[Potential application of improved hard tissue section technique in the clinical pathological diagnosis of bone and bone marrow].

Objective: To discuss the application value of hard tissue section in the clinicopathology diagnosis. Methods: From March 2021 to December 2021, bone slices of 19 patients (1 patient with osteochondroma, 2 patients with chondrosarcoma, 4 patients with osteosarcoma, 2 patients with fibrous dysplasia, 2 patients with bone metastasis from thyroid papillary carcinoma, 2 patients with osteomyelitis, 4 patients with giant cell tumor of bone, 2 patients with Ewing sarcoma) and 16 hemopathy patients were collected from the Department of Pathology, Shanghai Sixth People's Hospital. Of the osteopathy patients, there were 14 male and 5 female with a median age of 31 (10-66) years. Meanwhile, there were 7 male and 9 female with a median age of 28 (16-65) years among these hemopathy patients. Thirty-five cases were treated with modified hard tissue slicing technique and paraffin embedding technique, respectively. The advantages and disadvantages of the two methods for clinical diagnosis of bone disease were compared by Hematoxylin-Eosin staining (H&E staining), immunohistochemical staining (IHC), fluorescence in situ hybridization (FISH) and Sanger sequencing. Results: The improved resin-embedded method showed better histological morphology and cell structure. Besides, the expression of Ki67, SATB2, CD34, SMA, CD68,MPO,CD4 and CD33 in immunohistochemical staining in bone tissues which were embedded in resin were more clear in the accurate positive localization than those using paraffin-embedded. MDM2 of FISH exhibited a higher fluorescence intensity and more accurate location. Meanwhile, both methods treated with Sanger sequencing met the requirements of DNA purity and mutation detection. Conclusion: The improved hard tissue section method is simple and short time-consuming, which is suitable for optimizing the clinical bone and bone marrow pathological diagnosis process.

Performance and reading time of lung nodule identification on multidetector CT with or without an artificial intelligence-powered computer-aided detection system.

AIM: To compare the performance and reading time of different readers using automatic artificial intelligence (AI)-powered computer-aided detection (CAD) to detect lung nodules in different reading modes. MATERIALS AND METHODS: One hundred and fifty multidetector computed tomography (CT) datasets containing 340 nodules ≤10 mm in diameter were collected retrospectively. A CAD with vessel-suppressed function was used to interpret the images. Three junior and three senior readers were assigned to read (1) CT images without CAD, (2) second-read using CAD in which CAD was applied only after initial unassisted assessment, and (3) a concurrent read with CAD in which CAD was applied at the start of assessment. Diagnostic performances and reading times were compared using analysis of variance. RESULTS: For all readers, the mean sensitivity improved from 64% (95% confidence interval [CI]: 62%, 66%) for the without-CAD mode to 82% (95% CI: 80%, 84%) for the second-reading mode and to 80% (95% CI: 79%, 82%) for the concurrent-reading mode (p<0.001). There was no significant difference between the two modes in terms of the mean sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for both junior and senior readers and all readers (p>0.05). The reading time of all readers was significantly shorter for the concurrent-reading mode (124 ± 25 seconds) compared to without CAD (156 ± 34 seconds; p<0.001) and the second-reading mode (197 ± 46 seconds; p<0.001). CONCLUSION: In CAD for lung nodules at CT, the second-reading mode and concurrent-reading mode may improve detection performance for all readers in both screening and clinical routine practice. Concurrent use of CAD is more efficient for both junior and senior readers.

Serum fibroblast growth factor 23 and mineral metabolism in patients with euthyroid Graves' diseases: a case-control study.

This study investigated the alterations of mineral metabolism in patients with Graves' disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status. INTRODUCTION: FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves' disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved. METHODS: A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups. RESULTS: Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group. CONCLUSION: Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations. TRIAL REGISTRATION: Registration number: NCT01660308 and NCT02620085.

General hospital admission rates in people diagnosed with personality disorder.

OBJECTIVE: To determine the frequency of all-cause general hospital admissions for individuals with personality disorder (PD) in a large clinical population using linked secondary mental healthcare and hospitalisation data. METHOD: A retrospective cohort study, using anonymised electronic mental health records from South London and Maudsley NHS Foundation Trust (SLaM), linked to Hospital Episodes Statistics in England. People with PD aged 15 years or older, receiving care within SLaM between April 2007 and March 2013, were identified and compared to residents from the local catchment area. Standardised admission ratios (SARs) were calculated for all major categories of causes of general hospital admission for this defined group, with local residents in 2011 UK Census as the standard population. RESULTS: For the 7677 people identified with PD, SAR for all causes of admission was 2.75 (95% CI: 2.70, 2.81). Both men and women with PD had increased SARs across multiple ICD-10 categories, including circulatory, respiratory, digestive, nervous, and musculoskeletal system disorders and endocrine, blood and infectious disorders. Sensitivity analysis (removing the impact of repeated admissions by same individual for same diagnosis in the same year) yielded similar findings. CONCLUSIONS: By comparison with members of the general population, individuals with a diagnosis of personality disorder are at significantly higher risk of hospital admission resulting from a wide range of physical health problems.

Long-term antipsychotic polypharmacy prescribing in secondary mental health care and the risk of mortality.

OBJECTIVES: To investigate the association between long-term antipsychotic polypharmacy use and mortality; and determine whether this risk varies by cause of death and antipsychotic dose. METHODS: Using data from a large anonymised mental healthcare database, we identified all adult patients with serious mental illness (SMI) who had been prescribed a single antipsychotic or polypharmacy, for six or more months between 2007 and 2014. Multivariable Cox regression models were constructed, adjusting for sociodemographic, socioeconomic, clinical factors and smoking, to examine the association between APP use and the risk of death. RESULTS: We identified 10 945 adults with SMI who had been prescribed long-term antipsychotic monotherapy (76.9%) or APP (23.1%). Patients on long-term APP had a small elevated risk of mortality, which was significant in some but not all models. The adjusted hazard ratios for death from natural and unnatural causes associated with APP were 1.2 (0.9-1.4, P = 0.111) and 1.1 (0.7-1.9, P = 0.619) respectively. The strengths of the associations between APP and mortality outcomes were similar after further adjusting for % BNF antipsychotic dose (P = 0.031) or olanzapine equivalence (P = 0.088). CONCLUSION: The findings suggest that the effect of long-term APP on mortality is not clear-cut, with limited evidence to indicate an association, even after controlling for the effect of dose.

Transformation of excess mortality in people with schizophrenia and bipolar disorder in Taiwan.

BACKGROUND: Given the concerns regarding the adverse health outcomes associated with weight gain and metabolic syndrome in relation to use of second-generation antipsychotics (SGAs), we aimed in this study to explore whether the increase in the use of SGAs would have any impacts on the trend of excess mortality in people with schizophrenia and bipolar disorder (BPD). METHOD: Two nationwide samples of individuals with schizophrenia and BPD were identified in Taiwan's National Health Insurance Research Database in 2003 and in 2008, respectively. Age- and gender-standardized mortality ratios (SMRs) were calculated for each of the 3-year observation periods. The SMRs were compared between the calendar year cohorts, by disease group, and by causes of death. RESULTS: The mortality gap for people with schizophrenia decreased slightly, revealing an SMR of 3.40 (95% CI 3.30-3.50) for the 2003 cohort and 3.14 (3.06-3.23) for the 2008 cohort. The mortality gap for BPD individuals remained relatively stable with only those aged 15-44 years having an SMR rising significantly from 7.04 (6.38-7.76) to 9.10 (8.44-9.79). Additionally, in this group of BPD patients aged 15-44 years, the natural-cause-SMR increased from 5.65 (4.93-6.44) to 7.16 (6.46-7.91). CONCLUSIONS: Compared with the general population, the gap in the excess mortality for people with schizophrenia reduced slightly. However, the over 200% difference between the cohorts in the excess mortality for BPD individuals aged 15-44 years could be a warning sign. Future research to further examine the related factors underlying those changes is warranted.

Prevention of perceptual-motor decline by branched-chain amino acids, arginine, citrulline after tennis match.

Perceptual-motor performance in prolonged tennis matches may be affected by central fatigue. The purpose of this study was to investigate the supplementation of branched-chain amino acids (BCAA), arginine, and citrulline on tennis-specific perceptual-motor performance after a simulated match. Nine male tennis players consumed 0.17 g/kg BCAA, 0.05 g/kg arginine, and 0.05 g/kg citrulline (AA trial), or placebo (PB trial) 1 h before the match. In the perceptual-motor performance test before and after the match, the subjects hit balls to the opposite direction of the examiner's movement. The AA trial showed significantly higher rate of correct direction than the PB trial after the match (AA trial: 93.63 ± 1.28%, PB trial: 69.09 ± 2.40%). The AA trial also demonstrated significantly higher post-match accuracy and consistency than the PB trial. The AA trial showed significantly lower heart rate and ratings of perceive exertion during the match, concurrently with a significantly lower plasma total tryptophan/BCAA ratio. Similar post-match plasma NH3 concentrations were found in both trials while the AA trial was significantly higher in NOx concentration. This study suggested that the supplementation could prevent the decline in perceptual-motor performance through alleviation of central fatigue by BCAA and prevention of excess hyperammonemia by arginine and citrulline.

Vitamin D receptor variability and physical activity are jointly associated with low handgrip strength and osteoporosis in community-dwelling elderly people in Taiwan: the Taichung Community Health Study for Elders (TCHS-E).

UNLABELLED: We studied 472 elders to assess joint association of vitamin D receptor (VDR) variability and physical activity on low handgrip strength (LHS) and osteoporosis (OST). Our findings showed that higher risks of OST were associated with physically inactive elders with some specific VDR variations, highlighting the importance of promotion program for physical activity. INTRODUCTION: The aim of this study was to determine the joint association between VDR variability and physical activity on LHS and OST in community-dwelling elders. METHODS: Bone mineral density of the lumbar spine (LS), the femoral neck (FN), and the total hip were measured by dual-energy X-ray absorptiometry. Four single-nucleotide polymorphisms (SNPs) (rs7975232, rs1544410, rs2239185, and rs3782905) of the VDR gene were examined in 472 participants. RESULTS: Physical inactivity and each of the four SNPs were jointly associated with a significantly greater risk of LHS in people than that associated with each of the VDR SNPs or low physical activity alone. Physically inactive men with the AG or AA genotype of rs2239185 had a significantly greater risk of overall, LS, and FN OST than those of physically active men with the GG genotype [odds ratio (OR) 3.57, 95 % confidence interval (CI) 1.10-11.65; OR 4.74, 95 % CI 1.43-15.70; and OR 5.06, 95 % CI 1.08-23.71, respectively]. Similarly, physically inactive women with the CG or CC genotype of rs3782905 and the AG or AA genotype of rs1544410 had a significantly greater risk of FN OST than physically active women with the GG genotype (OR 5.33, 95 % CI 1.23-23.06 and OR 5.36, 95 % CI 1.11-25.94, respectively). CONCLUSIONS: VDR polymorphisms and physical activity are jointly associated with LHS and OST in elders. Health care programs should promote physical activity among elders as a cost-effective way to prevent LHS and OST, especially in those who may be genetically predisposed.

Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome.

OBJECTIVE: To investigate the association between neuroleptic malignant syndrome (NMS) and levels of antipsychotic exposure. METHOD: Electronic health record data systematically screened from a large mental health service provider in southeast London provided 67 NMS cases which were individually matched with 254 controls on age, gender, and primary psychiatric diagnosis. Data on psychotropic agents, combinations, dose, and dose change of antipsychotic prescriptions over the preceding 5 (oral agents) or 15 days (depot agents) were extracted and compared between groups using conditional logistic regression models. RESULTS: NMS was associated with higher number of antipsychotic agents used, use of first-generation agents or aripiprazole, use of first-generation agents only or cross-generation agents, and higher mean and maximum daily doses. In further analyses, associations with antipsychotics type remained significant when adjusted for dose, but those with dose were attenuated following adjustment for type. The specific use of haloperidol, aripiprazole, depot flupentixol, and benzodiazepines was independently associated with NMS. Non-white ethnicity was also found to be associated with NMS. CONCLUSION: NMS was primarily associated with type of antipsychotic and polypharmacy rather than overall dose. Variation in risk by ethnicity requires further research.

Associations between risk of mortality and atypical antipsychotic use in vascular dementia: a clinical cohort study.

OBJECTIVES: People with vascular dementia (VaD) are frequently prescribed atypical antipsychotics to treat behavioural and psychological symptoms, but there is an alarming lack of evidence regarding their safety or efficacy in VaD. This study sought to identify the mortality risk associated with the most commonly prescribed atypical antipsychotics in people with VaD compared with people not exposed to these drugs. METHODS: A clinical cohort study of 1531 people with VaD performed using anonymised versions of full electronic health records from the Clinical Record Interactive Search application at the South London and Maudsley NHS Foundation Trust. Patients were identified from 2007 to 2010, of whom 337 were exposed to quetiapine, risperidone or olanzapine. The main outcome measure was mortality. RESULTS: Patients exposed to atypical antipsychotics were not at increased risk of mortality [hazard ratio (HR) 1.05, 95% confidence interval (CI): 0.87-1.26]. Exposure to risperidone did not result in an increased risk of mortality (HR = 0.85; 95% CI: 0.59-1.24), and patients exposed to quetiapine had a non-significant numerical increase in mortality risk (HR = 1.14; 95% CI: 0.93-1.39; p-value = 0.20) compared with untreated patients. Too few patients were exposed to olanzapine alone to provide reliable results. CONCLUSIONS: The absence of a significant increase in mortality risk associated with atypical antipsychotics in people with VaD indicates that a clinical trial of antipsychotics focussing on the treatment of aggression and agitation in this patient group will be justified and feasible following further consideration of possible confounders, which will be critical to determine the role of antipsychotics in treatment of VaD.

HLA-B*15:02 is associated with anemia in patients with chronic hepatitis C treated with pegylated interferon-α and ribavirin.

To investigate the relationship between human leukocyte antigen (HLA) class I and II alleles and treatment-induced anemia in chronic hepatitis C (CHC) patients receiving combination therapy with pegylated interferon-α (PEG-IFN-α) and ribavirin (RBV). One hundred six naïve CHC patients (59 females and 47 males; mean age, 53.08 years) who underwent combination treatment were enrolled. The patients were considered positive for hemoglobin (Hb)-related side effects if the Hb concentrations dropped below 10 g/dl during PEG-IFN-α plus RBV treatment. The HLA-A, -B, -C, -DR, and -DQ loci were investigated by sequence-based genotyping. The effects of the clinical characteristics, virologic variables, and the HLA alleles on treatment-induced anemia were evaluated by a logistic regression analysis. Forty patients (37.7%) had Hb levels below 10 g/dl during the treatment course. Low baseline Hb levels and an advanced liver fibrosis stage were associated with decreases in Hb levels to below 10 g/dl. The occurrence of treatment-related anemia (Hb < 10 g/dl) was significantly associated with HLA-B*15:02 as shown by multivariate analysis (adjusted odds ratio, 8.13; 95% confidence interval: 1.19-55.70; P-value after Holm's procedure, 0.03). HLA-B*15:02 is associated with treatment-induced anemia in Taiwanese CHC patients receiving combination therapy with PEG-IFN-α plus RBV.

Clinical risk assessment rating and all-cause mortality in secondary mental healthcare: the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLAM BRC) Case Register.

BACKGROUND: Mental disorders are widely recognized to be associated with increased risk of all-cause mortality. However, the extent to which highest-risk groups for mortality overlap with those viewed with highest concern by mental health services is less clear. The aim of the study was to investigate clinical risk assessment ratings for suicide, violence and self-neglect in relation to all-cause mortality among people receiving secondary mental healthcare. METHOD: A total of 9234 subjects over the age of 15 years were identified from the South London and Maudsley Biomedical Research Centre Case Register who had received a second tier structured risk assessment in the course of their clinical care. A cohort analysis was carried out. Total scores for three risk assessment clusters (suicide, violence and self-neglect) were calculated and Cox regression models used to assess survival from first assessment. RESULTS: A total of 234 deaths had occurred over an average 9.4-month follow-up period. Mortality was relatively high for the cohort overall in relation to national norms [standardized mortality ratio 3.23, 95% confidence interval (CI) 2.83-3.67] but not in relation to other mental health service users with similar diagnoses. Only the score for the self-neglect cluster predicted mortality [hazard ratio (HR) per unit increase 1.14, 95% CI 1.04-1.24] with null findings for assessed risk of suicide or violence (HRs per unit increase 1.00 and 1.06 respectively). CONCLUSIONS: Level of clinician-appraised risk of self-neglect, but not of suicide or violence, predicted all-cause mortality among people receiving specific assessment of risk in a secondary mental health service.

Effects of prolonged intensive training on the resting levels of salivary immunoglobulin A and cortisol in adolescent volleyball players.

AIM: Concerns have been raised regarding the effects of prolonged intensive training on adolescent athletes. This study investigated the differences in mucosal immune functions and stress responses between intensively trained male adolescent volleyball players and age-matched sedentary controls. METHODS: Twelve male volleyball players (16.5 [0.7] years of age) and sixteen healthy sedentary male volunteers (17.1 [0.6] years of age) participated in this study. Volleyball players were engaged in regular and year-round training. Unstimulated saliva samples were collected from volleyball players during the high-intensity training period and from the counterparts at the same timepoints after at least 18 hours of rest. Concentrations of salivary total protein, secretory immunoglobulin A (SIgA), cortisol, and lactoferrin were measured. RESULTS: Results of this study revealed that the SIgA concentrations and the ratio of SIgA/total protein in volleyball players were significantly lower compared with those in sedentary controls. However, the salivary cortisol concentrations and the ratio of cortisol/total protein in volleyball players were markedly higher compared with those in sedentary controls. No significant difference was observed in lactoferrin levels between volleyball players and sedentary controls. CONCLUSION: The findings of this study suggest that the prolonged intensive training may elicit a sustained stress and induce a suppressive effect on mucosal immunity in regularly and intensively trained adolescent athletes.

[Influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome: A retrospective study].

Objective: To analyze the influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome. Methods: MRI and/or DECT were used to detect liver and cardiac iron content in 181 patients with MDS, among whom, 41 received regular iron chelation therapy during two examinations. The adjusted ferritin (ASF) , erythropoietin (EPO) , cardiac function, liver transaminase, hepatitis antibody, and peripheral blood T cell polarization were detected and the results of myelofibrosis, splenomegaly, and cyclosporine were collected and comparative analyzed in patients. Results: We observed a positive correlation between liver iron concentration and ASF both in the MRI group and DECT groups (r=0.512 and 0.606, respectively, P<0.001) , only a weak correlation between the heart iron concentration and ASF in the MRI group (r=0.303, P<0.001) , and no significant correlation between cardiac iron concentration and ASF in the DECT group (r=0.231, P=0.053) . Moreover, transfusion dependence in liver and cardiac [MRI group was significantly associated with the concentration of iron in: LIC: (28.370±10.706) mg/g vs (7.593±3.508) mg/g, t=24.30, P<0.001; MIC: 1.81 vs 0.95, z=2.625, P<0.05; DECT group: liver VIC: (4.269±1.258) g/L vs (1.078±0.383) g/L, t=23.14, P<0.001: cardiac VIC: 1.69 vs 0.68, z=3.142, P<0.05]. The concentration of EPO in the severe iron overload group was significantly higher than that in the mild to moderate iron overload group and normal group (P<0.001) . Compared to the low-risk MDS group, the liver iron concentration in patients with MDS with cyclic sideroblasts (MDS-RS) was significantly elevated [DECT group: 3.80 (1.97, 5.51) g/L vs 1.66 (0.67, 2.94) g/L, P=0.004; MRI group: 13.7 (8.1,29.1) mg/g vs 11.6 (7.1,21.1) mg/g, P=0.032]. Factors including age, bone marrow fibrosis, splenomegaly, T cell polarization, use of cyclosporine A, liver aminotransferase, and hepatitis antibody positive had no obvious effect on iron metabolism. Conclusion: There was a positive correlation between liver iron concentration and ASF in patients with MDS, whereas there was no significant correlation between cardiac iron concentration and ASF. Iron metabolism was affected by transfusion dependence, EPO concentration, and RS.

A Multicenter Virtual Multidisciplinary Sarcoma Case Conference Improves Outcome for a Rare Soft Tissue Sarcoma (Dermatofibrosarcoma Protuberans).

INTRODUCTION: The purpose of this study is to analyze the impact of a virtual multidisciplinary sarcoma case conference (VMSCC) on the outcomes of dermatofibrosarcoma protuberans (DFSP). METHODS: We compared margin status after surgery and disease-free survival (DFS) on two cohorts of patients with DFSP, one diagnosed from 2010 to 2015 and one from 2016 to 2020 (before and after virtual multidisciplinary sarcoma case conference (VMSCC) within Kaiser Permanente Northern California (KPNC), using Kaplan-Meier curves and Cox proportional hazard regression models. RESULTS: There was no significant difference between the two cohorts on demographics, tumor location, type of surgery, receipt of radiation, receipt of imatinib, or size of tumor. However, the percent of patients with positive margin after final surgery and the percent of local recurrence were significantly different: 6.5% and 6.3% for the 2010-2015 cohort, and .8% and 0% for the 2016-2020 cohort, respectively. CONCLUSION: Our data suggest that the outcomes of DFSP improved significantly after the implementation of VMSCC.

Impact of intense training and rapid weight changes on salivary parameters in elite female Taekwondo athletes.

The aim of this study is to examine the cumulative effects of prolonged intensive training with or without rapid weight changes (RWC) on salivary parameters of elite female Taekwondo (TKD) athletes. Ten elite female Taiwanese TKD athletes (ages: 21.3 ± 1.2 years of age, Ht 164.4 ± 5.6 cm) volunteered to participate in this study. Resting saliva samples were collected at 28-, 14-, 7-, and 1 day before and 1-, 7-, 21 days after a national competition. The levels of salivary immunoglobulin A (sIgA), cortisol, and lactoferrin were measured. In analyzing the anthropometric data, we found that a significant proportion (50%) of elite female TKD athletes had RWC shortly before and after a national competition. The participants were allocated either to the RWC or to the non-RWC group according to their weight change profiles. Our results showed that levels of sIgA and cortisol of athletes with RWC were significantly modulated during the study period. However, athletes without RWC only showed reduced lactoferrin after competition. The results presented here demonstrate that intensive training in combination with RWC affects the mucosal immunity and disrupts the cortisol stress response of elite female TKD athletes.

Changes of mucosal immunity and antioxidation activity in elite male Taiwanese taekwondo athletes associated with intensive training and rapid weight loss.

OBJECTIVE: The aim of this study was to investigate the cumulative effects of prolonged, intensive training and rapid weight loss on immunological parameters and antioxidation activity of elite male Taiwanese taekwondo athletes. DESIGN: 16 Elite male taekwondo athletes (mean age, 21.6 (1.3) years; mean height, 173.7 (5.5) cm) volunteered to participate in this study. Beginning at 30 days before a national competition, saliva samples were obtained during a 7-week training, the competition and the postcompetition period. Levels of salivary IgA, cortisol, lactoferrin and free-radical scavenging activity were measured at 30-, 14-, 7- and 1-day precompetition and 1-, 7- and 19-day postcompetition. Body weight and body fat were also recorded. RESULTS: The mean body weight was notably decreased during the week immediately before the competition. Results reveal that the levels of salivary IgA were differentially regulated during the training, competition and recovery period, while the salivary cortisol and lactoferrin concentrations and free-radical scavenging activity were not appreciably affected during the training and the competition period. Furthermore, the results of an upper respiratory tract infection incidence indicate that following the decreases of mucosal immunity, the risk of acquiring infection was significantly increased. CONCLUSIONS: Our results demonstrated that mucosal immunity in elite male taekwondo athletes is modulated by exercise and rapid weight reduction during the training, competition and recovery period. Cumulative effects of prolonged intensive training and rapid weight reduction suppressed mucosal immunity. Furthermore, because of the "open window" of impaired immunity during the precompetition period, the incidence of upper respiratory tract infection was significantly increased after the competition.

Detection of transforming growth factor alpha in normal, malignant, and hyperproliferative human keratinocytes.

Transforming growth factor alpha (TGF-alpha) is a 50-amino acid peptide, previously demonstrated only in transformed cell lines and human tumors, which is structurally homologous to epidermal growth factor (EGF). TGF-alpha expression in keratinocytes from normal individuals, patients with psoriasis, and patients with malignant skin diseases was investigated using an mAb raised against synthetic human TGF-alpha. mAb A1.5 reacted with TGF-alpha, but not EGF, in a sensitive ELISA. Keratinocytes in eight nodular basal cell carcinomas, one morpheic basal cell carcinoma, and one squamous cell carcinoma demonstrated intense membranous immunoperoxidase staining with mAb A1.5. Of even greater interest was the observation that the overlying normal epidermis, as well as the epidermis from five normal skin specimens, were stained by the mAb. Keratinocytes in plaques from 18 psoriasis patients were more intensely stained than those from normal skin. Cultured normal keratinocytes demonstrated membranous staining with mAb A1.5. Absorption of mAb A1.5 with synthetic human TGF-alpha completely removed the reactivity of mAb A1.5 with both basal cell tumors and normal epidermis. The demonstration of TGF-alpha in normal keratinocytes suggests that it plays a role in normal keratinocyte growth, wound healing, and in the pathogenesis of acanthosis.

Increase of plasma insulin by racecadotril, an inhibitor of enkephalinase, in Wistar rats.

Racecadotril is known as an inhibitor of enkephalinase. Increase of plasma insulin by racecadotril has been observed in rats while the mechanism of the action remains obscure. In the present study, intravenous injection of male Wistar rats with racecadotril significantly decreased blood glucose levels. However, this effect of racecadotril was not modified by naloxone at the dose sufficient to block opioid receptors. Thus, the blood glucose-lowering action of racecadotril might be through an endogenous opioid independent mechanism. Otherwise, we found that C-peptide content was also raised by racecadotril in parallel with the increase of insulin in Wistar rats. Thus, the blood glucose-lowering action of racecadotril was related to insulin secretion, but not through the inhibition of plasma insulin degradation. In addition, racecadotril showed no direct effect on insulin secretion in isolated islets or cultured HIT-T15 beta cells. The increase of plasma insulin and blood glucose-lowering action induced by racecadotril were reduced by pretreatment with atropine and enhanced by physotigmine. Direct inhibition of cholinesterase was not observed in brain homogenates treated with racecadotril. Moreover, actions of racecadotril were significantly reduced in rats receiving hemicholinium-3 at a sufficient dose to decrease endogenous acetylcholine. Activation of cholinergic tone is possibly involved in the blood glucose-lowering effect of racecadotril. Our results suggested that racecadotril increased insulin secretion to lower blood glucose mainly via regulation of parasympathetic tone in Wistar rats.

Role of mitogen-activated protein kinase in Zn-BC-AM PDT-induced apoptosis in nasopharyngeal carcinoma cells.

Photodynamic therapy (PDT) with a recently developed photosensitizer Zn-BC-AM was found to effectively induce apoptosis in a well-differentiated nasopharyngeal carcinoma (NPC) HK-1 cell line. Sustained activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK) as well as a transient increase in activation of extracellular signal-regulated kinase (ERK) were observed immediately after Zn-BC-AM PDT. A commonly used p38 MAPK/JNK pharmacological inhibitor PD169316 was found to reduce PDT-induced apoptosis of HK-1 cells. PD169316 also prevented the loss of Bcl-2 and Bcl-xL in PDT-treated HK-1 cells. However, inhibition of JNK with SP600125 had no effect on Zn-BC-AM PDT-induced apoptosis while inhibition of ERK with PD98059 or p38 MAPK with SB203580 significantly increased Zn-BC-AM PDT-induced apoptosis. Further study showed that knockdown of the p38beta isoform with siRNA also increased Zn-BC-AM PDT-induced apoptosis, indicating that the anti-apoptotic effect of PD169316 in PDT-treated HK-1 cells was probably independent of p38 MAPK or JNK activation. Taken together, the results suggest that inhibition of p38beta and ERK may enhance the therapeutic efficacy of Zn-BC-AM PDT on NPC cells. It should be noted that data only based on the use of PD169316 should be interpreted in caution.