The inotropic adaptation during late preconditioning against myocardial stunning is associated with an increase in FKBP12.6

The inotropic adaptation during late preconditioning against myocardial stunning is associated with an increase in FKBP12.6. by Laurence Lucats, Laurent Vinet, Alain Bizé, Xavier Monnet, Didier Morin, Jin Bo Su, Patricia Rouet-Benzineb, Olivier Cazorla, Jean-Jacques Mercadier, Luc Hittinger, Alain Berdeaux, Bijan Ghaleh. OBJECTIVES: Late preconditioning reduces contractile dysfunction during myocardial stunning. Mechanisms involving adaptation of calcium handling during excitation-contraction coupling to late preconditioning remain to be established. Thus, we investigated whether the late preconditioned myocardium is associated with contractile adaptation and changes in the cardiac ryanodine receptor (RyR2) and its regulatory protein FKBP12.6. METHODS: Chronically instrumented conscious dogs (coronary occluder, ultrasonic crystals for sonomicrometry) underwent a 10-min coronary artery occlusion followed by reperfusion. They were studied 24 h later in the late preconditioned state (day 1). RESULTS: Maximal velocity of wall thickening at day 1 was increased as compared to corresponding baseline at day 0 (39+/-4 vs. 30+/-3 mm/s, p < 0.05) although systolic wall thickening was similar (2.8+/-0.2 vs. 2.9+/-0.2 mm), demonstrating a significant change in left ventricular inotropic state. Intracoronary infusion of ryanodine (0.5-6 microg) induced a dose-dependent decrease in wall thickening. In the late preconditioned state, this negative inotropic response was significantly reduced vs. control state, suggesting changes in sarcoplasmic reticulum (SR) Ca2+-release through RyR2. Immunoquantification of FKBP12.6 revealed a 2.8 fold ventricular increase after late preconditioning as compared to the control state. The amount of RyR2 and its phosphorylated state were similar and binding experiments did not reveal any alterations in B(max) or K(D) for RyR2. Calsequestrin, SERCA2a and phospholamban levels were not altered by late preconditioning. CONCLUSIONS: The late preconditioned myocardium is characterized by an adaptation of regional function associated with an increased expression of FKBP12.6. This demonstrates an adaptation of the SR Ca2+-release through RyR2 during late preconditioning.     

Echocardiographic assessment of myocardial performance after prolonged strenuous exercise.

To determine the effect of strenuous prolonged exercise on systolic and diastolic left ventricular function, 11 non-elite marathon runners aged 37 +/- 7 years (mean +/- SD) were studied before and during early recovery from a marathon race. Cavity dimensions, wall thickness, and fractional shortening were computed from two-dimensionally guided M-mode echocardiograms. Doppler left ventricular inflow tract recordings were analysed for peak early and late velocities and their ratio. In seven subjects, heart frequency was recorded throughout the race. These subjects ran the marathon at 87 +/- 4% of their maximal heart rate. Left ventricular diastolic dimension was slightly reduced at the end of the race (49.4 +/- 4.2 mm to 47.3 +/- 5.1 mm; P less than 0.05). Fractional shortening remained unchanged, although blood pressure (P less than 0.001) and systolic wall stress (P less than 0.01) were decreased. The left ventricular filling pattern was unchanged, and the ratio of early to late velocities remained constant. These results suggest that the fractional shortening was a result of the opposing effects of changes in preload and afterload. However, the absence of a change in the end systolic dimension, despite a marked reduction in afterload and the occurrence of septal akinesia in one subject after the race could only suggest that strenuous prolonged exercise may alter myocardial performance.     

Early Myocardial Dysfunction and Benefits of Cardiac Treatment in Young X-Linked Duchenne Muscular Dystrophy Mice

Cardiovascular Drugs and Therapy - Duchenne muscular dystrophy (DMD) is associated with a progressive alteration in cardiac function. The aim of this study was to detect early cardiac dysfunction...     

Levodopa‐induced dyskinesias in tyrosine hydroxylase deficiency

The objective of this study was to characterize levodopa (l‐ dopa)–induced dyskinesias in patients with tyrosine hydroxylase deficiency. Clinical observation was carried out on 6 patients who were diagnosed with tyrosine hydroxylase deficiency and were treated with escalating doses of l‐ dopa. All 6 patients showed l ‐dopa‐induced dyskinesias of variable intensity early in the course of treatment and regardless of the age of initiation. l ‐Dopa–induced dyskinesias were precipitated by increases in the dose of l ‐dopa and also by febrile illnesses and stress. They caused dysfunction and distress in 2 patients. The dyskinesias were improved by decreasing the l ‐dopa dose or by slowing its titration upward. Increasing the dose frequency was helpful in 2 patients, and introducing amantadine was helpful in another 2 patients. l ‐Dopa–induced dyskinesias are a common phenomenon in tyrosine hydroxylase deficiency. The current observations show that l‐ dopa–induced dyskinesias are frequent in a dopamine‐deficient state in the absence of nigrostriatal degeneration. Although l ‐dopa–induced dyskinesias in tyrosine hydroxylase deficiency are phenomenologically similar to those that occur in Parkinson's disease, they are different in a number of other respects, suggesting intrinsic differences in the pathophysiologic basis of l‐ dopa–induced dyskinesias in the 2 conditions. © 2013 Movement Disorder Society     

Smoking is a risk factor of organ/space surgical site infection in orthopaedic surgery with implant materials

Purpose

In recent guidelines, smoking is reported as a factor increasing the risk of surgical site infection (SSI). The accurate analysis of the literature shows that this recommendation relies on low level of evidence in orthopaedic surgery with material implantation (arthroplasty components or implants for internal fixation). This study aimed to assess the attributable risk of smoking on organ/space SSI in orthopaedic surgery with implants.

Methods

Risk factors of organ/space SSI were studied in a prospective cohort including 3,908 patients from June 2003 to December 2006.

Results

Smoking was found as a significant risk factor for organ/space SSI. We also observed a significant difference between smokers and non-smokers for surgical wound complications (hematoma, discharge or wound dehiscence) during the period between surgical procedure and discharge from hospital.

Conclusion

This is the first large prospective report of a significant association between smoking and organ/space SSI in orthopaedic surgery with implants.     

Diagnosis and management of glutaric aciduria type I �C revised recommendations

Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. The neuropathological correlate is striatal injury which results from encephalopathic crises precipitated by infectious diseases, immunizations and surgery during a finite period of brain development, or develops insidiously without clinically apparent crises. Glutaric aciduria type I is caused by inherited deficiency of glutaryl-CoA dehydrogenase which is involved in the catabolic pathways of L-lysine, L-hydroxylysine and L-tryptophan. This defect gives rise to elevated glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine which can be detected by gas chromatography/mass spectrometry (organic acids) or tandem mass spectrometry (acylcarnitines). Glutaric aciduria type I is included in the panel of diseases that are identified by expanded newborn screening in some countries. It has been shown that in the majority of neonatally diagnosed patients striatal injury can be prevented by combined metabolic treatment. Metabolic treatment that includes a low lysine diet, carnitine supplementation and intensified emergency treatment during acute episodes of intercurrent illness should be introduced and monitored by an experienced interdisciplinary team. However, initiation of treatment after the onset of symptoms is generally not effective in preventing permanent damage. Secondary dystonia is often difficult to treat, and the efficacy of available drugs cannot be predicted precisely in individual patients. The major aim of this revision is to re-evaluate the previous diagnostic and therapeutic recommendations for patients with this disease and incorporate new research findings into the guideline.     

Torsion of a giant para-ovarian cyst. Conservative laparoscopic treatment

Adnexal torsion is a condition that may result in serious consequences, including adnexa removal. Recently, de-torsion has replaced salpingo-oophorectomy as the treatment for a twisted ischaemic adnexum, and the best way to do it seems to be laparoscopic surgery. A case of adnexal torsion caused by a giant para-ovarian cyst treated, with good results, by a conservative laparoscopic approach is reported.     

Determination of glucose in dried serum samples by Fourier-transform infrared spectroscopy.

BACKGROUND: Practical improvements are needed to allow measurement of glucose concentrations by Fourier- transform infrared (FT-IR) spectroscopy. We developed a new method that allows determination of the glucose concentration in dried sera. METHODS: We studied 32 serum samples after fourfold dilution and desiccation before FT-IR analyses on a spectrometer operated at a resolution of 2.0 cm(-1). We integrated all spectral windows at the surface of the spectrum in the C--O region. For comparison, glucose was measured in the sera by a glucose oxidase method. RESULTS: One peak within the spectrum was most specific for glucose (997-1062 cm(-1)). Its surface integration showed a strong relationship with reference data (r = 0.998; P <0.001). FT-IR analyses of five glucose solutions were performed to determine its specific absorption at the same peak. In this way, glucose concentrations in serum spectra could be measured. For the first time while using FT-IR spectroscopy, no manipulation of spectra nor use of internal standard was necessary to obtain results in high accordance with glucose concentration measured by a conventional (glucose-oxidase) method (S(y|x) = 0.25 mmol/L; r = 0. 998). CONCLUSIONS: FT-IR spectroscopy appears to be an easy and accurate method to determine glucose concentration and could be widely used to simultaneously identify and quantify several metabolites in biological fluids or tissues.