Body composition and physical fitness improve after 8 weeks of high-intensity circuit training using body weight in obese women.

BACKGROUND: We examined the effects of an 8-week modified high-intensity circuit training using body weight as resistance (HICTBW) on health-related physical fitness in sedentary obese women. METHODS: Twenty-four sedentary obese women were allocated into the HICTBW or a non-training control group (CG). The modified HICTBW was performed for eight weeks (three times per week). Training consisted of a 30-second workout and 10-second rest for 12 exercise poses per one circuit (one circuit in the first week), with an increase of one circuit every two weeks. Body weight and body composition included skeletal muscle mass (SMM), body fat mass (BFM), body fat percentage (BF%), visceral fat area (VFA), and skeletal muscle mass to visceral fat area ratio (MFR) were measured. Physical fitness included flexibility of the lower back and hamstrings (FlexLH), and leg and handgrip muscle strength (StrengthLeg, StrengthHG). Cardiovascular endurance included the Åstrand-Rhyming heart rate (HRÅstrand), relative maximum oxygen uptake (relative V̇O2max), and workload. RESULTS: All variables were obtained at baseline, week 4, and week 8. The HICTBW improved FlexLH, StrengthLeg, and relative V̇O2max from baseline to week 4 (All P<0.05). Improvements from baseline to week 8 were observed for SMM, BFM, BF%, VFA and MFR, FlexLH, StrengthLeg, HRÅstrand, relative V̇O2max, and workload (All P<0.05). Furthermore, the HICTBW elicited a higher change in SMM (+2.9%), BFM (-3.4%), BF% (-3.2%), MFR (+9.5%), FlexLH (+145.7%) and relative V̇O2max (+32.3%) than the CG at week-8 (All P<0.05). CONCLUSIONS: An eight-week modified HICTBW program thrice a week is an effective training modality to influence health-related physical fitness in sedentary obese women.

A Home-Based Exercise Program With Active Video Games for Balance, Motor Proficiency, Foot and Ankle Ability, and Intrinsic Motivation in Children With Chronic Ankle Instability: Feasibility Randomized Controlled Trial.

Background: Children with chronic ankle instability (CAI) frequently experience ankle unsteadiness, causing trips, falls, and ankle sprain injuries resulting in poor quality of life. A specific exercise program focused on physical and psychological purposes in children with CAI is needed. Objective: The purpose of this study was to investigate the feasibility of a 4-week home-based exercise training program using active video games (AVGs) for balance, motor proficiency, foot and ankle ability, and intrinsic motivation in children with CAI. Methods: Sixty children with CAI (mean age 10, SD 2 years) were randomly assigned to an experimental group (AVG group; n=30) or a control group (CG; n=30). The AVG group played 2 selected video games, Catching Fish and Russian Block, while the CG received the traditional exercise program for CAI. Both programs were scheduled for 30 minutes per day, 3 times per week, for 4 weeks at home. The single-leg stance test was used to assess static balance. The walking forward on a line and standing long jump tests were used to assess motor proficiency. The Foot and Ankle Ability Measure (FAAM) and the Intrinsic Motivation Inventory questionnaire were used to assess foot and ankle ability and intrinsic motivation, respectively. Assessments were conducted at baseline and after 4 weeks. Results: In the AVG group, the single-leg stand test (eyes open; on floor and on foam conditions), the FAAM (activities of daily living subscale), and intrinsic motivation (interest/enjoyment, pressure/tension, and value/usefulness dimensions) were improved compared with the CG (all P<.05). Motor proficiency did not differ between the 2 groups at the end of the 4-week program (P=.31 for the walking forward on a line, P=.34 for the standing long jump test). Conclusions: A 4-week home-based exercise training program using AVGs can be beneficial and may be an effective approach for improving balance, foot and ankle ability, and enhancing positive motivation by increasing the interest/enjoyment and value/usefulness dimensions and lowering the pressure/tension dimension in children with CAI that require long-term rehabilitation sessions.

Recovery Effects of Foam Rolling on Psychophysiological Responses in Thai National Male Ice Hockey Players.

We examined the short-term effects of foam rolling (FR), dynamic stretching (DS), and passive rest (PR) following simulated ice hockey exercise (IHE) on heart rate (HR), blood lactate (BL), leg choice reaction time (CRTleg), rating of perceived exertion (RPE), and global rating of change (GRC) in elite ice hockey players. The study followed a randomized cross-over design. Fifteen national male ice hockey players were assigned to the FR, DS, or PR interventions for 10 mins following 35- min of simulated IHE. HR and BL were obtained at 0-, 5- and 10-min post-intervention. CRTleg and RPE were assessed pre-and post-intervention. GRC was evaluated post-intervention. The PR decreased HR faster than the DS at 5-min of post-treatment. Whereas the FR and DS reduced BL levels faster than the PR at 5- and 10-min post-treatment. There was no difference in CRTleg among the FR, DS, and PR. The FR had lower RPE scores compared to the DS and PR post-treatment. As perceptual aspects, the FR was the most preferred treatment by ice hockey athletes. The FR and DS exerted more beneficial effects on BL but not on HR by the passive rest. The FR showed the most effective treatment on the psychological demands by improving RPE and perceptual responses over the DS and PR. Thus, the FR could be used as a choice for post-game recovery treatment on improving physiological and perceptual responses following an intense match-play in ice hockey players.

A low- dose of caffeine suppresses EEG alpha power and improves working memory in healthy University males.

The effects of a low dose of caffeine, administered in the morning, on brain wave activity and cognitive function were investigated in 25 healthy university Southeast Asian men (mean age ±standard deviation: 21 ± 2 years). Participants received a placebo (PLA) or a 50 mg caffeinated drink (CAF) under randomized, double-blind crossover conditions, with 1 week between conditions. Brain wave activity was assessed using electroencephalography (EEG) from a 5 min eyes-closed resting state. Cognitive function, i.e., visuomotor processing speed, working memory, and attention were assessed using the trail-making test A (Trails A) and B (Trails B), and digit span Forwards (DF), respectively. All tests were examined before drinking (BD), 30 min after drinking (AD), and 35 min after 5-min isokinetic exercise (AE). [Results] The CAF showed a significant decrease in the percentage changes from baseline (%∆) of alpha wave activity over the midline electrodes, i.e., frontal, central, and occipital areas after AD (p<0.05). Data from cognitive function tests were significantly improved after AD (p<0.05). A significant inverse correlation between the diminished alpha wave activity over the midline central and occipital cortical regions and the Trails B positive scores were observed (p<0.05). [Conclusion] The diminishment in resting alpha wave activity and improvement of cognitive function on working memory assessed by the Trails B following caffeine consumption would support the stimulant effects of low-dose caffeine as a morning wake-up drink in young adults.

The Effects of Constraining Head Rotation on Eye and Whole-Body Coordination During Standing Turns at Different Speeds.

A limitation of the ability to rotate the head with respect to the upper body has been associated with turning problems; however, the extent of head constraints on whole-body coordination has not been fully determined. The aim of this study was to limit head on body rotation and observe the effects on whole-body coordination during standing turns at various speeds. Twelve participants completed standing turns at 180°. A Vicon motion system and a BlueGain Electrooculography system were used to record movement kinematics and measure horizontal eye movements, respectively. All participants were tested at 3 randomized speeds, and under 2 conditions with or without their head constrained using a head, neck, and chest brace which restricted neck movement. A repeated-measures analysis of variance found a significant main effect of turning speed on the onset latency of all segments, peak head-thorax angular separation, and step characteristics. Constraining the head rotation had multiple significant effects including delayed onset latency and decreased intersegmental coordination defined as peak head segmental angular separations, increased total step and step duration, and decreased step size. This indicates the contribution of speed, head, and neck constraints, which have been associated with falls during turning and whole-body coordination.

Benefits of task-specific movement program on en bloc turning in Parkinson's disease: A randomized controlled trial.

INTRODUCTION: En bloc turning highlights a lack of rotational intersegmental coordination, which commonly impacts turning ability in people with Parkinson's disease (PD). Whilst this turning deficit responds fairly well to medical treatment, it may be further mitigated by performing specific exercise training. Thus, the present study aimed to examine the effects of a 4-week exercise program, which focused on task-specific movements (TSM program) on turning ability and clinical outcomes in people with PD. METHODS: Twenty-two adults (67 ± 6 years) with early-to-mid-stage idiopathic PD were randomly assigned to an experimental group (EG; n = 11) or a control group (CG; n = 11). The exercise group (EG) group received a 60-min per session TSM program for 4 weeks (a total of 15 sessions), while the CG group performed their routine rehabilitation program (a total of 12 sessions). Inertial measurement units were used to measure turning kinematics including; onset latency of body segments and stepping characteristics. Clinical outcomes included the Unified Parkinson's Disease Rating Scale (UPDRS), functional reach test (FRT), and fall efficacy scale international (FES-I). Assessments were conducted at baseline and after 4 weeks. RESULTS: In the EG, turning kinematics, UPDRS scores, FRT, and FES-I scale, were improved at the end of the 4-week program compared with the CG (all p < 0.05). IMPACT STATEMENT: A 4-week TSM program could be a promising alternative rehabilitation program for improving "en bloc" turns and clinical outcomes in PD patients.

Benefits of Thai Yoga on physical mobility and lower limb muscle strength in overweight/obese older women: A randomized controlled pilot trial.

BACKGROUND AND PURPOSE: Although Thai Yoga (TY) is reported to improve health-related fitness for the elderly, no study has yet carried out the effect of TY Program on physical mobility and lower-limb muscle strength in overweight/obese older women. MATERIALS AND METHODS: In a randomized controlled pilot design, twenty-two sedentary women with a BMI ≥ 23 kg/m2, aged 62 ± 1 years were randomly assigned to either a TY group for 60 min, 3 times a week or to a "no exercise" control (CON) group. Sit and reach (SRT), functional reach (FRT) and 30-s chair stand (CST-30), 8-foot up and go (8UGT), 6-min walk (6MWT)) and lower-limb muscle strength were measured at the beginning, 4, and 8 weeks. RESULTS: At week 4, a significant between groups was obtained in CST-30, 8UGT, and 6MWT. At week 8, FRT, 8UGT, 6MWT and knee flexor and extensor muscle strength were improved in the TY over the CON. Significant improvement was found in all variables within the TY, but no change was observed in the CON. CONCLUSION: An 8-week TY program appears to provide beneficial improvements in physical mobility in overweight/obese older women.

Effects of a 20-min Nap after Sleep Deprivation on Brain Activity and Soccer Performance.

We examined effects of a 20-min nap following 3 h of sleep deprivation on brain wave activity, auditory reaction time, the running-based anaerobic sprint test, leg muscle strength and the rating of perceived exertion in male college soccer players. Eleven players underwent three sleep conditions; normal sleep, sleep deprivation and 20-min nap after sleep deprivation. The sleep deprivation demonstrated an increase in the mean power of delta waves over the frontal area and a decrease in the mean power of alpha waves over the parietal area compared to the normal sleep. The nap and the sleep deprivation showed an increase in auditory reaction time compared with those in the normal sleep. The sleep deprivation demonstrated a decrease in the running-based anaerobic sprint test compared to the normal sleep, whereas the nap has partially reversed only minimal power and average power of the running-based anaerobic sprint test. The nap showed a recovery effect on leg muscle strength, but not on the rating of perceived exertion compared with the sleep deprivation. Thus, a 20-min nap after sleep deprivation did not completely return brain activity back to active state and did not entirely reverse the negative impact of sleep deprivation on soccer performance in soccer players.

Can We Accurately Measure Axial Segment Coordination during Turning Using Inertial Measurement Units (IMUs)?

Camera-based 3D motion analysis systems are considered to be the gold standard for movement analysis. However, using such equipment in a clinical setting is prohibitive due to the expense and time-consuming nature of data collection and analysis. Therefore, Inertial Measurement Units (IMUs) have been suggested as an alternative to measure movement in clinical settings. One area which is both important and challenging is the assessment of turning kinematics in individuals with movement disorders. This study aimed to validate the use of IMUs in the measurement of turning kinematics in healthy adults compared to a camera-based 3D motion analysis system. Data were collected from twelve participants using a Vicon motion analysis system which were compared with data from four IMUs placed on the forehead, middle thorax, and feet in order to determine accuracy and reliability. The results demonstrated that the IMU sensors produced reliable kinematic measures and showed excellent reliability (ICCs 0.80-0.98) and no significant differences were seen in paired t-tests in all parameters when comparing the two systems. This suggests that the IMU sensors provide a viable alternative to camera-based motion capture that could be used in isolation to gather data from individuals with movement disorders in clinical settings and real-life situations.

A pilot study on salivary cortisol secretion and auditory P300 event-related potential in patients with physical disability-related stress.

Objective: To evaluate the stress level and attention in workers with physical disabilities-related stress.Methods: Morning salivary cortisol was used as a stress marker while the event-related potential during the performance of the auditory oddball paradigm was conducted to investigate the attentive ability to sound stimuli. Eighteen injured workers (IP) and eighteen unaffected healthy adults (CP) were recruited for this study with half being men and the other half women (aged 21-55). Behavioral performance measures including reaction time (RT), accuracy rate, and commission error as well as the latency and amplitude of P300 wave over the central (Cz), centroparietal (CPz), and parietal (Pz) electroencephalogram electrode sites were used to compare the two groups.Results: This study demonstrated significantly higher salivary cortisol levels, longer RT, less accuracy to respond to the target during the auditory oddball paradigm in the IP group as compared to CP group. In addition, a significant prolongation of the peak latency of auditory P300 wave over CPz electrodes was also detected in IP group.Conclusion: The increased cortisol levels found in the IP group reflect the alteration of the basal hypothalamic-pituitary-adrenal axis as a result of the stresses of living with a physical disability. Delayed RT and the decreased in accuracy together with changing in peak latencies of auditory P300 wave indicate the impairment of attention networks in IP. Our study revealed that the patients with permanent physical disability.

Effect of Cold Shower on Recovery From High-Intensity Cycling in the Heat.

Ajjimaporn, A, Chaunchaiyakul, R, Pitsamai, S, and Widjaja, W. Effect of cold shower on recovery from high-intensity cycling in the heat. J Strength Cond Res 33(8): 2233-2240, 2019-Post-exercise cooling, e.g., cold water immersion has shown beneficial cardiovascular and hormonal effects during recovery from exercise in a hot environment. However, not much is known about the effects of a cold water shower (CWS) as a recovery intervention. This study examined the effects of a CWS on heart rate (HR), core temperature (Tc), salivary cortisol, and thermal comfort sensation (TCS) after exercise in the heat. Nine healthy male subjects (age, 21 ± 1 year) performed 45 minutes of cycling in a hot environment (35° C, 40-60% relative humidity) at 65% of peak oxygen uptake. Thereafter, subjects underwent the CWS condition (15 minutes, 15° C water shower) or control (SIT25; 15 minutes passive recovery in 25° C room) in a randomized crossover design. After each 15 minutes, subjects sat in a 25° C room for another 2-hour recovery. Heart rate, Tc, and TCS were recorded before and immediately after exercise, immediately after CWS or SIT25, and at 30 minutes, 1, and 2 hours during additional recovery. Salivary cortisol was collected at the same time points except at 30 minutes of the additional recovery period. Thermal comfort sensation was higher immediately after CWS (+4; very comfortable) than SIT25 (+1; just comfortable). The change of HR decreased faster with CWS (-18.3 ± 2.3%) than with SIT25 (-7.0 ± 4.6%) at the first 30-minute recovery time point (p < 0.01). No differences between recovery conditions were observed for the Tc or salivary cortisol at any time point during the 2-hour recovery period. The findings demonstrate that a 15-minute, 15° C CWS was not effective in reducing Tc or salivary cortisol during recovery from exercise in a hot environment. However, CWS can promote TCS by facilitating a faster HR recovery after 30-minute postintervention compared with passive recovery. The cooling benefits of a CWS could be only recommended to reduce cardiac stress after routine workout in a hot environment.

Acute physiological responses in pregnant women during exercises in different positions.

OBJECTIVE: This study measured acute physiological responses in pregnant women during short duration exercise in the supine (Sup), side-lying (Side), sitting (Sit), and standing (Std) positions. METHODS: In a cross-sectional study, 42 healthy pregnant women were divided into 3 groups of 14 persons each: G1, G2, and G3 (first, second, and third trimester, respectively). Baseline assessments were performed following a 30-min rest in the sitting position. Subsequent measurements were then obtained while exercising, without resistance, in the Sup, Side, Sit, and Std, respectively. Physiological parameters, including heart rate (HR), minute ventilation ( V˙E ), oxygen consumption ( V˙O2 ), carbon dioxide production ( V˙CO2 ), and oxygen pulse ( V˙O2 /HR), were collected using the indirect calorimetry. RESULTS: Comparing resting values, all groups had a significantly increased (1) HR, V˙E , and V˙CO2 during the Std, (2) V˙O2 values during the Sit and Std, and (3) O2 pulse values during short duration exercise in all positions except the Std, whereas only G2 and G3 had a significantly decreased HR during the Sup. CONCLUSION: This study points that acute physiological responses to the positional challenge similarly occur in all trimester of pregnant women. Short duration exercise in the Std positions exerts more physiologic stresses on cardiorespiratory functions than in the Sup, Side, and Sit positions.

Effect of New Zealand Blackcurrant Extract on Physiological Responses at Rest and during Brisk Walking in Southeast Asian Men: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

New Zealand blackcurrant (NZBC) extract affects cardiovascular and metabolic responses during rest and exercise in Caucasian men. Ethnicity and nutritional habits may affect responses to nutritional ergogenic aids. We examined the effects of NZBC extract on cardiovascular, metabolic, and physiological responses during seated rest and moderate-intensity exercise in Southeast Asian men. Seventeen healthy Thai men (age: 22 ± 3 years; body mass index (BMI): 21.8 ± 1.1 kg·m-2) participated. Resting metabolic equivalent (1-MET) was measured (Oxycon™ mobile, Germany), and an incremental walking protocol was completed to establish the relationship between walking speed and MET. In a double-blind, randomized, placebo-controlled, crossover design, cardiovascular (Physioflow, n = 12) and physiological responses (Oxycon, n = 17) were measured during both seated rest and a 30-min treadmill walk at five metabolic equivalent (5-MET), with either a seven-day intake of placebo (PL) or two capsules of NZBC extract (each 300 mg capsule contains 35% blackcurrant extract) with a 14-day washout. Paired t-tests were used with significance accepted at p < 0.05 and a trend for 0.05 > p ≤ 0.10. During 30 min of treadmill walking at 5-MET, no differences were observed for heart rate and substrate oxidation. With intake of NZBC during treadmill walking, there was a trend for increased stroke volume by 12% (PL: 83.2 ± 25.1; NZBC: 93.0 ± 24.3 mL; p = 0.072) and cardiac output increased by 12% (PL: 9.2 ± 2.6; NZBC: 10.3 ± 2.8 L·min-1; p = 0.057). Systemic vascular resistance decreased by 10% (PL: 779 ± 267; NZBC: 697 ± 245 dyn·s·cm-5; p = 0.048). NZBC extract had no effect on metabolic, physiological, and cardiovascular parameters during seated rest and exercise-induced fat oxidation in Thai men, in contrast to observations in Caucasian men. During treadmill walking, Thai men showed cardiovascular response, indicating vasodilatory effects during moderate-intensity exercise with the intake of NZBC extract. Our findings suggest that the ergogenic responses to anthocyanin intake from New Zealand blackcurrant may be ethnicity-dependent.

Effects of 8 weeks of modified hatha yoga training on resting-state brain activity and the p300 ERP in patients with physical disability-related stress.

[Purpose] We examined the effects of Hatha yoga on EEG and ERP in patients with physical disability-related stress. [Participants and Methods] Eighteen male and female injured workers with high stress levels, aged between 18 to 55 years, were evenly divided into two groups: untrained (CG) and trained (TG) modified hatha yoga groups. A modified Hatha yoga protocol was designed for this population by two certified yoga instructors, approved by a physical therapist, and conducted for one hour, three times weekly for 8 weeks. [Results] The results indicated a significant increase in alpha EEG activity over the frontal, central, and parietal electrodes and the delta EEG activity over the centroparietal electrode from pre- to post-training in TG. In addition, significantly faster auditory reaction time for target stimuli, as well as lower P300 peak latency of ERP in auditory oddball paradigm were obtained in TG after 8 weeks of yoga training compare to CG. [Conclusion] Changes in brain activity and ERP components following yoga training would support the psychophysiological effects of hatha yoga as an adjunct to routine rehabilitation.

A Cross-sectional Study of Resting Cardio-respiratory and Metabolic Changes in Pregnant Women.

[Purpose] We examined cardiorespiratory and metabolic changes across the 1st (G1), 2nd (G2) and 3rd (G3) trimesters in pregnant women. [Subjects and Methods] Forty-two healthy, active, non-smoking, pregnant women participated in this study. They were divided into G1, G2 and G3 groups depending on their mean gestational ages at the time of testing which were 10.5 ±2.9, 19.2 ±3.4, and 33.3 ±2.4 weeks of gestation, respectively. Cardio-respiratory and metabolic variables, VO2 (oxygen consumption), VCO2 (carbon dioxide production), and VE (minute ventilation), were measured using indirect calorimetry (IC, gas analyser) to estimate ventilatory equivalents of oxygen (VE/VO2) and carbon dioxide (VE/VCO2), RER (respiratory exchange ratio) and REE (resting energy expenditure). [Results] Women in the late pregnancy period had higher resting VCO2 and RER, whereas the VE/VCO2 ratio was significantly lower than in G1 and in G2. Even though the values of VO2 and REE increased throughout the course of pregnancy, no significant differences were found. [Conclusion] In pregnant women, resting cardiorespiratory and metabolic variables continuously changed throughout the 3 trimesters. Changes in VE/VCO2 and RER indicate shifting metabolic energy substrates. In addition, changes in cardiorespiratory variables, in parallel with gas exchange, indicate a better gas exchange process.

ZIP8 expression in human proximal tubule cells, human urothelial cells transformed by Cd+2 and As+3 and in specimens of normal human urothelium and urothelial cancer.

BACKGROUND: ZIP8 functions endogenously as a Zn+2/HCO3- symporter that can also bring cadmium (Cd+2) into the cell. It has also been proposed that ZIP8 participates in Cd-induced testicular necrosis and renal disease. In this study real-time PCR, western analysis, immunostaining and fluorescent localization were used to define the expression of ZIP8 in human kidney, cultured human proximal tubule (HPT) cells, normal and malignant human urothelium and Cd+2 and arsenite (As+3) transformed urothelial cells. RESULTS: It was shown that in the renal system both the non-glycosylated and glycosylated form of ZIP8 was expressed in the proximal tubule cells with localization of ZIP8 to the cytoplasm and cell membrane; findings in line with previous studies on ZIP8. The studies in the bladder were the first to show that ZIP8 was expressed in normal urothelium and that ZIP8 could be localized to the paranuclear region. Studies in the UROtsa cell line confirmed a paranuclear localization of ZIP8, however addition of growth medium to the cells increased the expression of the protein in the UROtsa cells. In archival human samples of the normal urothelium, the expression of ZIP8 was variable in intensity whereas in urothelial cancers ZIP8 was expressed in 13 of 14 samples, with one high grade invasive urothelial cancer showing no expression. The expression of ZIP8 was similar in the Cd+2 and As+3 transformed UROtsa cell lines and their tumor transplants. CONCLUSION: This is the first study which shows that ZIP8 is expressed in the normal urothelium and in bladder cancer. In addition the normal UROtsa cell line and its transformed counterparts show similar expression of ZIP8 compared to the normal urothelium and the urothelial cancers suggesting that the UROtsa cell line could serve as a model system to study the expression of ZIP8 in bladder disease.

Differences in the epigenetic regulation of MT-3 gene expression between parental and Cd+2 or As+3 transformed human urothelial cells.

BACKGROUND: Studies have shown that metallothionein 3 (MT-3) is not expressed in normal urothelium or in the UROtsa cell line, but is expressed in urothelial cancer and in tumors generated from the UROtsa cells that have been transformed by cadmium (Cd+2) or arsenite (As+3).The present study had two major goals. One, to determine if epigenetic modifications control urothelial MT-3 gene expression and if regulation is altered by malignant transformation by Cd+2 or As+3. Two, to determine if MT-3 expression might translate clinically as a biomarker for malignant urothelial cells released into the urine. RESULTS: The histone deacetylase inhibitor MS-275 induced MT-3 mRNA expression in both parental UROtsa cells and their transformed counterparts. The demethylating agent, 5-Aza-2'-deoxycytidine (5-AZC) had no effect on MT-3 mRNA expression. ChIP analysis showed that metal-responsive transformation factor-1 (MTF-1) binding to metal response elements (MRE) elements of the MT-3 promoter was restricted in parental UROtsa cells, but MTF-1 binding to the MREs was unrestricted in the transformed cell lines. Histone modifications at acetyl H4, trimethyl H3K4, trimethyl H3K27, and trimethyl H3K9 were compared between the parental and transformed cell lines in the presence and absence of MS-275. The pattern of histone modifications suggested that the MT-3 promoter in the Cd+2 and As+3 transformed cells has gained bivalent chromatin structure, having elements of being "transcriptionally repressed" and "transcription ready", when compared to parental cells. An analysis of MT-3 staining in urinary cytologies showed that a subset of both active and non-active patients with urothelial cancer shed positive cells in their urine, but that control patients only rarely shed MT-3 positive cells. CONCLUSION: The MT-3 gene is silenced in non-transformed urothelial cells by a mechanism involving histone modification of the MT-3 promoter. In contrast, transformation of the urothelial cells with either Cd+2 or As+3 modified the chromatin of the MT-3 promoter to a bivalent state of promoter readiness. Urinary cytology for MT-3 positive cells would not improve the diagnosis of urothelial cancer, but might have potential as a biomarker for tumor progression.

Zinc rescues dopaminergic SK-N-SH cell lines from methamphetamine-induced toxicity.

Methamphetamine (METH) is a potent inducer of dopamine (DA) release, and is toxic to DA neurons. It has been reported that the formation of free radicals is an early signaling event that mediates cell death caused by METH. Currently, studies suggest that the generation of free radicals by oxidative catabolism of DA and dysfunction of the mitochondrial respiration chain are important mediators of neuronal death in Parkinson's disease (PD) and one process may counter the effect of the other. In our previous study, we investigated the deleterious effects of METH-induced reactive oxygen species (ROS) and mitochondrial dysfunction in dopaminergic SK-N-SH cells in culture, and assessed whether zinc-metallothionein induction provided mitochondrial protection against METH-induced mitochondrial dysfunction. Our present data demonstrate that METH enhances lipid peroxidation and mitochondrial manganese superoxide dismutase (MnSOD) enzyme levels, and decreases the antioxidant-reduced glutathione (GSH) together with an inhibition of mitochondrial complex-I activity. Pre-treatment with zinc markedly prevents the increase of lipid peroxidation and provides mitochondrial protection by scavenging free radicals via metallothionein and by increasing mitochondrial GSH and complex-I levels, thus rescuing SK-N-SH cells from METH toxicity. It should be emphasized that, however, it is still not clear that effects of METH on cultured SK-N-SH reliably model the effects of METH in the intact animal. Further studies in the intact animal are needed.

Zinc protects SK-N-SH cells from methamphetamine-induced alpha-synuclein expression.

Methamphetamine (METH) is a well-known drug of abuse and neurotoxin that may cause temporary or permanent disturbances in the dopaminergic systems of the brain, predisposing individuals to Parkinsonism. Previously, we have shown that METH causes dopaminergic cell death by increasing the production of reactive oxygen species (ROS) and by depleting cellular ATP levels. These effects were abolished by pretreatment with ZnCl(2) which enhanced expression of the zinc binding protein, metallothionein. In the present study, the effects of ZnCl(2) on alpha-synuclein expression were examined further in METH-treated SK-N-SH cells in culture. We show that METH significantly increased alpha-synuclein expression in a dose-dependent manner after inducing oxidative stress. Pretreatment with ZnCl(2) (50microM) reversed this stimulatory effect. We propose that zinc mediates this neuroprotective response via the production of metallothionein.

Metallothionein provides zinc-mediated protective effects against methamphetamine toxicity in SK-N-SH cells.

Methamphetamine (METH) is a drug of abuse and neurotoxin that induces Parkinson's-like pathology after chronic usage by targeting dopaminergic neurons. Elucidation of the intracellular mechanisms that underlie METH-induced dopaminergic neuron toxicity may help in understanding the mechanism by which neurons die in Parkinson's disease. In the present study, we examined the role of reactive oxygen species (ROS) in the METH-induced death of human dopaminergic SK-N-SH cells and further assessed the neuroprotective effects of zinc and metallothionein (MT) against METH-induced toxicity in culture. METH significantly increased the production of reactive oxygen species, decreased intracellular ATP levels and reduced the cell viability. Pre-treatment with zinc markedly prevented the loss of cell viability caused by METH treatment. Zinc pre-treatment mainly increased the expression of metallothionein and prevented the generation of reactive oxygen species and ATP depletion caused by METH. Chelation of zinc by CaEDTA caused a significant decrease in MT expression and loss of protective effects of MT against METH toxicity. These results suggest that zinc-induced MT expression protects dopaminergic neurons via preventing the accumulation of toxic reactive oxygen species and halting the decrease in ATP levels. Furthermore, MT may prevent the loss of mitochondrial functions caused by neurotoxins. In conclusion, our study suggests that MT, a potent scavenger of free radicals is neuroprotective against dopaminergic toxicity in conditions such as drug of abuse and in Parkinson's disease.