3-Phosphoglycerate dehydrogenase (Phgdh) is the initial step enzyme in the phosphorylated pathway of L-serine biosynthesis. We have previously revealed in the brain that Phgdh is preferentially expressed in glial cells, but not in neurons, and that glia-borne L-serine exerts strong neurotrophic actions to neuronal survive, differentiation, and development. To investigate whether such an L-serine-meditated intercellular relationship is constructed in peripheral organs and tissues, we examined the kidney, which is one of the organs with the highest expression of Phgdh mRNA in the body. We found that Phgdh was distributed highly in the renal papilla and inner layer of the outer zone and moderately in the cortex, whereas it was almost negative in the outer layer of the outer zone. This heterogeneous distribution was due to selective expression in distinct tubular segments, i.e., the Bowman's capsule, proximal tubule, and thin limbs of the Henle's loop. Interestingly, neutral amino acid transporter ASCT1, which preferentially transports alanine, serine, cysteine, and threonine, was selectively expressed in Phgdh-negative tubular segments, i.e., the distal tubule and collecting duct. Therefore, either Phgdh or ASCT1 is provided to each segment of renal tubules, suggesting that metabolic interplay mediated by L-serine biosynthesis and supply may exist in the kidney too.
Mushroom (shiitake) extracts were dispersed with lecithin micelles to prepare superfine particles (0.05 to 0.2 μm in diameter) of β-1,3-glucan (micellary mushroom extracts). When mice were fed with these micelles of β-glucan (0.75 mg/day/mouse, smaller amounts of β-glucan), the number of lymphocytes yielded by the small intestine increased by up to 40%. More interestingly, the ratio of CD8αβ+TCRαβ+ cells/CD8αα+TCRαβ+ cells increased prominently. In parallel with this deviation in the distribution of lymphocyte subsets, tumor cytotoxicity against P815 cells and cytokine productions were also augmented. In other words, phylogenetically developed lymphocytes (CD8αβ+, TCRαβ+) were much more effectively activated by the oral administration of micellary β-glucan. These results suggest that smaller amounts of micellary β-glucan might be useful for the potentiation of intestinal immunity.
Tasting sweet food elicits insulin release prior to increasing plasma glucose levels, known as cephalic phase insulin release (CPIR). The characteristic of CPIR is that plasma insulin secretion occurs before the rise of the plasma glucose level. In this experiment, we examined whether taste stimuli placed on the tongue could induce CPIR. We used female Wistar rats and five basic taste stimuli: sucrose (sweet), sodium chloride (salty), HCl (sour), quinine (bitter) or monosodium glutamate (umami). Rats reliably exhibited CPIR to sucrose. Sodium chloride, HCl, quinine, or monosodium glutamate did not elicit CPIR. The non-nutritive sweetener saccharine elicited CPIR. However, starch, which is nutritive but non-sweet, did not elicit CPIR although rats showed a strong preference for starch which is a source of glucose. In addition, we studied whether CPIR was related to taste receptor cell activity. We carried out the experiment in rats with bilaterally cut chorda tympani nerves, one of the gustatory nerves. After sectioning, CPIR was not observed for sweet stimulation. From these results, we conclude that sweetness information conducted by thistaste nerve provides essential information for eliciting CPIR.
Dietary supplementation with an essential amino acid L-lysine has been shown to reduce chronic anxiety in humans with low dietary intake of L-lysine. A combination of L-lysine and L-arginine has been documented to normalize hormonal stress responses in humans with high trait anxiety. The present study was carried out in one hundred eight healthy Japanese adults. The aim of study was to find out whether a week-long oral treatment with L-lysine (2.64 g per day) and L-arginine (2.64 g per day) reduces trait and stress-induced state anxiety and basal levels of stress hormones. We confirmed that, without regard to gender, the amino acid treatment significantly reduced both trait anxiety and state anxiety induced by cognitive stress battery. In addition, we found that the treatment with L-lysine and L-arginine decreased the basal levels of salivary cortisol and chromogranin-A (a salivary marker of the sympatho-adrenal system) in male subjects. These results of this double-blind, placebo controlled and randomized study confirm the previous findings in humans and animals and point to a combination of L-lysine and L-arginine as a potentially useful dietary intervention in otherwise healthy humans with high subjective levels of mental stress and anxiety.
Excessive nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) aggravates acute lung injury (ALI) by producing peroxynitrite. We previously showed by immunostaining that the expression of iNOS was suppressed by inhalation of NG-nitro-L-arginine methyl ester in mice with Candida-induced ALI. This study tested the hypothesis that a novel iNOS inhibitor suppresses not only iNOS expression, but also iNOS messenger RNA (mRNA) production by interrupting a positive feedback loop at the time of NO production in Candida-induced ALI. Mice were pretreated by inhalation of saline or ONO-1714, a selective iNOS inhibitor, and were given an intravenous injection of Candida albicans to induce ALI. After inhalation of 1 mM aerosolized ONO-1714, the nitrite-nitrate concentration in bronchoalveolar lavage fluid (BALF) at 24 h was significantly lower than that after inhalation of saline. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels and neutrophils in BALF were decreased by inhalation of ONO-1714. Inhalation of ONO-1714 markedly suppressed nitrotyrosine production and inhibited the expression of iNOS mRNA as well as proteins in the lung. Survival was prolonged by inhalation of ONO-1714. We conclude that pretreatment with inhaled ONO-1714 suppresses the production of peroxinitrite and decreases oxidative stress associated with peroxinitrite in Candida-induced ALI.
We investigated whether nocturia in the elderly was improved by walking exercise, which involved walking rapidly for 30 min or more in the evening or night for 8 weeks. A questionnaire related to micturition and exercise, blood pressure, body composition analysis, blood biochemistry tests, and urinalysis were performed before and after 8 weeks of exercise to investigate the effects of walking. Thirty men (71 years old on average) continued the walking exercise for long enough to undergo evaluation. The number of episodes of nocturia decreased significantly (p < 0.001) from 3.3 ± 0.7 to 1.9 ± 0.8 after 8 weeks of walking exercise. The daytime urinary frequency, blood pressure, body weight, body fat ratio, edema ratio, serum catecholamines, triglycerides, and total cholesterol were also decreased. After 8 weeks of exercise, 20 of the subjects (67%) stated that sleep was deeper than before exercise. Assessment of the overall improvement showed that excellent or good results were obtained in 18 patients (60%). The main factor related to the influence of walking exercise on nocturia was that sleep became deeper, which increased the arousal threshold bladder volume. Walking exercise may also have a preventive effect on lifestyle-related diseases.
The aim of this study was to investigate the effect of proliferating tissue used in combination with bovine-derived xenograft (BDX) on the formation of new cementum and bone in dogs. Intrabony defects were treated with either BDX in conjunction with autogenous proliferating tissues (BDXplus-proliferating tissues: BDX-P group) or BDX alone (BDX-alone group). The control group received no BDX or proliferating tissues. The animals were sacrificed after 2, 4, and 8 weeks of the treatment, and tissues were histologically examined. Specimens from the control group were characterized by long junctional epithelium and little bone formation. The BDX-P group showed a statistically significant increase in new bone and cementum formation compared to the BDX-alone group (30.9% vs. 18.7, p < 0.01 and 87.8% vs. 61.8, p < 0.01). The ratio of proliferating cell nuclear antigen (PCNA)-positive cells in the newly formed connective tissue of the BDX-P group was significantly greater than that in the BDX-alone group. These findings suggest that the use of proliferating tissues in combination with BDX enhances new bone and cementum formation, offering potential as therapeutic material in periodontal regeneration.
We investigated the effect of laughter on salivary endocrinological stress marker chromogranin A (CgA). In saliva samples collected from 11 healthy males before and after watching a comic film or a non-humorous control film, salivary CgA levels were determined by enzyme-linked immunosorbent assay (ELISA). Samples taken after watching the comic film showed increased levels of CgA. This tendency was more pronounced in individuals with lower initial levels of stress. The control samples showed no significant change in CgA levels. Stress score, subjectively evaluated using a visual analog scale, decreased significantly after watching the comic film. These findings suggest that, in addition to a stress relief effect, laughter can bring about feeling uplifted or fulfilled.