[Antiplatelet duration in the elderly patients after percutaneous coronary intervention]. / Durée du traitement antiagrégant plaquettaire chez le sujet âgé stenté.

Ischemic heart disease is a leading cause of death in Europe. At the same time, older patients are at high risk for coronary heart disease and represent an increasing proportion of patients in the catheterization laboratory in the context of an ageing population. The elderly patients are also at higher bleeding risk, and were poorly represented in major randomized trials. Duration of dual antiplatelet therapy (DAPT), after percutaneous coronary intervention (PCI) should be modulated in a personalized way taking into account hemorrhagic and ischemic risk factors, using risk scores based on the latest recommendations of the European Society of Cardiology. Even if the optimal duration of DAPT after PCI is 6 months in case of stable coronary disease and 12 months in case of an acute coronary syndrome, it can be drastically reduced, up to one month in case of high hemorrhagic risk, or can be prolonged for more than 12 months in case of high ischemic risk. The use of latest generation drug eluting stents associated with a short duration of DAPT has thus demonstrated its safety compared to these durations. In case of triple therapy treatment, associating DAPT and anticoagulation therapy, DAPT is recommended to be as short as possible, potentially reduced to 1 month. Finally, the concomitant prescription of proton pump inhibitor is essential to prevent gastrointestinal bleedings. This literature review will discuss the hemorrhagic risk stratification and choice of DAPT in elderly patients.

[Sudden cardiac death and anomalous connections of the coronary arteries: What is known and what is unknown?] / Mort subite cardiaque et anomalies de connexion des artères coronaires : connaissances et questions.

Some anomalous connections of the coronary arteries may be associated with a risk of sudden cardiac death. In opposite with others cardiac diseases at risk of sudden cardiac death, the relationship between these congenital abnormalities and the risk of sudden cardiac death are not well understood. A correction of the anomaly is generally indicated after an aborted sudden cardiac death. Primary prevention strategy after the discovery of an anomaly at risk is debated. Even if the absolute risk of sudden death is very low, a pre-participation screening in young athletes may be discussed due to a non-rare incidence.

Effect of PACAP treatment on kidney morphology and cytokine expression in rat diabetic nephropathy.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide, exerting diverse effects. One of its frequently examined functions is cell protection, which is achieved mainly via inhibiting apoptotic, inflammatory and oxidative processes. All its three receptors (PAC1, VPAC1, VPAC2) are expressed in the kidney and PACAP has been shown to have protective effects against different renal pathologies. Diabetic nephropathy is the leading cause of end stage renal disease. The aim of the present study was to investigate the possible ameliorative effect of PACAP in streptozotocin-induced diabetic nephropathy and to evaluate its anti-inflammatory effect in this model. Diabetes was induced by a single intravenous injection of streptozotocin (65 mg/kg) in male Wistar rats. PACAP-treated animals were administered ip. 20 µg PACAP every second day, while untreated animals were given vehicle. Kidneys were removed after 8-weeks survival. Besides the complex histological analysis (glomerular PAS positive area/glomerulus area, tubular damage, arteriolar hyalinosis), expression of several cytokines was evaluated by cytokine array and Luminex assay. Histological analysis revealed severe diabetic changes in kidneys of control diabetic animals (glomerular PAS-positive area expansion, tubular damage, Armanni-Ebstein phenomenon). PACAP treatment significantly diminished the damage. Diabetic kidneys showed significant cytokine activation compared to their healthy controls. PACAP was effective in downregulation of several cytokines including CINC-1, TIMP-1, LIX, MIG, s-ICAM. To conclude, PACAP is effective in ameliorating diabetic nephropathy at least partly through its well-known anti-inflammatory effect. These results raise the opportunity for the use of PACAP as a possible therapeutic or preventive method in treating the complications of diabetes.

Ischaemic postconditioning reduces serum and tubular TNF-α expression in ischaemic-reperfused kidney in healthy rats.

OBJECTIVE: We studied the protective effects of postconditioning (PS) in healthy and hypercholesterolemic rats after renal ischaemia-reperfusion (IR) injury. We aimed to examine cytokine expression and apoptosis in tissue damage after revascularisation (TNF-α levels in serum and tissue). METHODS: Male Wistar rats (n = 32) were divided into four groups. The animals of normal feed groups (NF) were fed with normal rat chow and the cholesterol feed groups (CF) were fed with 1.5% cholesterol containing diet for 8 weeks. Anaesthetized rats underwent a 45-min cross-clamping in both kidney pedicles. Ischaemia was followed by 120-min reperfusion with or without PS protocol (group PS vs. IR). Postconditioning was induced by four intermittent periods of ischaemia-reperfusion of 15-s duration each. Serum cholesterol, triglyceride, urea and creatinine levels were determined. Proinflammation was characterized by the measurement of serum TNF-α. Tissue injury in kidney was determined by formaline-fixed, paraffin-embedded tissue sections. Tissue TNF-α levels were determined by immunohistochemistry. RESULTS: Significant elevation was observed in serum TNF-α level after IR injury in normal feed groups, which was reduced by PS. In CF group neither the elevation nor the postconditioning induced reduction were as significant as in the NF groups. In normal feed group PS caused a significant reduction in tissue TNF-α level which was significantly higher in CF. CONCLUSIONS: Ischaemic postconditioning proved to be an effective defense against IR in NF groups, but it was ineffective in CF groups in kidney tissue.

Morphology of glomerular hematuria is reproduced in vitro by carbonyl stress.

BACKGROUND: In glomerulonephritides, dysmorphic red blood cells (RBCs) with membrane blebs can be found in the urine; this is referred to as glomerular hematuria. Glomerulonephritides are characterized by increased carbonyl stress and elevated methylglyoxal (MGO) levels. MGO causes oxidative stress and intracellular calcium accumulation. In the present study, we investigated whether the effect of MGO-induced calcium accumulation in RBCs develops through increased oxidative stress. Furthermore, we studied whether MGO can lead to RBC membrane blebbing. METHODS: RBC suspensions from healthy volunteers were incubated with different concentrations of MGO at 37 degrees C. We measured oxidative stress and intracellular calcium level using fluorescent indicators. We determined the frequency of dysmorphic RBCs, and also performed scanning electron microscopy. RESULTS: MGO increased oxidative stress and caused accumulation of calcium in isolated RBCs. These effects could be prevented using antioxidants. In the presence of MGO, RBC membrane blebbing developed. CONCLUSION: According to our findings, MGO causes calcium accumulation through oxidative stress. Carbonyl and oxidative stress may play an important role in the formation of dysmorphic RBCs in glomerular hematuria.

Bilateral blepharochalasis.

Blepharochalasis is a rare disorder characterized by recurrent painless periorbital oedema, which leads to atrophy of the periorbital skin. Pathomechanism of the disease is probably immunological with a nearly complete loss of elastic fibres. The authors describe a 17-year-old woman, who was followed for 7 years. IgA deposits were found in the periorbital tissues, which confirm the immunological background of the condition. Electron microscopy results show that not only elastic but also collagen fibres were affected.

Cigarette smoke and its formaldehyde component inhibit bradykinin-induced calcium increase in pig aortic endothelial cells.

Bradykinin-induced increase in the intracellular concentration of free calcium evokes an activation of the endothelial nitric oxide synthase (eNOS) enzyme, producing nitric oxide (NO). Cigarette smoke inhibits the eNOS-NO-cGMP signaling pathway. The pathomechanism of this deleterious effect of smoke on NO production is unknown. The aim of this study was to investigate the effect of gas phase smoke trapped in a buffer (smoke buffer, SB) on the bradykinin-induced calcium increase in cultured endothelial cells. FURA-2-AM was used to detect bradykinin-induced calcium increase. A sensitive, fluorescent method using O-phthaldialdehyde was used for the determination of intracellular reduced glutathione (GSH) and protein-thiol levels. SB caused a time- and concentration-dependent inhibition of bradykinin-induced calcium increase. Formaldehyde, a component of SB, inhibited bradykinin-induced calcium increase in concentrations characteristic for SB. SB decreased both the intracellular GSH (0.22 +/- 0.06 vs. 2.23 +/- 0.32 mumol/g protein, SB vs. control, p < .001) and protein-thiol levels (4.98 +/- 0.54 vs. 7.31 +/- 0.97 microEqu GSH/g protein, SB vs. control, p < .05) in the endothelial cells. Intracellular GSH and protein-thiol levels were not changed by 80 microM formaldehyde. GSH (4 mM) prevented the effect of SB (p < .001) and formaldehyde (p < .05) on the bradykinin-induced calcium increase. Our data support the premise that SB inhibits bradykinin-induced calcium increase. This inhibition is partially due to protein-thiol oxidation but may also be caused by the formaldehyde content of SB, which inhibits calcium increase in a protein-thiol-independent manner.

[Early ischemic lesion of the myocardium in a case of unusual developmental anomaly of the coronary vessels and coronary thrombosis]. / A szívizom korai ischaemiás laesiója különleges szívkoszorúsveröér fejlödési rendellenesség és coronaria thrombosis esetében

An uncommon form of anomaly of coronary arteries is reported, similar to which had not as yet been published. A single right arteria coronaria was found having an only left branch with a thin vena-like wall, descending on the anterior surface of the heart. The lumen of the sclerotic right arteria was occluded by a thrombus at the point of origin of ramus descendens posterior. The cause of death was an acute cardiac failure, in which authors prescribe an important part to the anomaly of coronary arteries. Areas of myocard getting blood supply from the occluded arteria were investigated by the method of fuchsinorrhagia. Authors believe, that this reaction is suitable for the demonstration of the acute, early ishaemic lesions of the myocard.