Search

Studies in rats suggest that increases in fatty acid oxidation in skeletal muscle during exercise are related to the phosphorylation and inhibition of acetyl-CoA carboxylase (ACC), and secondary to this, a decrease in the concentration of malonyl-CoA. Studies in human muscle have not revealed a consistent decrease in the concentration of malonyl-CoA during exercise; however, measurements of ACC activity have not been reported. Thus, whether the same mechanism operates in human muscle in response to physical activity remains uncertain. To investigate this question, ACC was immunoprecipitated from muscle of human volunteers and its activity assayed in the same individual at rest and after one-legged knee-extensor exercise at 60, 85, and 100% of knee extensor VO2max. ACC activity was diminished by 50-75% during exercise with the magnitude of the decrease generally paralleling exercise intensity. Treatment of the immunoprecipitated enzyme with protein phosphatase 2A restored activity to resting values, suggesting the decrease in activity was due to phosphorylation. The measurement of malonyl-CoA in the muscles revealed that its concentration is 1/10 of that in rats, and that it is diminished (12-17%) during the higher-intensity exercises. The respiratory exchange ratio increased with increasing exercise intensity from 0.84 +/- 0.02 at 60% to 0.99 0.04 at 100% VO2max. Calculated rates of whole-body fatty acid oxidation were 121 mg/min at rest and 258 +/- 35, 264 +/- 63, and 174 +/- 76 mg/min at 60, 85, and 100% VO2max, respectively. The results show that ACC activity, and to a lesser extent malonyl-CoA concentration, in human skeletal muscle decrease during exercise. Although these changes may contribute to the increases in fat oxidation from rest to exercise, they do not appear to explain the shift from mixed fuel to predominantly carbohydrate utilization when exercise intensity is increased. [ABSTRACT FROM AUTHOR]

Background: The outcomes of percutaneous coronary intervention (PCI) in diabetic patients are still suboptimal, and it is unclear if diabetic patients might derive a benefit from the use of drug-coated balloons., Aims: To evaluate the impact of diabetes mellitus on the outcomes of patients undergoing PCI with sirolimus-coated balloon (SCB) MagicTouch (Concept Medical, India)., Methods: We conducted a subgroup analysis of the prospective, multicenter, investigator-initiated EASTBOURNE registry, evaluating the performance of MagicTouch SCB in patients with and without diabetes. The study primary endpoint was target lesion revascularization (TLR) at 12-month follow-up. Secondary clinical endpoints were major adverse clinical events (MACE), death, myocardial infarction (MI), and BARC 2-5 bleedings., Results: Among 2,083 enrolled patients, a total of 864 suffered from diabetes (41.5%). Patients with diabetes had a numerically higher occurrence of TLR (6.5% vs. 4.7% HR 1.38, 95%CI 0.91-2.08), all-cause death (3.8% vs. 2.6%, HR 1.81, 95%CI 0.95-3.46), and MACE (12.2% vs. 8.9%; HR 1.26 95%CI 0.92-1.74). The incidence of spontaneous MI was significantly higher among diabetic patients (3.4% vs. 1.5%, HR 2.15 95%CI 1.09-4.25); bleeding events did not significantly differ. The overall incidence of TLR was higher among in-stent restenosis (ISR) as compared to de-novo coronary lesions, irrespectively from diabetes status., Conclusions: In the EASTBOURNE DIABETES registry, diabetic patients treated with the MagicTouch SCB did not have a significant increase in TLR when compared to non-diabetic patients; moreover, diabetic status did not affect the study device performance in terms of TLR, in both de-novo lesions and ISR., (© 2024. The Author(s).)

Background: Drug-coated balloons (DCB) represent 1 of the most promising innovations in interventional cardiology and may represent a valid alternative to drug-eluting stents. Currently, some sirolimus-coated balloons (SCB) are being investigated for several coronary artery disease applications., Objectives: This study sought to understand the role of a novel SCB for the treatment of coronary artery disease., Methods: EASTBOURNE (All-Comers Sirolimus-Coated Balloon European Registry) is a prospective, multicenter, investigator-driven clinical study that enrolled real-world patients treated with SCB. Primary endpoint was target lesion revascularization (TLR) at 12 months. Secondary endpoints were procedural success, myocardial infarction (MI), all-cause death, and major adverse clinical events (a composite of death, MI, and TLR). All adverse events were censored and adjudicated by an independent clinical events committee., Results: A total population of 2,123 patients (2,440 lesions) was enrolled at 38 study centers in Europe and Asia. The average age was 66.6 ± 11.3 years, and diabetic patients were 41.5%. De novo lesions (small vessels) were 56%, in-stent restenosis (ISR) 44%, and bailout stenting occurred in 7.7% of the patients. After 12 months, TLR occurred in 5.9% of the lesions, major adverse clinical events in 9.9%, and spontaneous MI in 2.4% of the patients. The rates of cardiac/all-cause death were 1.5% and 2.5%, respectively. The primary outcome occurred more frequently in the ISR cohort (10.5% vs 2.0%; risk ratio: 1.90; 95% CI: 1.13-3.19). After multivariate Cox regression model, the main determinant for occurrence of the primary endpoint was ISR (OR: 5.5; 95% CI: 3.382-8.881)., Conclusions: EASTBOURNE, the largest DCB study in the coronary field, shows the safety and efficacy of a novel SCB in a broad population of coronary artery disease including small vessels and ISR patients at mid-term follow-up. (The All-Comers Sirolimus-Coated Balloon European Registry [EASTBOURNE]; NCT03085823)., Competing Interests: Funding Support and Author Disclosures The study was an independent, investigator-driven study which received fundings by Envision Scientific. This society had no role in the protocol definition, selection of centers, conduction of the study and interpretation of the results. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To present our initial clinical experience with ReLEx(®) flex (ReLEx) for moderate to high myopia. We compare efficacy, safety and corneal higher-order aberrations after ReLEx with femtosecond laser in situ keratomileusis (FS-LASIK)., Methods: Prospective study of ReLEx compared with a retrospective study of FS-LASIK. ReLEx is a new keratorefractive procedure, where a stromal lenticule is cut by a femtosecond laser and manually extracted. Forty patients were treated with ReLEx on both eyes. A comparable group of 41 FS-LASIK patients were retrospectively identified. Visual acuity, spherical equivalent (SE) and corneal tomography were measured before and 3 months after surgery., Results: Preoperative SE averaged -7.50 ± 1.16 D (ReLEx) and -7.32 ± 1.09 D (FS-LASIK). For all eyes, mean corrected distance visual acuity remained unchanged in both groups. For eyes with emmetropia as target refraction, 41% of ReLEx and 61% of FS-LASIK eyes had an uncorrected distance visual acuity of logMAR ≤ 0.10 at day 1 after surgery, increasing to, respectively, 88% and 69% at 3 months. Mean SE was -0.06 ± 0.35 D 3 months after ReLEx and -0.53 ± 0.60 D after FS-LASIK. The proportion of eyes within ±1.00 D after 3 months was 100% (ReLEx) and 85% (FS-LASIK). For a 6.0-mm pupil, corneal spherical aberrations increased significantly less in ReLEx than FS-LASIK eyes., Conclusions: ReLEx is an all-in-one femtosecond laser refractive procedure, and in this study, results were comparable to FS-LASIK. Refractive predictability and corneal aberrations at 3 months seemed better than or equal to FS-LASIK, whereas visual recovery after ReLEx was slower., (© 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.)

The aim of the present study was to investigate whether fish oil supplementation was able to modulate the acute-phase response to strenuous exercise. Twenty male runners were randomized to receive supplementation (n = 10) with 6.0 g fish oil daily, containing 3.6 g n-3 polyunsaturated fatty acids (PUFA), for 6 wk or to receive no supplementation (n = 10) before participating in The Copenhagen Marathon 1998. Blood samples were collected before the race, immediately after, and 1.5 and 3 h postexercise. The fatty acid composition in blood mononuclear cells (BMNC) differed between the fish oil-supplemented and the control group, showing incorporation of n-3 PUFA and less arachidonic acid in BMNC in the supplemented group. The plasma levels of tumor necrosis factor-alpha, interleukin-6, and transforming growth factor-beta(1) peaked immediately after the run, the increase being 3-, 92-, and 1.1-fold, respectively, compared with resting samples. The level of interleukin-1 receptor antagonist peaked 1.5 h after exercise, with the increase being 87-fold. However, the cytokine levels did not differ among the two groups. Furthermore, supplementation with fish oil did not influence exercise-induced increases in leucocytes and creatine kinase. In conclusion, 6 wk of fish oil supplementation had no influence on the acute-phase response to strenuous exercise.

We examined the pattern of activation and deactivation of the stress-activated protein kinase signalling molecules c-Jun NH2-terminal kinase (JNK) and p38 kinase in skeletal muscle in response to prolonged strenuous running exercise in human subjects. Male subjects (n = 14; age 32 +/- 2 years; VO2,max 60 +/- 2 ml kg-1 min-1) completed a 42.2 km marathon (mean race time 3 h 35 min). Muscle biopsies were obtained 10 days prior to the marathon, immediately following the race, and 1, 3 and 5 days after the race. The activation of JNK and p38, including both p38alpha and p38gamma, was measured with immune complex assays. The phosphorylation state of p38 (alpha and gamma) and the upstream regulators of JNK and p38, mitogen-activated protein kinase kinase 4 (MKK4) and mitogen-activated protein kinase kinase 6 (MKK6), were assessed using phosphospecific antibodies. JNK activity increased 7-fold over basal level immediately post-exercise, but decreased back to basal levels 1, 3 and 5 days after the exercise. p38gamma phosphorylation (4-fold) and activity (1.5-fold) increased immediately post-exercise and returned to basal levels at 1, 3 and 5 days following exercise. In contrast, p38alpha phosphorylation and activity did not change over the time course studied. MKK4 and MKK6 phosphorylation increased and decreased in a trend similar to that observed with JNK activity and p38gamma phosphorylation. Prolonged running exercise did not affect JNK, p38alpha, or p38gamma protein expression in the days following the race. This study demonstrates that both JNK and p38 intracellular signalling cascades are robustly, yet transiently increased following prolonged running exercise. The differential activation of the p38 isoforms with exercise in human skeletal muscle indicates that these proteins may have distinct functions in vivo.

1. The present study investigates to what extent and by which time course prolonged strenuous exercise influences the plasma concentration of pro-inflammatory and inflammation responsive cytokines as well as cytokine inhibitors and anti-inflammatory cytokines. 2. Ten male subjects (median age 27.5 years, range 24-37) completed the Copenhagen Marathon 1997 (median running time 3 : 26 (h : min), range 2 : 40-4 : 20). Blood samples were obtained before, immediately after and then every 30 min in a 4 h post-exercise recovery period. 3. The plasma concentrations of tumour necrosis factor (TNF)alpha, interleukin (IL)-1beta, IL-6, IL-1ra, sTNF-r1, sTNF-r2 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). The highest concentration of IL-6 was found immediately after the race, whereas IL-1ra peaked 1 h post exercise (128-fold and 39-fold increase, respectively, as compared with the pre-exercise values). The plasma level of IL-1beta, TNFalpha, sTNF-r1 and sTNF-r2 peaked in the first hour after the exercise (2. 1-, 2.3-, 2.7- and 1.6-fold, respectively). The plasma level of IL-10 showed a 27-fold increase immediately post exercise. 4. In conclusion, strenuous exercise induces an increase in the pro-inflammatory cytokines TNFalpha and IL-1beta and a dramatic increase in the inflammation responsive cytokine IL-6. This is balanced by the release of cytokine inhibitors (IL-1ra, sTNF-r1 and sTNF-r2) and the anti-inflammatory cytokine IL-10. The study suggests that cytokine inhibitors and anti-inflammatory cytokines restrict the magnitude and duration of the inflammatory response to exercise.

Muscle glycogen remains subnormal several days after muscle damaging exercise. The aims of this study were to investigate how muscle acid-soluble macroglycogen (MG) and acid-insoluble proglycogen (PG) pools are restored after a competitive marathon and also to determine whether glycogen accumulates differently in the various muscle fiber types. Six well-trained marathon runners participated in the study, and muscle biopsies were obtained from the vastus lateralis of the quadriceps muscle before, immediately after, and 1, 2, and 7 days (days 1, 2, and 7, respectively) after the marathon. During the race, 56 +/- 3.8% of muscle glycogen was utilized, and a greater fraction of MG (72 +/- 3.7%) was utilized compared with PG (34 +/- 6.5%). On day 2, muscle glycogen and MG values remained lower than prerace values, despite a carbohydrate-rich diet, but they had both returned to prerace levels on day 7. The PG concentration was lower on day 1 compared with before the race, whereas there were no significant differences between the prerace PG concentration and the concentrations on days 2 and 7. On day 2 the glycogen concentration was particularly low in the type I fibers, indicating that local processes are important for the accumulation pattern. We conclude that a greater fraction of human muscle MG than of PG is utilized during a marathon and that accumulation of MG is particularly delayed after the prolonged exercise bout. Furthermore, factors produced locally appear important for the glycogen accumulation pattern.

1. The effects of unaccustomed eccentric exercise on exercise metabolism during a subsequent bout of graded concentric exercise were investigated in seven healthy male subjects. Arterial and bilateral femoral venous catheters were inserted 2 days after eccentric exercise of one thigh (eccentric thigh) and blood samples were taken before and during graded two-legged concentric knee-extensor exercise. Muscle biopsies were obtained from the eccentric and control vastus lateralis before (rest) and after (post) the concentric exercise bout. 2. Maximal knee-extensor concentric exercise capacity was decreased by an average of 23 % (P < 0.05) in the eccentric compared with the control thigh. 3. The resting muscle glycogen content was lower in the eccentric thigh than in the control thigh (402 +/- 30 mmol (kg dry wt)-1 vs. 515 +/- 26 mmol (kg dry wt)-1, means +/- s.e.m., P < 0.05), and following the two-legged concentric exercise this difference substantially increased (190 +/- 46 mmol (kg dry wt)-1 vs. 379 +/- 58 mmol (kg dry wt)-1, P < 0.05) despite identical power and duration of exercise with the two thighs. 4. There was no measurable difference in glucose uptake between the eccentric and control thigh before or during the graded two-legged concentric exercise. Lactate release was higher from the eccentric thigh at rest and, just before termination of the exercise bout, release of lactate decreased from this thigh (suggesting decreased glycogenolysis), whereas no decrease was found from the contralateral control thigh. Lower glycerol release from the eccentric thigh during the first, lighter part of the exercise (P < 0.05) suggested impaired triacylglycerol breakdown. 5. At rest, sarcolemmal GLUT4 glucose transporter content and glucose transport were similar in the two thighs, and concentric exercise increased sarcolemmal GLUT4 content and glucose transport capacity similarly in the two thighs. 6. It is concluded that in muscle exposed to prior eccentric contractions, exercise at a given power output requires a higher relative workload than in undamaged muscle. This increases utilization of the decreased muscle glycogen stores, contributing to decreased endurance.

Our purpose was to investigate whether the slow rate of muscle glycogen resynthesis after a competitive marathon is associated with a decrease in the total muscle content of the muscle glucose transporter (GLUT-4). Seven well-trained marathon runners participated in the study, and muscle biopsies were obtained from the lateral head of the gastrocnemius muscle before, immediately after, and 1, 2, and 7 days after the marathon, as were venous blood samples. Muscle GLUT-4 content was unaltered over the experimental period. Muscle glycogen concentration was 758 +/- 53 mmol/kg dry weight before the marathon and decreased to 148 +/- 39 mmol/kg dry weight immediately afterward. Despite a carbohydrate-rich diet (containing at least 7 g carbohydrate.kg body mass-1.day-1), the muscle glycogen concentration remained 30% lower than before-race values 2 days after the race, whereas it had returned to before-race levels 7 days after the race. We conclude that the total GLUT-4 protein content is unaltered in the lateral gastrocnemius after a competitive marathon and that the slow recovery of muscle glycogen after the race apparently involves factors other than changes in the total content of this protein.

Our aim was to examine the effect of prior eccentric contractions on insulin action locally in muscle in the intact conscious rat. Anesthetized rats performed one-leg eccentric contractions through the use of calf muscle electrical stimulation followed by stretch of the active muscles. Two days later, basal and euglycemic clamp studies were conducted with the rats in the awake fasted state. Muscle glucose metabolism was estimated from 2-[14C(U)]deoxy-D-glucose and D-[3-3H] glucose administration, and comparisons were made between the eccentrically stimulated and nonstimulated (control) calf muscles. At midphysiological insulin levels, effects of prior eccentric exercise on muscle glucose uptake were not statistically significant. Maximal insulin stimulation revealed reduced incremental glucose uptake above basal (P < 0.05 in the red gastrocnemius; P < 0.1 in the white gastrocnemius and soleus) and impaired net glycogen synthesis in all eccentrically stimulated muscles (P < 0.05). We conclude that prior eccentric contractions impair maximal insulin action (responsiveness) on local muscle glucose uptake and glycogen synthesis in the conscious rat.

We have recently shown that eccentric contractions (Ecc) of rat calf muscles cause muscle damage and decreased glycogen and glucose transporter GLUT-4 protein content in the white (WG) and red gastrocnemius (RG) but not in the soleus (S) (S. Asp, S. Kristiansen, and E. A. Richter. J. Appl. Physiol. 79: 1338-1345, 1995). To study whether these changes affect insulin action, hindlimbs were perfused at three different insulin concentrations (0, 200, and 20,000 microU/ml) 2 days after one-legged eccentric contractions of the calf muscles. Compared with control, basal glucose transport was slightly higher (P < 0.05) in Ecc-WG and -RG, whereas it was lower (P < 0.05) at both submaximal and maximal insulin concentrations in the Ecc-WG and at maximal concentrations in the Ecc-RG. In the Ecc-S, the glucose transport was unchanged in hindquarters perfused in the absence or presence of a submaximal stimulating concentration of insulin, whereas it was slightly (P < 0.05) higher during maximal insulin stimulation compared with control S. At the end of perfusion the glycogen concentrations were lower in both Ecc-gastrocnemius muscles compared with control muscles at all insulin concentrations. Fractional velocity of glycogen synthase increased similarly with increasing insulin concentrations in Ecc- and control WG and RG. We conclude that insulin action on glucose transport but not glycogen synthase activity is impaired in perfused muscle exposed to prior eccentric contractions.

Smoking habits of different occupational groups were studied in a sample of persons who participated in health screening examinations carried out by the mobile clinic of the Institute of Occupational Health (Helsinki, Finland). The sample consisted of 1 990 men and 1 044 women. The smoking habits of the study population as a whole conformed with those of the entire Finnish population. Distinct differences in smoking habits were found, however, in different occupational groups. The effect of smoking habits on tentative rate ratios of lung cancer in occupational groups were estimated with a procedure presented by Olav Axelson. The groups were selected from extreme ends of the smoking habit variable. Extreme estimates were taken to maximize the confounding effect of smoking. When occupational groups were contrasted with the general population, the confounding effect was found to be smaller than usually believed.

Some recent epidemiologic studies have suggested that chlorinated phenoxy acid herbicides are human carcinogens. The mortality experience in a cohort of 1,926 men who had sprayed 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) during 1955-1971 has been followed prospectively from 1972 to 1980. The total phenoxy acid exposure was generally rather low because the duration of work had mostly been less than two months. In 1972-1976 mortality from all natural causes in the cohort was only 54% of the expected value (based on age-specific rates for the general population), and in the succeeding 4-a period 81% of the expected value. In the assessment of cancer, mortality allowance was made for 10- and 15-a periods of latency between the first exposure and the start of the recording of vital status during the follow-up. No increase in cancer mortality was detected, and the distribution of cancer types was unremarkable. No cases of death from lymphomas or soft tissue sarcomas were found. The study results must, however, be viewed with great caution owing to the small size of the cohort, the low past exposure, and the brief follow-up period.

For the study of the relationship between styrene exposure and symptoms and signs of central nervous dysfunctions, 98 male workers occupationally exposed to styrene were given clinical, neurophysiological and psychological examinations; also a symptom survey was made. Urinary mandelic acid concentrations, measured once a week during five consecutive weeks, were used to express the exposure intensity. Different unexposed groups were used for reference. No exposure-response relationship was observed between symptoms of ill health and the urinary mandelic acid concentration, although the exposed group as a whole expressed significantly more symptoms than the reference group. The occurrence of abnormal electroencephalograms was about 10% in the group of workers with mandelic acid concentrations below 700 mg/l, but it was 30% among those whose mandelic acid concentration exceeded 700 mg/l, a level corresponding to the 8-h time-weighted average (TWA) of styrene exposure of about 30 ppm. With regard to psychological functions, the first change in visuomotor accuracy became discernible when the urinary mandelic acid concentration exceeded 800 mg/l. A more pronounced decrement appeared in both visuomotor accuracy and psychomotor performance when the mandelic acid concentration exceeded 1,200 mg/l, which corresponds to an 8-h TWA of styrene exposure of about 55 ppm.

Wollastonite metasilicate fibers are rather similar in form, length, and diameter, but mineralogically different, to amphibole asbestos fibers. We have studied immunologic findings from 46 men exposed to wollastonite at a limestone quarry for at least 10 years. These workers showed a higher prevalence of positive serum rheumatoid factors than blood donors did. This finding resembles the one detected among asbestos workers. The group of wollastonite workers with radiological signs of pulmonary fibrosis had activities of serum angiotensin-converting enzyme that were similar to those of wollastonite workers without fibrosis. A mortality study of 238 quarry workers with 5,769 person-years was, as expected, nonpositive. It was interesting that one woman with 20 years of exposure to wollastonite and with no other known exposure to fibers revealed a malignant retroperitoneal mesenchymal tumor 30 years after the initial exposure. This kind of very rare tumor is difficult to distinguish from mesothelioma. However, this is only one case, and it is impossible to draw any definite conclusions.