Wearable Ion Sensors for the Detection of Sweat Ions Fabricated by Heat-Transfer Printing.

Wearable ion sensors for the real-time monitoring of sweat biomarkers have recently attracted increasing research attention. Here, we fabricated a novel chloride ion sensor for real-time sweat monitoring. The printed sensor was heat-transferred onto nonwoven cloth, allowing for easy attachment to various types of clothing, including simple garments. Additionally, the cloth prevents contact between the skin and the sensor and acts as a flow path. The change in the electromotive force of the chloride ion sensor was -59.5 mTV/log CCl-. In addition, the sensor showed a good linear relationship with the concentration range of chloride ions in human sweat. Moreover, the sensor displayed a Nernst response, confirming no changes in the film composition due to heat transfer. Finally, the fabricated ion sensors were applied to the skin of a human volunteer subjected to an exercise test. In addition, a wireless transmitter was combined with the sensor to wirelessly monitor ions in sweat. The sensors showed significant responses to both sweat perspiration and exercise intensity. Thus, our research demonstrates the potential of using wearable ion sensors for the real-time monitoring of sweat biomarkers, which could significantly impact the development of personalized healthcare.

Air-Bubble-Insensitive Microfluidic Lactate Biosensor for Continuous Monitoring of Lactate in Sweat.

This study aimed to develop a lactate sensor with a microchannel that overcomes the issue of air bubbles interfering with the measurement of lactate levels in sweat and to evaluate its potential for continuous monitoring of lactate in sweat. To achieve continuous monitoring of lactate, a microchannel was used to supply and drain sweat from the electrodes of the lactate sensor. A lactate sensor was then developed with a microchannel that has an area specifically designed to trap air bubbles and prevent them from contacting the electrode. The sensor was evaluated by a person while exercising to test its effectiveness in monitoring lactate in sweat and its correlation with blood lactate levels. Furthermore, the lactate sensor with a microchannel in this study can be worn on the body for a long time and is expected to be used for the continuous monitoring of lactate in sweat. The developed lactate sensor with a microchannel effectively prevented air bubbles from interfering with the measurement of lactate levels in sweat. The sensor showed a concentration correlation ranging from 1 to 50 mM and demonstrated a correlation between lactate in sweat and blood. Additionally, the lactate sensor with a microchannel in this study can be worn on the body for an extended period and is expected to be useful for the continuous monitoring of lactate in sweat, particularly in the fields of medicine and sports.

Hematopoietic contribution to skeletal muscle regeneration in acid alpha-glucosidase knockout mice.

Recent studies have shown that cells from bone marrow (BM) can give rise to differentiated skeletal muscle fibers. However, the mechanisms and identities of the cell types involved remain unknown. We performed BM transplantation in acid alpha-glucosidase (GAA) knockout mice, a model of glycogen storage disease type II, and our observations suggested that the BM cells contribute to skeletal muscle fiber formation. Furthermore, we showed that most CD45+:Sca1+ cells have a donor character in regenerating muscle of recipient mice. Based on these findings, CD45+:Sca1+ cells were sorted from regenerating muscles. The cell number was increased with granulocyte colony-stimulating factor after cardiotoxin injury, and the cells were transplanted directly into the tibialis anterior (TA) muscles of GAA knockout mice. Sections of the TA muscles stained with anti-laminin-alpha2 antibody showed that the number of CD45+:Sca1+ cells contributing to muscle fiber formation and glycogen levels were decreased in transplanted muscles. Our results indicated that hematopoietic stem cells, such as CD45+:Sca1+ cells, are involved in skeletal muscle regeneration.

Regional differences in vascular responsiveness of nasal mucosae isolated from naive guinea pigs.

OBJECTIVE: In the present study, the contractile response to norepinephrine (NE) and relaxing response to histamine and leukotriene D(4) (LTD(4)) were compared among the nasal mucosae of septa (S) and lateral (L) and medial turbinates (M) isolated from naive male Hartley guinea pigs. METHODS: The isometrical tension of the isolated nasal mucosae of the above regions was measured at a resting tension of 0.5 g by using a standard organ-bath technique. RESULTS: In each mucosal strip, NE induced a contraction in a concentration-dependent manner. A significant difference in efficacy (maximal response) of NE was found (L>M>S). In mucosal strips precontracted with NE (3x10(-5)M), both histamine and LTD(4) induced relaxing responses. The efficacy of histamine in S was significantly greater than those in L and M. The potency order of LTD(4) was L>M>S; a significant difference was observed between L and S. CONCLUSION: In conclusion, the present study demonstrated a distinct regional difference in the response to contractile and relaxant agonists of isolated nasal mucosae of guinea pigs.

Miglitol increases energy expenditure by upregulating uncoupling protein 1 of brown adipose tissue and reduces obesity in dietary-induced obese mice.

BACKGROUND: Miglitol is an oral anti-diabetic drug that acts by inhibiting carbohydrate absorption in the small intestine. Recent studies have shown that miglitol reduces obesity in humans and rodents. However, its mechanisms have remained unclear. The purpose of this study was to determine whether miglitol generates heat by activating uncoupling protein 1 (UCP1), an enzyme involved in thermogenesis, in brown adipose tissue (BAT) in mice. METHODS: Four-week-old male C57BL/6 J mice were fed a high-fat diet alone (HF) or a high fat diet plus miglitol (HFM). Oxygen consumption (VO2) was used to estimate metabolic rate. A thermal imaging camera was used to quantify heat generation from interscapular brown adipose tissue. We analyzed the protein and gene expressions of UCP1 and the expressions of four proteins related to ß3-adrenergic signaling in the pathway activating UCP1 (protein kinase A (PKA), hormone-sensitive lipase (HSL), p38 α mitogen-activated protein kinase (p38αMAPK) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α)). RESULTS: At 8 weeks, body weight, epididymal and subcutaneous white adipose tissue and the HOMA-R value of the HFM mice were significantly less than those of the HF mice. Food intake was not different between the HF and HFM mice. VO2 and BAT temperature were significantly higher in the HFM mice. Miglitol significantly enhanced the gene and protein expressions of UCP1 and the expressions of proteins related to ß3-adrenergic signaling. CONCLUSIONS: Miglitol's anti-obesity effect was attributed to increased energy expenditure by upregulating UCP1 in BAT (i.e., by thermogenesis) and to enhancement of ß3-adrenergic signaling in BAT.

Comparison of norepinephrine responsiveness of mucosal veins in vivo with that of isolated mucosal tissue in vitro in guinea pig nasal mucosa.

BACKGROUND: The vascular responsiveness of nasal mucosa has been determined frequently by using isolated mucosal tissues although it is not clear whether the response of the whole tissue truly reflects the response of the vasculature (especially veins) in mucosa. In this study, the in vivo responsiveness of mucosal veins was compared with in vitro responsiveness of isolated mucosal tissue in guinea pig nasal septa. METHODS: The in vivo venous responsiveness to norepinephrine (NE) of guinea pig nasal septal mucosa was measured by changes in the diameters of mucosal veins, stereomicroscopically. The in vitro responsiveness to NE of isolated nasal septal mucosae from guinea pigs also was determined by standard organ-bath technique. RESULTS: Application of NE induced concentration-dependent contractile responses both in vivo and in vitro with the pD2 (negative logarithm for 50% effective concentration [M] of NE) values of 5.23 +/- 0.29 and 5.00 +/- 0.17, respectively. CONCLUSION: The equal potencies obtained by the in vivo and in vitro experiments suggest that an increase in tension of isolated nasal mucosal tissue might be caused by the contraction of mucosal veins. Both the in vivo and the in vitro methods used in this study might be useful for determining vasoreactivity of nasal mucosa in experimental animals.

Increased expression of inducible nitric oxide synthase in nasal mucosae of guinea pigs with induced allergic rhinitis.

BACKGROUND: Nitric oxide (NO) is produced by the action of NO synthase (NOS) isoforms and is considered an important mediator of inflammatory response including airways. In this study, the changes in the expression levels of NOS isoforms in nasal mucosae were determined in a guinea pig model of allergic rhinitis. METHODS: An allergic rhinitis model was prepared in guinea pigs by repeated challenge with aerosolized dinitrophenylated ovalbumin antigen. Twenty-four hours after the last antigen challenge, the expression levels of NOS isoforms in nasal mucosae were determined by immunoblottings. Changes in the isometrical tension of isolated mucosal tissues of nasal septa induced by histamine were measured also. RESULTS: Although the expression levels of endothelial NOS (eNOS) and neuronal NOS (nNOS) in nasal mucosae were not affected by the repeated antigen exposure, the inducible NOS (iNOS) level was markedly and significantly increased in the challenged animals. In isolated nasal mucosal tissues, histamine induced a concentration-dependent relaxation, which was sensitive to an H1-receptor antagonist, mepyramine, and an NOS inhibitor, L-NMMA. No significant change in the histamine responsiveness was observed between the sensitized control and repeatedly antigen-challenged groups. CONCLUSION: The expression of three isoforms of NOS, including eNOS, nNOS, and iNOS, was presented in guinea pig nasal mucosa. A marked increase in iNOS expression in the repeatedly antigen-challenged animals suggests an important role of iNOS in the pathogenesis of allergic rhinitis. However, the pathophysiological role(s) of NO generated by iNOS in nasal allergy is still unclear.

Impaired norepinephrine-mediated contraction of isolated nasal mucosa in guinea pigs with allergic rhinitis.

BACKGROUND: One of the causes of nasal obstruction associated with allergic rhinitis probably is caused by the dilatation of plexus cavernosum in nasal mucosa. In this study, the change in vascular responsiveness of nasal mucosa was investigated in the septal mucosae isolated from guinea pigs with allergic rhinitis. METHODS: An allergic rhinitis model was prepared in guinea pigs by repeated challenge with aerosolized dinitrophenylated-ovalbumin antigen. Twenty-four hours after the last antigen challenge, the changes in the isometrical tension of isolated nasal septal mucosa were measured. RESULTS: In isolated nasal mucosal tissues, both norepinephrine (NE) and leukotriene D4 caused concentration-dependent contractile and relaxant responses, respectively. The NE-induced contractile response was significantly attenuated in nasal mucosae of the repeatedly antigen challenged guinea pigs. The mucosal relaxation induced by leukotriene D4 was slightly attenuated in this animal model of allergic rhinitis. CONCLUSION: This study shows an attenuation of NE-induced contraction of isolated nasal mucosa in the antigen-exposed guinea pigs. The impaired contractile response mediated by sympathetic alpha-adrenoceptors of nasal blood vessels might be involved in the development of nasal obstruction in allergic rhinitis.

Effects of 1400W, a potent selective inducible NOS inhibitor, on histamine- and leukotriene D4-induced relaxation of isolated guinea pig nasal mucosa.

To clarify the role of inducible nitric oxide synthase (iNOS) in the relaxation of nasal vasculature, the effects of a potent selective iNOS inhibitor, N-[(3-aminomethyl)benzyl]acetamidine (1400W), on histamine- and leukotriene D4 (LTD4)-induced relaxations of isolated nasal septal mucosae were examined in naive guinea pigs. In addition to eNOS and nNOS, Western blots demonstrated a distinct expression of iNOS in nasal mucosal tissues of naive guinea pigs. In isolated nasal septal mucosae precontracted with norepinephrine (3 x 10(-5)M), both histamine (10(-7)-10(-3)M) and LTD4 (10(-10)-10(-7)M) exhibited relaxations, which were inhibited by a NOS inhibitor NG-monomethyl-L-arginine (L-NMMA; 10(-4)M). The inhibitory effect of L-NMMA was reversed by L-arginine (10(-3)M), indicating that the relaxations induced by histamine and LTD4 are mediated by NO. Furthermore, both the histamine- and LTD4-induced relaxations were also significantly attenuated by 1400W (10(-5)M). These findings suggest an involvement of NO generated by iNOS in agonist-induced relaxation of nasal mucosal vasculature in naive guinea pigs.

Nutrient-enriched Diet in the Early Neonatal Period Influences the 3†year-old Height in Very Low Birth Weight Infants.

Nutrient-enriched milk has been advocated to enhance premature infants'growth and early nutritional intervention is effective for growth failure in very low birth weight infants (VLBWI). We studied the 3-yr-old physical growth of VLBWI who received nutrient enriched diets in the early neonatal period. VLBWI, who were born in 1996, received nutrient enriched milk around 1 mo of age. By contrast, in VLBWI born in 1998, nutrient enriched milk was started at 1-2 wk after birth. The daily calorie intake of VLBWI in 1998 had a tendency to be high compared to that of VLBWI in 1996. Height and body weight SD of 3-yr-old children who were born in 1998 tended to be greater than those of children who were born in 1996 (mean ± SD, -0.27 ± 0.54 vs. -1.01 ± 0.67; p=0.043, -0.47 ± 0.61 vs. -0.97 ± 1.10; p=0.31). Our study suggests that early feeding of nutrient-enriched milk for VLBWI in the neonatal period may affect their growth.

Elevated nasal mucosal G protein levels and histamine receptor affinity in a guinea pig model of nasal hyperresponsiveness.

BACKGROUND: Nasal hyperresponsiveness is a common feature of allergic rhinitis, but the underlying mechanisms have yet to be elucidated. The effects of repeated antigen inhalation on the characteristics of histamine H(1) receptors and expression levels of heterotrimeric guanosine 5'-triphosphate-binding proteins in nasal mucosa were investigated to understand the mechanisms of the pathogenesis of nasal hyperresponsiveness in allergic rhinitis. METHODS: Male Hartley guinea pigs were sensitized by the inhalation of dinitrophenylated ovalbumin antigen (10 mg of protein/ml) and repeatedly challenged by inhaling aerosolized dinitrophenylated ovalbumin antigen for 3 weeks. Twenty-four hours after the last antigen inhalation, in vivo nasal responsiveness to histamine was measured. [(3)H]Mepyramine binding assays and immunoblotting for alpha subunits of the G(q) protein were also performed using membrane preparations of isolated nasal mucosae. RESULTS: The histamine-induced increase in intranasal pressure was significantly augmented after repeated antigen challenge, indicating that nasal hyperresponsiveness was achieved. In saturation binding studies, no significant change was observed in the density and antagonist affinity of H(1) receptors in the hyperresponsive animals. On the other hand, the affinity of histamine for high-affinity agonist binding sites in the hyperresponsive group, measured by histamine competition binding studies, was much greater than that in control animals, and these results were affected by guanosine 5'-O-(3-thiotriphosphate) in both groups. Moreover, Galpha(q) levels in nasal mucosal homogenates were significantly increased after repeated antigen challenge. CONCLUSIONS: Elevated G protein levels in nasal mucosa might induce an increased binding affinity of histamine to its receptors, resulting in an augmented nasal response to histamine, that is, nasal hyperresponsiveness, in guinea pigs.

Extravascular collection of fluid around the vertebra resulting from malpositioning of a peripherally inserted central venous catheter in extremely low birth weight infants.

Peripherally inserted central venous catheters (PICCs) have allowed central venous access via peripheral veins for a long period. PICCs have become an indispensable tool in neonatal medicine. Despite their benefits, PICCs involve some risks, which include infection, thrombosis, malpositioning, and extravascular collection of fluid. We presented two patients with extravascular collection of fluid around the vertebra resulting from malpositioning of PICCs. The PICCs were placed via the saphenous veins in both patients. The PICCs were judged to be centrally placed in the inferior vena cava by means of supine abdominal roentgenograms. The next day one patient exhibited frequent apneic attacks and the other exhibited twitching movements. A lumbar puncture revealed extravascular collection of fluid around the vertebra. In lateral view chest-abdominal roentgenograms, the PICC tips were observed to be in the vertebral lumen. The PICCs were removed immediately and the condition of the patients improved. We stressed the usefulness of the lateral view abdominal roentgenograms for revealing the malpositioning of PICCs in the inferior vena cava.