An unusual case of fatal hypothermia involving topical diphenhydramine.

PURPOSE: Diphenhydramine is an antihistamine drug widely used to alleviate symptoms caused by allergies and the common cold. Diphenhydramine-involved fatalities have been reported in the past but usually involving overdose by ingestion. We report a peculiar case of fatal hypothermia during non-winter season involving topical diphenhydramine. METHODS: A 23-year-old male with no known preexisting medical conditions was found dead in the bathroom of his apartment with a small amount of running water on his back. Postmortem examinations and toxicological analysis on blood and urine were performed. RESULTS: Color difference was apparent between the right and left cardiac blood. Wischnewski spots were observed in the gastric mucosa. Histological examination revealed no obvious findings that could attribute to serious cardiovascular events. Drug screening by gas chromatograph-tandem mass spectrometry (GC/MS/MS) detected diphenhydramine in blood and urine. Further quantification revealed the postmortem concentrations to be 0.44 µg/mL in blood and 2500 µg/mL in urine. CONCLUSIONS: The cause of death was determined to be hypothermia. Diphenhydramine-induced drowsiness and possible intrinsic cardiac factor may have led to prolonged impaired consciousness, preventing his ability to escape from the running cold water leading to hypothermia and death.

Low Back Pain Exacerbation Is Predictable Through Motif Identification in Center of Pressure Time Series Recorded During Dynamic Sitting.

Background: Low back pain (LBP) is a common health problem - sitting on a chair for a prolonged time is considered a significant risk factor. Furthermore, the level of LBP may vary at different times of the day. However, the role of the time-sequence property of sitting behavior in relation to LBP has not been considered. During the dynamic sitting, small changes, such as slight or big sways, have been identified. Therefore, it is possible to identify the motif consisting of such changes, which may be associated with the incidence, exacerbation, or improvement of LBP. Method: Office chairs installed with pressure sensors were provided to a total of 22 office workers (age = 43.4 ± 8.3 years) in Japan. Pressure sensors data were collected during working days and hours (from morning to evening). The participants were asked to answer subjective levels of pain including LBP. Center of pressure (COP) was calculated from the load level, the changes in COP were analyzed by applying the Toeplitz inverse covariance-based clustering (TICC) analysis, COP changes were categorized into several states. Based on the states, common motifs were identified as a recurring sitting behavior pattern combination of different states by motif-aware state assignment (MASA). Finally, the identified motif was tested as a feature to infer the changing levels of LBP within a day. Changes in the levels of LBP from morning to evening were categorized as exacerbated, did not change, or improved based on the survey questions. Here, we present a novel approach based on social spider algorithm (SSA) and probabilistic neural network (PNN) for the prediction of LBP. The specificity and sensitivity of the LBP inference were compared among ten different models, including SSA-PNN. Result: There exists a common motif, consisting of stable sitting and slight sway. When LBP level improved toward the evening, the frequency of motif appearance was higher than when LBP was exacerbated (p < 0.05) or the level did not change. The performance of the SSA-PNN optimization was better than that of the other algorithms. Accuracy, precision, recall, and F1-score were 59.20, 72.46, 40.94, and 63.24%, respectively. Conclusion: A lower frequency of a common motif of the COP dynamic changes characterized by stable sitting and slight sway was found to be associated with the exacerbation of LBP in the evening. LBP exacerbation is predictable by AI-based analysis of COP changes during the sitting behavior of the office workers.

Hemodialysis raises oxidative stress through carbon-centered radicals despite improved biocompatibility.

Leukocyte activation and the resulting oxidative stress induced by bioincompatible materials during hemodialysis impact the prognosis of patients. Despite multiple advances in hemodialysis dialyzers, the prognosis of hemodialysis patients with complications deeply related to oxidative stress, such as diabetes mellitus, remains poor. Thus, we re-evaluated the effects of hemodialysis on multiple reactive oxygen species using electron spin resonance-based methods for further improvement of biocompatibility in hemodialysis. We enrolled 31 patients in a stable condition undergoing hemodialysis using high-flux polysulfone dialyzers. The effects of hemodialysis on reactive oxygen species were evaluated by two methods: MULTIS, which evaluates serum scavenging activities against multiple hydrophilic reactive oxygen species, and i-STrap, which detects lipophilic carbon-center radicals. Similar to previous studies, we found that serum hydroxyl radical scavenging activity significantly improved after hemodialysis. Unlike previous studies, we discovered that scavenging activity against alkoxyl radical was significantly reduced after hemodialysis. Moreover, patients with diabetes mellitus showed a decrease in serum scavenging activity against alkyl peroxyl radicals and an increase in lipophilic carbon-center radicals after hemodialysis. These results suggest that despite extensive improvements in dialyzer membranes, the forms of reactive oxygen species that can be eliminated during dialysis are limited, and multiple reactive oxygen species still remain at increased levels during hemodialysis.

Impact of green tea intake on the pharmacokinetics of celiprolol in healthy subjects.

OBJECTIVE: To assess the effect of green tea intake on the pharmacokinetics of the ß-blocker celiprolol. MATERIALS AND METHOD: In an open-label crossover study, 3 healthy subjects were given water or a green tea beverage daily for 3 days. On day 4, each subject received a single oral dose of 200 mg celiprolol with water or green tea. Serum and urinary concentrations of celiprolol were measured for up to 24 hours. RESULTS: Green tea intake decreased the area under the serum concentration-time curve and urinary excretion of celiprolol by 98.6 and 98.0%, respectively. CONCLUSION: Green tea intake might have a negative impact on the clinical effectiveness of celiprolol.

Direct detection of diclofenac radical produced by ultraviolet irradiation using electron spin resonance method.

Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly used as an antipyretic analgesic owing to its strong anti-inflammatory action in clinical treatment. However, diclofenac can cause injury, with gastrointestinal mucosal lesions and skin photosensitivity as the main side effects. In general, photosensitive drugs contain photosensitive chemical sites, and form free radicals under ultraviolet irradiation, leading to phototoxic reactions. Therefore, this study focuses on free radical production in photosensitive reactions of diclofenac. The free radical production mechanism of diclofenac under ultraviolet irradiation, which might result in photo-toxicity, was clarified using a direct electron spin resonance method. When diclofenac was irradiated with ultraviolet light (254 nm), diclofenac radicals were generated depending on the ultraviolet irradiation time and stably present for 30 min at room temperature. Diclofenac radicals were produced by the ultraviolet irradiation system depending on the dose of diclofenac until 2 mM. Therefore, diclofenac radicals might directly or indirectly react with various biomolecules to cause phototoxicity, other side effects, and new diclofenac pharmacology owing to its stability of diclofenac radicals.

Elimination of intravenous alendronate by hemodialysis: A kinetic study.

INTRODUCTION: The potential utility of intravenous alendronate for the treatment of osteoporosis in hemodialysis patients was recently reported. However, the pharmacokinetics of intravenous alendronate in patients on hemodialysis is not clear. METHODS: Six hemodialysis patients (mean age, 80.5 years) with osteoporosis who had received intravenous alendronate prior to the study were enrolled. The participants received a 30-min infusion of 900-µg alendronate intravenously at the beginning of the dialysis session. The blood flow rate (Qb) and dialysate flow rate (Qd) were set at 200 mL/min and 500 mL/min, respectively. All patients used the same dialyzer (1.5-m2 polysulfone membrane). At the completion of administration, plasma and dialysate samples were collected, and alendronate concentrations were determined using metal-free high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS). RESULTS: The plasma arterial alendronate concentration was 150.9 ± 46.09 ng/mL. It decreased through the dialyzer to 76.1 ± 34.1 ng/mL (venous alendronate concentration). Mean alendronate clearance was 113.9 ± 25.6 mL/min. Mean alendronate removal by hemodialysis, measured by the difference in arterial-venous concentrations, was 51.8%. CONCLUSIONS: Fifty percent of intravenous alendronate was removed by hemodialysis, which is nearly equal to elimination of alendronate in patients with normal renal function. The elimination by hemodialysis would decrease the risk of excessive accumulation in bone. UMIN 000027182.

High-throughput method to analyze tegafur and 5-fluorouracil in human tears and plasma using hydrophilic interaction liquid chromatography/tandem mass spectrometry.

RATIONALE: We developed a new high-throughput method to analyze tegafur (FT) and 5-fluorouracil (5-FU) in tear and plasma samples using hydrophilic interaction liquid chromatography (HILIC)/tandem mass spectrometry (MS/MS). METHODS: The tear samples (10 µL) spiked with FT, 5-FU, and 5-chlorouracil (internal standard) were diluted using 40 µL of 2 M ammonium acetate and 250 µL of acetonitrile with 2% formic acid; 20 µL of plasma spiked with the two drugs and internal standard was diluted with 80 µL of 2 M ammonium acetate and 500 µL of acetonitrile with 2% formic acid. After centrifugation, the clear supernatant extract (15 µL) was directly injected into the HILIC/MS/MS instrument, and each drug was separated on a Unison UK-Amino column (50 mm × 3 mm i.d., 3 µm particle size) with a linear gradient elution system composed of 10 mM ammonium acetate (pH 6.8) and acetonitrile at a flow rate of 0.7 mL/min. We performed quantification by multiple reaction monitoring (MRM) with negative-ion atmospheric-pressure chemical ionization. RESULTS: Distinct peaks were observed for the drugs on each MRM channel within 2 min. The regression equations showed good linearity within the range 0.04-4.0 µg/mL for the tear and plasma samples with detection limits at 0.02-0.04 µg/mL. Recoveries for target analytes (FT and 5-FU) for the tear and plasma samples were in the 94-128% and 94-104% ranges, respectively. The intra- and inter-day coefficients of variation for the two drugs were lower than 10.8%. The accuracies of quantitation were 97-115% for both samples. CONCLUSIONS: We established a high-throughput, reproducible, and practical procedure for analyzing FT and 5-FU in human tear and plasma samples using HILIC/MS/MS analysis with an aminopropyl-bonded mixed-mode separation column. This method can be applied to the high-throughput routines used in clinical analyses.

Effects of orally administered lactoferrin and lactoperoxidase on symptoms of the common cold.

OBJECTIVES: Lactoferrin (LF) and lactoperoxidase (LPO) are present in human saliva. LF has been demonstrated to show antibacterial and antiviral activities. In saliva, LPO catalyzes the hydrogen peroxide-dependent oxidation of thiocyanate to hypothiocyanite that exhibits antimicrobial and antiviral properties. A randomized, open-label, parallel-group clinical trial was conducted to examine the effectiveness of sucking tablets containing LF and LPO (LF+LPO) in alleviating symptoms of the common cold and/or influenza infection. METHODS: A total of 407 subjects were randomized into two groups, treatment and non-treatment groups, and each group was further classified into subgroups habitually wearing a face mask, washing their hands, or gargling. The common cold, influenza, and gastrointestinal symptoms were used to evaluate the effectiveness, and the incidence and duration of symptoms were statistically analyzed. RESULTS: The incidence and duration of common cold, gastrointestinal symptoms, and influenza infection were not statistically different between treatment and non-treatment groups. LF+LPO tablets were moderately effective in reducing the incidence and duration of common cold symptoms in the subgroup that did not gargle and especially to shorten significantly the duration of fever higher than 38°C in the subgroup that did not wear a face mask. CONCLUSION: The results suggested that the effect of ingestion of the tablet is not obvious in alleviating common cold symptoms but may be helpful when the subjects do not follow precautionary measures such as gargling and the use of a protective face mask.

Dose-dependent decrease in anti-oxidant capacity of whole blood after irradiation: A novel potential marker for biodosimetry.

Many reports have demonstrated that radiation stimulates reactive oxygen species (ROS) production by mitochondria for a few hours to a few days after irradiation. However, these studies were performed using cell lines, and there is a lack of information about redox homeostasis in irradiated animals and humans. Blood redox homeostasis reflects the body condition well and can be used as a diagnostic marker. However, most redox homeostasis studies have focused on plasma or serum, and the anti-oxidant capacity of whole blood has scarcely been investigated. Here, we report changes in the anti-oxidant capacity of whole blood after X-ray irradiation using C57BL/6 J mice. Whole-blood anti-oxidant capacity was measured by electron spin resonance (ESR) spin trapping using a novel spin-trapping agent, 2-diphenylphosphinoyl-2-methyl-3,4-dihydro-2H-pyrrole N-oxide (DPhPMPO). We found that whole-blood anti-oxidant capacity decreased in a dose-dependent manner (correlation factor, r > 0.9; P < 0.05) from 2 to 24 days after irradiation with 0.5-3 Gy. We further found that the red blood cell (RBC) glutathione level decreased and lipid peroxidation level increased in a dose-dependent manner from 2 to 6 days after irradiation. These findings suggest that blood redox state may be a useful biomarker for estimating exposure doses during nuclear and/or radiation accidents.

High-throughput determination of valproate in human samples by modified QuEChERS extraction and GC-MS/MS.

A new high-throughput method was developed for analysis of valproate in human plasma samples by QuEChERS extraction and gas chromatography-tandem mass spectrometry (GC-MS/MS). Plasma samples (0.2 ml) spiked with valproate and secobarbital-d5 (internal standard) were diluted with 1.3 ml of distilled water. Acetonitrile (1 ml) was added followed by 0.4 g MgSO4 and 0.1 g NaOAC. After a centrifugation step (2000 g for 10 min), 1 ml of the supernatant was transferred to a dispersive-solid phase extraction (dSPE) tube containing 150 mg MgSO4 and 50 mg C18. This mixture was vortexed and centrifuged at 3000 g for 5 min, and then the upper layer was evaporated to dryness under a stream of nitrogen. The residue was dissolved in 40 µl ethyl acetate, and a 1-µl aliquot was injected into the GC-MS/MS. The GC separation of the compounds was achieved on a fused-silica capillary column Rxi-5Sil MS (30 m × 0.25 mm i.d.; 0.25-µm film thickness) and detected by MS/MS operating in electron ionization ion source mode. The regression equations showed excellent linearity (r > 0.9997) from 50 to 5000 ng/ml for plasma, with limit of detection of 10 ng/ml. The extraction efficiency of valproate for plasma ranged between 71.2%-103.5%. The coefficient of variation was <18.5%. The method was successfully applied to actual analyses of an autopsy case. This method can be useful for simple and reliable measurements of valproate in clinical and toxicological analyses; it can be integrated in screening and simultaneous determination methods for multiple drugs and poisons in the further studies.

Highly sensitive determination of alendronate in human plasma and dialysate using metal-free HPLC-MS/MS.

A highly sensitive method was developed for the analysis of alendronate in human plasma and dialysate using MonoSpin™ SAX® extraction and metal-free high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) following methylation with trimethylsilyldiazomethane. The chromatographic separation of the derivatives for alendronate and alendronate-d6 was achieved on an L-column2 ODS metal-free column (50 mm  ×  2 mm i.d., particle size 3 µm) with a linear gradient elution system composed of 10 mM ammonium acetate (pH 6.8) and acetonitrile at a flow rate of 0.3 ml/min. Quantification was performed by multiple reaction monitoring (MRM) with positive-ion electrospray ionization (ESI). Distinct peaks were observed for alendronate and for the internal standard on each channel within 1 min. The regression equations showed good linearity within the ranges of 2.0-100 ng/0.5 ml for the plasma and 1.0-100 ng/0.5 ml for the dialysate, with the limits of detection at 1.0 ng/0.5 ml for the plasma and 0.5 ng/0.5 ml for the dialysate. Extraction efficiencies for alendronate for the plasma and dialysate were 41.1-51.2% and 63.6-73.4%, respectively. The coefficient of variation (CV) was ≤8.5%. The method was successfully applied to the analyses of real plasma and dialysate samples derived after intravenous administration of alendronate.

The detection of influenza virus at the community pharmacy to improve the management of local residents with influenza or influenza-like disease.

BACKGROUND: As of 2014, community pharmacies in Japan are approved by the Ministry of Health, Labour and Welfare to measure lipid panel, HbA1c, glucose, ALT, AST and γ-GTP, but not to screen for influenza virus. We provided influenza virus screening tests at a community pharmacy to triage people with symptoms suggestive of influenza. Participants were given appropriate advice on how to prevent the spread of and safeguard against influenza. We subsequently evaluated the effects of community pharmacy-based influenza virus screening and prevention measures. METHODS: Local residents with symptoms suggestive of influenza participated in this study. Influenza virus screening tests using nasal samples were provided to the pharmacy, and we assessed samples for the presence of influenza virus. The study consisted of a preliminary interview, informed consent, and screening test on Day 1, and mail-in survey on Day 14. RESULTS: A total 52 local residents participated in the study. The number of participants and influenza virus positive results followed the same trend as the influenza epidemic in the study area. Influenza virus was found in 28.8% of samples. There was no significant difference between the appearance ratios of subjective symptoms among influenza-positive and influenza-negative groups. The percentages of participants who were first screened at the pharmacy, and those who were first screened at a clinic and then tested again at the pharmacy, were 71.2% (37/52) and 28.8% (15/52), respectively. In the latter group, 14 of 15 were negative by screening at the clinic, and one was diagnosed with influenza without testing. Subsequently, 46.8% (7/15) of participants tested positive for influenza by pharmacy-based screening. According to the mail-in survey, all influenza-positive (100%, 7/7) and 35.3% (6/17) of influenza-negative participants visited the clinic after being tested at the community pharmacy; test results between the community pharmacy and clinic were consistent. A total 64.7% (11/17) of symptomatic participants who tested negative recovered spontaneously at home. CONCLUSIONS: Implementation of influenza virus screening followed by provision of appropriate advice for both influenza-positive and influenza-negative participants at the community pharmacy showed a significant effect on improving the health of the local community.

Rapid and highly sensitive analysis of benzodiazepines and tandospirone in human plasma by automated on-line column-switching UFLC-MS/MS.

A high-throughput method was developed for the detection of 31 benzodiazepine drugs and tandospirone in human plasma by on-line column-switching ultra-fast liquid chromatography-tandem mass spectrometry. Plasma samples (100µl) spiked with the 32 drugs and oxazepam-d5 (internal standard) were diluted with 300µl of 13.3mM ammonium acetate/acetonitrile (33:67, v/v). After centrifugation and filtration, the clear supernatant was injected directly onto the extraction column (Oasis HLB cartridge column). The following procedure was fully automated. The analytes retained on the extraction column were eluted by backflushing of the extraction column and introduced into an analytical column (SUMIPAX ODS D-Swifter column, 30mm×3.0mm i.d.; particle size 2µm) by column switching. Quantification was performed by multiple reaction monitoring with positive-ion electrospray ionization. Distinct peaks appeared for each drug and the internal standard on each channel within 7min, including the extraction time. All drugs spiked into plasma showed recoveries of 83-95%. The regression equations for the 32 drugs showed excellent linearities in the range of 50-2000pg/ml of plasma and the limits of detection ranged from 20 to 50pg/ml. The lower and upper limits of quantitation were 50-100ng/ml and 2000pg/ml, respectively. Intra- and interday coefficients of variation for none of the drugs were greater than 13.6%. The accuracies of quantitation were 87-112%. The multiple reaction monitoring information-dependent acquisition of enhanced product ions method enabled the quantification and confirmation of diazepam, triazolam, and lorazepam obtained from actual plasma.

Development of the Virtual Physical Assessment Learning Material That Allows the Learners to Check Drug Efficacy and Early Detection of Adverse Effects through Virtual Experience.

We utilized the information and communication technology to develop the physical assessment (PA) learning materials in the virtual experience type. This learning material consists of two parts which include case learning and basic learning. We created example scenarios about various conditions that a pharmacist may experience in medical scenes such as in a hospital ward, community pharmacy, home, and drugstore. Illustrations of a virtual patient's avatar before and after taking the medicines were incorporated in the learning materials. The virtual training includes a stethoscope that was used in examining sounds (heart, pulmonary and bowel sounds) that served as evidences in the confirmation of drug efficacy and its possible adverse effects. In addition, we included the images of each body part, the 24 format question items, the palpation (rate and rhythm) of the radial artery, brachial artery and pedal artery, the clinical data obtained from several medical equipment, the pupillary reflex, and the urine dipstick test. This way, learners are able to experience PA with reference to the subjective and objective data from patient reception and questions. The virtual patient's avatar displayed on the monitor features auscultatory sounds on the stethoscope. It also features clinical data obtained from other medical equipment that can give the learners an interactive way of learning about various medical conditions. For evaluation, we gave out questionnaires on the virtual PA to pharmacy students. As a result, a high evaluation was reflected in terms of the degree of usefulness for both case learning and basic learning.

Physical Assessment Education Using Various Simulators.

Pharmacists are in demand not only because of their knowledge of medical therapy but also due to their skills in basic physical assessment and emergency care as medical personnel. Pharmaceutical education has developed using patient simulators in bedside training, seminars in hospital pharmacies, and physical assessment practice at the Kyushu University of Health and Welfare School of Pharmaceutical Sciences. We first explain the outline of the method to confirm basic vital signs with simulators and then demonstrate some simulations to enable the reproduction of drug misadministration/changes in condition. In addition, we check students' knowledge of and skill in the advanced objective structured clinical examination through practical examinations to test their technical ability in physical assessment. Furthermore, we conduct case study exercises in which students perform physical assessments and collect basic information on patient background. The Stan, Heart SIM, and Physico simulators are used. As examples of drug misadministration, the reproduction of asystole from fatal arrhythmia after the rapid intravenous injection of potassium preparations and ventricular fibrillation from tachycardia after an overdose of insulin are presented to student pharmacists utilizing the simulators. The simulation of anaphylactic shock and hyperglycemia is also possible as examples of changes in condition. Overall, pharmaceutical simulation education provides pharmacy students and pharmacists with experience in the types of medical treatment performed by various healthcare professionals, leading to explorations of the new roles of pharmacists in team medical care.

Instructing students to measure their own bone density and prepare a simulated health class during pharmacy school improves their awareness and understanding of osteoporosis prevention.

BACKGROUND: Osteoporosis is estimated to afflict over 200 million people worldwide and healthcare professionals are needed to successfully intervene. The aim of this study was to assess cognitive changes in students pertaining to the primary prevention of osteoporosis after measuring their bone density and having them participate in a simulated health class during pharmacy school. METHODS: Third year pharmacy students participated in the training program, which consisted of measuring their bone density using quantitative ultrasound and preparing educational materials and conducting a simulated health class. The students' knowledge concerning the prevention and education on osteoporosis was surveyed using questionnaires before and after the training. RESULTS: The bone area ratio (BAR) in 24 % of the students was evaluated as category 4 (slightly low) or 5 (low or caution). Regression analysis indicated a significant relationship between the BAR and amount of exercise reported in both males (p = 0.005) and females (p = 0.004). The student-made educational materials were prepared in line with the requirements of the Japanese 2011 guidelines. The student response rates for the importance of food, exercise, and the bone density measurement in youth were significantly increased after the training (p < 0.001 in all). More than 95 % of students reported that the program was useful, improved their understanding, and important, with 94 % satisfied with the experience. CONCLUSIONS: This experience-based educational program combining measuring the bone density and the preparation and presentation of a simulated health class appeared to improve the awareness and understanding of osteoporosis prevention in pharmacy students.

Orally Administered Mucolytic Drug l-Carbocisteine Inhibits Angiogenesis and Tumor Growth in Mice.

Angiogenesis, the formation of new blood vessels from pre-existing vessels, is essential for the growth and metastasis of tumors. In this study, we found that l-carbocisteine, a widely used expectorant, potently inhibits angiogenesis in vitro and in vivo. An in vivo Matrigel plug assay revealed that l-carbocisteine (2.5 mg/kg i.p. twice daily) significantly inhibited vascular endothelial growth factor (VEGF)-induced angiogenesis. l-Carbocisteine also suppressed VEGF-stimulated proliferation, migration, and formation of capillary-like structures of human umbilical vein endothelial cells (HUVECs). We examined the signaling pathways affected in VEGF-stimulated HUVECs, and found that l-carbocisteine significantly inhibited VEGF-induced phosphorylation of phospholipase C (PLC) γ, protein kinase C (PKC) µ, and extracellular signal-related kinases (ERK) 1/2, which have been shown to be essential for angiogenesis. However, these inhibitory effects of l-carbocisteine were not observed in the HeLa human cervical cancer cell line. An in vivo study of Colon-26 tumor-bearing mice found that tumor volumes were significantly smaller in mice treated with l-carbocisteine (150 mg/kg administered orally twice daily) in comparison with vehicle-treated mice. However, l-carbocisteine had no direct effect on Colon-26 cell proliferation or ERK activation. Collectively, our results suggest that l-carbocisteine inhibits tumor angiogenesis by suppressing PLCγ/PKC/ERK signaling.

Improving Walking, Muscle Strength, and Balance in the Elderly with an Exergame Using Kinect: A Randomized Controlled Trial.

BACKGROUND: Many issues prevent elderly individuals from exercising in daily life. There is a need for a system that allows elderly individuals to engage in exercise regularly at a low cost. We developed an exergame that uses a Kinect(®) sensor (Microsoft Corp., Redmond, WA) and conducted a randomized controlled trial of the effects of using this exergame on muscle strength and balance in healthy elderly individuals. SUBJECTS AND METHODS: We enrolled 57 healthy elderly individuals and randomly divided them into an intervention group (n=29) and a control group (n=28) using a table of random numbers. All participants underwent gait analyses and were examined using the Berg Balance Scale (BBS), Functional Reach Test (FRT), and the 30-second chair-stand (CS-30) test before the intervention. Participants in the intervention group played the exergame once or twice a week, up to a total of 24 times. The tests were repeated after intervention, and the scores were compared with those obtained before intervention. RESULTS: Our results indicated that walking, muscle strength, and motor function improved in participants in the intervention group. Decreased double standing time (P=0.03), minimum foot clearance (P=0.04), BBS scores (P<0.01), CS-30 scores (P<0.01), and FRT scores (P<0.01) significantly improved in the intervention group compared with values in the control group. CONCLUSIONS: The Kinect-based exergame developed in this study was found to be effective in improving walking, muscular strength, and balance in elderly people.

Determination of nonsteroidal anti-inflammatory drugs in human tear and plasma samples using ultra-fast liquid chromatography-tandem mass spectrometry.

PURPOSE: To evaluate a new rapid and sensitive method for analyzing human tears and plasma for nonsteroidal anti-inflammatory drugs (NSAIDs) and investigate the influence of the transfer of NSAIDs in an ocular lesion. METHODS: In this cross-over study, a single dose of 200 mg of ibuprofen and 60 mg of loxoprofen sodium were orally administered to six healthy Japanese subjects. Collected samples were analyzed by ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS). RESULTS: Recoveries of the two drugs spiked in the tears and plasma were 96.0-117.0 % in the tears and 99.0-105.7 % in the plasma. Regression equations for both NSAIDs showed excellent linearity from 0.02-1.0 µg/ml for the tears and 0.1-5.0 µg/ml for the plasma, with the limits of detection at 0.02 µg/ml for tears and 0.1 µg/ml for plasma. CONCLUSION: This new high-throughput NSAID determination method only requires a small tear amount (10 µl) and plasma volume (20 µl) and thus will be useful in clinical and toxicological analyses. Analytical results also showed the presence of ibuprofen and loxoprofen in the actual tears and plasma, which confirms the transition of NSAIDs from the tears to the plasma.

Pleiotropic Effects of Levofloxacin, Fluoroquinolone Antibiotics, against Influenza Virus-Induced Lung Injury.

Reactive oxygen species (ROS) and nitric oxide (NO) are major pathogenic molecules produced during viral lung infections, including influenza. While fluoroquinolones are widely used as antimicrobial agents for treating a variety of bacterial infections, including secondary infections associated with the influenza virus, it has been reported that they also function as anti-oxidants against ROS and as a NO regulator. Therefore, we hypothesized that levofloxacin (LVFX), one of the most frequently used fluoroquinolone derivatives, may attenuate pulmonary injuries associated with influenza virus infections by inhibiting the production of ROS species such as hydroxyl radicals and neutrophil-derived NO that is produced during an influenza viral infection. The therapeutic impact of LVFX was examined in a PR8 (H1N1) influenza virus-induced lung injury mouse model. ESR spin-trapping experiments indicated that LVFX showed scavenging activity against neutrophil-derived hydroxyl radicals. LVFX markedly improved the survival rate of mice that were infected with the influenza virus in a dose-dependent manner. In addition, the LVFX treatment resulted in a dose-dependent decrease in the level of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress) and nitrotyrosine (a nitrative marker) in the lungs of virus-infected mice, and the nitrite/nitrate ratio (NO metabolites) and IFN-γ in BALF. These results indicate that LVFX may be of substantial benefit in the treatment of various acute inflammatory disorders such as influenza virus-induced pneumonia, by inhibiting inflammatory cell responses and suppressing the overproduction of NO in the lungs.