Rescue of High Glucose Impairment of Cultured Human Osteoblasts Using Cinacalcet and Parathyroid Hormone.

Patients with type 2 diabetes mellitus (T2DM) experience a higher risk of fractures despite paradoxically exhibiting normal to high bone mineral density (BMD). This has drawn into question the applicability to T2DM of conventional fracture reduction treatments that aim to retain BMD. In a primary human osteoblast culture system, high glucose levels (25 mM) impaired cell proliferation and matrix mineralization compared to physiological glucose levels (5 mM). Treatment with parathyroid hormone (PTH, 10 nM), a bone anabolic agent, and cinacalcet (CN, 1 µM), a calcimimetic able to target the Ca2+-sensing receptor (CaSR), were tested for their effects on proliferation and differentiation. Strikingly, CN+PTH co-treatment was shown to promote cell growth and matrix mineralization under both physiological and high glucose conditions. CN+PTH reduced apoptosis by 0.9-fold/0.4-fold as measured by Caspase-3 activity assay, increased alkaline phosphatase (ALP) expression by 1.5-fold/twofold, increased the ratio of nuclear factor κ-B ligand (RANKL) to osteoprotegerin (OPG) by 2.1-fold/1.6-fold, and increased CaSR expression by 1.7-fold/4.6-fold (physiological glucose/high glucose). Collectively, these findings indicate a potential for CN+PTH combination therapy as a method to ameliorate the negative impact of chronic high blood glucose on bone remodeling.

The impact of waiting time for orthopaedic consultation on pain levels in individuals with osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: Time spent waiting for access to orthopaedic specialist health services has been suggested to result in increased pain in individuals with osteoarthritis (OA). We assessed whether time spent on an orthopaedic waiting list resulted in a detrimental effect on pain levels in patients with knee or hip OA. METHODS: We searched Ovid MEDLINE, EMBASE and EBSCOhost databases from inception until September 2021. Eligible articles included individuals with OA on an orthopaedic waitlist and not receiving active treatment, and reported pain measures at two or more time points. Random-effects meta-analysis was used to estimate the pooled effect of waiting time on pain levels. Meta-regression was used to determine predictors of effect size. RESULTS: Thirty-three articles were included (n = 2,490 participants, 67 ± 3 years and 62% female). The range of waiting time was 2 weeks to 2 years (20.8 ± 18.8 weeks). There was no significant change in pain over time (effect size = 0.082, 95% CI = -0.009, 0.172), nor was the length of time associated with longitudinal changes in pain over time (ß = 0.004, 95% CI = -0.005, 0.012). Body mass index was a significant predictor of pain (ß = -0.043, 95% CI = -0.079, 0.006), whereas age and sex were not. CONCLUSIONS: Pain remained stable for up to 1 year in patients with OA on an orthopaedic waitlist. Future research is required to understand whether pain increases in patients waiting longer than 1 year.

The role of estrogens in osteosarcopenia: from biology to potential dual therapeutic effects.

Osteoporosis and sarcopenia are two conditions associated with aging and characterized by a simultaneous decline in bone and muscle mass, respectively. These conditions share common risk factors (genetic, endocrine, nutritional and lifestyle factors) and biological pathways that often co-exist in a syndrome known as osteosarcopenia. Among the endocrine causes, estrogens play a critical role, especially in women. Estrogens have been demonstrated to exert a positive effect on bone and muscle development and maintenance. For this reason, menopause is characterized by a loss in bone mineral density and skeletal muscle quality and quantity. To date, studies indicate a positive effect of hormonal therapy on the prevention and management of osteoporosis, to the point that estrogen is prescribed as a first-line treatment for osteoporosis by the major international authorities. While results on sarcopenia are still disputable, such that estrogens are not recommended to prevent muscle loss in postmenopausal women, increased response to anabolic stimuli with estrogen therapy suggests similar beneficial effects on muscle as seen with bone, particularly when combined with resistance exercise.

Osteocalcin and its forms respond similarly to exercise in males and females.

INTRODUCTION: Acute exercise increases osteocalcin (OC), a marker of bone turnover, and in particular the undercarboxylated form (ucOC). Males and females differ in baseline levels of total OC and it is thought the hormonal milieu may be driving these differences. Males and females adapt differently to the same exercise intervention, however it is unclear whether the exercise effects on OC are also sex-specific. We tested whether the responses of OC and its forms to acute High Intensity Interval Exercise (HIIE) and High Intensity Interval Training (HIIT) differed between males and females. Secondly, we examined whether sex hormones vary with OC forms within sexes to understand if these are driving factor in any potential sex differences. METHODS: Total OC (tOC), undercarboxylated OC (ucOC), and carboxylated OC (cOC) were measured in serum of 96 healthy participants from the Gene SMART cohort (74 males and 22 females) at rest, immediately after, and 3 h after a single bout of HIIE, and at rest, 48 h after completing a four week HIIT intervention. Baseline testosterone and estradiol were also measured for a subset of the cohort (Males = 38, Females = 20). Linear mixed models were used to a) uncover the sex-specific effects of acute exercise and short-term training on OC forms and b) to examine whether the sex hormones were associated with OC levels. RESULTS: At baseline, males had higher levels of tOC, cOC, and ucOC than females (q < 0.01). In both sexes tOC, and ucOC increased to the same extent after acute HIIE. At baseline, in males only, higher testosterone was associated with higher ucOC (ß = 3.37; q < 0.046). Finally, tOC and ucOC did not change following 4 weeks of HIIT. CONCLUSION/DISCUSSION: While there were no long-term changes in OC and its forms. tOC and ucOC were transiently enhanced after a bout of HIIE similarly in both sexes. This may be important in metabolic signalling in skeletal muscle and bone suggesting that regular exercise is needed to maintain these benefits. Overall, these data suggest that the sex differences in exercise adaptations do not extend to the bone turnover marker, OC.

Effects of calcium supplementation on circulating osteocalcin and glycated haemoglobin in older women.

One year of calcium supplementation in older women led to modest reductions in total osteocalcin and undercarboxylated osteocalcin (ucOC), with no changes in muscle or fat mass, or glycated haemoglobin. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control. INTRODUCTION: Total osteocalcin (TOC) is a marker of bone turnover, while its undercarboxylated form has beneficial effects on glucose metabolism in mice. This post hoc analysis of a randomised double-blind, placebo-controlled trial examined whether 1 year of calcium supplementation affected circulating TOC, undercarboxylated osteocalcin (ucOC) or glycated haemoglobin (HbA1c) in 1368 older community-dwelling women (mean age 75.2 ± 2.7 years). METHODS: Women enrolled in the Calcium Intake Fracture Outcome Study trial (1998-2003) were supplemented with 1.2 g/d of elemental calcium (in the form of calcium carbonate) or placebo. Circulating TOC, ucOC and HbA1c was measured at 1 year (1999). RESULTS: After 1 year of calcium supplementation, TOC and ucOC levels were 17% and 22% lower compared with placebo (mean 22.7 ± 9.1 vs. 27.3 ± 10.9 µg/L and 11.1 ± 4.9 vs. 13.0 ± 5.7 µg/L, both P < 0.001). Carboxylated osteocalcin/ucOC was 6% lower after calcium supplementation (P < 0.05). Despite this, no differences in HbA1c were observed (calcium, 5.2 ± 0.6 vs. placebo, 5.3 ± 0.8%; P = 0.08). Calcium supplementation did not affect BMI, whole body lean or fat mass. In exploratory analyses, total calcium (dietary and supplemental) was inversely related to TOC and ucOC, indicating calcium intake is an important dietary determinant of osteocalcin levels. CONCLUSION: One year of calcium supplementation in older women led to modest reductions in TOC and ucOC, with no changes in muscle or fat mass, or HbA1c. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control.

Acute continuous moderate-intensity exercise, but not low-volume high-intensity interval exercise, attenuates postprandial suppression of circulating osteocalcin in young overweight and obese adults.

Bone remodeling markers (BRMs) are suppressed following the consumption of a meal. Our findings indicate that a single session of continuous moderate-intensity exercise, but not low-volume high-intensity interval exercise, performed 1 h after a meal attenuates the postprandial suppression of BRMs. INTRODUCTION: Acute exercise transiently increases BRMs including osteocalcin (tOC) and the undercarboxylated form of osteocalcin (ucOC), a hormone that is implicated in glucose regulation. The effects of acute exercise and exercise-intensity on postprandial levels of tOC and ucOC are unknown. METHODS: Twenty-seven adults that were overweight or obese (age 30 ± 1 years; BMI 30 ± 1 kg∙m-2; mean ± SEM) were randomly allocated to perform a single session of low-volume high-intensity interval exercise (LV-HIIE; nine females, five males) or continuous moderate-intensity exercise (CMIE; eightfemales, five males) 1 h after consumption of a standard breakfast. Serum tOC, ucOC, and ucOC/tOC were measured at baseline, 1 h, and 3 h after breakfast consumption on a rest day (no exercise) and the exercise day (exercise 1 h after breakfast). RESULTS: Compared to baseline, serum tOC and ucOC were suppressed 3 h after breakfast on the rest day (- 10 ± 1% and - 6 ± 2%, respectively; p < 0.05), whereas ucOC/tOC was elevated (2.5 ± 1%; p = 0.08). Compared to the rest day, CMIE attenuated the postprandial-induced suppression of tOC (rest day - 10 ± 2% versus CMIE - 5 ± 2%, p < 0.05) and ucOC (rest day - 6 ± 4% versus CMIE 11 ± 2%, p < 0.05), and increased postprandial ucOC/tOC (rest day 3 ± 2% versus CMIE 15 ± 1%, p < 0.05). In contrast, LV-HIIE did not alter postprandial tOC, ucOC, or ucOC/tOC (all p > 0.1). CONCLUSIONS: Acute CMIE, but not LV-HIIE, attenuates the postprandial-induced suppression of tOC and ucOC. CMIE may be an effective tool to control the circulating levels of BRMs following meal consumption in overweight/obese adults.

Four days of simulated shift work reduces insulin sensitivity in humans.

AIM: The aim of this study was to investigate the effects of 4 consecutive simulated night shifts on glucose homeostasis, mitochondrial function and central and peripheral rhythmicities compared with a simulated day shift schedule. METHODS: Seventeen healthy adults (8M:9F) matched for sleep, physical activity and dietary/fat intake participated in this study (night shift work n = 9; day shift work n = 8). Glucose tolerance and insulin sensitivity before and after 4 nights of shift work were measured by an intravenous glucose tolerance test and a hyperinsulinaemic euglycaemic clamp respectively. Muscles biopsies were obtained to determine insulin signalling and mitochondrial function. Central and peripheral rhythmicities were assessed by measuring salivary melatonin and expression of circadian genes from hair samples respectively. RESULTS: Fasting plasma glucose increased (4.4 ± 0.1 vs. 4.6 ± 0.1 mmol L-1 ; P = .001) and insulin sensitivity decreased (25 ± 7%, P < .05) following the night shift, with no changes following the day shift. Night shift work had no effect on skeletal muscle protein expression (PGC1α, UCP3, TFAM and mitochondria Complex II-V) or insulin-stimulated pAkt Ser473, pTBC1D4Ser318 and pTBC1D4Thr642. Importantly, the metabolic changes after simulated night shifts occurred despite no changes in the timing of melatonin rhythmicity or hair follicle cell clock gene expression across the wake period (Per3, Per1, Nr1d1 and Nr1d2). CONCLUSION: Only 4 days of simulated night shift work in healthy adults is sufficient to reduce insulin sensitivity which would be expected to increase the risk of T2D.

Multifaceted interaction of bone, muscle, lifestyle interventions and metabolic and cardiovascular disease: role of osteocalcin.

Undercarboxylated osteocalcin (ucOC) may play a role in glucose homeostasis and cardiometabolic health. This review examines the epidemiological and interventional evidence associating osteocalcin (OC) and ucOC with metabolic risk and cardiovascular disease. The complexity in assessing such correlations, due to the observational nature of human studies, is discussed. Several studies have reported that higher levels of ucOC and OC are correlated with lower fat mass and HbA1c. In addition, improved measures of glycaemic control via pharmacological and non-pharmacological (e.g. exercise or diet) interventions are often associated with increased circulating levels of OC and/or ucOC. There is also a relationship between lower circulating OC and ucOC and increased measures of vascular calcification and cardiovascular disease. However, not all studies have reported such relationship, some with contradictory findings. Equivocal findings may arise because of the observational nature of the studies and the inability to directly assess the relationship between OC and ucOC on glycaemic control and cardiovascular health in humans. Studying OC and ucOC in humans is further complicated due to numerous confounding factors such as sex differences, menopausal status, vitamin K status, physical activity level, body mass index, insulin sensitivity (normal/insulin resistance/T2DM), tissue-specific effects and renal function among others. Current observational and indirect interventional evidence appears to support a relationship between ucOC with metabolic and cardiovascular disease. There is also emerging evidence to suggest a direct role of ucOC in human metabolism. Further mechanistic studies are required to (a) clarify causality, (b) explore mechanisms involved and

Impaired muscle function in a mouse surgical model of post-traumatic osteoarthritis.

OBJECTIVES: Using a mouse surgical model of post-traumatic osteoarthritis (OA), we sought to determine if muscle function is altered following acute joint injury and whether this relates to OA progression. DESIGN: Male C57BL/6 mice underwent surgical transection of the medio-meniscal tibial ligament destabilisation of the medial meniscus (DMM) or sham surgery on one knee. Tibialis anterior (TA) muscle function was assessed in situ at 1, 4 and 8 weeks post-surgery. Cartilage damage and joint inflammation were assessed by histologic scoring. Muscle mRNA expression was quantified by qRT-PCR. RESULTS: Tetanic and twitch force production between DMM and sham muscle did not differ at 1 week post-surgery. Muscle function improved in both groups with time, but specific force production in DMM muscles was 18% and 22% lower than sham muscles at 4 and 8 weeks post-surgery respectively. At 8 weeks post-surgery, DMM muscles had a 40% slower relaxation rate and reduced expression of sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (Serca) pump mRNA compared to sham muscles; both observations indicate likely alterations in muscle Ca(2+) handling. There were no histologic signs of muscle atrophy or inflammation in DMM TA muscles. Specific force production in both sham and DMM mice showed a negative correlation with the severity of joint inflammation. CONCLUSIONS: Acute knee injury in the DMM model of post-traumatic OA leads to a persistent deficit in TA muscle function that occurs in the absence of muscle atrophy. This study highlights that the impact of acute knee injury is unlikely to be limited to the muscles controlling knee movement.

The level of FoxO1 and IL-15 in skeletal muscle, serum and synovial fluid in people with knee osteoarthritis: a case control study.

UNLABELLED: The molecular regulation of muscle function in knee osteoarthritis is unclear. Elevated muscle atrophy regulation marker expression was associated with reduced muscle strength in knee osteoarthritis. The level of protein expression appears to be different between muscle, knee joint and serum, suggesting that inflammation is regulated differently within these tissues. INTRODUCTION: Impaired muscle function is common in knee osteoarthritis (OA). Numerous biochemical molecules have been implicated in the development of OA; however, these have only been identified in the joint and serum. We compared the expression of interleukin-15 (IL-15) and Forkhead box protein-O1 (FoxO1) in muscle of patients with knee OA and asymptomatic individuals and examined whether IL-15 was also present in the joint and serum. METHODS: Muscle and blood samples were collected from 19 patients with knee OA and 10 age-matched asymptomatic individuals. Synovial fluid and muscle biopsies were collected from the OA group during knee replacement surgery. IL-15 and FoxO1 were measured in the skeletal muscle. IL-15 abundance was also analysed in the serum of both groups and synovial fluid from the OA group. Knee extensor strength was measured and correlated with IL-15 and FoxO1 in the muscle. RESULTS: FoxO1 protein expression was higher (p = 0.04), whereas IL-15 expression was lower (p = 0.02) in the muscle of the OA group. Strength was also lower in the OA group and was inversely correlated with FoxO1 expression. No correlation was found between IL-15 in the joint, muscle or serum. CONCLUSION: Skeletal muscle, particularly the quadriceps, is affected in people with knee OA where elevated FoxO1 protein expression was associated with reduced muscle strength. While IL-15 protein expression in the muscle was lower in the knee OA group, no correlation was found between the expression of IL-15 protein in the muscle, joint and serum, which suggests that inflammation is regulated differently within these tissues. Australian Clinical Trials Registry (ACTR) number: ACTRN12613000467730 ( http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12613000467730&isBasic=True ).

The effects of muscle contraction and recombinant osteocalcin on insulin sensitivity ex vivo.

UNLABELLED: We tested whether GPRC6A, the putative receptor of undercarboxylated osteocalcin (ucOC), is present in mouse muscle and whether ucOC increases insulin sensitivity following ex vivo muscle contraction. GPPRC6A is expressed in mouse muscle and in the mouse myotubes from a cell line. ucOC potentiated the effect of ex vivo contraction on insulin sensitivity. INTRODUCTION: Acute exercise increases skeletal muscle insulin sensitivity. In humans, exercise increases circulating ucOC, a hormone that increases insulin sensitivity in rodents. We tested whether GPRC6A, the putative receptor of ucOC, is present in mouse muscle and whether recombinant ucOC increases insulin sensitivity in both C2C12 myotubes and whole mouse muscle following ex vivo muscle contraction. METHODS: Glucose uptake was examined in C2C12 myotubes that express GPRC6A following treatment with insulin alone or with insulin and increasing ucOC concentrations (0.3, 3, 10 and 30 ng/ml). In addition, glucose uptake, phosphorylated (p-)AKT and p-AS160 were examined ex vivo in extensor digitorum longus (EDL) dissected from C57BL/6J wild-type mice, at rest, following insulin alone, after muscle contraction followed by insulin and after muscle contraction followed by recombinant ucOC then insulin exposure. RESULTS: We observed protein expression of the likely receptor for ucOC, GPRC6A, in whole muscle sections and differentiated mouse myotubes. We observed reduced GPRC6A expression following siRNA transfection. ucOC significantly increased insulin-stimulated glucose uptake dose-dependently up to 10 ng/ml, in differentiated mouse C2C12 myotubes. Insulin increased EDL glucose uptake (∼30 %, p < 0.05) and p-AKT and p-AKT/AKT compared with rest (all p < 0.05). Contraction prior to insulin increased muscle glucose uptake (∼25 %, p < 0.05), p-AKT, p-AKT/AKT, p-AS160 and p-AS160/AS160 compared with contraction alone (all p < 0.05). ucOC after contraction increased insulin-stimulated muscle glucose uptake (∼12 % p < 0.05) and p-AS160 (<0.05) more than contraction plus insulin alone but without effect on p-AKT. In the absence of insulin and/or of contraction, ucOC had no significant effect on muscle glucose uptake. CONCLUSIONS: GPRC6A, the likely receptor of osteocalcin (OC), is expressed in mouse muscle. ucOC treatment augments insulin-stimulated skeletal muscle glucose uptake in C2C12 myotubes and following ex vivo muscle contraction. ucOC may partly account for the insulin sensitizing effect of exercise.

Life is three dimensional-as in vitro cancer cultures should be.

For many decades, fundamental cancer research has relied on two-dimensional in vitro cell culture models. However, these provide a poor representation of the complex three-dimensional (3D) architecture of living tissues. The more recent 3D culture systems, which range from ridged scaffolds to semiliquid gels, resemble their natural counterparts more closely. The arrangement of the cells in 3D systems allows better cell-cell interaction and facilitates extracellular matrix secretion, with concomitant effects on gene and protein expression and cellular behavior. Many studies have reported differences between 3D and 2D systems as regards responses to therapeutic agents and pivotal cellular processes such as cell differentiation, morphology, and signaling pathways, demonstrating the importance of 3D culturing for various cancer cell lines.

Oxygen (O2) kinetics during early recovery from peak exercise in patients with Type 2 diabetes.

AIMS: To examine the oxygen (O(2)) kinetics during early recovery from peak exercise in patients with Type 2 diabetes and to examine whether oxygen O(2) recovery is associated with fasting glucose and HbA(1c) in this population. METHODS: Eighty-nine participants (52 men) aged 51.8 ± 7.1 years (mean ± SD) were divided into three groups: normal weight (BMI ≤ 25.0 kg/m(2)), overweight/obese without diabetes (BMI ≥ 26 kg/m(2)) and overweight/obese with Type 2 diabetes. Participants were assessed for their aerobic power (VO(2peak)) on a cycle ergometer, provided a fasting blood sample and underwent a series of anthropometric measurements. Early recovery period was measured for 60 s from cessation of exercise and expressed as percentage of VO(2peak) (higher percentage represents slower recovery). RESULTS: No significant differences were observed for age between the three study groups. Both the overweight/obese groups without diabetes and with Type 2 diabetes had higher BMI than the normal weight group, with no significant differences between overweight/obese participants without diabetes and those with diabetes. Participants with Type 2 diabetes had lower VO(2peak) than overweight/obese participants without diabetes and normal weight individuals (19.6 ± 4.8, 22.6 ± 5.4 and 25.7 ± 5.3 ml kg(-1) min(-1), respectively, P < 0.004 for overall trends). Participants with Type 2 diabetes also had slower recovery in oxygen O(2) kinetics after exercise, compared with both normal weight and overweight/obese individuals without diabetes (56.5 ± 7.7, 49.2 ± 7.2, 47.7 ± 7.4%, P < 0.004 for overall trends). Multiple regression analysis revealed that percentage of oxygen O(2) recovery was a stronger predictor than VO(2peak), BMI or age for fasting glucose and HbA(1c). CONCLUSIONS: Patients with Type 2 diabetes have lower VO(2peak) and prolonged oxygen O(2) recovery from peak exercise. However, only prolonged oxygen O(2) recovery was associated with fasting glucose and HbA(1c).

The effect of acute exercise on undercarboxylated osteocalcin in obese men.

SUMMARY: The purpose of this study was to examine if the reduction in glucose post-exercise is mediated by undercarboxylated osteocalcin (unOC). Obese men were randomly assigned to do aerobic or power exercises. The change in unOC levels was correlated with the change in glucose levels post-exercise. The reduction in glucose post-acute exercise may be partly related to increased unOC. INTRODUCTION: Osteocalcin (OC) in its undercarboxylated (unOC) form may contribute to the regulation of glucose homeostasis. As exercise reduces serum glucose and improves insulin sensitivity in obese individuals and individuals with type 2 diabetes (T2DM), we hypothesised that this benefit was partly mediated by unOC. METHODS: Twenty-eight middle-aged (52.4 ± 1.2 years, mean ± SEM), obese (BMI = 32.1 ± 0.9 kg m(-2)) men were randomly assigned to do either 45 min of aerobic (cycling at 75% of VO(2peak)) or power (leg press at 75% of one repetition maximum plus jumping sequence) exercises. Blood samples were taken at baseline and up to 2 h post-exercise. RESULTS: At baseline, unOC was negatively correlated with glucose levels (r = -0.53, p = 0.003) and glycosylated haemoglobin (HbA1c) (r = -0.37, p = 0.035). Both aerobic and power exercises reduced serum glucose (from 7.4 ± 1.2 to 5.1 ± 0.5 mmol L(-1), p = 0.01 and 8.5 ± 1.2 to 6.0 ± 0.6 mmol L(-1), p = 0.01, respectively). Aerobic exercise significantly increased OC, unOC and high-molecular-weight adiponectin, while power exercise had a limited effect on OC and unOC. Overall, those with higher baseline glucose and HbA1c had greater reductions in glucose levels after exercise (r = -0.46, p = 0.013 and r = -0.43, p = 0.019, respectively). In a sub-group of obese people with T2DM, the percentage change in unOC levels was correlated with the percentage change in glucose levels post-exercise (r = -0.51, p = 0.038). CONCLUSIONS: This study reports that the reduction in serum glucose post-acute exercise (especially aerobic exercise) may be partly related to increased unOC.

Inflammation, hepatic enzymes and resistance training in individuals with metabolic risk factors.

AIMS: Increases in inflammatory markers, hepatic enzymes and physical inactivity are associated with the development of the metabolic syndrome (MetS). We examined whether inflammatory markers and hepatic enzymes are correlated with traditional risk factors for MetS and studied the effects of resistance training (RT) on these emerging risk factors in individuals with a high number of metabolic risk factors (HiMF, 2.9 +/- 0.8) and those with a low number of metabolic risk factors (LoMF, 0.5 +/- 0.5). METHODS: Twenty-eight men and 27 women aged 50.8 +/- 6.5 years (mean +/- sd) participated in the study. Participants were randomized to four groups, HiMF training (HiMFT), HiMF control (HiMFC), LoMF training (LoMFT) and LoMF control (LoMFC). Before and after 10 weeks of RT [3 days/week, seven exercises, three sets with intensity gradually increased from 40-50% of one repetition maximum (1RM) to 75-85% of 1RM], blood samples were obtained for the measurement of pro-inflammatory cytokines, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT). RESULTS: At baseline, HiMF had higher interleukin-6 (33.9%), CRP (57.1%), GGT (45.2%) and ALT (40.6%) levels, compared with LoMF (all P < 0.05). CRP, GGT and ALT correlated with the number of risk factors (r = 0.48, 0.51 and 0.57, respectively, all P < 0.01) and with other anthropometric and clinical measures (r range from 0.26 to 0.60, P < 0.05). RT did not significantly alter inflammatory markers or hepatic enzymes (all P > 0.05). CONCLUSIONS: HiMF was associated with increased inflammatory markers and hepatic enzyme concentrations. RT did not reduce inflammatory markers and hepatic enzymes in individuals with HiMF.

Possible control mechanisms of feather follicle movement in the pectoral tract of the chicken.

Feather follicle movement control was studied on feathers of the pectoral tract in the anaesthetized chicken. Dissection of nerves leading to the follicles showed that their origin was at least partially in the sympathetic ganglia. Reflectoric ruffling of feathers could be obtained after adequate stimulation. Intravenous injections of drugs in doses which influenced the circulation gave the following results: Adrenaline caused erection of feathers which was abolished by phentolamine. Noradrenaline caused up and down movements after injection only at high doses. Similar results were obtained by placing of skin pieces in saline containing the drugs. The reaction to drugs was typical always for a given group of feathers. Killing of birds and anaesthesia caused general erection of feathers which was not abolished by phentolamine. The findings suggest that adrenergic synapses are involved in feather follicle movement control, but at least another mechanism (CNS) regulates feather follicle movement.

Nerves and muscles regulating feather follicle movements in the chicken.

It was found that most feather follicles posses more than a single muscle system but only single nerve endings were observed in a feather follicle. It seems that muscles exist which antagonize each other. Anastomoses of nerves originating from different sources and flowing of mixed nerves into the feather follicle could explain the antagonistic action of the muscles on the feather follicle.

Heart rate and myocardial substrate preference during normal and hypoxic perfusion of the heart in vivo.

Selective utilization of carbohydrates and FFA by the heart was studied on the open-chest dog preparation. The heart was paced at frequencies from 120-240/min, and arterial and coronary venous blood samples were taken at these frequencies both during normal ventilation and hypoxia (arterial PO2 similar to 55 mmHg). The concentrations of glucose, lactate, pyruvate, and FFA were determined, and substrate utilization was calculated from these values and coronary blood flow. It was found that increased heart rate, particularly during hypoxia, increased utilization of both glucose and FFA. However, the relative amount of the energy produced from glucose utilization was minimal during hypoxia and most glucose underwent glycolysis only. Thus, whereas in control conditions of the relation between carbohydrate and FFA was about 60% to 40% during hyposia and high frequency the relation was reversed and almost 90% of all energy produced was supplied by FFA.