, suggesting that osteoporosis cannot be diagnosed or predicted by use of the QUS method. Combination with DXA is necessary, such as primary screening by QUS followed by secondary screening by DXA.

Maf is a family of oncogenes which encodes a nuclear bZip transcription factor protein and has been originally identified from the avian oncogenic retrovirus, AS42. Maf genes have been reported to have critical roles in embryological development and cellular differentiation. In this study, in situ hybridization with 35S-labeled antisense riboprobes was used to investigate the distribution of c-maf mRNA in balb/c mouse kidneys from 12 (E12) through 17 days (E17) of gestation and then 1 and 4 weeks after birth. Immunocytochemistry of 4-week-old mouse kidney using anti-c-maf antisera was also performed. Kidney and liver sections from c-maf knockout mice at 4 weeks were stained with hematoxylin–eosin, and their histological features were examined. Expression of c-maf mRNA was first detected on E16 in the renal proximal tubules, and it was expressed through 4 weeks after birth. In the c-maf knockout mice at 4 weeks the cytoplasmic volume of the proximal tubule and liver cell was smaller. These findings suggest that expression of the c-maf gene may be involved in the embryological development and/or cell differentiation of kidney and liver cells.

PURPOSE To examine the involvement of p27(KIP1) in the regulation of the proliferation of the developing corneal endothelium. METHODS Central and peripheral corneas in C57Bl6 mice at postnatal day (P)1, P11, and 12 weeks after birth were analyzed by immunocytochemistry with anti-p27(KIP1), -p57(KIP2), and -proliferating cell nuclear antigen (PCNA) antibodies. Nuclear staining was performed with 4',6'-diamino-2-phenylindole (DAPI) in wholemounts of corneal endothelium of the center and peripheral cornea in wild-type and p27(KIP1) knockout (-/-) mice at 12 weeks of age. p27(KIP1-/-) and control mice were injected with bromodeoxyuridine (BrdU) once on P7, twice per day on P8 and P9, and once on P10 and then were analyzed by a BrdU cell-proliferation assay on P11. RESULTS On P1, p27(KIP1) immunoreactivity was detected in a small number of corneal endothelial cells, and many endothelial cells expressed PCNA. At P11 and 12 weeks after birth, p27(KIP1) immunoreactivity was detected in many corneal endothelial cells. PCNA-positive cells in the endothelium were rare on P11 and completely absent at 12 weeks after birth. p57(KIP2) was not detected in either corneal epithelium or endothelium at P1, P11, or 12 weeks after birth. In wholemounts of corneal endothelium at 12 weeks of age, the number of endothelial nuclei in the p27(KIP1-/-) mice was significantly higher than that in wild-type mice in both the center and peripheral regions of the cornea. In the BrdU assay, positive cells were abundant in the corneal endothelium of p27(KIP1-/-) mice, whereas there were few positive cells in control mice. PCNA immunoreactivity in the endothelium of the p27(KIP1-/-) mice was completely absent at 12 weeks after birth. CONCLUSIONS These results suggest that p27(KIP1) is involved in the regulation of proliferation in the endothelium of the developing cornea.

To investigate the effect of fibroblast growth factors (FGFs) on cellular differentiation, we employed a multipotent mouse embryonal carcinoma cell line, P19, which differentiates into cardiac muscle, skeletal muscle and neural cells in the presence of the appropriate concentrations of retinoic acid (RA). Under conditions appropriate for cardiac muscle differentiation, the expression of FGF-1 was significantly enhanced before any tissue-specific gene was induced. In contrast, up-regulation of the FGF-2 gene was observed with skeletal muscle-inducing concentrations of RA. Exogenous FGF-1, under skeletal muscle-inducing conditions, suppressed the expression of marker genes for skeletal muscle and induced cardiac alpha myosin heavy chain (alphaMHC) gene with up-regulation of bone morphogenetic protein-4 (BMP-4) and GATA-4. Unlike FGF-1, exogenous FGF-2 promoted skeletal muscle differentiation. These results indicate that FGF-1 and FGF-2 play different roles in P19 cell differentiation induced by RA.

To characterize in vivo changes of adenylate cyclase activity in rabbit ciliary processes during the circadian cycle.After removal of vitreous, lens, retina and choroid from freshly enucleated rabbit eyes, the anterior segment and attached sclera was chilled in cold buffer containing the non-selective phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Then ciliary processes were excised and homogenized in ice cold trichloro-acetic acid (TCA) 2.5 min after IBMX treatment. Increased cyclic AMP in response to PDE inhibition was measured in ciliary processes at six times during the circadian cycle, after preganglionic section of the cervical sympathetic trunk (decentralization, DX), and after topical instillation of hydroxyamphetamine, timolol, brimonidine, rauwolscine or a soluble derivative of forskolin.The increase of rabbit ciliary process cyclic AMP levels in response to PDE inhibition with IBMX was enhanced at night. Much of the enhanced nocturnal increase persisted in constant dark and was blunted by DX. Topical instillation of hydroxyamphetamine enhanced the increase during the day; whereas, timolol, a beta-adrenergic antagonist, or brimonidine, an alpha2-adrenergic agonist, blunted the IBMX induced increase. Neither instillation of rauwolscine, an alpha2-adrenergic antagonist, nor the soluble forskolin derivative enhanced the increase of cyclic AMP after IBMX.The technique reported here can be used to estimate ciliary process adenylate cyclase activity in vivo. There is a circadian rhythm of adenylate cyclase activity in rabbit ciliary processes that is driven in part by ocular sympathetic input and stimulation of beta-adrenergic receptors.

PURPOSE: To evaluate the long-term safety and efficacy, in a large series of patients, of polyacrylic intraocular lens implants 1 and 3 years after surgery, compared with polymethylmethacrylate intraocular lens implants. METHODS: This was a randomized, prospective study of 1,514 eyes of 1,202 patients that were examined for a 1-year follow-up study and 1,264 eyes of 990 patients that were examined for a 3-year follow-up study. All the patients were prospectively randomized to receive a polyacrylic or polymethylmethacrylate intraocular lens implant. A standardized surgical protocol was performed using a phacoemulsification technique and capsulorhexis. Any surgical complications were excluded, and all patients had standard postoperative medication and follow-up. Postoperative measurements included spectacle-corrected visual acuity, occurrence of postoperative sight-threatening or lens-related complications, and adverse reactions. Results were compared between the polyacrylic intraocular lens and polymethylmethacrylate intraocular lens groups. Results were also compared with standards for polymethylmethacrylate intraocular lens that were established by the US Food and Drug Administration and a previous study for silicone lens. RESULTS: The overall complete follow-up rates were 79.9% for 1-year follow-up and 69.5% for 3-year follow-up. At 1 year, the mean logarithm of the minimum angle of resolution (logMAR) of visual acuity was 0.037 ± 0.150 and 0.042 ± 0.154 in best case patients of the polyacrylic intraocular lens group and polymethylmethacrylate intraocular lens group, respectively. At 3 years, the mean logMAR visual acuity was 0.038 ± 0.155 and 0.054 ± 0.181 in best case patients in the polyacrylic intraocular lens group and polymethylmethacrylate intraocular lens group. There was no significant difference between groups at 1 and 3 years. At 1 year, 96.8% of best case patients in the polyacrylic intraocular lens group and 95.8% of those in the polymethylmethacrylate intraocular lens group achieved corrected visual acuity of 0.5 or better. At 3 years, 96.4% of best case patients in the polyacrylic intraocular lens group and 94.9% of those in the polymethylmethacrylate group achieved a corrected visual acuity of 0.5 or better; no significant difference was found at 1 and 3 years. The rate of sight-threatening complications was 1.2% for the polyacrylic intraocular lens group of all patients and 1.5% for the polymethylmethacrylate intraocular lens group at 1 year, and 1.6% for the polyacrylic intraocular lens group and 1.4% for the polymethylmethacrylate intraocular lens group at 3 years. No significant difference was found between the groups. The cumulative rate of Nd:YAG capsulotomy for the polyacrylic intraocular lens group (7.1%) was significantly lower than that for the polymethylmethacrylate intraocular lens group (38.1%) through 3 years ( P CONCLUSIONS: Polyacrylic intraocular lenses demonstrated safe and effective performance through long-term follow-up at a level equal to or better than polymethylmethacrylate intraocular lenses. Patients undergoing polyacrylic intraocular lens implantation achieved excellent postoperative visual acuity and experienced a low rate of postoperative complications, adverse reactions, and Nd:YAG capsulotomy. These long-term clinical results are an important outcome database for the ongoing use of this foldable optic material.

Since hammer toes in cerebral paralysis are hyperflexed, body weight bears on the nails. It causes severe pain and finally gait disturbance. We treated three cases of hammer toe in cerebral paralysis. All of them were above 15 years of age showed and rigo-spastic type paralysis, or so-called double hemiplegia. They were treated by lengthening of digital flexor tendon, arthrodesis of PIP joint or both. One case resulted in good. Another case resulted in nothing. The last case needed revision.

We used proteins in rat lung lavage fluid to successfully produce an antiserum against Clara cell secretory products. When used with the immunoperoxidase method, the antiserum specifically stained cells of the bronchiolar lining, which are morphologically consistent with Clara cells, as well as a few columnar cells in the bronchial and tracheal mucosa. B-5-fixed lung tissue furthermore demonstrated the immunoreactive layer over the bronchiolar epithelium. The alveolar and bronchial lining layers, on the other hand, were not immunoreactive, although a trace of granular immunoreactivity was seen in the latter. It was suggested that Clara cells produce and secrete some proteinaceous materials, which are mainly localized in the bronchiolar area after secretion and are seldom transferred into the alveolar lining layer. Our antibody cross-reacted with the Clara cells of mice, but not with those of hamsters, guinea pigs, rabbits, dogs, cats, monkeys, and man. The high degree of specificity of this antisera to Clara cells in formalin-fixed materials should make it a valuable tool for identifying Clara cell change in non-neoplastic lung pathology and in obtaining some insights into cell origin in neoplastic diseases.