Prevalence of iron-deficient but non-anemic university athletes in Japan: an observational cohort study.

BACKGROUND: Iron deficiency (ID) and iron deficiency anemia (IDA) are long-standing health problems in athletes, affecting both performance and health. ID prevalence in young athletes remains high and a matter of concern. ID and IDA can lead to fatigue, reduced endurance, and decreased oxygen transport, potentially compromising athletic performance. We hypothesized that ID would still be a major health concern in university athletes across sports clubs in Japan. PURPOSE: The study aimed to investigate the prevalence of ID and IDA in athletes participating in Kendo, badminton, baseball, and handball at the University of Tsukuba (Tsukuba, Ibaraki Prefecture, Japan). The study also examined the correlation between hypoferritinemia and other variables, such as previous use of iron supplements, body mass index (BMI), energy intake, and years of athletics. METHODS: Between January and December 2019, 126 university athletes, consisting of 79 males and 47 females, underwent physical measurements and blood tests. The blood test included complete blood count, levels of serum ferritin, serum iron, and total iron-binding capacity. The anemia was defined in accordance with the WHO criteria. Daily energy and iron intake were estimated with the food frequency questionnaire in Japanese (FFQg). Thirty-four female athletes responded to a survey about their menstruation and low-dose estrogen-progestin (LEP) usage. RESULTS: While none of the athletes had anemia, 22 (47%) female athletes exhibited serum ferritin levels of 30 ng/mL or less, defining them as hypoferritinemia. The multivariate logistic regression model revealed that a shorter duration of the athletic experience (adjusted odd ratio [95% confidence interval]: 0.62 [0.43-0.90]), lower energy intake (0.994 [0.989-0.999]), and higher dietary iron intake (4.40 [1.12-17.26]) were associated with hypoferritinemia. Seventeen (50%) female athletes reported a decline in subjective performance during menstruation, albeit two took LEP regularly. CONCLUSIONS: This study reveals that ID is a prevalent health concern among young female athletes across sports clubs. It underscores the need for their education on the importance of assessing ID status. Limitation includes the nature of single-site and observational study, the absence of hepcidin measurement, and an unspecified amount of exercise. Comprehensive investigations are needed to elucidate the causes and optimal treatments for ID in young athletes.

Blueberry Leaf Extract Prevents Lacrimal Hyposecretion in Sjögren's Syndrome-like Model of Non-obese Diabetic Mice.

BACKGROUND/AIM: This study evaluated the effect of blueberry leaf hot water extract (BLEx) on Sjögren's syndrome (SS)-like lacrimal hyposecretion in male non-obese diabetic (NOD) mice. MATERIALS AND METHODS: NOD or BALB/c mice were fed 1% BLEx or control (AIN-93G) for 2 weeks from the age of 4 to 6 weeks. Pilocarpine-induced tear volume was measured using a phenol red-impregnated thread. The lacrimal glands were evaluated histologically by H&E staining. The IL-1ß and TNF-α levels in the lacrimal gland tissue were measured by ELISA. The mRNA expression levels of secretion-related proteins were measured by real-time PCR. LC3 I/II and arginase 1 expression levels were measured by western blot. RESULTS: After feeding with BLEx, pilocarpine-induced tear secretion in NOD mice was increased. In contrast, the mRNA expression levels of the cholinergic muscarinic M3 receptor, aquaporin 5, and ion channels related to lacrimal secretion were not changed by BLEx administration. In addition, the protein expression of arginase 1, which was recently reported to be involved in tear hyposecretion in NOD mice, was also not improved by BLEx administration. Although infiltration in the lacrimal gland of NOD mice was not decreased, the levels of TNF-α and the autophagy-related protein LC3 were significantly suppressed by BLEx treatment. CONCLUSION: BLEx treatment may ameliorate lacrimal hyposecretion in NOD mice by delaying the progression of autoimmune disease by suppressing autophagy in lacrimal glands.

Blueberry stem extract and stem active components prevent blue light-emitting diode light-induced retinal photoreceptor cell damage in vitro.

Blue light causes retinal damage that can lead to ocular diseases such as age-related macular degeneration. In this study, we determined the protective effect of blueberry stem extract (BStEx) and active components on blue light-emitting diode (LED) light-induced retinal photoreceptor cell damage in vitro. Photoreceptor cells cultured in the presence of BStEx or components were exposed to blue light to induce cell damage. BStEx, fractions of BStEx containing proanthocyanidins, chlorogenic acid, catechin, and epicatechin prevented the cell damage and/or inhibited the generation of reactive oxygen species (ROS). Furthermore, BStEx reduced apoptosis and cell death, and inhibited the phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase leading to cellular apoptosis induced by blue light exposure. These findings suggest that BStEx and components exert a protective effect against blue light-induced photoreceptor cell damage through the inhibition of MAPK phosphorylation and ROS production.

UHPLC-MS/MS method for simultaneous quantification of doripenem, meropenem, ciprofloxacin, levofloxacin, pazufloxacin, linezolid, and tedizolid in filtrate during continuous renal replacement therapy.

BACKGROUND: Since severe infections frequently cause acute kidney injury (AKI), continuous renal replacement therapy (CRRT) is often initiated for regulation of inflammatory mediators and renal support. Thus, it is necessary to decide the antibiotic dosage considering the CRRT clearance in addition to residual renal function. Some of the hemofilters used in CRRT are known to adsorb antibiotics, and clearance of antibiotics may differ depending on the adsorptive characteristics of hemofilters. Although assay systems for blood and CRRT filtrate concentrations are required, no method for measuring antibiotics concentrations in filtrate has been reported. We developed a UHPLC-MS/MS method for simultaneous quantification of antibiotics commonly used in ICU, comprising carbapenems [doripenem (DRPM) and meropenem (MEPM)], quinolones [ciprofloxacin (CPFX), levofloxacin (LVFX) and pazufloxacin (PZFX)] and anti-MRSA agents [linezolid (LZD), and tedizolid (TZD)] in CRRT filtrate samples. METHODS: Filtrate samples were pretreated by protein precipitation. The analytes were separated with an ACQUITY UHPLC CSH C18 column under a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid and 2 mM ammonium formate. RESULTS: The method showed good linearity over wide ranges. Within-batch and batch-to-batch accuracy and precision for each drug fulfilled the criteria of the US Food and Drug Administration guidance. The recovery rate was more than 87.20%. Matrix effect ranged from 99.57% to 115.60%. Recovery rate and matrix effect did not differ remarkably between quality control samples at different concentrations. CONCLUSION: This is the first report of a simultaneous quantification method of multiple antibiotics in filtrate of CRRT circuit.

Amelioration of Endotoxemia by a Synthetic Analog of Omega-3 Epoxyeicosanoids.

Sepsis, a systemic inflammatory response to pathogenic factors, is a difficult to treat life-threatening condition associated with cytokine and eicosanoid storms and multi-organ damage. Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic (EPA) and docosahexaenoic acid, are the precursors of potent anti-inflammatory lipid mediators, including 17,18-epoxyeicosatetraenoic acid (17,18-EEQ), the main metabolite of EPA generated by cytochrome P450 epoxygenases. Searching for novel therapeutic or preventative agents in sepsis, we tested a metabolically robust synthetic analog of 17,18-EEQ (EEQ-A) for its ability to reduce mortality, organ damage, and pro-inflammatory cytokine transcript level in a mouse model of lipopolysaccharide (LPS)-induced endotoxemia, which is closely related to sepsis. Overall survival significantly improved following preventative EEQ-A administration along with decreased transcript level of pro-inflammatory cytokines. On the other hand, the therapeutic protocol was effective in improving survival at 48 hours but insignificant at 72 hours. Histopathological analyses showed significant reductions in hemorrhagic and necrotic damage and infiltration in the liver. In vitro studies with THP-1 and U937 cells showed EEQ-A mediated repression of LPS-induced M1 polarization and enhancement of IL-4-induced M2 polarization of macrophages. Moreover, EEQ-A attenuated the LPS-induced decline of mitochondrial function in THP-1 cells, as indicated by increased basal respiration and ATP production as well as reduction of the metabolic shift to glycolysis. Taken together, these data demonstrate that EEQ-A has potent anti-inflammatory and immunomodulatory properties that may support therapeutic strategies for ameliorating the endotoxemia.

Validation of a lateral flow immunochromatographic assay for tinea unguium diagnosis.

Tinea unguium is a common nail disease caused by dermatophytes. Although direct potassium hydroxide (KOH) microscopy and fungal culture are considered the gold standard for diagnosing this disease, their accuracy is insufficient. A lateral flow immunochromatographic assay (LFIA) kit, using a monoclonal antibody against Trichophyton rubrum, was developed and its sensitivity was recently improved 50% in vitro relative to its earlier version. The present study aimed to validate the clinical utility of this improved LFIA kit for diagnosing tinea unguium in comparison with direct KOH microscopy. A similar trial was simultaneously performed using scale samples from patients with tinea pedis to determine the assay's diagnostic potential. Nail samples, approximately 2 mg in weight, were collected from 112 non-treated tinea unguium patients and 56 non-tinea unguium patients. Samples from 25 tinea pedis patients and 20 non-tinea pedis patients were also collected. The sensitivity and specificity of the LFIA kit for tinea unguium was 84.8% (95/112) (95% confidence interval [CI], 76.8-90.9) and 83.9% (47/56) (95% CI, 71.7-92.4), respectively. The inconsistency rate was 15.5% (26/168) (95% CI, 10.4-21.9). The sensitivity and specificity of the LFIA kit for tinea pedis was 84.0% (21/25) and 100.0% (20/20), respectively. These results suggest that for diagnosing tinea unguium, the LFIA kit is a useful supplement to, but not a replacement for, direct KOH microscopy. For definitive diagnosis of suspected cases, appropriate sampling, repeated examinations, and a combination of diagnostic techniques are essential.

Evaluation of Peripheral Electrostimulation Thresholds in Human Model for Uniform Magnetic Field Exposure.

The external field strength according to the international guidelines and standards for human protection are derived to prevent peripheral nerve system pain at frequencies from 300-750 Hz to 1 MHz. In this frequency range, the stimulation is attributable to axon electrostimulation. One limitation in the current international guidelines is the lack of respective stimulation thresholds in the brain and peripheral nervous system from in vivo human measurements over a wide frequency range. This study investigates peripheral stimulation thresholds using a multi-scale computation based on a human anatomical model for uniform exposure. The nerve parameters are first adjusted from the measured data to fit the peripheral nerve in the trunk. From the parameters, the external magnetic field strength to stimulate the nerve was estimated. Here, the conservativeness of protection limits of the international guidelines and standards for peripheral stimulation was confirmed. The results showed a margin factor of 4-6 and 10-24 times between internal and external protection limits of Institute of Electrical and Electronics Engineers standard (IEEE C95.1) and International Commission on Non-Ionizing Radiation Protection guidelines, with the computed pain thresholds.

Prevalence of iron deficiency among university kendo practitioners in Japan: an observational cohort study.

BACKGROUND: Iron deficiency is widely recognized as being the cause of anemia in athletes, although iron status in athletes of Kendo, a traditional Japanese martial art based on swordsmanship and practiced as an educational sport, has not been widely investigated. METHODS: We performed a health assessment on anemia and serum ferritin levels, along with nutrient intake evaluation, for Kendo practitioners in a university in Japan. RESULTS: A total of 56 Kendo practitioners (39 male and 17 female) aged between 18 and 23 years participated in the study. No individuals exhibited WHO-defined anemia (less than 13 or 12 g/dL of hemoglobin levels in male or female), while hypoferritinemia (less than 30 ng/mL) was found in seven (41%) females but not in males. Significantly higher body mass index was found in the female athletes with hypoferritinemia compared to females with normo-ferritinemia in sub-analysis (median [interquartile range]; 25.6 [24.2, 26.9] versus 22.6 [21.7, 24.1], respectively. p < 0.05). No significant differences in the intake of iron were registered between males and females (with and without hypoferritinemia) using data from a food-frequency questionnaire survey. CONCLUSION: No apparent anemia was found in adolescent Kendo practitioners, although this study confirmed the presence of hypoferritinemia in several female athletes. Careful follow-up, involving both clinical and nutritional assessment, will be necessary for them to prevent progression into anemia. A future study with larger cohorts in multiple sites is warranted to assess the prevalence of iron deficiency for validation and, if necessary, to devise a strategy for improving the iron status in Kendo athletes.

Effect of L-Carnitine on Amino Acid Metabolism in Elderly Patients Undergoing Regular Hemodialysis.

INTRODUCTION: Among patients regularly undergoing hemodialysis, hypocarnitinaemia often develops as a consequence of inadequate dietary intake, reduced synthesis in the body, and considerable losses during hemodialysis. OBJECTIVES: To evaluate the effects of L-carnitine supplementation on patients with end-stage kidney disease (ESKD) who underwent hemodialysis. METHODS: Thirty-one patients with ESKD, comprising 18 men and 13 women, with a median age of 72 (range 58-89) years, who underwent regular hemodialysis received treatment with L-carnitine for 1 year. The total and free carnitine, acylcarnitine, and amino acids (AA) levels before and after L-carnitine treatment were analyzed, and the blood biochemistry results and clinical profiles of the subjects were compared before and after treatment. RESULTS: The median (interquartile range [IQR]) serum total and free carnitine and acylcarnitine levels significantly increased from 34.5 (28.2-44.3), 20.9 (15.8-27.6), and 14.1 (11.2-17.6) µmol/L, respectively to 407.4 (371.6-493.5), 270.2 (228.3-316.0), and 155.0 (136.1-168.5) µmol/L, respectively, after treatment (all p < 0.001). The median (IQR) blood valine, tyrosine, phenylalanine, and citrulline levels increased from 0.94 (0.80-1.09), 0.45 (0.39-0.55), 0.61 (0.56-0.79), and 1.04 (0.79-1.26) mg/dL, respectively to 1.24 (1.13-1.54), 0.76 (0.62-0.85), 0.90 (0.70-1.04), and 1.22 (0.92-1.39) mg/dL, respectively, following L-carnitine treatment (p < 0.001, p < 0.001, p = 0.002, and p = 0.030, respectively); however, the median (IQR) blood arginine level decreased from 0.20 (0.13-0.24) to 0.09 (0.06-0.14) mg/dL after treatment (p < 0.001). The median (IQR) percentage fractional shortening (41.5 vs. 41.9%; p = 0.012) and left ventricular ejection fraction (65.2 vs. 67.3%; p = 0.036) increased significantly following treatment. CONCLUSIONS: L-Carnitine increased the blood acylcarnitine levels, enhanced fatty acid metabolism, and affected AAs metabolism; this may be beneficial for energy production within the cardiac and skeletal muscles.

Pharmacokinetics of ceftriaxone in patients undergoing continuous renal replacement therapy.

BACKGROUND: The duration of time for which the serum levels exceed the minimum inhibitory concentration (MIC) is an important pharmacokinetics (PK)/pharmacodynamics (PD) parameter correlating with efficacy for the antibiotic, ceftriaxone (CTRX). However, no reports exist regarding the PK or PD in patients undergoing continuous renal replacement therapy (CRRT). The purpose of this study was to examine the PK and safety of CTRX in patients undergoing CRRT in order to establish safer and more effective regimens. METHODS: CTRX (1 g once a day) was intravenously administered four or more times to nine patients undergoing CRRT. Blood was collected after administration to measure CTRX concentrations in serum and the filtration fraction of CRRT by high-performance liquid chromatography. In addition to calculating PK parameters from serum CTRX, we (a) estimated by simulation CTRX concentrations when the dose interval was extended to once every 2 or 3 days, (b) calculated CTRX clearance via CRRT from CTRX concentrations in the filtration fraction, and (c) assessed the safety of CTRX use. RESULTS: Total body clearance and the half-life of CTRX were 7.46 mL/min (mean) and 26.5 h, respectively, in patients undergoing CRRT. CTRX was found in the filtration fraction, and the estimated clearance by CRRT was about 70% of total body clearance. Simulations revealed that even when the dose interval is increased to 2 or 3 days, CTRX would retain its efficacy. CONCLUSIONS: Our findings suggest that, depending on the condition of patients undergoing CRRT, CTRX could be used safely against pathogens with a CTRX MIC ≤2 µg/mL, even when extending the dose interval.

Interaction between Pirenzepine and Ninjinto, a Traditional Japanese Herbal Medicine, on the Plasma Gut-Regulated Peptide Levels in Humans.

The Japanese herbal medicine (Kampo) Ninjinto has been used for the treatment of gastroenteritis, esogastritis, gastric atony, gastrectasis, vomiting, and anorexia. The pharmacological effects of Ninjinto on the gastrointestine are due to changes in the levels of gut-regulated peptide, such as motilin, somatostatin, calcitonin gene-related peptide (CGRP), substance P, and vasoactive intestinal polypeptide (VIP). The release of these peptides is controlled by acetylcholine (ACh) from the preganglionic fibers of the parasympathetic nerve. Thus, we examined the effects of the selective M1 muscarinic receptor antagonist pirenzepine on the elevation of Ninjinto-induced plasma the area under the plasma gut-regulated peptide concentration-time curve from 0 to 240 min (AUC0→240 min) in humans. Oral pretreatment with pirenzepine significantly reduced the Ninjinto-induced elevation of plasma motilin and substance P release (AUC0→240 min). Combined treatment with Ninjinto and pirenzepine significantly increased the release of plasma somatostatin (AUC0→240 min) compared with administration of Ninjinto alone or placebo. Ninjinto appeared to induce the release of substance P and motilin into plasma mainly through the activation of M1 muscarinic receptors, and pirenzepine may affect the pharmacologic action of Ninjinto by the elevation of plasma substance P, motilin, and somatostatin.

Is peak concentration needed in therapeutic drug monitoring of vancomycin? A pharmacokinetic-pharmacodynamic analysis in patients with methicillin-resistant staphylococcus aureus pneumonia.

BACKGROUND: We analyzed the pharmacokinetic-pharmacodynamic relationship of vancomycin to determine the drug exposure parameters that correlate with the efficacy and nephrotoxicity of vancomycin in patients with methicillin-resistant Staphylococcus aureus pneumonia and evaluated the need to use peak concentration in therapeutic drug monitoring (TDM). METHODS: Serum drug concentrations of 31 hospitalized patients treated with vancomycin for methicillin-resistant S. aureus pneumonia were collected. RESULTS: Significant differences in trough concentration (Cmin)/minimum inhibitory concentration (MIC) and area under the serum concentration-time curve (AUC0-24)/MIC were observed between the response and non-response groups. Significant differences in Cmin and AUC0-24 were observed between the nephrotoxicity and non-nephrotoxicity groups. Receiver operating characteristic curves revealed high predictive values of Cmin/MIC and AUC0-24/MIC for efficacy and of Cmin and AUC0-24 for safety of vancomycin. CONCLUSIONS: These results suggest little need to use peak concentration in vancomycin TDM because Cmin/MIC and Cmin are sufficient to predict the efficacy and safety of vancomycin.

Establishment and clinical application of a highly sensitive enzyme immunoassay for determination of N-acetyl-seryl-aspartyl-lysyl-proline.

N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a natural inhibitor of pluripotent hematopoietic stem cell proliferation and is normally found in human plasma. Because AcSDKP is hydrolyzed by the N-terminal active site of angiotensin converting enzyme and partially eliminated in urine, its plasma level is a result of a complex balance between its production, hydrolysis by ACE, and renal elimination. In this study, we attempted to establish an enzyme immunoassay (EIA) for quantifying AcSDKP-like immunoreactive substance (IS), which is applicable for monitoring plasma AcSDKP levels in healthy subjects and patients with chronic renal failure. Using ß-D-galactosidase-labeled Gly-γAbu-SDKP as a marker antigen, an anti-rabbit IgG-coated immunoplate as a bound/free separator and 4-methylumbelliferyl-ß-D-galactopyranoside as a fluorogenic substrate, a highly sensitive and specific EIA was developed for the quantification of AcSDKP-IS in human plasma. The lower limit of quantification was 0.32 fmol/well, and the sharp inhibition competitive EIA calibration curve obtained was linear between 8.0 and 513 fmol/ml. This EIA was so sensitive that only 10 µl plasma sample was required for a single assay. The coefficients of variation (reproducibility) for human plasma concentrations of 0.2 and 2.1 pmol/ml were 7.2 and 7.7%, respectively, for inter-assay and 13.3 and 7.8% for intra-assay comparisons. Plasma AcSDKP-IS level was significantly higher in patients with chronic renal failure (0.92 ± 0.39 pmol/ml) compared with healthy subjects (0.29 ± 0.07 pmol/ml). These results suggest that our EIA may be useful to evaluate plasma AcSDKP level as a biomarker in various patients.

Comparison of the effects of pantethine and fursultiamine on plasma gastrointestinal peptide levels in healthy volunteers.

Pantethine and fursultiamine have been evaluated for their clinical usefulness in the treatment and prevention of uncomplicated postoperative adhesive intestinal obstruction. In recent years, the actions of drugs used to treat gastrointestinal diseases have been elucidated pharmacologically from the viewpoints of gastrointestinal peptide levels. We examined the effects of pantethine and fursultiamine on plasma levels of calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, motilin- and substance P (SP)-like immunoreactive substances (IS) in healthy subjects. An open-labeled study was conducted on five healthy volunteers. Each subject was administered a single oral dose of pantethine, fursultiamine and placebo at intervals of one month. Venous blood samples were collected before and at 20, 40, 60, 90, 120, 180 and 240 min after each administration. Plasma peptide levels were measured using a highly sensitive enzyme immunoassay. A single oral dose of pantethine resulted in significant increases of plasma CGRP- and VIP-IS levels compared to placebo. Furthermore, areas under the plasma concentration-time curves (AUC(0-240)) of CGRP- and VIP-IS were significantly higher after pantethine administration compared with placebo. On the other hand, fursultiamine had no effect on plasma levels and AUC(0-240) of CGRP-, VIP-, motilin- and SP-IS. This study demonstrated the different effects of pantethine and fursultiamine from the viewpoint of plasma gastrointestinal peptide changes. The pharmacological effects of pantethine may be closely related to the changes in plasma CGRP- and VIP-IS levels.