Effects of different exercise intensities or durations on salivary IgA secretion.

PURPOSE: This study aimed to examine changes in salivary immunoglobulin A (s-IgA) secretion at different intensities or durations of acute exercise. METHODS: Twelve healthy untrained young males were included in randomized crossover trials in Experiment 1 (cycling exercise for 30 min at a work rate equivalent to 35%, 55%, and 75% maximal oxygen uptake [ V ˙ O2max]) and Experiment 2 (cycling exercise at 55% V ˙ O2max intensity for 30, 60, and 90 min). Saliva samples were collected at baseline, immediately after, and 60 min after each exercise. RESULTS: Experiment 1: The percentage change in the s-IgA secretion rate in the 75% V ˙ O2max trial was significantly lower than that in the 55% V ˙ O2max trial immediately after exercise (- 45.7%). The percentage change in the salivary concentration of cortisol, an s-IgA regulating factor, immediately after exercise significantly increased compared to that at baseline in the 75% V ˙ O2max trial (+ 107.6%). A significant negative correlation was observed between the percentage changes in saliva flow rate and salivary cortisol concentration (r = - 0.52, P < 0.01). Experiment 2: The percentage change in the s-IgA secretion rate in the 90-min trial was significantly lower than that in the 30-min trial immediately after exercise (-37.0%). However, the percentage change in salivary cortisol concentration remained the same. CONCLUSION: Our findings suggest that a reduction in s-IgA secretion is induced by exercise intensity of greater than or equal to 75% V ˙ O2max for 30 min or exercise duration of greater than or equal to 90 min at 55% V ˙ O2max in healthy untrained young men.

Inhalation adherence for asthma and COPD improved during the COVID-19 pandemic: a questionnaire survey at a university hospital in Japan.

Background: Good adherence to an inhaled medication protocol is necessary for the management of asthma and chronic obstructive pulmonary disease (COPD), and several interventions to improve adherence have been reported. However, the impact of patient life changes and psychological aspects on treatment motivation is obscure. Here, we investigated changes in inhaler adherence during the COVID-19 pandemic and how lifestyle and psychological changes affected it.Methods: Seven-hundred sixteen adult patients with asthma and COPD who had visited Nagoya University Hospital between 2015 and 2020 were selected. Among them, 311 patients had received instruction at a pharmacist-managed clinic (PMC). We distributed one-time cross-sectional questionnaires from January 12 to March 31, 2021. The questionnaire covered the status of hospital visits, inhalation adherence before and during the COVID-19 pandemic, lifestyles, medical conditions, and psychological stress. The Adherence Starts with Knowledge-12 (ASK-12) was used to assess adherence barriers.Results: Four-hundred thirty-three patients answered the questionnaire. Inhalation adherence was significantly improved in both diseases during the COVID-19 pandemic. The most common reason for improved adherence was fear of infection. Patients with improved adherence were more likely to believe that controller inhalers could prevent COVID-19 from becoming more severe. Improved adherence was more common in patients with asthma, those not receiving counseling at PMC, and those with poor baseline adherence.Conclusions: Inhalation adherence for asthma and COPD improved in the COVID-19 pandemic. The patients seemed to realize the necessity and benefits of the medication more strongly than before the pandemic, which motivated them to improve adherence.

Influence of the Menstrual Cycle on Muscle Glycogen Repletion After Exhaustive Exercise in Eumenorrheic Women.

ABSTRACT: Matsuda, T, Takahashi, H, Nakamura, M, Ogata, H, Kanno, M, Ishikawa, A, and Sakamaki-Sunaga, M. Influence of the menstrual cycle on muscle glycogen repletion after exhaustive exercise in eumenorrheic women. J Strength Cond Res 37(4): e273-e279, 2023-The purpose of this study was to investigate the effect of the menstrual cycle on muscle glycogen repletion postexercise. Eleven women with regular menstrual cycles (age: 20.2 ± 1.3 years, height: 161.1 ± 4.8 cm, and body mass: 55.5 ± 5.7 kg) were assessed in 3 phases of the cycle: the early follicular phase (E-FP), late follicular phase (L-FP), and luteal phase (LP). Each test day began with glycogen-depleting exercise, followed by 5 hours of recovery. Muscle glycogen concentrations, using 13 C-magnetic resonance spectroscopy, and estradiol, progesterone, blood glucose, blood lactate, free fatty acid (FFA), and insulin concentrations were measured at t = 0, 120, and 300 minutes postexercise. During the 5-hour recovery period, subjects consumed 1.2g·(kg body mass) -1 ·h -1 of carbohydrates every 30 minutes. The muscle glycogen concentrations increased at t = 120 and t = 300 minutes postexercise ( p < 0.01) but were not significantly different between the menstrual cycle phases ( p = 0.30). Blood lactate concentrations were significantly higher in the L-FP and LP than in the E-FP ( p < 0.05). Nonetheless, the blood glucose, FFA, insulin concentrations, and the exercise time until exhaustion in the E-FP, L-FP, and LP were similar (blood glucose, p = 0.17; FFA, p = 0.50; insulin, p = 0.31; exercise time, p = 0.67). In conclusion, the menstrual cycle did not influence muscle glycogen repletion after exercise.

Duloxetine attenuates pain in association with downregulation of platelet serotonin transporter in patients with burning mouth syndrome and atypical odontalgia.

OBJECTIVE: The aim of this study was evaluation of the association between severity of pain and expression of total or ubiquitinated serotonin transporter (SERT) protein in patients with burning mouth syndrome and atypical odontalgia (BMS/AO), who were treated by duloxetine. METHODS: Patients with BMS/AO were assessed for severity of pain using the visual analog scale (VAS), and expression of total and ubiquitinated SERT protein in platelets before (baseline) and 12 weeks after duloxetine-treatment. RESULTS: The expression of total and ubiquitinated SERT protein at baseline in all patients (n = 33) were higher and lower, respectively, compared to those in healthy controls. 12 weeks after duloxetine-treatment, there was no difference in the total SERT protein levels between patients (n = 21) and healthy controls. In the 16 patients who could be measured, mean VAS scores and total SERT protein levels were significantly decreased after the treatment, compared to those at baseline. There was tendency for a positive correlation between total SERT protein levels and VAS scores in these patients. CONCLUSIONS: Our findings indicate that duloxetine relieves pain in association with downregulation of platelet SERT expression in patients with BMS/AO.

Effect of administration of monophasic oral contraceptive on the body composition and aerobic and anaerobic capacities of female athletes.

AIM: To examine the effects of administration of monophasic oral contraceptive (OC) on the body composition and aerobic and anaerobic capacities of female athletes. METHODS: Ten female athletes (23.0 ± 4.1 years old) participated in this study. All the subjects were examined during the menstrual cycle (early follicular [EF], middle luteal [ML]) and OC cycle (inactive OC, and active OC phases). After the menstrual cycle measurements, all the subjects began taking OC. The athletes tested using a body composition, circumferences, the lactate curve test, the maximal oxygen consumption test, and the Wingate test during all phases. RESULTS: Waist circumference was lower during the OC cycle than menstrual cycle (P < 0.05), and the other circumferences of parts were not different during the menstrual or OC cycles. However, there were no differences in body composition before and after taking OC. The phase of the menstrual or OC cycle did not affect maximal oxygen consumption, heart rate max or power output at a blood lactate concentration of 2 and 4 mmol/L between the menstrual and OC cycle phases. Although, the peak blood lactate level after the Wingate test was higher during the OC cycle (inactive OC phase, 13.0 ± 2.4 mmol/L; active OC phase, 12.4 ± 3.0 mmol/L) than during the menstrual cycle (EF phase, 11.9 ± 2.1 mmol/L; ML phase, 11.4 ± 2.1 mmol/L; P < 0.05), the peak and average power in the Wingate test did not change during the menstrual and OC cycle phases. CONCLUSION: Administration of monophasic OC did not affect the body composition or aerobic and anaerobic capacities of female athletes.

Effect of ice slurry ingestion on core temperature and blood pressure response after exercise in a hot environment.

Delays in the restoration of thermoregulation after exercise in a hot environment has been associated with post-exercise hypotension. This study tested the hypothesis that simultaneous internal cooling and rehydration by ingesting ice slurry prevents the excessive decrease in mean arterial pressure (MAP) and promotes recovery of core and skin temperatures in male athletes. Seven male athletes participated in this randomized controlled trial with a crossover design. The participants ran on a treadmill at 75% of their maximal oxygen uptake in the heat (35 °C, 60% relative humidity), up to exhaustion. Immediately after exercise, participants ingested either 4 g⋅kg -1 body weight of ice slurry (0.5 °C, ICE) or a control beverage (28 °C, CON). The participants then recovered by sitting for 20 min. We measured participants' rectal temperature (Tre), skin temperature (Tsk), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), and physiological strain index (PSI) before exercise (Pre), after running to exhaustion (PEx), and at 0 (P0), 10 (P10), and 20 (P20) minutes after ice slurry or control beverage ingestion. MAP, CO, HR, TPR, or PSI did not change significantly during the recovery period. At P10 and P20, Tre and Tsk significantly decreased in the ICE group compared to the CON group (p < 0.05). These results suggested that ingestion of ice slurry, post-exercise, promoted core and skin temperature recovery but did not affect the central and peripheral cardiovascular responses during the acute recovery period.

Adenovirus Vectors Expressing Eight Multiplex Guide RNAs of CRISPR/Cas9 Efficiently Disrupted Diverse Hepatitis B Virus Gene Derived from Heterogeneous Patient.

Hepatitis B virus (HBV) chronically infects more than 240 million people worldwide, causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Genome editing using CRISPR/Cas9 could provide new therapies because it can directly disrupt HBV genomes. However, because HBV genome sequences are highly diverse, the identical target sequence of guide RNA (gRNA), 20 nucleotides in length, is not necessarily present intact in the target HBV DNA in heterogeneous patients. Consequently, possible genome-editing drugs would be effective only for limited numbers of patients. Here, we show that an adenovirus vector (AdV) bearing eight multiplex gRNA expression units could be constructed in one step and amplified to a level sufficient for in vivo study with lack of deletion. Using this AdV, HBV X gene integrated in HepG2 cell chromosome derived from a heterogeneous patient was cleaved at multiple sites and disrupted. Indeed, four targets out of eight could not be cleaved due to sequence mismatches, but the remaining four targets were cleaved, producing irreversible deletions. Accordingly, the diverse X gene was disrupted at more than 90% efficiency. AdV containing eight multiplex gRNA units not only offers multiple knockouts of genes, but could also solve the problems of heterogeneous targets and escape mutants in genome-editing therapy.

Fabrications of boron-containing apatite ceramics via ultrasonic spray-pyrolysis route and their responses to immunocytes.

Immunotherapy without side effects has been expected as a novel medical treatment for cancer. However, drugs such as cytokines typically used for immunotherapy are very expensive. Therefore, we propose the concept of immunoceramics that affect the immune system. Previous studies have shown that polymers including the phenylboronic acid group activate lymphocytes. This activation may be due to interaction between the sugar chains in cells and the OH group in B(OH)3 formed via dissociation of the BO2 group. In the present study, boron-containing apatite (BAp; Ca9.5+0.5x{(PO4)6-x(BO3)x}{(BO2)1-xOx} (0 ≤ x ≤ 1)) was successfully fabricated via the ultrasonic spray-pyrolysis (USSP) route. We examined the material properties of the BAp ceramics with an aim to application as immunoceramics and the responses of immune cells to the BAp ceramics. The crystalline phases of the BAp ceramics included the apatite phase and infrared (IR) absorption of BO2 and BO3 groups was detected in the BAp ceramics. The cellular response of immune cells derived from mice spleens to dense BAp ceramics was examined next. The proportion of helper T cells and killer T cells on BAp (x = 0.4) ceramics increased compared to that on hydroxyapatite (Ca10(PO4)6(OH)2; HAp) ceramics and on a control. These results indicate that BAp (x = 0.4) ceramics fabricated via the USSP route can be expected to act as immunoceramics that can affect the immune system.

Effects of evening partial body cryostimulation on the skin and core temperatures.

Cryostimulation is widely used to treat inflammation, rheumatism, acute soft tissue injuries, and neurodegeneration. It helps prevent injury and promotes recovery. This study aimed to examine the duration of the effects of evening partial body cryostimulation (PBC) on core and skin temperatures. Seven male athletes participated in this study. On the day of PBC, at 18:00, each athlete was exposed to PBC (approx. -180 °C) in a specially designed cabin for 3 min. On the control day, at 18:00, the participants sat still on a sofa for 10 min. On both days, bedtime was at around 23:00. Wrist and abdominal skin temperatures, except during PBC, were recorded with Thermochron thermistors after 17:30. Core temperatures were monitored with an ingestible and telemetric core body temperature sensor and a data recorder. The circadian rhythm of the core temperature was observed on both days. The core temperature at 22:30 was found to be lower on the PBC day. Wrist and abdominal skin temperatures recovered after PBC; however, the residual effects on both were different. The abdominal skin temperature at 22:30 was lower on the PBC day. Subjective sleep quality and next morning sleepiness did not differ between the conditions. These results suggested that the effects of a 3-min evening PBC session on the core and skin temperatures lasted for several hours. However, these differences did not affect the subjective sleep quality.

Identification of undesirable white-colony-forming yeasts appeared on the surface of Japanese kimchi.

To identify yeasts involved in white-colony formation on Japanese commercial kimchi products, three types of kimchi were prepared and fermented at four different temperatures. At 4 °C, yeast colonies did not appear until 35 days, while more rapid white-colony formation occurred at higher temperatures (10, 15, and 25 °C). Combination of PCR-DGGE and direct isolation of yeasts from white colonies revealed that Kazachstania exigua and K. pseudohumilis were responsible for the white-colony formation. Inoculation of the isolated Kazachstania strains into fresh kimchi successfully reproduced white-colony formation at 15 °C but not at 4 °C. Growth experiments in liquid medium revealed that Kazachstania spp. grew fast at 15 °C even in the presence of acidulants, which are commonly added to Japanese kimchi products for prevention of yeast growth. These results suggest that white-colony formation on Japanese kimchi is caused by the genus Kazachstania, and that one of important factors determining white-colony formation is its fermentation temperature.

Effect of Compression Garments on Controlled Force Output After Heel-Rise Exercise.

Kato, E, Nakamura, M, and Takahashi, H. Effect of compression garments on controlled force output after heel-rise exercise. J Strength Cond Res 32(4): 1174-1179, 2018-The purpose of this study was to elucidate the effects of compression garments (CG) on controlled force output after strenuous exercise. Sixteen healthy volunteers completed trials both with CG and without CG (control trial: CON) on 2 separate, random days which were at least 1 month apart. Both trials required participants to perform heel-rise exercises from maximal dorsiflexion to maximal plantar flexion 20 times with a single leg. The subjects repeated 3 sets of the exercise and took a rest for 2 minutes between sets. Before and after the heel-rise exercise, mechanical (stiffness) and architectural properties of the gastrocnemius medialis muscle were evaluated using the ultrasound method. Also, isometric maximal voluntary contraction (MVC) of plantar flexion was measured, and the subjects maintained 20% MVC of plantar flexion torque for 20 seconds as steadily as possible (steadiness task) as an index of force control. Repeated 2-way analysis of variance analysis (CG/CON × time) indicated that all the parameters declined immediately after heel-rise exercise in both CG and CON trials. Maximal voluntary contraction did not show different tendencies between CG and CON trials, but muscle stiffness and steadiness declined less in CG than CON (p < 0.05). In conclusion, CG are considered to positively benefit controlled force output after strenuous exercise.

Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B.

UNLABELLED: It has been proposed that the hepatitis C virus (HCV) NS4B protein triggers the membranous HCV replication compartment, but the underlying molecular mechanism is not fully understood. Here, we screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis and identified 202 host proteins. Subsequent screening of replicon cells with small interfering RNA identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. The interaction between PREB and NS4B was confirmed by immunoprecipitation, immunofluorescence, and proximity ligation assays. PREB colocalized with double-stranded RNA and the newly synthesized HCV RNA labeled with bromouridine triphosphate in HCV replicon cells. Furthermore, PREB shifted to detergent-resistant membranes (DRMs), where HCV replication complexes reside, in the presence of NS4B expression in Huh7 cells. However, a PREB mutant lacking the NS4B-binding region (PREBd3) could not colocalize with double-stranded RNA and did not shift to the DRM in the presence of NS4B. These results indicate that PREB locates at the HCV replication complex by interacting with NS4B. PREB silencing inhibited the formation of the membranous HCV replication compartment and increased the protease and nuclease sensitivity of HCV replicase proteins and RNA in DRMs, respectively. Collectively, these data indicate that PREB promotes HCV RNA replication by participating in the formation of the membranous replication compartment and by maintaining its proper structure by interacting with NS4B. Furthermore, PREB was induced by HCV infection in vitro and in vivo. Our findings provide new insights into HCV host cofactors. IMPORTANCE: The hepatitis C virus (HCV) protein NS4B can induce alteration of the endoplasmic reticulum and the formation of a membranous web structure, which provides a platform for the HCV replication complex. The molecular mechanism by which NS4B induces the membranous HCV replication compartment is not understood. We screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis, followed by screening with small interfering RNA. We identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. PREB is induced by HCV infection and recruited into the replication complex by interaction with NS4B. Recruited PREB promotes HCV RNA replication by participating in the formation of the membranous HCV replication compartment. To our knowledge, the effect of NS4B-binding protein on the formation of the membranous HCV replication compartment is newly described in this report. Our findings are expected to provide new insights into HCV host cofactors.

Oral contraceptive therapy reduces serum relaxin-2 in elite female athletes.

AIM: Recent investigations have demonstrated that athletes with high relaxin-2 levels have a high risk of anterior cruciate ligament injuries, while athletes taking oral contraceptives (OC) have low relaxin-2 levels. It has not yet been clarified whether taking OC reduces relaxin-2 levels. The purpose of this study was to investigate changes in relaxin-2 levels in athletes taking OC. METHODS: Levels of relaxin-2, estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone were measured in serum samples (n = 183) from 106 elite female athletes. Five athletes with serum relaxin-2 concentrations > 6 pg/mL during the luteal phase were recruited to assess the effect of OC therapy. RESULTS: Serum relaxin-2 concentrations were significantly higher during the luteal phase (n = 57) than in the follicular phase (n = 72), or in athletes on OC therapy (n = 10) (P < 0.001, P < 0.001 and P < 0.05, respectively). In the luteal phase, 36.8% (21/57) of the athletes had relaxin levels > 6 pg/mL. In 23 athletes, serum relaxin-2 concentrations were measured during both the follicular and luteal phases, revealing that relaxin-2 levels were significantly higher in the luteal phase compared with the follicular phase. In 5 out of 23 athletes, serum relaxin-2 concentrations were > 6 pg/mL in the luteal phase and during the second cycle of OC therapy, relaxin-2 concentrations decreased dramatically to below the detection limit (0.26 pg/mL). CONCLUSIONS: High serum relaxin-2 concentrations were only detected during the luteal phase. In athletes with high relaxin-2 concentrations during the luteal phase, OC therapy decreased serum relaxin-2 levels.

Cytocompatibility of HeLa Cells to Nano-Sized Ceramics Particles.

In this study, we investigated the behaviors and cytocompatibility response of human cervical carcinoma (HeLa) cells expose to nano-sized particles. Cultivated cells exposed to titanium oxide and indium oxide nanoparticles remained highly viable. In the presence of copper oxide (CuO); however, the cells became seriously inflamed. To understand the mechanism by which CuO causes cell death, we evaluated cell death and apoptosis cytometry. CuO induced cells apoptosis more strongly than exposure to titania nanoparticles. Confocal fluorescence microscopy revealed that the nano-sized particles penetrate the cells.

[From Bioartificial Liver Development to Laboratory Medicine -In Vitro and In Vivo Stable Isotope-Labeled Glucose Breath Tests -].

The urea breath test was developed for the diagnosis of Helicobacter pylori infection. In this test, we measure exhaled ¹³CO2 using POCone developed in Japan, which is an infrared spectrometry photometer. Based on the urea breath test, we subsequently developed the in vitro ¹³C-glucose exhaling test. In this test, ¹³C-glucose is added in the circulation culture medium, and ¹³CO2 generated with a bioartificial liver is measured by the POCone. The quantity of discharged ¹³CO2 reflects the energy-producing ability of the bioartifi- cial liver. Therefore, we can simply and easily observe the viability of a bioartificial liver and the effect of drugs on carbohydrate metabolism in the bioartificial liver in real time. According to the results of a bioartificial liver study, we developed the fasting ¹³C-glucose breath test, which can quickly determine hepatic insu- lin resistance in humans with marked sensitivity. The bioartificial liver study unexpectedly led to the development of a new stable isotope breath test. [Review].

Identification of a novel cell-penetrating peptide targeting human glioblastoma cell lines as a cancer-homing transporter.

Cell-penetrating peptides (CPPs) as a novel biomedical delivery system have been highly anticipated, since they can translocate across biological membranes and are capable of transporting their cargo inside live cells with minimal invasiveness. However, non-selective internalization in various cell types remains a challenge in the clinical application of CPPs, especially in cancer treatment. In this study, we attempted to identify novel cancer-homing CPPs to target glioblastoma multiforme (GBM), which is often refractory and resistant to treatment. We screened for CPPs showing affinity for the human GBM cell line, U87MG, from an mRNA display random peptide library. One of the candidate peptides which amino-acid sequence was obtained from the screening showed selective cell-penetrating activity in U87MG cells. Conjugation of the p16(INK4a) functional peptide to the GBM-selective CPP induced cellular apoptosis and reduced phosphorylated retinoblastoma protein levels. This indicates that the CPP was capable of delivering a therapeutic molecule into U87MG cells inducing apoptosis. These results suggest that the novel CPP identified in this study permeates with high affinity into GBM cells, revealing it to be a promising imaging and therapeutic tool in the treatment of glioblastoma.

Changes in roller skiing economy among Nordic combined athletes leading up to the competition season.

The purpose of this study was to compare roller skiing economy during different training phases in Nordic combined (NC) athletes and determine the aerobic and anaerobic factors responsible for changes in skiing economy. Seven elite NC athletes underwent incremental load tests on a large buried treadmill in both spring and autumn using roller skis. Measurements included oxygen uptake, respiratory exchange ratio, and blood lactate concentration. Roller skiing economy was calculated from aerobic and anaerobic energy system contributions, and overall roller skiing economy was determined by combining the two. Comparisons were made between the skiing economies obtained in the two measurement sessions. Physical characteristics and incremental test performance remained consistent between the two measurement sessions. The overall skiing economy at each speed significantly improved toward the competition season (p < 0.05). Similarly, the contribution of anaerobic energy system at each speed showed significant improvement (p < 0.05). In contrast, the contribution of aerobic energy system did not change between the two measurement sessions. This study reveals that NC athletes enhance their skiing economy at the same speed during submaximal efforts in preparation for the competition season. This improvement is predominantly associated with an improvement in the contribution of anaerobic energy system.

Investigation of a new implant surface modification using phosphorylated pullulan.

Various implant surface treatment methods have been developed to achieve good osseointegration in implant treatment. However, some cases remain impossible to treat with implants because osseointegration is not obtained after implantation, and the implants fail. Thus, this study focused on phosphorylated pullulan because of its adhesiveness to titanium (Ti) and bone, high biocompatibility, and early replacement with bone. In this study, the response of bone-related cells to phosphorylated pullulan was evaluated to develop a new surface treatment method. Saos-2 (human osteosarcoma-derived osteoblast-like cells), MC3T3-E1 (mouse calvaria-derived osteoblast-like cells), and RAW264.7 (mouse macrophage-like cells) were used. In evaluating cellular responses, phosphorylated pullulan was added to the culture medium, and cell proliferation and calcification induction tests were performed. The proliferation and calcification of cells on the surface of Ti disks coated with phosphorylated pullulan were also evaluated. In addition, bone morphogenetic protein-2 (BMP-2), an osteogenic factor, was used to evaluate the role of phosphorylated pullulan as a drug carrier in inducing calcification on Ti disks. Phosphorylated pullulan tended to promote the proliferation of osteoblast-like cells and the formation of calcification on Ti disks coated with phosphorylated pullulan. Ti disks coated with phosphorylated pullulan loaded with BMP-2 enhanced calcification. Phosphorylated pullulan inhibited osteoclast-like cell formation. These results are due to the properties of phosphorylated pullulan, such as adhesiveness to titanium and drug-loading function. Therefore, phosphorylated pullulan effectively promotes bone regeneration when coated on titanium implants and is useful for developing a new surface treatment method.

Duloxetine improves chronic orofacial pain and comorbid depressive symptoms in association with reduction of serotonin transporter protein through upregulation of ubiquitinated serotonin transporter protein.

ABSTRACT: Chronic orofacial pain (COP) is relieved by duloxetine (DLX) and frequently causes depressive symptoms. The aim of this study was to confirm effects of DLX on pain and depressive symptoms, and to associate with their effectiveness in platelet serotonin transporter (SERT) expression, which is a target molecule of DLX and plasma serotonin concentration in COP patients with depressive symptoms. We assessed for the severity of pain and depressive symptoms using the Visual Analog Scale (VAS) and 17-item Hamilton Depression Rating Scale (HDRS), respectively. Chronic orofacial pain patients were classified into 2 groups based on their HDRS before DLX-treatment: COP patients with (COP-D) and without (COP-ND) depressive symptoms. We found that the VAS and HDRS scores of both groups were significantly decreased after DLX treatment compared with those before DLX treatment. Upregulation of total SERT and downregulation of ubiquitinated SERT were observed before DLX treatment in both groups compared with healthy controls. After DLX treatment, there were no differences in total SERT of both groups and in ubiquitinated SERT of COP-D patients compared with healthy controls; whereas, ubiquitinated SERT of COP-ND patients remained downregulated. There were positive correlations between changes of serotonin concentrations and of VAS or HDRS scores in only COP-D patients. Our findings indicate that DLX improves not only pain but also comorbid depressive symptoms of COP-D patients. Duloxetine also reduces platelet SERT through upregulation of ubiquitinated SERT. As the result, decrease of plasma serotonin concentrations may be related to the efficacy of DLX in relieving pain and depression in COP patients.

[Promoting Appropriate Use of Medications by "Lectures and Practices Regarding Medicine" for the Regional Community Residents].

We held lectures and practices for the regional community residents with the aim of promoting appropriate use of medications. To evaluate the usefulness of our activity, we conducted medicine-related questionnaire surveys (pre- and post-questionnaires) before and after the lectures and practices, and satisfaction with the activity questionnaire surveys (post-questionnaires) after them. We also evaluated the effect of age difference on the results by dividing the participants into elderly (age ≥65) and non-elderly (age <65), before the analysis. In the both (elderly and non-elderly) groups, the ratio of positive answers in several items of post-questionnaire regarding appropriate use of medications was higher than that of pre-questionnaire. These results suggest that the basic medicine-related knowledge improved by attending the lectures and practices, and indicate that the knowledge of the regional community residents is higher than we imagined. Furthermore, there was no difference in the ratio of positive answers between the both groups, suggesting that our activity is applicable to a wide range of age groups. Our activity benefitted the participants, and not only provided education to the regional community residents regarding appropriate drug use, but also lead to the development of regional community activity, by the coming together of the regional community residents of various age.