Mechanisms underlying the cardioinhibitory and pressor responses elicited from the medullary neurons in the gigantocellular tegmental field of cats

A stimulation of the gigantocellular tegmental field (FTG) in the medulla oblongata often increases systemic arterial blood pressure (SAP) and decreases heart rate (HR). We investigated if the cardioinhibitory/depressor areas, including the nucleus ambiguus (NA), the dorsal motor nucleus of vagus (DMV) and the caudal ventrolateral medulla (CVLM), underlied the functional expression of FTG neurons in regulating cardiovascular responses. In 73 chloralose-urethane anesthetized cats, the HR, SAP and vertebral nerve activity (VNA) were recorded. Neurons in the FTG, NA, DMV and CVLM were stimulated by microinjection of sodium glutamate (25 mM Glu, 70 nl). To study if the NA, DMV, and CVLM relayed the cardioinhibitory messages from the FTG, 24 mM kainic acid (KA, 100 nl) was used as an excitotoxic agent to lesion neurons in the NA, DMV or CVLM. We found that the cardioinhibition induced by FTG stimulation was significantly reduced by KA lesioning of the ipsilateral NA or DMV. Subsequently, a bilateral KA lesion of NA or DMV abolished the cardioinhibitory responses of FTG. Compared to the consequence of KA lesion of the DMV, only a smaller bradycardia was induced by FTG stimulation after KA lesion of the NA. The pressor response induced by Glu stimulation of the FTG was reduced by the KA lesion of the CVLM. Such an effect was dominant ipsilaterally. Our findings suggested that both NA and DMV mediated the cardioinhibitory responses of FTG. The pressor message from the FTG neurons might be partly working via a disinhibitory mechanism through the depressor neurons located in the CVLM.     

Thr164Ile polymorphism of the human beta2-adrenoceptor exhibits blunted desensitization of cardiac functional responses in vivo

In subjects heterozygous for Thr164Ile beta2-adrenoceptor (beta2AR) polymorphism, cardiac responses to beta2AR agonist stimulation are blunted. In this study, we investigated agonist-induced desensitization of Thr164Ile beta2ARs. For this purpose, we assessed in six subjects with heterozygous Thr164Ile beta2ARs and in 10 subjects with homozygous wild-type (WT) beta2ARs the effects of 2-wk oral treatment with 3 x 5 mg/day terbutaline on terbutaline infusion-induced increases in heart rate (HR) and contractility [measured as shortening of HR-corrected duration of electromechanical systole (QS2c)]. Compared with WT beta2AR subjects, Thr164Ile subjects exhibited a blunted terbutaline-induced maximum increase in HR (WT 32 +/- 4 beats/min, Thr164Ile 19 +/- 3 beats/min, P < 0.05) and contractility (WT -54 +/- 2 ms, Thr164Ile -37 +/- 6 ms, P < 0.05). Two-week oral terbutaline treatment desensitized cardiac beta2AR responses to terbutaline infusion (increase in HR: WT 10 +/- 2 beats/min, Thr164Ile 8 +/- 4 beats/min; increase in contractility: WT -22 +/- 5 ms Thr164Ile: -17 +/- 6 ms); however, the extent of desensitization was larger in WT than Thr164Ile beta2AR subjects. Thus, after 2-wk oral terbutaline treatment cardiac, beta2AR responses did not differ anymore between WT and Thr164Ile beta2AR subjects. We conclude that agonist-induced desensitization of cardiac beta2ARs is more pronounced in WT than Thr164Ile subjects. Thus cardiac Thr164Ile subjects appear to be somewhat protected against agonist-induced desensitization.     

Effects of a heart rate-based recovery period on hormonal, neuromuscular, and aerobic performance responses during 7 weeks of strength training in men

The purpose of this study was to compare hormonal, neuromuscular, and aerobic performance changes between a constant 2-minute interset recovery time and an interset recovery time based on individual heart rate (HR) responses during a 7-week (3 sessions per week, 3 × 10 repetition maximum [RM]) hypertrophic strength training period. The HR-dependent recovery time was determined with a Polar FT80 HR monitor, whereas the control groups used constant 2-minute periods between sets. From 24 male subjects who were divided in 2 equal groups, 21 completed the study (FT80, n = 12; CONTROL, n = 9). Serum blood samples analyzed for testosterone (TES) and cortisol (COR) were taken before and after the 7-week training period at rest. Concentric knee extension 1RM was measured before, after 4 weeks, and at the end of the training period. Concentric knee extension and knee flexion 10RM, central activation ratio (CAR), and maxVO2 were measured before and after the training. Serum TES concentrations were significantly higher after the training period in FT80 (p < 0.001), whereas no significant changes were observed in the CONTROL. Serum COR and maxVO2 were unchanged in both groups. In FT80 (p < 0.001), the increase in 10RM was higher (p < 0.05) than in CONTROL (p < 0.001). Central activation ratio increased in both groups, with the significant increase observed in FT80 (p < 0.05). The higher TES responses, 10RM, and CAR development in FT80 suggest that an HR-based recovery period system of the FT80 may be more efficient in this type of hypertrophic strength training (3 × 10RM). The protocol in this study may be considered as a metabolic training cycle that coaches and trainers can use within a longer periodized training program.     

High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability

Intellectual disability (ID) is a heterogeneous disorder caused by chromosomal abnormalities, monogenic factors and environmental factors. 22q13 deletion syndrome is a genetic disorder characterized by severe ID. Although the frequency of 22q13 deletions in ID is unclear, it is believed to be largely underestimated. To address this issue, we used Affymetrix Human SNP 6.0 array to detect the 22q13 deletions in 234 Chinese unexplained ID patients and 103 controls. After the Quality Control (QC) test of raw data, 22q13 deletions were found in four out of 230 cases (1.7%), while absent in parents of the cases and 101 controls. A review of genome-wide microarray studies in ID was performed and the frequency of 22q13 deletions from the literatures was 0.24%, much lower than our report. The overlapping region shared by all 4 cases encompasses the gene SHANK3. A heterozygous de novo nonsense mutation Y1015X of SHANK3 was identified in one ID patient. Cortical neurons were prepared from embryonic mice and were transfected with a control plasmid, shank3 wild-type (WT) or mutant plasmids. Overexpression of the Y1015 mutant in neurons significantly affected neurite outgrowth compared with shank3 WT. These findings suggest that 22q13 deletions may be a more frequent cause for Chinese ID patients than previously thought, and the SHANK3 gene is involved in the neurite development.     

Relationship between the 30-second wingate test and characteristics of isometric and explosive leg strength in young subjects

The aim of this study was to investigate a possible relation between power performance of the Wingate test (WT) and isometric leg strength (ILS) and explosive leg strength (ELS) characteristics in young men and women with different physical fitness levels. A total of 166 subjects, including 98 young men and 68 young women, were included in the study. The subjects were divided into a regular exercise group and a sedentary group. The physical and body mass index characteristics of the subjects were not different, and they had not taken part in the directed jumping. When the regular exercise and sedentary groups were considered together with men, women, and total population groups, no significant correlation existed between WT anaerobic fatigue index and ILS and ELS (p > 0.05), but significant positive correlations existed among peak power, peak power per weight, mean power, mean power per weight, and WT power, which were recorded in 5-second intervals (p < 0.001). Although the 5-second WT parameters were significantly correlated with ILS and ELS for the first 15-second period, this correlation was more pronounced for the last 15 seconds for all groups (p < 0.01). As a result, this study indicated that regular physical activity has a positive significant relation on WT power, ILS, and ELS in both sedentary men and women and those engaged in regular sports activities.     

Long-term effect of losartan administration on blood pressure, heart and structure of coronary artery of young spontaneously hypertensive rats

Alterations in geometry and structure of coronary arteries have marked consequences on blood flow to the respective area. We evaluated long-term effect of losartan on blood pressure (BP), heart weight/body weight (HW/BW), geometry and structure of septal branch of coronary artery (RS) of young SHR and Wistar rats. Four-week-old Wistar rats and SHR were used. Losartan was administered (20 mg/kg/day) in drinking water by gavage for 5 weeks. BP was measured by plethysmographic method. Cardiovascular system was perfused with a fixative (120 mm Hg). RS was processed for electron microscopy. Wall thickness of intima + media (WT), inner diameter (ID), cross-sectional area of intima + media (CSA), volume densities (VD) of endothelial cells (EC), extracellular matrix (ECM) of intima, smooth muscle cells (SMC) and ECM of media were evaluated. BP of 4-week-old SHR did not differ from that of Wistar rats. BP, HW/BW, WT, CSA, WT/ID, CSAs of SMC, ECM of media were increased in 9-week-old SHR, whereas their VD and CSA of EC were decreased. Losartan administration decreased BP and HW/BW in both groups. Geometry of RS was affected only in SHR (reduction of WT, CSA, WT/ID and increased of ID, circumferential tension, VD and CSA of EC). Losartan administration reduced BP and myocardial mass in both groups and beneficially affected geometry and structure of coronary artery in SHR.     

Kinematics Analyses Related to Stretch-Shortening Cycle during Soccer Instep Kicking After Different Acute Stretching

ABSTRACT: Amiri-Khorasani, M, MohammadKazemi, R, Sarafrazi, S, Riyahi-Malayeri, S, and Sotoodeh, V. Kinematics analyses related to stretch-shortening cycle during soccer instep kicking after different acute stretching. J Strength Cond Res 26(11): 3010-3017, 2012-The purpose of this study was to examine the effects of static and dynamic stretching within a preexercise warm-up on angular velocity of knee joint, deepest knee flexion (DKF), and duration of eccentric and concentric contractions, which are relative to the stretch-shortening cycle (SSC) during instep kicking in professional soccer players. The kicking motions of dominant legs were captured from 18 Olympic professional male soccer players (height: 180.38 ± 7.34 cm; weight: 69.77 ± 9.73 kg; age: 19.22 ± 1.83 years) using 4 digital video cameras at 50 Hz. There was a significant difference in the DKF after the dynamic stretching (-3.22 ± 3.10°) vs. static stretching (-0.18 ± 3.19°) relative to the no-stretching method with p < 0.001. Moreover, there was significant difference in eccentric duration after the dynamic stretching (0.006 ± 0.01 seconds) vs. static stretching (-0.003 ± 0.01 seconds) relative to the no-stretching method with p < 0.015. There was a significant difference in the concentric duration after the dynamic stretching (-0.007 ± 0.01 seconds) vs. static stretching (0.002 ± 0.01 seconds) relative to the no-stretching method with p < 0.001. There was also a significant difference in knee angular velocity after the dynamic stretching (4.08 ± 3.81 rad·s) vs. static stretching (-5.34 ± 4.40 rad·s) relative to the no-stretching method with p < 0.001. We concluded that dynamic stretching during warm-ups, as compared with static stretching, is probably the most effective way as preparation for the kinematics characteristics of soccer instep kick, which are relative to the SSC.     

Effects of low calorie diet-induced weight loss on post-exercise heart rate recovery in obese men

[Purpose]

Heart Rate Recovery (HRR) after maximum exercise is a reactivation function of vagus nerve and an independent risk factor that predicts cardiovascular disease and mortality. Weight loss obtained through dietary programs has been employed as a therapy to reduce risks of cardiovascular disease and obesity.

[Methods]

Eighteen subjects of middle aged obese men (age 44.8 ± 1.6 yrs, BMI 29.7 ± 0.5 kg/m²) were selected for this study. As a weight loss direction, the nutritional direction of low-calorie diet mainly consisted of carbohydrate, protein, and fat has been conducted for 3 months. Blood pressure was measured after overnight fasting, and blood samples were collected from the antecubital vein before and after weight loss program. All the pre- and post-exercise ‘HRR decay constant’s were assessed by using values of HRR (heart recovery rate; 2 minutes) and HR measured after reached to the maximal oxygen uptake (VO₂max) exploited the bicycle ergometer.

[Results]

After the completion of weight loss program, body weight and BMI were significantly decreased, but the Heart Rate (HR) after maximum exercise and in steady state were not changed significantly (p > 0.05). The post-exercise HRR after the weight loss did not show significant changes in perspectives of 30 seconds (-16.6 ± 2.3 to -20.2 ± 2.1 beats/min, p > 0.05) and 60 seconds (-33.5 ± 3.4 to -34.6 ± 2.8 beats/min, p > 0.05) respectively but in perspectives of 90 seconds (-40.9 ± 2.6 to -48.1 ± 3.1 beats/min, p < 0.05) and 120 seconds (-48.6 ± 2.6 to -54.3 ± 3.5 beats/min, p < 0.05), they were decreased significantly. Pre-’HRR decay constant’s of 0.294 ± 0.02 %/second were significantly increased to post-values of 0.342 ± 0.03 %/second (p = 0.026). Changes in ‘HRR decay constant’ were significantly correlated with changes in blood glucose (r = -0.471, p < 0.05) and maximal oxygen consumption (VO₂max, r = 0.505, p < 0.05) respectively.

[Conclusions]

The low-calorie diet directed to obese middle aged men for 3 months significantly improved the HRR after maximum exercise, and this improvement in cardiovascular autonomic nerve system was estimated to be involved with improvements in blood glucose and maximal oxygen consumption.     

Activity and structural comparisons of solution associating and monomeric channel-forming peptides derived from the glycine receptor m2 segment

A number of channel-forming peptides derived from the second transmembrane (TM) segment (M2) of the glycine receptor alpha(1) subunit (M2GlyR), including the 22-residue sequence NK(4)-M2GlyR p22 wild type (WT) (KKKKPARVGLGITTVLTMTTQS), induce anion permeation across epithelial cell monolayers. In vitro assays suggest that this peptide or related sequences might function as a candidate for ion channel replacement therapy in treating channelopathies such as cystic fibrosis (CF). The wild-type sequence forms soluble associations in water that diminish its efficacy. Introduction of a single substitution S22W at the C-terminus, NK(4)-M2GlyR p22 S22W, eliminates the formation of higher molecular weight associations in solution. The S22W peptide also reduces the concentration of peptide required for half-maximal anion transport induced across Madin-Darby canine kidney cells (MDCK) monolayers. A combination of 2D double quantum filtered correlation spectroscopy (DQF-COSY), total correlation spectroscopy (TOCSY), nuclear Overhauser effect spectroscopy (NOESY), and rotating frame nuclear Overhauser effect spectroscopy (ROESY) data were recorded for both the associating WT and nonassociating S22W peptides and used to compare the primary structures and to assign the secondary structures. High-resolution structural studies were recorded in the solvent system (40% 2,2,2-Trifluoroethanol (TFE)/water), which gave the largest structural difference between the two peptides. Nuclear Overhauser effect crosspeak intensity provided interproton distances and the torsion angles were measured by spin-spin coupling constants. These constraints were put into the DYANA modeling program to generate a group of structures. These studies yielded energy-minimized structures for this mixed solvent environment. Structure for both peptides is confined to the 15-residue transmembrane segments. The energy-minimized structure for the WT peptide shows a partially helical extended structure. The S22W peptide adopts a bent conformation forming a hydrophobic pocket by hydrophobic interactions.     

The effect of a traditional dance training program on dynamic balance of individuals with mental retardation

The purpose of this study was to evaluate the influence of a Greek traditional dance training program on the dynamic balance of individuals with mental retardation (MR). A total of 17 individuals participated in this study. Ten individuals with mild or moderate MR and 7 individuals with mild or moderate MR who studied in special schools were assigned to intervention (MR-I) and control (MR-C) groups, respectively. Pretraining and posttraining exercise tests were performed to determine the dynamic balance ability. Dynamic balance ability was measured by means of a balance deck (Lafayette, Lafayette, IN, USA) in 30-, 45-, and 60-second intervals. The MR-I group underwent a 16-week Greek traditional dance training program at a frequency of 3 times per week and for a duration of 45 minutes per season. Posttraining results showed that the individuals with MR in the MR-I group improved during treatment, from their baseline scores on dynamic balance measurements (30 seconds: p < 0.01, 45 seconds: p < 0.05, 60 seconds: p < 0.05). The MR-C group did not show any improvement between the 2 measurements. In conclusion, individuals with MR may be able to improve their dynamic balance when performing a systematic and well-designed Greek traditional dance training program.     

Age, gender and circadian or circasemidian blood pressure and heart rate variation of children.

Systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) of clinically healthy children (24 boys and 15 girls) 3 to 7 years of age were measured with a standard mercury sphygmomanometer at 3-hour intervals for 24 hours in April 1991. The children slept and/or rested from 2100 to 0700 and napped from 1230 to 1530; they had meals at 0730, 1200 and 1800. A statistically significant circadian and about 12-hour (circasemidian) component of variation is documented for SBP and DBP of boys and girls and for HR of boys. No gender difference was found for the circadian and circasemidian components. A positive correlation with age is found for the MESOR and circadian amplitude of SBP and DBP (p < 0.05); a negative correlation with age is found for the MESOR of HR (p < 0.001).     

An outpatient-based clinical program for diabetes prevention: an update

ObjectiveTo update outcomes of the Diet-ExerciseActivity-Lifestyle (DEAL) program, a clinic-based diabetes prevention intervention.MethodsChanges in weight, fasting blood glucose, and 2-hour glucose after a 75-g oral glucose tolerance test were evaluated in patients who enrolled in the DEAL program between January 2007 and August 2009.ResultsThe 221 qualified participants had a mean age of 62 years, weight of 87.4 kg, body mass index of 31.2 kg/m², fasting glucose level of 109 mg/dL, and 2-hour glucose value of 138 mg/dL. Among the program participants, 67% were women and 88% were white; 56% had isolated impaired fasting glucose, 5% had impaired glucose tolerance only, and 39% had both. The 6-month follow-up medical appointment was kept by 72% of program participants, but only 56% attended the 12-month visit. By 6 months after baseline, 59% had significantly lower fasting glucose concentrations, 59% had improvement in 2-hour glucose levels, and 61% had weight loss. Nearly 40%, however, were nonresponders and had increased fasting glucose, 2-hour glucose, and weight by 6 months. By the 12-month visit, significant declines in fasting glucose (P < .001), 2-hour glucose (P < .001), and weight (P = .008) occurred in comparison with baseline values; however, no significant changes occurred in these measures between the 6and 12-month visits (P > .30 for all).ConclusionMost DEAL participants showed improvement in glucose levels and weight, but some patients exhibited worsening glucose intolerance. Factors underlying nonresponse need to be identified. Ongoing experience and analysis should help revise the DEAL program so that outcomes for all participating patients will improve. (Endocr Pract. 2012;18:200-208)     

Relation between lean body mass and thyroid volume in competition rowers before and during intensive physical training.

OBJECTIVE: Lean body mass is a better determinant of thyroid size than body weight as demonstrated in a previous crosssectional study. We now evaluated if intra-individual changes in body composition and especially changes in lean body mass, due to physical training, could give rise to changes in thyroid volume. SUBJECTS AND METHODS: We investigated 17 freshmen (group 1) before and after six months of competition rowing; controls (group II) were 19 senior rowers, already participating in a training program for more than 2 years. RESULTS: In group I body weight (BW; p < 0.01), lean body mass (LBM; p < 0.05), fat weight (FW; p < 0.05), body mass index (BMI; p < 0.01) and thyroid volume (TV; p = 0.08) all decreased; in group II body composition and thyroid volume did not change at all during the 6 months observation period. Whereas serum TSH and T3 did not change, free thyroxine (FT4) concentrations increased slightly in both groups (p < 0.01), presumably caused by the combination of exercise and insufficient energy intake. Taking together all subjects, baseline TV was directly related to BW (r = 0.35, p<0.05), to LBM (r=0.40, p<0.05) and to BMI (r=0.43, p < 0.01) but not to FW (r = - 0.06, NS). The decrease in thyroid volume was related to the decrease in LBM (r = 0.32, p = 0.05), in BW (r = 0.49, p < 0.005), in FW (r = 0.42, p = 0.01) and in BMI (r = 0.53, p = 0.001). CONCLUSIONS: After a six-month period of intensive physical training, changes in thyroid volume correlate directly with changes in body composition.     

The effectiveness of 3 stretching techniques on hamstring flexibility using consistent stretching parameters

This study compares the effects of 3 common stretching techniques on the length of the hamstring muscle group during a 4-week training program. Subjects were 19 young adults between the ages of 21 and 35. The criterion for subject inclusion was tight hamstrings as defined by a knee extension angle greater than 20 degrees while supine with the hip flexed 90 degrees . The participants were randomly assigned to 1 of 4 groups. Group 1 (n = 5) was self-stretching, group 2 (n = 5) was static stretching, group 3 (n = 5) was proprioceptive neuromuscular facilitation incorporating the theory of reciprocal inhibition (PNF-R), and group 4 (n = 4) was control. Each group received the same stretching dose of a single 30-second stretch 3 days per week for 4 weeks. Knee extension angle was measured before the start of the stretching program, at 2 weeks, and at 4 weeks. Statistical analysis (p < or = 0.05) revealed a significant interaction of stretching technique and duration of stretch. Post hoc analysis showed that all 3 stretching techniques increase hamstring length from the baseline value during a 4-week training program; however, only group 2 (static stretching) was found to be significantly greater than the control at 4 weeks. These data indicate that static stretching 1 repetition for 30 seconds 3 days per week increased hamstring length in young healthy subjects. These data also suggest that active self-stretching and PNF-R stretching 1 repetition for 30 seconds 3 days per week is not sufficient to significantly increase hamstring length in this population.     

An investigation into the recovery process of a maximum stretch-shortening cycle fatigue protocol on drop and rebound jumps

The aim of this study was to investigate the recovery process of a maximal stretch-shortening cycle (SSC) fatigue workout on the biomechanical performance of drop jump (DJ) and rebound jump (RBJ) on a force sledge apparatus. Thirteen elite level rugby players performed sledge DJs and RBJs before and 15, 45, 120, and 300 seconds after a maximum SSC fatigue workout. Flight time, ground contact time (CT), peak force, reactive strength index (RSI), and leg-spring stiffness were the dependent variables. The DJ results showed that after 15 seconds recovery, there was a significant reduction in flight time (FT) (p < 0.01), RSI (p < 0.001), peak force (p < 0.01), and leg stiffness (p < 0.001). Similarly, the results for the RBJ indicated that the fatigue workout significantly reduced FT (p < 0.001), peak force (p < 0.01), RSI (p < 0.01), and significantly increased CT (p < 0.05) at the 15-second interval. The results also indicated a potentiation effect at the 300-second interval because of significant increases in RSI, peak force, and leg stiffness (p < 0.05) for the RBJ and significant increases in RSI (p < 0.05), peak force, and leg stiffness (p < 0.01) and a significant decrease in ground CT (p < 0.05) for the DJ. A maximal SSC fatigue workout had both an inhibiting and potentiating effect on DJ and RBJ performance depending on the recovery interval. The efficiency of the SSC function was reduced immediately after the cessation of the fatigue workout. A potentiation effect was evident for both jumps 300 seconds postfatigue.     

Enhanced baroreflex sensitivity in free-moving calponin knockout mice

Calponin is an actin binding protein in vascular smooth muscle that modifies contractile responses. However, its role in mean arterial pressure (MAP) regulation has not been clarified. To assess this, MAP and heart rate (HR) were measured in calponin knockout (KO) mice, and the results were compared with those in wild-type (WT) mice. The measurements were performed every 100 ms during a 60-min free-moving state each day for 3 days. Mice in both groups rested during approximately 70% of the total measuring period. The mean HR during rest was significantly lower in KO mice than in WT mice but with no significant difference in MAP between the groups. The change in HR response (deltaHR) to spontaneous change in MAP (deltaMAP) varied in a wider range in KO mice with an 80% increase in the coefficient of variation for HR (P < 0.05), whereas MAP in KO mice was controlled in a narrow range similar to that in WT mice. The baroreflex sensitivity (deltaHR/deltaMAP), determined from the change in HR to the spontaneous change in MAP, was twofold higher in KO mice than that in WT mice (P < 0.01), whereas there were no significant differences in the baroreflex sensitivity determined by intravascular administration of phenylephrine and sodium nitroprusside between the two groups (P > 0.1). The MAP response to the administrated doses of phenylephrine in KO mice was reduced to one-half of that in WT mice (P < 0.01) but with no significant difference in the response to sodium nitroprusside between the groups. The differences in HR variability and the spontaneous baroreflex sensitivity between the two groups completely disappeared after carotid sinus denervation. These results suggest that the higher variability in HR for KO mice was caused by the increased spontaneous arterial baroreflex sensitivity, though not detected by the intra-arterial administration of the drug, and that the higher variability of HR may be a compensatory adaptation to the blunted alpha-adrenergic response of peripheral vessels to sympathetic nervous activity.     

The impact of the ovarian microenvironment on the anti-tumor effect of SPARC on ovarian cancer

A lack of host-derived SPARC promotes disease progression in an intraperitoneal (IP) ID8 mouse model of epithelial ovarian cancer (EOC). Since orthotopic injection (OT) of ID8 cells better recapitulates high-grade serous cancer, we examined the impact of host-derived SPARC following OT injection. Sparc(-/-) and wild-type (WT) mice were injected with ID8 cells either OT or IP and tumors were analyzed at the moribund stage. Sparc(-/-) mice had reduced survival and fewer well-defined abdominal lesions compared with WT controls after IP injection, whereas no differences were observed in survival or abdominal lesions between Sparc(-/-) and WT mice after OT injection. No differences in mass or collagen content were observed in ovarian tumors between OT-injected Sparc(-/-) and WT mice. The abdominal wall of the IP-injected Sparc(-/-) mice exhibited immature and less abundant collagen fibrils compared with WT mice both in injected and non-injected controls. In contrast to human EOC, SPARC was expressed by the tumor cells but was absent in reactive stroma of WT mice. Exposure to the ovarian microenvironment through OT injections alters the metastatic behaviour of ID8 cells, which is not affected by the absence of host-derived SPARC.     

Effects of twenty-eight days of beta-alanine and creatine monohydrate supplementation on the physical working capacity at neuromuscular fatigue threshold

The purpose of this study was to examine the effects of 28 days of beta-alanine (b-Ala) and creatine monohydrate (CrM) supplementation on the onset of neuromuscular fatigue by using the physical working capacity at neuromuscular fatigue threshold (PWC(FT)) test in untrained men. Fifty-one men (mean age +/- SD = 24.5 +/- 5.3 years) volunteered to participate in this 28-day, double-blind, placebo-controlled study and were randomly assigned to 1 of 4 groups: placebo (PLA; 34 g dextrose; n = 13), CrM (5.25 g CrM plus 34 g dextrose; n = 12), b-Ala (1.6 g b-Ala plus 34 g of dextrose; n = 12), or b-Ala plus CrM (CrBA; 5.25 g CrM plus 1.6 g b-Ala plus 34 g dextrose; n = 14). The supplement was ingested 4 times per day for 6 consecutive days, then twice per day for 22 days before posttesting. Before and after the supplementation, subjects performed a continuous incremental cycle ergometry test while a surface electromyographic signal was recorded from the vastus lateralis muscle to determine PWC(FT). The adjusted mean posttest PWC(FT) values (covaried for pretest PWC(FT) values) for the b-Ala and CrBA groups were greater than those for the PLA group (p < or = 0.05). However, there were no differences between the CrM vs. PLA, CrBA vs. b-Ala, CrM vs. b-Ala, or CrM vs. CrBA groups (p > 0.05). These findings suggested that b-Ala supplementation may delay the onset of neuromuscular fatigue. Furthermore, there appeared to be no additive or unique effects of CrM vs. b-Ala alone on PWC(FT).