Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques.

PURPOSE: The use of receptor-targeted antibodies conjugated to photosensitizers is actively being explored to enhance treatment efficacy. To facilitate clinical testing, we evaluated cetuximab conjugated to IRDye700DX (IR700) in cynomolgus macaques. PROCEDURES: Total IR700 and intact cetuximab-IR700 were measured in 51 tissues at 2 and 14 days after intravenous injection of 40 and 80 mg/kg cetuximab-IR700, respectively, and compared with an unlabeled cetuximab-dosed control group (two each per sex per time point per group). RESULTS: The IR700 retrieved from all tissues at 2 and 14 days after dosing was estimated at 34.9 ± 1.8 and 2.53 ± 0.67% of the total dose, respectively. The tissues with the highest levels of intact cetuximab-IR700 at 2 days after dosing were the blood, lung, and skin. Formalin-fixed paraffin-embedded tissue sections at 2 days after dosing showed the highest IR700 signals in the axillary lymph node, mammary gland, and gall bladder. CONCLUSIONS: Both IR700 and intact cetuximab-IR700 biodistributions were consistent with known epidermal growth factor receptor (EGFR) expression, and changes between 2 and 14 days were consistent with rapid metabolism and excretion of the cetuximab-IR700.

Recovery time of motor evoked potentials following lengthening and shortening muscle action in the tibialis anterior.

Motor evoked potentials (MEP) at rest remain facilitated following an isometric muscle contraction. Because the pre-synaptic and post-synaptic control of shortening (SHO) and lengthening (LEN) contractions differs, the possibility exists that the recovery of the MEP is also task specific. The time course of MEP recovery was assessed in the tibialis anterior following SHO and LEN (0.26 rad/s) at 25% and 80% of maximal voluntary contraction. Following LEN and SHO contractions, the MEP recovered to baseline levels within 10s. Despite task-specific differences between SHO and LEN contractions, the MEP facilitation from the augmented neurotransmitter release appears to be short lasting and not influenced by contraction type.

Peak and average rectified EMG measures: which method of data reduction should be used for assessing core training exercises?

Core strengthening and stability exercises are fundamental for any conditioning training program. Although surface electromyography (sEMG) is used to quantify muscle activity there is a lack of research using this method to investigate the core musculature and core stability. Two types of data reduction are commonly used for sEMG; peak and average rectified EMG methods. Peak EMG has been infrequently reported in the literature with regard to the assessment of core training while even fewer studies have incorporated average rectified EMG data (ARV). The aim of the study was to establish the repeatability of peak and average rectified EMG data during core training exercises and their interrelationship. Ten male highly trained athletes (inter-subject repeatability group; age, 18 ± 1.2 years; height, 176.5 ± 3.2 cm; body mass, 71 ± 4.5 kg) and one female highly trained athlete (intra-subject repeatability group; age; 27 years old; height; 180 cm; weight; 53 kg) performed five maximal voluntary isometric contractions (MVIC) and five core exercises, chosen to represent a range of movement and muscle recruitment patterns. Peak EMG and ARV EMG were calculated for eight core muscles (rectus abdominis, RA; external oblique, EO; internal oblique, IO; multifidis, MF; latissimus dorsi, LD; longissimus, LG; gluteus maximus, GM; rectus femoris, RF) using sEMG. Average coefficient of variation (CV%) for peak EMG across all the exercises and muscles was 45%. This is in comparison to 35% for the ARV method, which was found to be a significant difference (P<0.05), therefore implying that the ARV method is the more reliable measure for these types of exercise. Analysis of the inter-subject and intra-subject CV% values suggest that these exercises and muscles are sufficiently repeatable using sEMG. Five muscles were highly correlated (R>0.70; RA, EO, MF, GM, LG) between peak and ARV EMG suggesting, that for these core muscles, the two methods provide a similar evaluation of muscle activity. However, for other muscles (IO, RF, LD) the relationship was found to range from poor to moderate (R=0.10-0.70). The relationship between peak and ARV EMG was also affected by exercise type. Dynamic low and high-threshold exercises and asymmetrical low-threshold exercises had a moderate correlation between the variables (R=0.74-0.81), while the static exercise showed a poor correlation (R=0.46). It can be concluded that there are similarities between the two EMG variables, however due to the effect of type of exercise and muscle on the EMG data, both methods should be included in any future EMG study on the core musculature and core stability exercises.

Hormonal responses to a 160-km race across frozen Alaska.

BACKGROUND: Severe physical and environmental stress seems to have a suppressive effect on the hypothalamic-pituitary-gonadal (HPG) axis in men. Examining hormonal responses to an extreme 160-km competition across frozen Alaska provides a unique opportunity to study this intense stress. OBJECTIVE: To examine hormonal responses to an ultra-endurance race. METHODS: Blood samples were obtained from 16 men before and after racing and analyzed for testosterone, interleukin-6 (IL-6), growth hormone (GH) and cortisol. Six subjects (mean (SD) age 42 (7) years; body mass 78.9 (7.1) kg; height 1.78 (0.05) m raced by bicycle (cyclists) and 10 subjects (age 35 (9) years; body mass 77.9 (10.6) kg; height, 1.82 (0.05) m) raced by foot (runners). Mean (SD) finish times were 21.83 (6.27) and 33.98 (6.12) h, respectively. RESULTS: In cyclists there were significant (p< or =0.05) mean (SD) pre-race to post-race increases in cortisol (254.83 (135.26) to 535.99 (232.22) nmol/l), GH (0.12 (0.23) to 3.21 (3.33) microg/ml) and IL-6 (2.36 (0.42) to 10.15 (3.28) pg/ml), and a significant decrease in testosterone (13.81 (3.19) to 5.59 (3.74) nmol/l). Similarly, in runners there were significant pre-race to post-race increases in cortisol (142.09 (50.74) to 452.21 (163.40) ng/ml), GH (0.12 (0.23) to 3.21 (3.33) microg/ml) and IL-6 (2.42 (0.68) to 12.25 (1.78) pg/ml), and a significant decrease in testosterone (12.32 (4.47) to 6.96 (3.19) nmol/l). There were no significant differences in the hormonal levels between cyclists and runners (p>0.05). CONCLUSIONS: These data suggest a suppression of the hypopituitary-gonadal axis potentially mediated by amplification of adrenal stress responses to such an ultra-endurance race in environmentally stressful conditions.

Influence of muscle strength and total work on exercise-induced plasma growth hormone isoforms in women.

The purpose of this investigation was to determine the influence of physical strength and the ability to do more total work on human growth hormone (GH) variants to a heavy resistance exercise protocol in untrained women. From a distribution of 100 healthy, untrained women, the strongest 10 women (S) and the weakest 10 women (W) were compared for GH responses pre- and post an acute heavy resistance exercise test (AHRET, 6 sets of 10 RM squats, 2 minutes rest between sets). Blood samples were obtained pre-exercise and immediately post-exercise and subsequently analysed in total as well as fractionated by Sephacryl S-100R column chromatography into three molecular weight size classes: fraction A: > 60 kD, fraction B: 30-60 kD, fraction C: < 30 kD. For each total sample as well as each fraction, immunoreactive GH was measured via the Nichols IRMA, while bioactive GH was measured via the hypox rat tibial line bioassay and Diagnostic Systems Laboratory's immunofunctional GH ELISA. No exercise-induced changes or differences between groups were observed in the tibial line bioassay. However, the S group displayed a significantly higher pre-exercise resting value in the total fraction than the W group. Conversely, the W group exhibited a significantly higher pre-exercise value in the smaller molecular weight fraction C. With regards to the immunofunctional and immunoreactive assays, the total fraction, fraction A, and fraction B demonstrated significant (P < or = 0.05) exercise-induced increases in both the S and W group despite no group differences. For the Nichols and immunofunctional assays significant exercise-induced changes were observed in the smaller molecular weight C fraction in the W group but not the S group. However, the S group displayed a significantly higher pre-exercise value in fraction C relative to the W group. These data demonstrate for the first time that differences exist in the GH molecular weight variants between strong and weak untrained women, with the lower molecular weight variants seemingly less responsive to greater amounts of exercise in stronger women, thus suggesting differential regulation of GH molecular weight variants during resistance exercise due to pre-existing physical parameters.

Safety measures of L-carnitine L-tartrate supplementation in healthy men.

The purpose of this investigation was to examine the effects of ingestion of L-CARNIPURE (L-carnitine L-tartrate [LCLT]) on alterations in a complete blood cell profile and in circulating metabolic enzymes. Using a balanced, placebo (P), cross-over design (1 week washout), 10 healthy, active men volunteered and acted as their own control taking either a P or LCLT supplement (3 g.day(-1)) for 3 weeks. Postabsorptive morning blood samples were obtained both before and after 21 days of P and LCLT supplementation. Serum samples were analyzed for clinical chemistries including a complete chemistry panel with markers of liver and renal function along with various minerals and electrolytes. In addition, whole blood was analyzed for a complete blood count with differential. It was determined that there were no statistically significant differences between the LCLT and the placebo conditions for any of the variables examined. The results of this study suggest that LCLT, when used as a dietary supplement, has no adverse effects on metabolic and hematological safety variables in normally healthy men.