Vertebrate SLRP family evolution and the subfunctionalization of osteoglycin gene duplicates in teleost fish.

BACKGROUND: Osteoglycin (OGN, a.k.a. mimecan) belongs to cluster III of the small leucine-rich proteoglycans (SLRP) of the extracellular matrix (ECM). In vertebrates OGN is a characteristic ECM protein of bone. In the present study we explore the evolution of SLRP III and OGN in teleosts that have a skeleton adapted to an aquatic environment. RESULTS: The SLRP gene family has been conserved since the separation of chondrichthyes and osteichthyes. Few gene duplicates of the SLRP III family exist even in the teleosts that experienced a specific whole genome duplication. One exception is ogn for which duplicate copies were identified in fish genomes. The ogn promoter sequence and in vitro mesenchymal stem cell (MSC) cultures suggest the duplicate ogn genes acquired divergent functions. In gilthead sea bream (Sparus aurata) ogn1 was up-regulated during osteoblast and myocyte differentiation in vitro, while ogn2 was severely down-regulated during bone-derived MSCs differentiation into adipocytes in vitro. CONCLUSIONS: Overall, the phylogenetic analysis indicates that the SLRP III family in vertebrates has been under conservative evolutionary pressure. The retention of the ogn gene duplicates in teleosts was linked with the acquisition of different functions. The acquisition by OGN of functions other than that of a bone ECM protein occurred early in the vertebrate lineage.

Morphofunctional characterization of the three main adipose tissue depots in rainbow trout (Oncorhynchus mykiss).

Visceral adipose tissue (VAT) is the primary fat reservoir and energy source in fish. Other relevant fat depots include subcutaneous adipose tissue (SAT), located under epithelial layers, and intramuscular adipose tissue (IMAT), found between the myotomes. The present study investigates the morphological, gene expression and functional characteristics of these different depots in rainbow trout (Oncorhynchus mykiss). Commercial rainbow trout of two different average weights were sampled for histology, lipid quantification and fatty acids profile. Mature adipocytes were isolated for gene expression analyses of lipid metabolic markers. Both VAT and SAT showed large adipocytes, and high total lipid content, suggesting hypertrophic growth. Adipocytes in IMAT were consistently smaller regardless of fish size. While fatty acid composition was similar across depots, SAT had lower levels of palmitic acid and higher levels of polyunsaturated fatty acids that act as precursors of phospholipids and eicosanoids such as eicosapentaenoic acid, compared to VAT and IMAT. Gene expression analyses revealed higher levels of fatty acid transporters, lipolysis and ß-oxidation markers in VAT and SAT compared to IMAT, suggesting a more active lipid metabolism. These data support the role of VAT as the main energy depot, while SAT may act as a secondary reservoir, and IMAT potentially serves as an occasional energy source for muscles. This study provides valuable insights into the distinct properties of the different fat depots in fish, which may help to optimize strategies to modulate adiposity for improved health, metabolism, and product quality.

Effect of guar gum on glucose and lipid metabolism in white sea bream Diplodus sargus.

The aim of this study was to assess the role of soluble non-starch polysaccharide (guar gum) on white sea bream Diplodus sargus, glucose and lipid metabolism. A control diet was formulated to contain 40 % crude protein, 14 % crude lipids and 35 % pregelatinized maize starch, and three other diets were formulated similar to the control diet except for guar gum, which was included at 4 % (diet GG4), 8 % (diet GG8) or 12 % (diet GG12). Diets were fed to the fish for 9 weeks on a pair-feeding scheme. Guar gum had no effect on growth performance, feed efficiency, glycaemia, cholesterolaemia and plasma triacylglyceride levels. Hepatic glucokinase and pyruvate kinase activities, liver glycogen content and liver insulin-like growth factor-I gene expression were not affected by dietary guar gum, while fructose-1,6-bisphosphatase activity was lower in fish fed guar gum-supplemented diets. Hepatic glucose-6-phosphate dehydrogenase activity was higher in fish fed diets GG4 and GG8 than in the control group. Overall, data suggest that in contrast to mammals guar gum had no effect on white sea bream glucose utilization and in lowering plasma cholesterol and triacylglyceride levels. However, it seems to contribute to lower endogenous glucose production.

Regulation of lipoprotein lipase gene expression by insulin and troglitazone in rainbow trout (Oncorhynchus mykiss) adipocyte cells in culture.

Adipose tissue plays a central role regulating the balance between deposition and mobilization of lipid reserves. Lipoprotein lipase (LPL) is a key enzyme controlling lipid accumulation in mammals and fish. In the present study, we have examined the expression of LPL in rainbow trout cultured adipocytes and we have investigated the effect of troglitazone, a member of thiazolidinediones (TZDs), and insulin on its expression. LPL gene expression increased from day 1 until day 12 of culture, and the level was maintained up to day 21. The addition of insulin at 10 nM and 1.7 µM increased significantly LPL gene expression in undifferentiated cells (days 7 to 12 maintained in growth medium). Nevertheless, treatment of day 7 cells incubated in growth medium with troglitazone (5 µM) or troglitazone plus insulin (1 µM each), tended to enhance LPL expression. In addition, LPL mRNA levels increased significantly in the presence of 1 µM and 5 µM of troglitazone (days 7 to 12) when the cells were induced to differentiate by addition of differentiation medium. Although troglitazone alone (1 µM) did not stimulate lipid accumulation in the cells neither in growth nor in differentiation medium, the simultaneous presence of troglitazone (1 µM) and insulin (1 µM) increased significantly the content of triglycerides in adipocyte cells maintained in growth medium (days 7 to 12). These results indicate that insulin and troglitazone regulate LPL gene expression during adipocyte differentiation and suggest that both factors may have combined effects in the modulation of adipogenesis.

Acute Myocarditis after COVID-19 vaccination: A case report.

INTRODUCTION: The etiology of myocarditis often remains undetermined. A large variety of infectious agents, systemic diseases, drugs, and toxins can cause the disease. We report the case of a 19-year-old man who developed myocarditis three days after Pfizer-BioNTech COVID-19 booster vaccination. CASE REPORT: A 19-year-old man, presenting with troponin-positive acute chest pain, was referred to our department. He had received the Pfizer-BioNTech COVID-19 vaccine three days prior to his admission. The diagnosis of acute myocarditis was confirmed by cardiovascular magnetic resonance imaging. Patient hemodynamic status remained stable during hospitalization. The left ventricular ejection fraction was preserved during hospital stay and at one-month follow-up. We found no evidence for another infectious or autoimmune etiology. CONCLUSION: Although imputability of the vaccine cannot be formally established on the basis of this case report, the findings raise the possibility of an association between mRNA COVID-19 vaccination and acute myocarditis.

Development of diet-induced fatty liver disease in the aging mouse is suppressed by brief daily exposure to low-magnitude mechanical signals.

The age-induced decline in the body's ability to fight disease is exacerbated by obesity and metabolic disease. Using a mouse model of diet-induced obesity, the combined challenge of a high-fat diet and age on liver morphology and biochemistry was characterized, while evaluating the potential of 15 min per day of high frequency (90 Hz), extremely low-magnitude (0.2 G) mechanical signals (LMMS) to suppress lipid accumulation in the liver. Following a 36-week protocol (animals 43 weeks of age), suppression of hepatomegaly and steatosis was reflected by a 29% lower liver mass in LMMS animals as compared with controls. Average triglyceride content was 101.7+/-19.4 microg mg(-1) tissue in the livers of high-fat diet control (HFD) animals, whereas HFD+LMMS animals realized a 27% reduction to 73.8+/-22.8 microg mg(-1) tissue. In HFD+LMMS animals, liver free fatty acids were also reduced to 0.026+/-0.009 microEq mg(-1) tissue from 0.035+/-0.005 microEq mg(-1) tissue in HFD. Moderate to severe micro- and macrovesicular steatosis in HFD was contrasted to a 49% reduction in area covered by the vacuoles of at least 15 microm(2) in size in HFD+LMMS animals. These data provide preliminary evidence of the ability of LMMS to attenuate the progression of fatty liver disease, most likely achieved indirectly by suppressing adipogenesis and thus the total adipose burden through life, thereby reducing a downstream challenge to liver morphology and function.

Insulin and insulin-like growth factor I signaling pathways in rainbow trout (Oncorhynchus mykiss) during adipogenesis and their implication in glucose uptake.

Primary cultures of rainbow trout (Oncorhynchus mykiss) adipocytes were used to examine the main signaling pathways of insulin and insulin-like growth factor I (IGF-I) during adipogenesis. We first determined the presence of IGF-I receptors (IGF-IR) and insulin receptors (IR) in trout preadipocytes (day 5) and adipocytes (day 14). IGF-IRs were more abundant and appeared to be in higher levels in differentiated cells than in preadipocytes, whereas IRs were detected in lower but constant levels throughout the culture. The cells were immunoreactive against ERK1/2 MAPK, and AKT/PI3K, components of the two main signal transduction pathways for insulin and IGF-I receptors. Stimulation of MAPK phosphorylation by IGF-I was higher in preadipocytes than in adipocytes, while no effects were observed in MAPK phosphorylation after incubation of cells with insulin. AKT phosphorylation increased in the presence of both insulin and IGF-I, with higher levels of stimulation in adipocytes than in preadipocytes. Activation of both pathways was blocked by the use of specific inhibitors of MAPK (PD98059) and AKT (wortmannin). We describe here, for the first time, the effects of IGF-I and insulin on 2-deoxyglucose uptake in primary culture of trout adipocytes. IGF-I was more potent in stimulating glucose uptake than insulin, and PD98059 and wortmannin inhibited the stimulation of glucose uptake by this growth factor, suggesting that IGF-I plays an important metabolic role in trout adipocytes. Our results suggest that differential activation of the MAPK and AKT pathways are involved in the IGF-I- and insulin-induced effects of trout adipocytes during the various stages of adipogenesis.

[Acute autoimmune myocarditis secondary to Graves' disease: a case report]. / Myocardite aiguë auto-immune secondaire à une maladie de Basedow : à propos d'un cas.

INTRODUCTION: Interactions between heart and thyroid are strong. Main cardiac complications of Graves' disease are supra-ventricular tachycardia or high output cardiac failure, without real myocardial involvement. OBSERVATION: A 40-year-old man with history of refractory Graves' disease was hospitalized for an acute chest pain with elevated cardiac biomarkers and normal coronarography. Acute myocarditis was confirmed by cardiac MRI. We found no evidence for an infectious etiology. We retained the hypothesis of acute autoimmune myocarditis in the context of active Graves' disease. CONCLUSION: Acute myocarditis is an exceptional complication of Graves' disease, with most likely an autoimmune mechanism. Possible occurrence of fulminant rhythmic or hemodynamic complications justify minimal cardiological check-up before introducing beta blockers.

[Particularities of African descent patient's electrocardiogram]. / Particularités de l'électrocardiogramme du patient d'origine Africaine.

Particularities of African descent patient's electrocardiogram have been described for many years. Variations such as higher QRS voltage, early repolarization pattern, precordial T-wave inversion and anterior ST segment elevation associated with T-wave inversion are more frequently observed. Ignorance of these variations can lead to misdiagnosis or therapeutic negligence. We present the electrocardiographic particularities attributed to the patient of African origin.

Regulatory mechanisms involved in muscle and bone remodeling during refeeding in gilthead sea bream.

The tolerance of fish to fasting offers a model to study the regulatory mechanisms and changes produced when feeding is restored. Gilthead sea bream juveniles were exposed to a 21-days fasting period followed by 2 h to 7-days refeeding. Fasting provoked a decrease in body weight, somatic indexes, and muscle gene expression of members of the Gh/Igf system, signaling molecules (akt, tor and downstream effectors), proliferation marker pcna, myogenic regulatory factors, myostatin, and proteolytic molecules such as cathepsins or calpains, while most ubiquitin-proteasome system members increased or remained stable. In bone, downregulated expression of Gh/Igf members and osteogenic factors was observed, whereas expression of the osteoclastic marker ctsk was increased. Refeeding recovered the expression of Gh/Igf system, myogenic and osteogenic factors in a sequence similar to that of development. Akt and Tor phosphorylation raised at 2 and 5 h post-refeeding, much faster than its gene expression increased, which occurred at day 7. The expression in bone and muscle of the inhibitor myostatin (mstn2) showed an inverse profile suggesting an inter-organ coordination that needs to be further explored in fish. Overall, this study provides new information on the molecules involved in the musculoskeletal system remodeling during the early stages of refeeding in fish.

In vivo quantification of subcutaneous and visceral adiposity by micro-computed tomography in a small animal model.

Accurate and precise techniques that identify the quantity and distribution of adipose tissue in vivo are critical for investigations of adipose development, obesity, or diabetes. Here, we tested whether in vivo micro-computed tomography (microCT) can be used to provide information on the distribution of total, subcutaneous and visceral fat volume in the mouse. Ninety C57BL/6J mice (weight range: 15.7-46.5 g) were microCT scanned in vivo at 5 months of age and subsequently sacrificed. Whole body fat volume (base of skull to distal tibia) derived from in vivo microCT was significantly (p<0.001) correlated with the ex vivo tissue weight of discrete perigonadal (R(2)=0.94), and subcutaneous (R(2)=0.91) fat pads. Restricting the analysis of tissue composition to the abdominal mid-section between L1 and L5 lumbar vertebrae did not alter the correlations between total adiposity and explanted fat pad weight. Segmentation allowed for the precise discrimination between visceral and subcutaneous fat as well as the quantification of adipose tissue within specific anatomical regions. Both the correlations between visceral fat pad weight and microCT determined visceral fat volume (R(2)=0.95, p<0.001) as well as subcutaneous fat pad weight and microCT determined subcutaneous fat volume (R(2)=0.91, p<0.001) were excellent. Data from these studies establish in vivo microCT as a non-invasive, quantitative tool that can provide an in vivo surrogate measure of total, visceral, and subcutaneous adiposity during longitudinal studies. Compared to current imaging techniques with similar capabilities, such as microMRI or the combination of DEXA with NMR, it may also be more cost-effective and offer higher spatial resolutions.

[Cardiovascular complications of doping products]. / Complications cardiovasculaires des produits dopants.

Doping is the use of a substance that artificially increases an individual's physical ability for competition purpose. Products and methods used in doping are not without risk, especially at cardiovascular level. Here we review the most common doping substances in sport and their cardiovascular consequences.

Insulin regulation of lipoprotein lipase (LPL) activity and expression in gilthead sea bream (Sparus aurata).

Lipoprotein lipase (LPL) is a key enzyme in lipoprotein metabolism by virtue of its capacity to hydrolyze triglycerides circulating in the form of lipoprotein particles. Here we analyzed the fasting effects of LPL in gilthead sea bream (Sparus aurata) and also present the first study in fish of the role of insulin as a potential modulator of both LPL activity and expression. Fasting for 2 weeks provoked a clear decrease in adipose tissue LPL activity, concomitant with lower levels of plasma insulin, while no effects were observed in red muscle. To elucidate the specific role of insulin, increases of plasma insulin were experimentally induced by arginine and insulin injections. However, arginine predominantly stimulated glucagon over insulin secretion in this fish species while LPL activity did not change significantly in adipose tissue. Instead, insulin administration induced an increase in adipose tissue LPL activity 3 h after the injection, whereas LPL activity in red muscle was not affected. Changes in LPL activity were accompanied by an increase in LPL mRNA levels in the adipose tissue of insulin-injected gilthead sea bream, although changes in LPL expression were delayed in time with respect to variations in LPL activity. Finally, LPL mRNA levels in red muscle were similar between control and insulin-injected gilthead sea bream, suggesting that insulin does not play a direct role in the regulation of LPL in this tissue. The current study shows that LPL activity is regulated by nutritional condition and underscores the importance of insulin as a modulator of LPL activity and expression in the adipose tissue of gilthead sea bream.

[Initial management of ST-elevation myocardial infarction in 2014: From guidelines to practices, survey of 176 French interventional cardiologists]. / Prise en charge initiale du syndrome coronaire aigu avec sus-décalage du segment ST en 2014 : des recommandations à la pratique, enquête auprès de 176 cardiologues interventionnels français.

BACKGROUND: Real life management of myocardial infarction has not recently been evaluated in France. AIMS: To describe ST-elevation myocardial infarction management in France in 2014 and to compare it with current guidelines. METHODS: A multicentre study was performed. An e-mail questionnaire was sent to French interventional cardiologists. Demographic data of interventional cardiologists, procedural aspects of percutaneous coronary intervention, antithrombotic treatments and patient rehabilitation have been investigated. RESULTS: One hundred and seventy-six answers were analysed. Most of centres realized more than 600 annual angioplasties. An average of 209 myocardial infarctions were managed per centre in 2014, more often in academic than in general or private centres (respectively 51, 32 and 17% of infarctions). Anti-GPIIbIIIa (34% of the cases) and thromboaspiration were not systematic but depend on patient's characteristics, according to guidelines. Radial access was favoured in 85% of the cases and increased for the last decade. Drug eluting stents were used in 62% of cases. Unfractionated heparin and enoxaparine accounted for more than 80% of anticoagulants treatments. Overall, use of clopidogrel was as high as that of prasugrel or ticagrelor although clopidogrel is recommended in second-line. Cardiovascular rehabilitation was proposed to more than 50% of patients. CONCLUSION: In spite of heterogeneity of ST-elevation myocardial infarction management in 2014, real-life practices generally comply with current guidelines.

[Infective endocarditis: Clinical features and prognosis between 2004 and 2014 in a non-teaching hospital]. / Endocardite infectieuse : caractéristiques cliniques et pronostic entre 2004 et 2014 dans un hôpital non universitaire.

AIMS: Despite diagnostic and therapeutic advances, infective endocarditis (IE) remains a severe disease. The aim of the study was to describe clinical features and prognosis of patients with IE in a non-teaching hospital and compare them with current data and a similar study conducted 10 years earlier in the same center. METHODS: We performed a single institution retrospective study including all patients with Duke-Li definite IE between 2004 and 2014. RESULTS: Ninety-four patients were included. Results are consistent with current French and international data, including in-hospital death rate of 16%. In accordance with literature, we report on an increase in Staphylococcus and health care-associated IE and endocarditis on pacemaker leads, but without significant difference compared to our previous study. In univariate analyses, renal failure, age over 77 years and Staphylococcus aureus IE were associated with in-hospital mortality. In multivariate analyses, predictors of in-hospital death were renal failure and lack of surgery. There was a non-significant trend of excess mortality in Staphylococcus endocarditis and in patients with heart failure. CONCLUSION: IE remains a severe disease and S. aureus is more often involved. IE seems to be safely managed in a peripheral hospital provided that there is a partnership with a reference hospital.

[Inferior myocardial infarction complicated by complete heart block and cardiac arrest following a gadolinium injection: A case of Kounis syndrome]. / Infarctus du myocarde inférieur compliqué de bloc auriculo-ventriculaire complet et d'arrêt cardiocirculatoire dans les suites d'une injection de gadolinium : à propos d'une observation de syndrome de Kounis.

Kounis syndrome is an allergic acute coronary syndrome. It occurs on healthy or pathological arteries. Its complications, although often benign, can lead to cardiac arrest and death. Its triggering factors are multiple and include contrast products used in diagnostic imaging. We report the case of an 81 years old patient affected by hepatocellular carcinoma, who presented a type 2 Kounis syndrome with inferior myocardial infarction, complicated by cardiac arrest related to complete heart block following a gadoteric acid injection.

[Acute coronary syndrome with impaired left ventricular function in a carbon monoxide poisoning]. / Syndrome coronaire aigu avec dysfonction ventriculaire gauche lors d'une intoxication au monoxyde de carbone.

Carbon monoxide poisoning is the leading cause of death by poisoning in France. Neuropsychological symptoms are most common. We report on a patient with acute coronary syndrome and transient left ventricular dysfunction in carbon monoxide poisoning. Patient improved under hyperbaric oxygen therapy. Coronary angiography shows no significant lesion leading to myocardial stunning diagnose. Patients exposed to carbon monoxide must have systematic cardiac evaluation with electrocardiogram and dosage of biomarkers.

Acute myocardial infarction and coronary artery dissection following rugby-related blunt chest trauma in France.

Coronary artery (CA) dissection following blunt chest trauma is a life-threatening and rare event. Its occurrence in the setting of a contact sport like rugby is even less common. We report on two cases of young adult presenting with segment elevation myocardial infarction related to CA dissection following rugby game. Both were successfully treated with stent implantation. We discuss the mechanism, diagnosis, and optimal management of blunt chest trauma-induced CA dissection.

[Painless anterior acute myocardial infarction in a transplanted heart]. / Infarctus du myocarde antérieur indolore chez un transplanté cardiaque.

Cardiac allograft vasculopathy is the major determinant of long-term survival in patients after heart transplantation. Clinical presentations are congestive heart failure, ventricular arrhythmias and sudden cardiac death. Acute coronary syndrome is a rare presentation of cardiac allograft vasculopathy due to myocardial denervation. We present the case of a 31-year-old patient, who had undergone heart transplantation 6 months earlier and who developed a painless anterior myocardial infarction revealed by syncope. He was successfully treated by percutaneous coronary intervention with drug eluting stent implantation.

Growth-promoting effects of sustained swimming in fingerlings of gilthead sea bream (Sparus aurata L.).

Fish growth is strongly influenced by environmental and nutritional factors and changing culture conditions can help optimize it. The importance of early-life experience on the muscle phenotype later in life is well known. Here, we study the effects of 5 weeks of moderate and sustained swimming activity (5 BL s(-1)) in gilthead sea bream during early development. We analysed growth and body indexes, plasma IGF-I and GH levels, feed conversion, composition [proximate and isotopic ((15)N/(13)C)] and metabolic key enzymes (COX, CS, LDH, HOAD, HK, ALAT, ASAT) of white muscle. Moderate and continuous exercise in fingerlings of gilthead sea bream increased plasma IGF-I, whereas it reduced plasma GH. Under these conditions, growth rate improved without any modification to feed intake through an increase in muscle mass and a reduction in mesenteric fat deposits. There were no changes in the content and turnover of muscle proteins and lipid reserves. Glycogen stores were maintained, but glycogen turnover was higher in white muscle of exercised fish. A lower LDH/CS ratio demonstrated an improvement in the aerobic capacity of white muscle, while a reduction in the COX/CS ratio possibly indicated a functional adaptation of mitochondria to adjust to the tissue-specific energy demand and metabolic fuel availability in exercised fish. We discuss the synergistic effects of dietary nutrients and sustained exercise on the different mitochondrial responses.