AMP-Activated Kinase (AMPK) Activation by AICAR in Human White Adipocytes Derived from Pericardial White Adipose Tissue Stem Cells Induces a Partial Beige-Like Phenotype.

Beige adipocytes are special cells situated in the white adipose tissue. Beige adipocytes, lacking thermogenic cues, morphologically look quite similar to regular white adipocytes, but with a markedly different response to adrenalin. White adipocytes respond to adrenergic stimuli by enhancing lipolysis, while in beige adipocytes adrenalin induces mitochondrial biogenesis too. A key step in the differentiation and function of beige adipocytes is the deacetylation of peroxisome proliferator-activated receptor (PPARγ) by SIRT1 and the consequent mitochondrial biogenesis. AMP-activated protein kinase (AMPK) is an upstream activator of SIRT1, therefore we set out to investigate the role of AMPK in beige adipocyte differentiation using human adipose-derived mesenchymal stem cells (hADMSCs) from pericardial adipose tissue. hADMSCs were differentiated to white and beige adipocytes and the differentiation medium of the white adipocytes was supplemented with 100 µM [(2R,3S,4R,5R)-5-(4-Carbamoyl-5-aminoimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate (AICAR), a known activator of AMPK. The activation of AMPK with AICAR led to the appearance of beige-like morphological properties in differentiated white adipocytes. Namely, smaller lipid droplets appeared in AICAR-treated white adipocytes in a similar fashion as in beige cells. Moreover, in AICAR-treated white adipocytes the mitochondrial network was more fused than in white adipocytes; a fused mitochondrial system was characteristic to beige adipocytes. Despite the morphological similarities between AICAR-treated white adipocytes and beige cells, functionally AICAR-treated white adipocytes were similar to white adipocytes. We were unable to detect increases in basal or cAMP-induced oxygen consumption rate (a marker of mitochondrial biogenesis) when comparing control and AICAR-treated white adipocytes. Similarly, markers of beige adipocytes such as TBX1, UCP1, CIDEA, PRDM16 and TMEM26 remained the same when comparing control and AICAR-treated white adipocytes. Our data point out that in human pericardial hADMSCs the role of AMPK activation in controlling beige differentiation is restricted to morphological features, but not to actual metabolic changes.

New perspectives in the renin-angiotensin-aldosterone system (RAAS) II: albumin suppresses angiotensin converting enzyme (ACE) activity in human.

About 8% of the adult population is taking angiotensin-converting enzyme (ACE) inhibitors to treat cardiovascular disease including hypertension, myocardial infarction and heart failure. These drugs decrease mortality by up to one-fifth in these patients. We and others have reported previously that endogenous inhibitory substances suppress serum ACE activity, in vivo, similarly to the ACE inhibitor drugs. Here we have made an effort to identify this endogenous ACE inhibitor substance. ACE was crosslinked with interacting proteins in human sera. The crosslinked products were immunoprecipitated and subjected to Western blot. One of the crosslinked products was recognized by both anti-ACE and anti-HSA (human serum albumin) antibodies. Direct ACE-HSA interaction was confirmed by binding assays using purified ACE and HSA. HSA inhibited human purified (circulating) and human recombinant ACE with potencies (IC50) of 5.7 ± 0.7 and 9.5 ± 1.1 mg/mL, respectively. Effects of HSA on the tissue bound native ACE were tested on human saphenous vein samples. Angiotensin I evoked vasoconstriction was inhibited by HSA in this vascular tissue (maximal force with HSA: 6.14 ± 1.34 mN, without HSA: 13.54 ± 2.63 mN), while HSA was without effects on angiotensin II mediated constrictions (maximal force with HSA: 18.73 ± 2.17 mN, without HSA: 19.22 ± 3.50 mN). The main finding of this study is that HSA was identified as a potent physiological inhibitor of the ACE. The enzymatic activity of ACE appears to be almost completely suppressed by HSA when it is present in its physiological concentration. These data suggest that angiotensin I conversion is limited by low physiological ACE activities, in vivo.

[Cardiovascular actions of a standardized polyphenol concentrate on patients undergoing coronary bypass grafting: a randomized, double-blind, placebo-controlled study]. / Standardizált polifenol-koncentrátum keringési hatásai koszorúérmutéten átesett betegeken: randomizált, kettos vak-, placebokontrollos vizsgálat.

In this study the authors analyzed the action of Flavon Max product on the cardiovascular system of patients with severe coronary disease. Two randomized, double-blind, placebo controlled trials were carried out using impedance-cardiography, arteriography, vascular Doppler and biochemical laboratory methods. The results demonstrate that Augmentation Index measured with arteriography and C reactive protein (CRP) levels were significantly ameliorated after 2 x 2 months Flavon Max therapy. In conclusion, this product is beneficial as adjuvant in the treatment of atherosclerotic coronary disease.

[Simple surgical method for intraoperative evaluation of adequacy of tricuspid annuloplasty]. / Egyszeru sebészi módszer a tricuspidalis annuloplasztika eredményének mutét alatti értékelésére.

In tricuspid annuloplasty intraoperative "real time" evaluation using transoesophageal echocardiography requires normal flow to get reliable result. It means that the patient has to be already weaned from the cardiopulmonary bypass by the time of evaluation. In the authors' experience a well functioning tricuspid annuloplasty prevents back-flow through the valve. It can be observed on on-pump beating heart. If the tricuspid valve is competent, it is unnecessary to suck the blood flowing back through the coronary sinus while closing the right atrium. This observation seems to correlate well with post cardiopulmonary bypass transoesophageal echocardiography measurements and the control transthoracic echocardiography right before discharging the patients. These statements are based on a group of 72 patients. Sixty-nine patients (95.8%) were discharged (early mortality 4.2%). Only in one case we could observe a discrepancy between the intraoperative surgical observation and the postoperative echocardiographic finding. Development of functional tricuspid regurgitation in left-sided heart disease is a warning sign for myocardial impairment, which is an indication for surgery. Tricuspid annuloplasty can be performed even with moderate to medium grade regurgitation because it improves the early and late outcome. The described method is an adequate method for intraoperative evaluation of the repaired tricuspid valve competency.

[Excision of the calcified mitral valve with ultrasound scalpel]. / A meszes mitralis billentyu sebészi kimetszése ultrahangvágóval.

Mitral valve excision using ultrasound device has not been a routine procedure yet. We used an ultrasonic scalpel for the excision of the calcified mitral valves, which shorten operation time. Further, this technique permits an excision of the valve without applying traction or elevation of the valve from the level of the annulus. This method was first tested on twenty fresh porcine hearts. Subsequently, this technique was carried out with very good results in 15 consecutive patients with calcified or scarred, and distorted mitral valves. Histological samples were taken from the excised human and porcine valves. In porcine histological specimens the destructive effect of the ultrasonic scalpel was measured of an average of 0.7 mm (minimum 0.5 mms, maximum 0.8 mms). However, in the human heart, this effect was an average of 1.1 mms (minimum 0.6 mms, maximum 2.2 mms). There were no early or late complications observed in any case. The authors recommend this technique for excision of calcified mitral valves in cardiac surgery.

[A complementary clinical method to minimize air embolism during open-heart surgery]. / Kiegészíto klinikai módszer a nyitott szívmutéteknél fellépo légembolisatio csökkentésére.

Air from the left heart is ejected even up to several hours after cardiopulmonary bypass (CPB) despite the use of CO2. The following method is complementary in addition to surgical de-airing in order to further reduce the chance of air embolism, especially from the pulmonary veins. After re-expanding the lungs with standard bag inflation, the ventilation is restarted in consultation with the surgeon. The ventilator is set to the respiratory minute volume used before the CPB but at a respiratory frequency of 10/minutes whereas the regularly beating heart is filled from the heart lung machine. Transoesophageal echocardiography (TEE) reliably controls the effect.

[Ebstein's anomaly--experiences with surgical treatment in adulthood]. / Ebstein-anomália--a felnottkorban végzett mutétekkel kapcsolatos tapasztalatok.

INTRODUCTION: Long time results with operative treatment of Ebstein anomaly were examined. PATIENTS AND METHODS: From January 1985 to March 2001 16 patients with Ebstein anomaly were operated on. Ages ranged from 16 to 49 years at the time of operation. In 7 cases tricuspid valve repair was possible, and in 9 cases prosthetic valve was inserted. In all but one biological prosthesis has been used. In 15 cases atrial septal defect occurred as a concomitant anomaly, which was closed by direct suture in 9 cases and with patch (2 Dacron, 4 pericardium) in 6 cases. RESULTS: There was no early death (30 days postoperatively). 1 patient following tricuspid repair was reoperated on at the 9th postoperative day because of significant tricuspid insufficiency. Tricuspid valve replacement was performed with a biological prostheses. There were 3 late deaths: 2 patients (12.5%) in the first postoperative year (1 cardiac cause, 1 unknown), 1 patient died 6 years postoperatively following reoperation. There were 3 more patients requiring reoperation (total reoperation rate 28.6%) one of them a few days after the primary operation and two others 9 and 11 years following the first operation. 13 patients were recalled to control investigations. The authors could not contact 2 patients, 1 patient living abroad could not appear at our clinic. 10 patients have been investigated 6 months to 16 years after the operation. There were 9 patients in New York Heart Association class I or II. 2 patients had their own repaired valve; both had tricuspid insufficiency grade III. Both were completely active. 8 patients had previously tricuspid valve replacement and good valve function, but six of them have not been working any more. There were 5 female patients under 35 at the time of operation and 2 of them had successful pregnancies. CONCLUSIONS: Patients with Ebstein anomaly in NYHA stage III-IV. can be successfully treated surgically.