A novel extrusion-based 3D bioprinting system for skeletal muscle tissue engineering.

Three-dimensional (3D) bioprinting is an emerging technology, which turned out to be an optimal tool for tissue engineering approaches. To date, different printing systems have been developed. Among them, the extrusion-based approach demonstrated to be the most suitable for skeletal muscle tissue engineering, due to its ability to produce and deposit printing fibers in a parallel pattern that well mimic the native skeletal muscle tissue architecture. In tissue bioengineering, a key role is played by biomaterials, which must possess the key requisite of 'printability'. Nevertheless, this feature is not often well correlated with cell requirements, such as motives for cellular adhesion and/or absorbability. To overcome this hurdle, several efforts have been made to obtain an effective bioink by combining two different biomaterials in order to reach a good printability besides a suitable biological activity. However, despite being efficient, this strategy reveals several outcomes limitations. We report here the development and characterization of a novel extrusion-based 3D bioprinting system, and its application for correction of volumetric muscle loss (VML) injury in a mouse model. The developed bioprinting system is based on the use of PEG-Fibrinogen, a unique biomaterial with excellent biocompatibility, well-suited for skeletal muscle tissue engineering. With this approach, we obtained highly organized 3D constructs, in which murine muscle progenitors were able to differentiate into muscle fibers arranged in aligned bundles and capable of spontaneously contracting when culturedin vitro. Furthermore, to evaluate the potential of the developed system in future regenerative medicine applications, bioprinted constructs laden with either murine or human muscle progenitors were transplanted to regenerate theTibialis Anteriormuscle of a VML murine model, one month after grafting.

Circuit resistance training and cardiovascular health in breast cancer survivors.

OBJECTIVE: Cardiovascular disease is the leading cause of death in breast cancer survivors. While evidence shows circuit resistance training (CRT) is effective for improving muscle and cardiorespiratory fitness, whether CRT is an efficacious therapy for decreasing cardiovascular risk in cancer survivors is unclear. METHODS: Fifty-one breast cancer survivors were recruited to either 12 weeks CRT (n = 26), or a non-exercising wait-list control (n = 25). Two supervised 60 min CRT sessions per week were undertaken, comprising resistance and functional exercises, and aerobic exercise stations. Primary outcome measure was the gold-standard assessment of arterial stiffness, aortic pulse wave velocity (PWV). Secondary outcomes included: cardiorespiratory fitness (CRF), upper and lower body strength, arterial wave reflections, central blood pressure and rate pressure product. RESULTS: Compared to the control group, the CRT group had a statistically significant medium effect decrease in PWV 0.9 m/s (95% CI: 0.1, 1.7). There were large effect improvements in VO2 max (4.3 ml kg-1  min-1 , 95% CI: 5.8, 2.8), upper and lower body strength (3.7 kg, 95% CI: 1.9, 5.6 and 10.4 kg, 1.6, 19.1) respectively. CONCLUSION: Findings support the existing literature demonstrating that 12 weeks CRT improves muscle and cardiorespiratory fitness and is also an effective strategy for decreasing a proven cardiovascular risk factor in breast cancer survivors.

Cardiorespiratory fitness predicts cardiovascular health in breast cancer survivors, independent of body composition, age and time post-treatment completion.

BACKGROUND: Breast cancer treatment may increase non-cancer related mortality risk due to unintended cardiovascular consequences. The aim of this study was to investigate the strongest correlate of cardiovascular health (CVH) in female breast cancer survivors, cardiorespiratory fitness or fatness. METHODS: Fifty-one women (59 ± 9 years, BMI 26.4 ± 4.8 kg/m2) previously diagnosed and treated for primary breast cancer were assessed using pulse wave analysis to determine central arterial wave reflection (augmentation index, AIx) and central systolic blood pressure (cSBP). A composite Z score calculated which incorporated central double product and AIx, as an indicator of CVH. Dual energy X-ray absorptiometry was used to obtain total body fat percentage (BF%). Cardiorespiratory fitness was determined using the single-stage walk test to predict maximal oxygen uptake ([Formula: see text]). RESULTS: Linear regression analysis revealed that fitness was associated with AIx after adjusting for BF %, age and time post-treatment completion (ß = - 0.271, p = 0.010). A significant association between BF% and AIx after adjusting for fitness and age was found (ß = 0.166, p = 0.0005); however, this association was lost when time post-treatment was included in the model (ß = 0.166, p = 0.167). Both fitness (ß = - 0.347, p = 0.0005) and BF% (ß = 0.333, p = 0.013) were independently associated with CVH in the fully adjusted model. CONCLUSIONS: This study provides evidence for an association between cardiorespiratory fitness and cardiovascular health in female breast cancer survivors. While fatness may be associated with cardiovascular health, it appears to be more strongly associated with age.

Inhibition of calcium/calmodulin-dependent kinase II restores contraction and relaxation in isolated cardiac muscle from type 2 diabetic rats.

BACKGROUND: Calcium/calmodulin-dependent kinase II-delta (CaMKIIδ) activity is enhanced during hyperglycemia and has been shown to alter intracellular calcium handling in cardiomyocytes, ultimately leading to reduced cardiac performance. However, the effects of CaMKIIδ on cardiac contractility during type 2 diabetes are undefined. METHODS: We examined the expression and activation of CaMKIIδ in right atrial appendages from non-diabetic and type 2 diabetic patients (n = 7 patients per group) with preserved ejection fraction, and also in right ventricular tissue from Zucker Diabetic Fatty rats (ZDF) (n = 5-10 animals per group) during early diabetic cardiac dysfunction, using immunoblot. We also measured whole heart function of ZDF and control rats using echocardiography. Then we measured contraction and relaxation parameters of isolated trabeculae from ZDF to control rats in the presence and absence of CaMKII inhibitors. RESULTS: CaMKIIδ phosphorylation (at Thr287) was increased in both the diabetic human and animal tissue, indicating increased CaMKIIδ activation in the type 2 diabetic heart. Basal cardiac contractility and relaxation were impaired in the cardiac muscles from the diabetic rats, and CaMKII inhibition with KN93 partially restored contractility and relaxation. Autocamtide-2-related-inhibitor peptide (AIP), another CaMKII inhibitor that acts via a different mechanism than KN93, fully restored cardiac contractility and relaxation. CONCLUSIONS: Our results indicate that CaMKIIδ plays a key role in modulating performance of the diabetic heart, and moreover, suggest a potential therapeutic role for CaMKII inhibitors in improving myocardial function during type 2 diabetes.

The effectiveness of a standard drill connected to a core biopsy needle: How to obtain specimens in very strong bone tumors.

INTRODUCTION: Core biopsy is today recognized as the gold standard for the diagnosis of bone lesions; unfortunately, when the bone is too solid it can be very difficult to penetrate it; in case of failure, open biopsy is indicated but it is associated with greater contamination and complications. A possible solution is to connect a common orthopedic drill to the core biopsy needle. The aim of the presenting study was to present a technique useful for performing biopsies in case of very strong bone lesions and to evaluate the adequacy and quality of the obtained specimen. MATERIALS AND METHODS: A standard bone biopsy set was connected to a commercial drill to perform bone biopsies. Data was collected over a 2-year period (2015-2016). Information regarding technical success, diagnostic data and complication rates was all collated to assess the technical feasibility of this technique. RESULTS: Out of 357 bone biopsies, 34 patients underwent the procedure using a common orthopedic drill connected to a core biopsy needle. Diagnostic material was obtained in each patient and the artifacts were considered irrelevant. No major complications occurred in any patient. DISCUSSION: The use of a core biopsy needle connected to a common orthopedic drill facilitates the penetration of thick cortical bone by simply applying continuous speed and pressure; nevertheless, the biopsy needle we use is not designed for a drilling procedure and for this reason it can be damaged, but if the biopsy is performed with particular attention, the mechanical failure can be avoided CONCLUSIONS: Bone biopsy using a commercial hand drill has a technically high success rate with minimal complications. Further studies with more cases are necessary to verify our results.

The Type 2 Diabetic Heart: Its Role in Exercise Intolerance and the Challenge to Find Effective Exercise Interventions.

The metabolic and microvascular benefits of regular exercise for people with diabetes are unequivocal. However, cardiovascular disease, which disproportionately affects people with diabetes, is not reduced by regular exercise, and heart disease remains the leading cause of death for people with type 2 diabetes. 'Subclinical' changes in the function of the diabetic left ventricle are common and reduce cardiac reserve and exercise capacity. This review describes the changes in resting and exercising left ventricular function, and the possible causes of these changes, and introduces the possibility that more vigorous exercise may be needed to improve left ventricular function and reduce rates of cardiovascular disease in people with type 2 diabetes.

Type 1 Diabetes Duration Decreases Pulmonary Diffusing Capacity during Exercise.

BACKGROUND: Diabetes damages peripheral tissues; however, its effects on the lung are less known. Lung diffusing capacity (DLCO) is influenced by alveolar-capillary membrane conductance (DM) and pulmonary capillary blood volume (VC), both of which are reduced in adults with type 1 diabetes (T1D). OBJECTIVE: We sought to determine if diabetes duration affects DLCO, DM, VC, and cardiac output (Q). METHODS: 24 T1D patients (10.7-52.8 years) and 24 non-diabetic controls were recruited and had DLCO, DM, VC, and Q measured at rest and during exercise (40, 70 and 90% VO2max). RESULTS: When stratified into two groups based on age (young, <20.6 years old), there were no significant differences in DLCO, DM, VC, or Q (all of which were normalized to body surface area [BSA]) in the young group or in the old group. When stratified by diabetes duration (short duration, 0.33-8.9 years vs. long duration, 9.6-28 years), the T1D patients in the long duration group had lower DLCO/BSA and DM/BSA compared to the controls (p < 0.05). There were no differences in any of the variables in the short duration group. CONCLUSIONS: This study has shown that duration of diabetes is associated with decrements in diffusing capacity and its components.

Cardiovascular control during exercise in type 2 diabetes mellitus.

Controlled studies of male and female subjects with type 2 diabetes mellitus (DM) of short duration (~3-5 years) show that DM reduces peak VO2 (L·min(-1) and mL·kg(-1)·min(-1)) by an average of 12-15% and induces a greater slowing of the dynamic response of pulmonary VO2 during submaximal exercise. These effects occur in individuals less than 60 years of age but are reduced or absent in older males and are consistently associated with significant increases in the exercise pressor response despite normal resting blood pressure. This exaggerated pressor response, evidence of exertional hypertension in DM, is manifest during moderate submaximal exercise and coincides with a more constrained vasodilation in contracting muscles. Maximum vasodilation during contractions involving single muscle groups is reduced by DM, and the dynamic response of vasodilation during submaximal contractions is slowed. Such vascular constraint most likely contributes to exertional hypertension, impairs dynamic and peak VO2 responses, and reduces exercise tolerance. There is a need to establish the effect of DM on dynamic aspects of vascular control in skeletal muscle during whole-body exercise and to clarify contributions of altered cardiovascular control and increased arterial stiffness to exertional hypertension.

Increased Efferent Cardiac Sympathetic Nerve Activity and Defective Intrinsic Heart Rate Regulation in Type 2 Diabetes.

Elevated sympathetic nerve activity (SNA) coupled with dysregulated ß-adrenoceptor (ß-AR) signaling is postulated as a major driving force for cardiac dysfunction in patients with type 2 diabetes; however, cardiac SNA has never been assessed directly in diabetes. Our aim was to measure the sympathetic input to and the ß-AR responsiveness of the heart in the type 2 diabetic heart. In vivo recording of SNA of the left efferent cardiac sympathetic branch of the stellate ganglion in Zucker diabetic fatty rats revealed an elevated resting cardiac SNA and doubled firing rate compared with nondiabetic rats. Ex vivo, in isolated denervated hearts, the intrinsic heart rate was markedly reduced. Contractile and relaxation responses to ß-AR stimulation with dobutamine were compromised in externally paced diabetic hearts, but not in diabetic hearts allowed to regulate their own heart rate. Protein levels of left ventricular ß1-AR and Gs (guanine nucleotide binding protein stimulatory) were reduced, whereas left ventricular and right atrial ß2-AR and Gi (guanine nucleotide binding protein inhibitory regulatory) levels were increased. The elevated resting cardiac SNA in type 2 diabetes, combined with the reduced cardiac ß-AR responsiveness, suggests that the maintenance of normal cardiovascular function requires elevated cardiac sympathetic input to compensate for changes in the intrinsic properties of the diabetic heart.

Prior maximal exercise decreases pulmonary diffusing capacity during subsequent exercise.

Pulmonary diffusion (DLCO) increases during exercise due to greater pulmonary capillary volume (Vc) and membrane diffusing capacity (DM). However, after heavy exercise there is a reduction in resting DLCO. It is unclear whether this post-exercise effect will attenuate the normal increase in DLCO, Vc and DM during subsequent exercise and whether this affects SpO2 (pulse oximeter). DLCO, Vc, DM, cardiac output and SpO2 were measured at rest, moderate (~70% VO2peak) and heavy (~90 VO2peak) exercise in 9 subjects during 2 sessions separated by ~90 min. DLCO, Vc and DM increased during exercise (P<0.05). DLCO (P<0.05) and Vc (P<0.10), but not DM or SpO2 were lower in session 2 compared to the first. Reductions in DLCO and Vc appeared to be smallest during rest (1-4%) and greatest at high-intensity exercise (8-20%), but the interaction was not significant. SpO2 decreased by 4.9% and 5.1% from rest to high-intensity exercise during the first and second exercise bout, but these changes were not different. These data confirm that a bout of high-intensity exercise reduces DLCO and Vc, and may indicate that these changes are exacerbated during subsequent high-intensity exercise. Despite these changes, SpO2 was not affected by previous exercise.

Impaired relaxation despite upregulated calcium-handling protein atrial myocardium from type 2 diabetic patients with preserved ejection fraction.

BACKGROUND: Diastolic dysfunction is a key factor in the development and pathology of cardiac dysfunction in diabetes, however the exact underlying mechanism remains unknown, especially in humans. We aimed to measure contraction, relaxation, expression of calcium-handling proteins and fibrosis in myocardium of diabetic patients with preserved systolic function. METHODS: Right atrial appendages from patients with type 2 diabetes mellitus (DM, n = 20) and non-diabetic patients (non-DM, n = 36), all with preserved ejection fraction and undergoing coronary artery bypass grafting (CABG), were collected. From appendages, small cardiac muscles, trabeculae, were isolated to measure basal and ß-adrenergic stimulated myocardial function. Expression levels of calcium-handling proteins, sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) and phospholamban (PLB), and of ß1-adrenoreceptors were determined in tissue samples by Western blot. Collagen deposition was determined by picro-sirius red staining. RESULTS: In trabeculae from diabetic samples, contractile function was preserved, but relaxation was prolonged (Tau: 74 ± 13 ms vs. 93 ± 16 ms, non-DM vs. DM, p = 0.03). The expression of SERCA2a was increased in diabetic myocardial tissue (0.75 ± 0.09 vs. 1.23 ± 0.15, non-DM vs. DM, p = 0.007), whereas its endogenous inhibitor PLB was reduced (2.21 ± 0.45 vs. 0.42 ± 0.11, non-DM vs. DM, p = 0.01). Collagen deposition was increased in diabetic samples. Moreover, trabeculae from diabetic patients were unresponsive to ß-adrenergic stimulation, despite no change in ß1-adrenoreceptor expression levels. CONCLUSIONS: Human type 2 diabetic atrial myocardium showed increased fibrosis without systolic dysfunction but with impaired relaxation, especially during ß-adrenergic challenge. Interestingly, changes in calcium-handling protein expression suggests accelerated active calcium re-uptake, thus improved relaxation, indicating a compensatory calcium-handling mechanism in diabetes in an attempt to maintain diastolic function at rest despite impaired relaxation in the diabetic fibrotic atrial myocardium. Our study addresses important aspects of the underlying mechanisms of diabetes-associated diastolic dysfunction, which is crucial to developing new therapeutic treatments.

Systolic and diastolic abnormalities reduce the cardiac response to exercise in adolescents with type 2 diabetes.

OBJECTIVE: To better understand the cardiac limitations during exercise in adolescents with type 2 diabetes mellitus (T2DM), we measured left ventricular performance with magnetic resonance imaging (MRI) during exercise in diabetic and nondiabetic adolescents. RESEARCH DESIGN AND METHODS: Thirteen subjects with T2DM, 27 overweight/obese nondiabetic (ObeseND) subjects, and 19 nondiabetic nonobese control subjects were recruited. Cardiac (left ventricular) MRI scans were performed at rest and during submaximal exercise. RESULTS: Vo2 peak indexed to fat-free mass was reduced in T2DM and ObeseND subjects compared with control subjects (P < 0.0001). Indexed cardiac output increased less during exercise and was 20% lower in T2DM subjects due to reduced stroke volume. This was a consequence of reduced ventricular filling with smaller end-diastolic volume, which decreased further during exercise in T2DM subjects, but not in ObeseND or control subjects. End-systolic volume was also smaller in T2DM subjects. These changes were associated with increased resting and exercise diastolic blood pressure, and total peripheral resistance in T2DM subjects. CONCLUSIONS: Independently of obesity, T2DM impairs cardiac function during exercise in adolescents.

Differential features of muscle fiber atrophy in osteoporosis and osteoarthritis.

UNLABELLED: We demonstrated that osteoporosis is associated with a preferential type II muscle fiber atrophy, which correlates with bone mineral density and reduced levels of Akt, a major regulator of muscle mass. In osteoarthritis, muscle atrophy is of lower extent and related to disease duration and severity. INTRODUCTION: Osteoarthritis (OA) and osteoporosis (OP) are associated with loss of muscle bulk and power. In these diseases, morphological studies on muscle tissue are lacking, and the underlying mechanisms of muscle atrophy are not known. The aim of our study was to evaluate the OP- or OA-related muscle atrophy and its correlation with severity of disease. Muscle levels of Akt protein, a component of IGF-1/PI3K/Akt pathway, the main regulator of muscle mass, have been determined. METHODS: We performed muscle biopsy in 15 women with OP and in 15 women with OA (age range, 60-85 years). Muscle fibers were counted, measured, and classified by ATPase reaction. By statistical analysis, fiber-type atrophy was correlated with bone mineral density (BMD) in the OP group and with Harris Hip Score (HHS) and disease duration in the OA group. Akt protein levels were evaluated by Western blot analysis. RESULTS: Our findings revealed in OP a preferential type II fiber atrophy that inversely correlated with patients' BMD. In OA, muscle atrophy was of lower extent, homogeneous among fiber types and related to disease duration and HHS. Moreover, in OP muscle, the Akt level was significantly reduced as compared to OA muscles. CONCLUSIONS: This study shows that in OP, there is a preferential and diffuse type II fiber atrophy, proportional to the degree of bone loss, whereas in OA, muscle atrophy is connected to the functional impairment caused by the disease. A reduction of Akt seems to be one of the mechanisms involved in OP-related muscle atrophy.

Variability of physicochemical properties of an epoxy resin sealer taken from different parts of the same tube.

AIM: To analyse several physicochemical properties of AH Plus (Dentsply DeTrey, Konstanz, Germany), including setting time, flow, radiopacity and the degree of conversion (DC); and to correlate the results with the source of the material: from the beginning, middle or end of the tubes in which they were supplied. METHODOLOGY: Three experimental groups were established for each property investigated. Group 1 corresponded to material taken from the beginning of tubes A and B; Group 2 corresponded to material taken from the middle of each tube; and group 3 corresponded to that from the end of each tube. The setting time, flow and radiopacity were studied according to American National Standards Institute/American Dental Association (ANSI/ADA) Specification 57. DC was determined from infrared spectra, which were recorded at 1-h intervals for the first 6 h; then, at 2-h intervals for the next 14 h; then, at 24 and 30 h. Data were analysed statistically by analysis of variance (anova), Tukey-Kramer, Kruskal-Wallis and Dunn tests, with a significance level of 5%. RESULTS: Group 1 had a significantly longer setting time (2303 ± 1058 min) (P < 0.05). Group 3 had the lowest flowability (30.0 ± 0.7 mm) and the highest radiopacity (14.85 ± 1.8 mm Al) (P < 0.05). No differences were found for the DC test (P > 0.05). CONCLUSION: The results suggest that segregation occurs between the organic and inorganic components of AH Plus sealer, thereby changing the setting time, flow and radiopacity.

The larger exercise stroke volume in endurance-trained men does not result from increased left ventricular early or late inflow or tissue velocities.

AIM: To determine whether the larger exercise stroke volume in senior endurance-trained athletes results from an attenuation of age-related alterations in left ventricular (LV) early diastolic filling or a more vigorous late filling. METHODS: Body composition (DEXA), VO(2)peak, stroke volume (CO(2) rebreathing) and Doppler measures of early and late mitral inflow and mitral annular velocities were collected at seated upright rest and heart rate-matched exercise (100 and 120 bpm) in trained and untrained younger (18-30 years) men and trained and untrained older (60-80 years) healthy men. RESULTS: Ageing had a greater effect than training status on seated rest mitral inflow and tissue Doppler imaging parameters, as shown by a lower peak early-to-late mitral inflow velocity ratio (E/A ratio) and slower peak early mitral annular velocity (Em) in older compared with younger men. Exercise stroke volume was unaffected by healthy ageing; however, Em, an index of early LV lengthening rate and relaxation, was slower (P < 0.001), while measures of atrial systole were increased (P < 0.001) during exercise in older men. Stroke volume during exercise was larger in the trained men (P < 0.001); however, early and late mitral inflow and tissue velocities were not different between trained and untrained men. CONCLUSION: The larger exercise stroke volume in trained older male athletes does not seem to be related to faster filling or lengthening velocities during early or late filling. Thus, a larger, more compliant left ventricle in combination with an increased blood volume may explain the larger LV filling volumes in trained seniors.

Effect of reduced total blood volume on left ventricular volumes and kinetics in type 2 diabetes.

AIM: Although impaired left ventricular (LV) diastolic function is commonly observed in patients with type 2 diabetes, it remains unclear whether the impairment is caused by altered LV relaxation or changes in LV preload. The purpose of this study was to examine the influence of LV function and LV loading conditions on stroke volume in men with type 2 diabetes. METHODS: Cardiac magnetic resonance imaging scans were performed in eight men with type 2 diabetes and 11 non-diabetic men matched for age, weight and physical activity level. Total blood volume was determined with the Evans blue dye dilution technique. RESULTS: End-diastolic volume (EDV), the ratio of peak early to late mitral inflow velocity (E/A) and stroke volume were lower in men with type 2 diabetes than in non-diabetic individuals. Peak filling rate and peak ejection rate were not different between diabetic and non-diabetic individuals; however, men with type 2 diabetes had proportionally longer systolic duration than non-diabetic individuals. Heart rate was higher and total blood volume was lower in men with type 2 diabetes. The lower total blood volume was correlated with a lower EDV in men with type 2 diabetes. CONCLUSIONS: Men with type 2 diabetes have an altered cardiac cycle and lower end-diastolic and stroke volume. A lower total blood volume and higher heart rate in men with type 2 diabetes suggest that changes in LV preload, independent of changes in LV relaxation or contractility, influence LV diastolic filling and stroke volume in this population.

Structural and functional cardiac abnormalities in adolescent girls with poorly controlled type 2 diabetes.

OBJECTIVE: Type 2 diabetes is associated with left ventricular hypertrophy (LVH) and diastolic dysfunction, which may eventually lead to clinical heart failure. We sought to determine the cardiovascular effects of adolescent-onset type 2 diabetes. RESEARCH DESIGN AND METHODS: We recruited diabetic girls (8 with type 2 and 11 with type 1 diabetes) from a hospital diabetes service and nondiabetic control subjects (9 lean and 11 overweight) from the schools of the diabetic subjects. Echocardiography and measurements were performed by a single observer, blinded to subject group allocation, and included M-mode left ventricular dimensions, two-dimensional left ventricular mass, Doppler diastolic flows, estimation of left ventricular filling pressure, and systolic longitudinal motion. Left ventricular mass was indexed to height and fat-free body mass. ANOVA was used to compare the groups. RESULTS: The groups were similar in age and height, but significant differences in body composition were observed. Subjects with type 2 diabetes had larger left ventricular dimensions and left ventricular mass, which persisted when indexed to height. Diastolic filling was impaired in both diabetic groups, and systolic longitudinal function was lower in the type 2 diabetic group. Half of the group with type 2 diabetes met the published criteria for LVH and left ventricular dilatation; 25% had evidence of elevated left ventricular filling pressure in association with structural abnormalities. CONCLUSIONS: This study has demonstrated preclinical abnormalities of cardiac structure and function in adolescent girls with type 2 diabetes, despite the short duration of diabetes and highlights the potential high cardiovascular risk occurring in adolescent type 2 diabetes.

Impaired stroke volume and aerobic capacity in female adolescents with type 1 and type 2 diabetes mellitus.

AIM/HYPOTHESIS: This study was designed to determine whether type 2 diabetic adolescents have reduced aerobic capacity and to investigate the role of cardiac output and arteriovenous oxygen difference (a-vO(2)) in their exercise response. METHODS: Female adolescents (age 12-18 years) with type 2 diabetes mellitus (n = 8) and type 1 diabetes mellitus (n = 12) and obese (n = 10) and non-obese (n = 10) non-diabetic controls were recruited for this study. Baseline data included maximal aerobic capacity (cycle ergometer) and body composition. Cardiac output and a-vO(2) were determined at rest and during submaximal exercise. RESULTS: Diabetic groups had lower aerobic capacity than non-diabetic groups (p < 0.05). Adolescents with type 2 diabetes had lower aerobic capacity than the type 1 diabetic group. Maximal heart rate was lower in the type 2 diabetic group (p < 0.05). Exercise stroke volume was 30-40% lower at 100 and 120 beats per min in the diabetic than in the non-diabetic groups (p < 0.05). The a-vO(2) value was not different in any condition. CONCLUSIONS AND INTERPRETATION: Type 2 diabetic adolescents have reduced aerobic capacity and reduced heart rate response to maximal exercise. Furthermore, type 2 and type 1 diabetic adolescent girls have a blunted exercise stroke volume response compared with non-diabetic controls. Central rather than peripheral mechanisms contribute to the reduced aerobic capacity in diabetic adolescents. Although of short duration, type 2 diabetes in adolescence is already affecting cardiovascular function in adolescents.

Variation in blood levels of inflammatory markers related and unrelated to smoking cessation in women.

This study assessed the influence of short-term changes in smoking habit on blood levels of inflammatory markers, which have been associated with increased cardiovascular risk. Five inflammatory markers were measured before and 6 weeks after attempting smoking cessation in 138 healthy women. In the 48 participants who stopped smoking, white blood cell count (-0.7+/-1.2 x 10(9)/L; P<.001) and fibrinogen (-0.6+/-1.5 micromol/L; P<.01) decreased, but there was no significant (P>.1) change in the plasma level of C-reactive protein (median change +0.1; interquartile range -0.2, 0.9 mg/L), intercellular adhesion molecule 1 (+17+/-75 ng/mL), or CD40 ligand (+0.4+/-2.1 ng/mL). Most of the individual variation in inflammatory marker levels was unrelated to changes in smoking habit.