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Background: Transcatheter aortic valve implantation (TAVI) is a well-established treatment for symptomatic patients with aortic stenosis. Yet, the impact of sex differences and public vs. private procedural setting on TAVI outcomes remain uncertain., Methods: The RIBAC-NT (Brazilian Registry for Evaluation of Transcatheter Aortic Valve Replacement Outcomes) dataset included 3194 TAVI patients from 2009 to 2021. This retrospective analysis explored disparities in baseline characteristics, procedural and in-hospital outcomes stratifying patients by sex and procedural setting. Temporal trends were also investigated., Results: We included 1551 (49 %) female and 1643 (51 %) male patients. Women were older (83 [78-87] vs. 81 [75-85] years; p < 0.01) but had a lower prevalence of diabetes mellitus (30.2 % vs. 36.3 %, p < 0.01) and coronary artery disease (39.0 % vs. 52.2 %, p < 0.01). However, women had a 3-fold higher higher risk of life-threatening bleeding (6.1 % vs. 2.4 %, p < 0.01). Women presented higher procedural and in-hospital mortality rates (4.4 % vs. 2.5 % and 7.7 % vs. 4.5 %, all p < 0.01, respectively). Although public hospitals presented ~2-fold higher procedural mortality rate compared with private settings (5.0 % vs. 2.7 %, p < 0.01), after multivariable analysis procedural setting was not independently associated with in-hospital mortality., Conclusions: Women had higher procedural and in-hospital mortality rates after TAVI as compared with men, while facing higher life-threatening bleeding and adverse events rates. Although public hospitals exhibited higher mortality rates than private centers, procedural setting was not independently associated with in-hospital mortality., Competing Interests: Declaration of competing interest Dr. de Brito has served as proctor for Edwards LifeSciences and Medtronic. Drs Carvalho, Sarmento-Leite, Mangione, and Lemos have served as proctor for Medtronic. Dr. Ribeiro has served as proctor for Edwards LifeSciences. Dr. Grube has served as proctor for Medtronic and Boston Scientific. Dr. Abizaid has received research grants from Edwards Lifesciences, Medtronic and Boston Scientific., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Our objective was to evaluate the productive parameters of ewes and their lambs in relation to ewe age and to develop models for predicting lamb weight at birth and weaning in a tropical warm-climate pasture. Individual data were collected from 273 ewes and 273 lambs, between 2013 and 2021. During this period all animals were kept on pastures of Brachiaria brizantha cv. Marandu All lambs in the experiments were supplemented in creep-feeding. A descriptive statistical analysis was performed using the PROC SUMMARY procedure in SAS (SAS University Edition, SAS Institute Inc. Cary, CA, USA). Pearson correlation coefficients between variables were estimated using the PROC CORR procedure in SAS (SAS University Edition, SAS Institute Inc. Cary, CA, USA). Model adjustments and variable selection were performed using PROC REG in SAS (SAS University Edition, SAS Institute Inc. Cary, CA, USA). The STEPWISE option and Mallow's C(p) were used to select the variables included in the equations. Outliers were identified by evaluating the studentized residuals based on the predicted values from the equations. Residual analysis was predicted by regression minus observed values and those that fell outside the range of -2.5 to 2.5 were removed. Several statistics were used to assess the predictability of the equations, including the coefficients of determination (r 2 ) and mean standard error (RMSE). The average ewe age at lambing was 3.4 ± 1.7 years, with an average weight of 56.9 ± 8,9 kg and average body condition score (BCS) of 2,4 ± 0.8 points. The average ewe age at weaning was 51.1 ± 7.9, with average BCS of 1.8 ± 0.8 points. The average lamb at birthing was 3.9 ± 0.9 kg. The average lamb at weaning was 21.0 ± 4.9, with daily gain of 0.2 ± 0.1 kg/day and total gain of 17.1 ± 4.7 kg birth to weaning. The lamb produced by ewe at lambing was 5.3 ± 1.7 kg/ewe. The lamb weaned by ewe at weaning was 28.7 ± 10.8 kg/ewe. The ratios of lamb produced per ewe at birth and at weaning were 0.1 ± 0.03 and 0.6 ± 0.2, respectively. The lamb's birth weight showed a positive linear relationship with the age of the ewe, increasing by 115 g per year of age. The regression equations adjusted for ewe age had maximum points ranging from 4.2 to 5.2, occurring at average age of 4,7 years. The other characteristics showed a quadratic tendency. The results suggest the culling of ewes at five years of age to generate lambs with ideal weight at birth and at weaning raised in warm tropical pastures., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The objective was to evaluate the effect of the supplementation with natural antioxidants from Yerba mate (Ilex paraguariensis St. Hil.) on the performance, carcass and meat characteristics, and fatty acid profile in meat and fat of Texel × Ile de France lambs kept in Brachiaria-grass pasture. Twenty lambs with a mean age of 90 days and 26.3 kg of BW were distributed in a completely randomized design in two treatments with 10 replicates/treatment: Control-protein-energy supplement based on corn and soybean meal (150 g/kg DM of crude protein) without the addition of natural antioxidant yerba mate and Yerba Mate - energy protein supplement with the addition of yerba mate (110 g/kg DM). There was no treatment effect on animal performance and carcass characteristics. The subcutaneous fat thickness was significantly higher for lambs treated without yerba mate. There was no effect of nutritional treatments on the oxidative markers of lamb meat. The muscle of the animals treated with yerba mate showed a higher concentration of unsaturated and polyunsaturated fatty acids elaidic, linolenic, thymnodonic, docosadienoic, and ceorvonic. The fat of the animals treated with yerba mate showed a higher concentration of palmitoleic acid, linoelaidic acid, heneicosanoic acid, dihomo-γ-linolenic acid, and arachidonic acid. The concentration of polyunsaturated fatty acids was significantly higher in meat and fat of lambs treated with yerba mate. Including yerba mate in the diet of lambs kept on Brachiaria pastures improves the lipid profile of polyunsaturated fatty acids in meat and fat, without altering the performance of the animals., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

One limitation to transradial access (TRA) is the occurrence of spasms (RAS), for which the use of prophylactic medications is recommended. Improvement in TRA material combined with the increase in operators' expertise, might mitigate this benefit. We assess the effect of preventive nitroglycerin on RAS during TRA, evaluating the role of the operator's experience. Patients received 500 μg nitroglycerin or placebo. The operator's expertise was classified as: inexperienced (I), intermediate (M), and experienced (E). 2040 patients were included. Prophylactic use of nitroglycerin did not reduce RAS (10.8% vs. 13.4% (placebo), p = 0.07). RAS incidence was 14.5% in I, 12.5% in M, and 9.7% in E (p = 0.01). In group I, nitroglycerin reduced RAS (17.4% vs. 11.1%, p = 0.04), which was not observed in other groups. Overall, nitroglycerin does not prevent RAS, which is more common among inexperienced operators. More experienced operators could abolish preventive nitroglycerin use., (© 2023 Wiley Periodicals LLC.)

The hypothesis tested is that the association of soybean grain and yerba mate as an antioxidant source can increase the concentration of polyunsaturated fatty acids (PUFA) with lower oxidation of milk from lactating ewes reared in tropical pastures. Sixteen ewes were randomly distributed in a 2x2 factorial scheme (with or without yerba mate at 110 g / kg of dry matter (DM); with or without soybean grain at 210 g/kg of DM). Yerba mate intake reduced DM intake, and concentrations of ether extract (EE), protein, lactose, defatted dry extract, density, omega-3 concentrations, and the ratio between saturated/monounsaturated fatty acids (FA), but increased the concentration of monounsaturated FA and the sequestering power of free radicals by DPPH without altering the concentrations of conjugated dienes and the concentrations of substances reactive to thiobarbituric acid in milk. Supplementation with soybean grain decreased the birth weight of the lambs and increased the concentrations of conjugated linoleic acid (CLA), PUFA, omega - 6, omega ratio - 6/omega - 3, and total blood cholesterol. The addition of yerba mate did not influence the oxidative profile of milk. Supplementation with soybean grain improved the FA profile of milk, increasing the concentrations of CLA and PUFA. The results suggest that the association of yerba mate and soybean grain helps to improve the fat quality of milk from ewes raised in tropical pastures, as shown by the enhanced antioxidant activity, although it does not help prevent oxidation of milk rich in PUFA., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Aims: To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events., Methods and Results: Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79-1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66-1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75-1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups., Conclusion: Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting., Clinical Trial Registration: ClinicalTrials.gov number: NCT04001504., Competing Interests: Conflict of interest: H.A.R.F. reports research grants from AstraZeneca and Brazilian Ministry of Health; R.H.M.F. reports research grants and personal fees from AstraZeneca, Bayer, Biomm and Servier; and research grants from Amgen, Pfizer, EMS, Aché, CytoDin, Brazilian Ministry of Health, University Health Network (received from his institution), and Lemann Foundation Research Fellowship. A.Z. reports research scholarships from the Brazilian National Council for Scientific and Technological Development (CNPq) and the Lemann Foundation Research Fellowship; M.F. reports research grants from Brazilian Ministry of Health; P.A.L., supported in part by a grant from The National Council for Scientific and Technological Development (CNPq)—Brazil (grant # 308733/2016-9); non-paid clinical advisor of Flouit, a scientific computing initiative; part of Argonauts, an innovation facilitator; B.R.N. is partially financed CNPq (Bolsa de produtividade em pesquisa, 312382/2019-7), by the Edwards Lifesciences Foundation (Improving the Prevention and Detection of Heart Valve Disease Across the Lifespan, 2021) and by FAPEMIG (grant APQ-000627-20); J.C.N. reports research grants from Amgen, Astrazeneca, Bayer, CSL Behring, Daiichi Sankyo, Dalcor, Esperion, Janssen, Novartis, NovoNordisk, Sanofi and Vifor, research support from the Brazilian Council for Scientific and Technological Development (CNPq); O.B. received research grants (paid to his institution) from AstraZeneca, Pfizer, Bayer, Amgen, Servier, BMS, and Novartis. The other authors declare no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The aim of this study was to evaluate whether administration of nitroglycerin at the beginning or end of a transradial approach (TRA) procedure would preserve radial patency., Background: The TRA is becoming the preferred vascular access route in coronary interventions. Radial artery occlusion (RAO) is the most frequent complication. Routine vasodilator treatment aims to reduce spasm and possibly prevent RAO., Methods: The authors designed a prospective, multicenter, randomized, double-blind, 2-by-2 factorial, placebo-controlled trial encompassing patients undergoing the TRA. Patients were randomized to either 500 μg nitroglycerin or placebo; each arm was also subrandomized to early (upon sheath insertion) or late (right before sheath removal) nitroglycerin administration to evaluate the superiority of nitroglycerin in the prevention of RAO with 24 hours on Doppler ultrasound., Results: A total of 2,040 patients were enrolled. RAO occurred in 49 patients (2.4%). Fifteen of these patients (30.6%) showed re-establishment of flow at 30 days. Nitroglycerin, compared with placebo, did not reduce the risk for RAO at either of the 2 time points (early, 2.5% vs 2.3% [P = 0.66]; late, 2.3% vs 2.5% [P = 0.66]). By multivariable analysis, the presence of spasm (OR: 3.53; 95% CI: 1.87-6.65; P < 0.001) and access achieved with more than 1 puncture attempt (OR: 2.58; 95% CI: 1.43-4.66; P = 0.002) were independent predictors of RAO., Conclusions: The routine use of nitroglycerin was not associated with a reduction in the rate of RAO, regardless of the time of administration (at the beginning or end of the TRA procedure)., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To report clinical, angiographic characteristics, outcomes, and predictors of unsuccessful procedures in patients who underwent chronic total occlusion (CTO) percutaneous coronary interventions (PCI) in Latin America., Background: CTO PCI has been increasingly performed worldwide, but there is a lack of information in this region., Methods: An international multicenter registry was developed to collect data on CTO PCI performed in centers in Latin America. Patient, angiographic, procedural and outcome data were evaluated. Predictors of unsuccessful procedures were assessed by multivariable analysis., Results: We have included data related to 1,040 CTO PCIs performed in seven countries in Latin America (Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, and Puerto Rico). The mean age was 64 ± 10 years, and CTO PCI was performed mainly for angina control (81%) or treatment of a large ischemic area (30%). Overall technical success rate was 82.5%, and it was achieved with antegrade wire escalation in 81%, antegrade dissection/re-entry in 8% and with retrograde techniques in 11% of the successful procedures. Multivariable analysis identified moderate/severe calcification, a blunt proximal cap and a previous attempt as independent predictors of unsuccessful procedures. In-hospital major adverse cardiovascular events (MACE) occurred in 3.1% of the cases, death in 1% and cardiac tamponade in 0.9% CONCLUSIONS: CTO PCI in Latin America has been performed mainly for ischemia relief. Procedures were associated with a success rate above 80% and low incidence of MACE. Predictors of unsuccessful procedures were similar to those previously reported in the literature., (© 2020 Wiley Periodicals, Inc.)

Objectives: The aim of this study was to compare two hemostatic techniques, minimum pressure technique and patent hemostasis, on radial artery occlusion (RAO) after transradial catheterization., Background: RAO is an infrequent complication of transradial procedures. One of the strategies used to reduce this complication is the patent hemostasis technique. Use of minimum pressure in hemostatic wristband, without monitoring patency, might have the same efficacy for preventing RAO., Methods: This is a multicenter study encompassing patients submitted to transradial catheterization. After pneumatic wristband application, the band was deflated to the lowest allowable volume while preserving hemostasis. Radial artery patency was subsequently evaluated. The group with no return of plethysmographic curve was labeled "minimum pressure," and the group in which the signal returned was labeled "patent hemostasis." RAO was verified by Doppler evaluation within the first 24 hours of the procedure., Results: A total of 1082 patients were enrolled, with mean age of 61.4 ± 10.4 years. The majority (61.0%) were male and 34.5% had diabetes. Patent hemostasis was achieved in only 213 cases (20%). Early RAO occurred in 16 patients (1.8%) in the minimum pressure group and in 4 patients (1.9%) in the patent hemostasis group (P=.97). No major bleeding was observed among the entire cohort. EASY scale for hematoma grade was similar between the cohorts (EASY grades 1-3: 7.0% in the minimum pressure group vs 7.5% in the patent hemostasis group; P=.96)., Conclusion: Checking radial patency during hemostatic compression may not be necessary after the procedure when adopting a mild and short hemostatic compression.

Background: Previous evidence suggests that acute treatment with statins reduce atherosclerotic complications, including periprocedural myocardial infarction, but currently, there are no large, adequately powered studies to define the effects of early, high-dose statins in patients with acute coronary syndrome (ACS) and planned invasive management., Objectives: The main goal of Statins Evaluation in Coronary procedUres and REvascularization (SECURE-PCI) Trial is to determine whether the early use of a loading dose of 80 mg of atorvastatin before an intended percutaneous coronary intervention followed by an additional dose of 80 mg 24 hours after the procedure will be able to reduce the rates of major cardiovascular events at 30 days in patients with an ACS., Design: The SECURE-PCI study is a pragmatic, multicenter, double-blind, placebo-controlled randomized trial planned to enroll around 4,200 patients in 58 different sites in Brazil. The primary outcome is the rate of major cardiovascular events at 30 days defined as a composite of all-cause mortality, nonfatal acute myocardial infarction, nonfatal stroke, and coronary revascularization., Summary: The SECURE PCI is a large randomized trial testing a strategy of early, high-dose statin in patients with ACS and will provide important information about the acute treatment of this patient population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Marine invertebrates have been attracting the attention of researchers for their application in nutrition, agriculture, and the pharmaceutical industry, among others. Concerning sea anemones (Cnidaria), little is known regarding their metabolic profiles and potential value as a source of pharmacologically-active agents. In this work, the chemical profiles of two species of sea anemones Actinia equina and Anemonia sulcata , were studied by high-performance liquid chromatography with diode-array detection (HPLC-DAD) and its impact upon immune and gastric cells was evaluated. In both species, the methylpyridinium alkaloid homarine was the major compound in aqueous extracts. The extracts were effective in reducing lipopolysaccharide (LPS)-induced levels of nitric oxide (NO) and intracellular reactive oxygen species (ROS) in a macrophage model of inflammation. Both the extracts and the alkaloid homarine were effective in inhibiting phospholipase A₂ (PLA₂), a pivotal enzyme in the initial steps of the inflammatory cascade. In order to mimic the oral consumption of these extracts; their effect upon human gastric cells was evaluated. While no caspase-9 activation was detected, the fact that the endoplasmic reticulum-resident caspase-4, and also caspase-3, were activated points to a non-classical mechanism of apoptosis in human gastric cells. This work provides new insights on the toxicity and biological potential of sea anemones increasingly present in human nutrition.

Weight regain after caloric restriction results in accelerated fat storage in adipose tissue. This catch-up fat phenomenon is postulated to result partly from suppressed skeletal muscle thermogenesis, but the underlying mechanisms are elusive. We investigated whether the reduced rate of skeletal muscle contraction-relaxation cycle that occurs after caloric restriction persists during weight recovery and could contribute to catch-up fat. Using a rat model of semistarvation-refeeding, in which fat recovery is driven by suppressed thermogenesis, we show that contraction and relaxation of leg muscles are slower after both semistarvation and refeeding. These effects are associated with (i) higher expression of muscle deiodinase type 3 (DIO3), which inactivates tri-iodothyronine (T3), and lower expression of T3-activating enzyme, deiodinase type 2 (DIO2), (ii) slower net formation of T3 from its T4 precursor in muscles, and (iii) accumulation of slow fibers at the expense of fast fibers. These semistarvation-induced changes persisted during recovery and correlated with impaired expression of transcription factors involved in slow-twitch muscle development. We conclude that diminished muscle thermogenesis following caloric restriction results from reduced muscle T3 levels, alteration in muscle-specific transcription factors, and fast-to-slow fiber shift causing slower contractility. These energy-sparing effects persist during weight recovery and contribute to catch-up fat.

Background: Arterial access is a major site of bleeding complications after invasive coronary procedures. Among strategies to decrease vascular complications, the radial approach is an established one. Vascular closure devices provide more comfort to patients and decrease hemostasis and need for bed rest. However, the inconsistency of data proving their safety limits their routine adoption as a strategy to prevent vascular complications, requiring evidence through adequately designed randomized trials. The aim of this study is to compare the radial versus femoral approach using a vascular closure device for the incidence of arterial puncture site vascular complications among non-ST-segment elevation acute coronary syndrome patients submitted to an early invasive strategy., Methods: ARISE is a national, multicenter, non-inferiority randomized clinical trial. Two hundred patients with non-ST-segment elevation acute coronary syndrome will be randomized to either radial or femoral access using a vascular closure device. The primary outcome is the occurrence of vascular complications at an arterial puncture site 30 days after the procedure, including major bleeding, retroperitoneal hematoma, compartment syndrome, hematoma ≥ 5 cm, pseudoaneurysm, arterio-venous fistula, infection, limb ischemia, arterial occlusion, adjacent nerve injury or the need for vascular surgical repair., Results: Enrollment was initiated in September 2012, and until October 2013 91 patients were included. The inclusion phase is expected to last until the second half of 2014., Conclusions: The ARISE trial will help define the role of a vascular closure device as a bleeding avoidance strategy in patients with NSTEACS., Trial Registration: ClinicalTrials.gov identifier: NCT01653587.

We investigated whether palmitoleic acid, a fatty acid that enhances whole body glucose disposal and suppresses hepatic steatosis, modulates triacylglycerol (TAG) metabolism in adipocytes. For this, both differentiated 3T3-L1 cells treated with either palmitoleic acid (16:1n7, 200 μM) or palmitic acid (16:0, 200 μM) for 24 h and primary adipocytes from wild-type or PPARα-deficient mice treated with 16:1n7 (300 mg·kg(-1)·day(-1)) or oleic acid (18:1n9, 300 mg·kg(-1)·day(-1)) by gavage for 10 days were evaluated for lipolysis, TAG, and glycerol 3-phosphate synthesis and gene and protein expression profile. Treatment of differentiated 3T3-L1 cells with 16:1n7, but not 16:0, increased basal and isoproterenol-stimulated lipolysis, mRNA levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) and protein content of ATGL and pSer(660)-HSL. Such increase in lipolysis induced by 16:1n7, which can be prevented by pharmacological inhibition of PPARα, was associated with higher rates of PPARα binding to DNA. In contrast to lipolysis, both 16:1n7 and 16:0 increased fatty acid incorporation into TAG and glycerol 3-phosphate synthesis from glucose without affecting glyceroneogenesis and glycerokinase expression. Corroborating in vitro findings, treatment of wild-type but not PPARα-deficient mice with 16:1n7 increased primary adipocyte basal and stimulated lipolysis and ATGL and HSL mRNA levels. In contrast to lipolysis, however, 16:1n7 treatment increased fatty acid incorporation into TAG and glycerol 3-phosphate synthesis from glucose in both wild-type and PPARα-deficient mice. In conclusion, palmitoleic acid increases adipocyte lipolysis and lipases by a mechanism that requires a functional PPARα.

Background: Unsuccessful radial artery puncture, inability to advance the guide catheter to the ascending aorta, and inadequate guide catheter support represent mechanisms of transradial approach failure. With the rationale of sharing the same efficacy and safety promoted by radial access, the transulnar approach represents an alternative access site for percutaneous coronary procedures., Methods: Between May 2007 and May 2012, 11,059 coronary invasive procedures were performed in a single institution: 10,108 by transradial approach (91.4%), 541 by transfemoral approach (4.9%), and 410 by transulnar approach (3.7%). Patients who underwent coronary procedures through transulnar access were included in a prospective registry of effectiveness and safety., Results: Diagnostic procedures accounted for 71.8% of cases, and the right ulnar access was the most common route (88.9%). Procedure success was high (98.5%), with a crossover rate of 1.5% (6 cases), of which 5 were achieved through the contralateral radial access and 1 through femoral approach. Complications related to access site were low (3.9%), consisting mostly of minor bleeding due to subcutaneous hematomas. There were no cases of major bleeding, nerve injury, pseudoaneurysm, arteriovenous fistula, or necessity of vascular surgical repair., Conclusions: The transulnar approach represents an alternative to the transradial approach in selected cases when performed by radial-trained operators, sharing a high success rate and extremely low incidence of access-site complications., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Treatment of acute coronary syndrome has been based on the prevention of ischemic complications by means of antithrombotic therapy and invasive strategies. The desired reduction reached in the recurrence of ischemic events reveals its price, an increase in the occurrence of major bleeding. Initially tolerated as a benign complication, it is now shown to be an important predictor of mortality. Greater attention dedicated to the prognostic impact of bleeding is recent, motivated by the development of new antithrombotic agents. Detailed analysis of the risk factors for myocardial infarction or bleeding is an important issue and allows institution of individualized approach.

Current notions about mechanisms by which catch-up growth predisposes to later type 2 diabetes center upon those that link hyperinsulinemia with an accelerated rate of fat deposition (catch-up fat). Using a rat model of semistarvation-refeeding in which catch-up fat is driven solely by elevated metabolic efficiency associated with hyperinsulinemia, we previously reported that insulin-stimulated glucose utilization is diminished in skeletal muscle but increased in white adipose tissue. Here, we investigated the possibility that hyperinsulinemia during catch-up fat can be contributed by changes in the secretory response of pancreatic beta-cells to glucose. Using the rat model of semistarvation-refeeding showing catch-up fat and hyperinsulinemia, we compared isocalorically refed and control groups for potential differences in pancreatic morphology and in glucose-stimulated insulin secretion during in situ pancreas perfusions as well as ex vivo isolated islet perifusions. Between refed and control animals, no differences were found in islet morphology, insulin content, and the secretory responses of perifused isolated islets upon glucose stimulation. By contrast, the rates of insulin secretion from in situ perfused pancreas showed that raising glucose from 2.8 to 16.7 mmol/l produced a much more pronounced increase in insulin release in refed than in control groups (p < 0.01). These results indicate a role for islet secretory hyperresponsiveness to glucose in the thrifty mechanisms that drive catch-up fat through glucose redistribution between skeletal muscle and adipose tissue. Such beta-cell hyperresponsiveness to glucose may be a key event in the link between catch-up growth, hyperinsulinemia and risks for later type 2 diabetes.

Background: Radial access, besides providing greater comfort to the patient and reduction of hospital costs, promotes unequivocal reduction of vascular complications, with possible prognosis implication. A series of cases has shown that when its use is not suitable, ulnar access presents itself as a viable and effective alternative., Objective: To evaluate the safety and effectiveness of ulnar approach in the performance of coronary procedures after failed attempt in obtaining radial access., Methods and Results: From May 2007 to February 2009, 115 patients underwent 122 coronary procedures via ulnar access and were included in a prospective registry. The average age was 61.3 +/- 11.1 years, 67 (58%) were female and 36 (31%) were diabetic. Procedure success was achieved in 116 (95%) cases. There were no cases of major bleeding, transfusions or vascular repair surgery among the complications. There were hematomas in 4.9% of the cases, though mostly superficial, light to moderate spasms in 4% and asymptomatic ulnar artery occlusion, with no evidence of ischemia in 1.6%., Conclusions: The ulnar artery is a feasible and effective alternative approach to perform coronary procedures. When radial access is not available, it presents a similar safety profile with virtually no occurrence of hemorrhagic complications.

Occurrence of ischemic complications after transulnar coronary procedures is virtually absent. The presence of a complete deep palmar arch in approximately 95% of the population as well as the great capacity of the collateral circulation of the hand might justify these findings. We report the occurrence of complications in 62 patients submitted to coronary procedures through the transulnar approach, without assessment of the integrity of the deep palmar arch by the inverse Allen's test. The rate of asymptomatic occlusion of the ulnar artery was 3%, without any ischemic complication. We believe the performance of Allen's test is not necessary when using transulnar access.

Pancreatic beta-cells are able to respond to nutrients, principally glucose, as the primary stimulus for insulin exocytosis. This unique feature requires translation of metabolic substrates into intracellular messengers recognized by the exocytotic machinery. Central to this signal transduction mechanism, mitochondria integrate and generate metabolic signals, thereby coupling glucose recognition with insulin secretion. In response to a glucose rise, nucleotides and metabolites are generated by mitochondria and participate, together with cytosolic Ca2+, in the stimulation of insulin exocytosis. Mitochondrial defects, such as mutations and ROS (reactive oxygen species) production, might be associated with beta-cell failure in the course of diabetes. mtDNA (mitochondrial DNA) mutation A3243G is associated with MIDD (mitochondrial inherited diabetes and deafness). A common hypothesis to explain the link between the genotype and the phenotype is that the mutation might impair mitochondrial metabolism expressly required for beta-cell functions, although this assumption lacks direct demonstration. mtDNA-deficient cellular models are glucose-unresponsive and are defective in mitochondrial function. Recently, we used clonal cytosolic hybrid cells (namely cybrids) harbouring mitochondria derived from MIDD patients. Compared with control mtDNA from the same patient, the A3243G mutation markedly modified metabolic pathways. Moreover, cybrid cells carrying patient-derived mutant mtDNA exhibited deranged cell Ca2+ handling and elevated ROS under metabolic stress. In animal models, transgenic mice lacking expression of the mitochondrial genome specifically in beta-cells are diabetic and their islets are incable of releasing insulin in response to glucose. These various models demonstrate the fragility of nutrient-stimulated insulin secretion, caused primarily by defective mitochondrial function.

Aims/hypothesis: Mitochondrial DNA (mtDNA) mutations cause several diseases, including mitochondrial inherited diabetes and deafness (MIDD), typically associated with the mtDNA A3243G point mutation on tRNALeu gene. The common hypothesis to explain the link between the genotype and the phenotype is that the mutation might impair mitochondrial metabolism expressly required for beta cell functions. However, this assumption has not yet been tested., Methods: We used clonal osteosarcoma cytosolic hybrid cells (namely cybrids) harbouring mitochondria derived from MIDD patients and containing either exclusively wild-type or mutated (A3243G) mtDNA. According to the importance of mitochondrial metabolism in beta cells, we studied the impact of the mutation on key parameters by comparing stimulation of these cybrids by the main insulin secretagogue glucose and the mitochondrial substrate pyruvate., Results: Compared with control mtDNA from the same patient, the A3243G mutation markedly modified metabolic pathways leading to a high glycolytic rate (2.8-fold increase), increased lactate production (2.5-fold), and reduced glucose oxidation (-83%). We also observed impaired NADH responses (-56%), negligible mitochondrial membrane potential, and reduced, only transient ATP generation. Moreover, cybrid cells carrying patient-derived mutant mtDNA exhibited deranged cell calcium handling with increased cytosolic loads (1.4-fold higher), and elevated reactive oxygen species (2.6-fold increase) under glucose deprivation., Conclusions/interpretation: The present study demonstrates that the mtDNA A3243G mutation impairs crucial metabolic events required for proper cell functions, such as coupling of glucose recognition to insulin secretion.

Pyruvate promotes hyperpolarization of the inner mitochondrial membrane. However, in isolated mitochondria, pyruvate could participate in a futile cycle leading to mitochondrial depolarization. Here, we investigated this paradox in intact human cells by measuring parameters reflecting mitochondrial activation in response to 1 mM pyruvate and 5 mM glucose. NAD(P)H levels were elevated similarly by both substrates. Conversely, pyruvate induced a first transient phase of mitochondrial depolarization before the establishment of the expected sustained hyperpolarization. This correlated with kinetics of cytosolic ATP levels exhibiting a first phase decrease followed by an increase. Therefore, pyruvate transiently depolarizes mitochondria and reduces ATP in intact cells.

The Arabidopsis thaliana uncoupling protein (UCP) gene was expressed in Escherichia coli and isolated protein reconstituted into liposomes. Linoleic acid-induced H+ fluxes were sensitive to purine nucleotide inhibition with an apparent K(i) (in mM) of 0.8 (GDP), 0.85 (ATP), 0.98 (GTP), and 1.41 (ADP); the inhibition was pH-dependent. Kinetics of AtPUMP1-mediated H+ fluxes were determined for lauric, myristic, palmitic, oleic, linoleic, and linolenic acids. Properties of recombinant AtPUMP1 indicate that it represents a plant counterpart of animal UCP2 or UCP3. This work brings the functional and genetic approaches together for the first time, providing strong support that AtPUMP1 is truly an UCP.