The influence of triglyceride and low-density-lipoprotein target levels on microcirculation: Is there a difference?

Background and aims: This study aimed to validate the role of high low-density lipoprotein cholesterol [LDL-C] and triglyceride [TG] treatment target levels on the microcirculation in a very high and high cardiovascular risk group. Methods: 119 patients with high or very high cardiovascular [CV] risk were included. We have registered the main co-morbidities, smoking habits, body mass index [BMI] and the lipid lowering medication. Hematocrit, whole blood viscosity [WBV] and plasma viscosity [PV], red blood cell [RBC] aggregation and deformability and fibrinogen, total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], LDL-C and TG levels were determined. Results: The investigation found significantly higher PV values in patients with non-target LDL-C, associated with higher fibrinogen level. Non-target TG was related to deteriorated microcirculatory parameters, as significantly higher RBC aggregation, lower RBC deformability, and higher WBV and PV. The main microcirculatory benefit in diabetes could be gained from target level of TG, in chronic coronary syndrome [CCS] patients it is more advantageous to reach both LDL-C and TG target. Conclusion: The results could highlight, that TG should play a role in failing microcirculation and cause potentially life-threatening complications, which would worsen the survival and quality of life of high or very high risk CV patients.

Resveratrol and beyond: The Effect of Natural Polyphenols on the Cardiovascular System: A Narrative Review.

Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality worldwide. Unhealthy dietary habits have clearly been shown to contribute to the development of CVDs. Beyond the primary nutrients, a healthy diet is also rich in plant-derived compounds. Natural polyphenols, found in fruits, vegetables, and red wine, have a clear role in improving cardiovascular health. In this review, we strive to summarize the results of the relevant pre-clinical and clinical trials that focused on some of the most important natural polyphenols, such as resveratrol and relevant flavonoids. In addition, we aim to identify their common sources, biosynthesis, and describe their mechanism of action including their regulatory effect on signal transduction pathways. Finally, we provide scientific evidence regarding the cardiovascular benefits of moderate, long-term red wine consumption.

Evaluation of Incidence and Risk Factors of Sudden Cardiac Death in Patients with Chronic Coronary Syndrome Attending Physical Training.

INTRODUCTION: Regular physical activity is recommended to patients with chronic coronary syndrome (CCS). However, vigorous physical exercise occurs as a risk factor of sudden cardiac death (SCD). The effect of short-term and irregular exercise is controversial. The aim of this research is to assess the role of regular training in the incidence of SCD and to identify risk factors among patients with CCS participating in a long-term training program. METHODS: Data of risk factors, therapy, and participation were collected retrospectively for a 10-year period, assessing the length and regularity of participation. The incidence of SCD and related mortality was registered. ANOVA, χ2 test, and multinominal logistic regression and stepwise analysis were performed. RESULTS: The Incidence of chronic kidney disease (CKD) was higher (p < 0.01) and taking beta-blockers (BBs) was lower (p = 0.04) in the SCD group. Irregular training, lack of BBs, smoking, and CKD increased the risk of SCD, while female sex, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers (ACEI/ARBs), and BBs decreased the risk of SCD. CONCLUSIONS: Taking ACEI/ARBs and BBs proved to be a protective factor, emphasizing the use of optimal medical therapy. Assessment of cardiac risk factors and control of comorbidities also proved to be important. The occurrence of SCD was connected to irregular physical activity, probably relating to the adverse effects of ad hoc exercising.

Association Between Achieved Low-Density Lipoprotein Cholesterol Levels and Long-Term Cardiovascular and Safety Outcomes: An Analysis of FOURIER-OLE.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for atherosclerotic cardiovascular disease. However, the optimal achieved LDL-C level with regard to efficacy and safety in the long term remains unknown. METHODS: In FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), 27 564 patients with stable atherosclerotic cardiovascular disease were randomized to evolocumab versus placebo, with a median follow-up of 2.2 years. In the open-label extension (FOURIER-OLE), 6635 of these patients were transitioned to open-label evolocumab regardless of initial treatment allocation in the parent trial and were followed for an additional median of 5 years. In this prespecified analysis, we examined the relationship between achieved LDL-C levels (an average of the first 2 LDL-C levels measured) in FOURIER-OLE (available in 6559 patients) and the incidence of subsequent cardiovascular and safety outcomes. We also performed sensitivity analyses evaluating cardiovascular and safety outcomes in the entire FOURIER and FOURIER-OLE patient population. Multivariable modeling was used to adjust for baseline factors associated with achieved LDL-C levels. RESULTS: In FOURIER-OLE, 1604 (24%), 2627 (40%), 1031 (16%), 486 (7%), and 811 (12%) patients achieved LDL-C levels of <20, 20 to <40, 40 to <55, 55 to <70, and ≥70 mg/dL, respectively. There was a monotonic relationship between lower achieved LDL-C levels-down to very low levels <20 mg/dL-and a lower risk of the primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, hospital admission for unstable angina or coronary revascularization) and the key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) that persisted after multivariable adjustment (adjusted Ptrend<0.0001 for each end points). No statistically significant associations existed in the primary analyses between lower achieved LDL-C levels and increased risk of the safety outcomes (serious adverse events, new or recurrent cancer, cataract-related adverse events, hemorrhagic stroke, new-onset diabetes, neurocognitive adverse events, muscle-related events, or noncardiovascular death). Similar findings were noted in the entire FOURIER and FOURIER-OLE cohort up to a maximum follow-up of 8.6 years. CONCLUSIONS: In patients with atherosclerotic cardiovascular disease, long-term achievement of lower LDL-C levels, down to <20 mg/dL (<0.5 mmol/L), was associated with a lower risk of cardiovascular outcomes with no significant safety concerns. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01764633.

Hemorheological Parameters in Diabetic Patients: Role of Glucose Lowering Therapies.

Diabetes mellitus influences several important hemorheological parameters including blood viscosity, erythrocyte aggregation and deformability. In the present study, 159 type-2 diabetic patients and 25 healthy controls were involved. Patient's age, body weight, body mass index (BMI), smoking habits, physical activity, history of cardiovascular diseases, current antidiabetic therapy and concomitant medication were recorded. Patients were grouped according to their antidiabetic treatment with insulin, or with one or more of the following antidiabetic drugs: metformin, sulfonylureas, acarbose, or no antidiabetic therapy. Hemorheological measurements (hematocrit, erythrocyte aggregation, plasma fibrinogen, whole blood and plasma viscosity), von Willebrand factor activity, and platelet aggregation measurements were performed. Platelet aggregation was investigated with the method of Born. Plasma viscosity and red blood cell aggregation were significatly higher in diabetes. No significant difference was found in hemorheological parameters between different antidiabetic regimens. Whole blood and plasma viscosity and red blood cell aggregation correlated with glucose levels but not with HbA1C levels. In conclusion, plasma and whole blood viscosity, as well as red blood cell aggregation appear to be associated with concurrent hyperglycemia, but not with the quality of glycemic control or the applied antidiabetic treatment. Platelet aggregation induced by ADP or epinephrine does not seem to be associated with diabetes even at subthreshold doses.

The Effect of Resveratrol on the Cardiovascular System from Molecular Mechanisms to Clinical Results.

Cardiovascular diseases are the leading causes of death worldwide. The cardioprotective effects of natural polyphenols such as resveratrol (3,5,4-trihydroxystilbene) have been extensively investigated throughout recent decades. Many studies of RES have focused on its favorable effects on pathological conditions related to cardiovascular diseases and their risk factors. The aim of this review was to summarize the wide beneficial effects of resveratrol on the cardiovascular system, including signal transduction pathways of cell longevity, energy metabolism of cardiomyocytes or cardiac remodeling, and its anti-inflammatory and antioxidant properties. In addition, this paper discusses the significant preclinical and human clinical trials of recent years with resveratrol on cardiovascular system. Finally, we present a short overview of antiviral and anti-inflammatory properties and possible future perspectives on RES against COVID-19 in cardiovascular diseases.

Management of patients treated for myocardial infarction in different regions of Hungary and patient survival for 10 years / Szívinfarktus miatt kezelt betegek ellátása Magyarország különbözo régióiban és a betegek 10 éves túlélése.

Összefoglaló. Elozmény: A szívinfarktus miatt kezelt betegek ellátásának regionális adataira és a betegek hosszú távú kórlefolyására vonatkozó hazai kutatás eddig nem történt. Célkituzés: A vizsgálat célja a Magyar Infarktus Regiszter pilotidoszakában rögzített betegeknél az ellátás és a 10 éves túlélés elemzése a magyarországi nagyrégiókban. Módszer: A Magyar Infarktus Regiszter (késobbi neve: Nemzeti Szívinfarktus Regiszter) 2010. január 1. és 2013. december 31. között a centrumok önkéntes részvételével 23 142 beteg adatait rögzítette, akik írásban hozzájárultak egészségügyi és klinikai adataik kezeléséhez. Az adatgyujtés a Kutatásetikai Bizottság engedélyével rendelkezett. A vizsgált populációban 12 104, ST-elevációval járó myocardialis infarctuson (STEMI) és 10 768, ST-elevációval nem járó myocardialis infarctuson (NSTEMI) átesett beteg szerepelt. A feldolgozott adatok 128 220 betegévre vonatkoznak, amelyeket nagyrégiók szerint (Nyugat-, Közép- és Kelet-Magyarország) hasonlítottunk össze. Eredmények: A STEMI-betegek 78,4%-ánál, az NSTEMI-betegek 51,6%-ánál történt katéteres érmegnyitás (PCI). NSTEMI esetén a Közép-Magyarország és Nyugat-Magyarország régiókban a beavatkozás gyakoribb volt, mint a Kelet-Magyarország régióban (p<0,01). Az utánkövetés során a PCI a Nyugat-Magyarország régióban, a revascularisatiós szívmutét (CABG) a Nyugat-Magyarország és a Kelet-Magyarország régióban szignifikánsan gyakoribb volt, mint a Közép-Magyarország régióban (p<0,01). A STEMI-betegek között a 10 év alatt a férfiak 49,2%-a, a nok 46,6%-a halt meg, az NSTEMI-csoportban 63%, illetve 57,6%. Az akut szakban elvégzett PCI mindkét betegcsoportban, nemben, az utánkövetés minden idopontjában és a vizsgált régiókban csökkentette a halálozást (p<0,01). A STEMI-betegek esetén a túlélés a régiók között nem különbözött (p = 0,72), míg az NSTEMI után a 10 éves túlélés a Nyugat-Magyarország régióban jobb volt (p<0,01). Következtetés: A magyarországi nagyrégiók között az infarktusos betegek ellátásában és prognózisában regionális különbségek vannak. Orv Hetil. 2021; 162(36): 1438-1450. HISTORY: Regional data on patients' care for myocardial infarction and the long-term follow up of patients have not yet been studied in Hungary. OBJECTIVE: The study aims to analyze the care and 10-year survival of patients recorded during the Hungarian Myocardial Infarction Registry's pilot period in large regions of Hungary. METHOD: Between Jan 1, 2010 and Dec 31, 2013, the Hungarian Myocardial Infarction Registry recorded data on 23 142 patients with voluntary participation. The Research Ethics Committee approved the program. The study included 12 104 patients with ST-elevation myocardial infarction (STEMI) and 10 768 patients with non-ST-elevation myocardial infarction (NSTEMI). The data processed refer to 128 220 patient years based on large regions (West, Central and East Hungary). RESULTS: Percutaneous coronary intervention occurred in 78.4% of STEMI patients and 51.6% of NSTEMI patients. In the NSTEMI group, percutaneous coronary interventions (PCIs) in the Central-Hungary and West-Hungary regions were significantly more common than in the East-Hungary region (p<0.01). During follow-up, PCI in the West-Hungary region, revascularization surgery in the West-Hungary and East-Hungary regions were significantly more common than in the Central-Hungary region (p<0.01). Among STEMI patients, 49.2% of men and 46.6% of women died within 10 years, while in the NSTEMI group 63% and 57.6%, respectively. PCI reduced mortality in both patient groups, sex, at all times of follow-up and in the regions studied (p<0.01). As for STEMI patients, survival was similar in all regions (p = 0.72), while after NSTEMI, 10-year survival in the West-Hungary region was better (p<0.01). CONCLUSION: There are regional differences in the care and prognosis of patients with myocardial infarction. Orv Hetil. 2021; 162(36): 1438-1450.

BGP-15 Protects against Heart Failure by Enhanced Mitochondrial Biogenesis and Decreased Fibrotic Remodelling in Spontaneously Hypertensive Rats.

Heart failure (HF) is a complex clinical syndrome with poor clinical outcomes despite the growing number of therapeutic approaches. It is characterized by interstitial fibrosis, cardiomyocyte hypertrophy, activation of various intracellular signalling pathways, and damage of the mitochondrial network. Mitochondria are responsible for supplying the energy demand of cardiomyocytes; therefore, the damage of the mitochondrial network causes cellular dysfunction and finally leads to cell death. BGP-15, a hydroxylamine derivative, is an insulin-sensitizer molecule and has a wide range of cytoprotective effects in animal as well as in human studies. Our recent work was aimed at examining the effects of BGP-15 in a chronic hypertension-induced heart failure model. 15-month-old male SHRs were used in our experiment. The SHR-Baseline group represented the starting point (n = 7). Animals received BGP-15 (SHR-B, n = 7) or placebo (SHR-C, n = 7) for 18 weeks. WKY rats were used as age-matched normotensive controls (n = 7). The heart function was monitored by echocardiography. Histological preparations were made from cardiac tissue. The levels of signalling proteins were determined by Western blot. At the end of the study, systolic and diastolic cardiac function was preserved in the BGP-treated animals. BGP-15 decreased the interstitial collagen deposition via decreasing the activity of TGFß/Smad signalling factors and prevented the cardiomyocyte hypertrophy in hypertensive animals. BGP-15 enhanced the prosurvival signalling pathways (Akt/Gsk3ß). The treatment increased the activity of MKP1 and decreased the activity of p38 and JNK signalling routes. The mitochondrial mass of cardiomyocytes was also increased in BGP-15-treated SHR animals due to the activation of mitochondrial biogenesis. The mitigation of remodelling processes and the preserved systolic cardiac function in hypertension-induced heart failure can be a result-at least partly-of the enhanced mitochondrial biogenesis caused by BGP-15.

Haemorheological and haemostatic alterations in coeliac disease and inflammatory bowel disease in comparison with non-coeliac, non-IBD subjects (HERMES): a case-control study protocol.

INTRODUCTION: Haemorheological and haemostatic changes predispose to the development of arterial and venous thrombotic events; however, limited information is available on the status of these changes in coeliac disease (CeD) and inflammatory bowel disease (IBD). In this study, we aim to describe the haemorheological and haemostatic profiles of CeD and IBD patients in a Hungarian cohort of patients to investigate whether any alterations contribute to elevated thrombotic risk. METHODS AND ANALYSIS: This is a case-control study involving newly diagnosed and followed CeD and IBD patients with age-matched and sex-matched non-CeD, non-IBD subjects with an allocation ratio of 1:1:1.After informed consent is obtained, a detailed medical history will be collected, including venous and arterial thrombotic risk factors and medications. Symptoms in CeD patients will be assessed with the Gastrointestinal Symptoms Rating Scale, and disease activity in IBD patients will be determined by disease-specific scores. Dietary adherence will be assessed among CeD patients with a thorough interview together with a measurement of self-reported adherence, dietary knowledge and urine analysis (detection of gluten immunogenic peptides). In addition to routine laboratory parameters, haemorheological (ie, erythrocyte deformability and aggregation, viscosity of whole blood and plasma) and haemostatic parameters (eg, protein C, protein S and antithrombin) with immunological indicators (ie, coeliac-specific serology and antiphospholipid antibodies) will be measured from venous blood for every participant.Primary and secondary outcomes will be haemorheological and haemostatic parameters, respectively. Univariate and multivariate statistics will be used to compare CeD and IBD patients to control subjects. Subgroup analysis will be performed by disease type in IBD, (Crohn's disease and ulcerose colitis), dietary adherence in CeD, and disease activity in IBD and CeD. ETHICS AND DISSEMINATION: The study was approved by the Regional and Local Research Ethics Committee, University of Pécs (Ref. No. 6917). Findings will be disseminated at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN49677481.

Marked differences in frequencies of statin therapy relevant SLCO1B1 variants and haplotypes between Roma and Hungarian populations.

BACKGROUND: SLCO1B1 polymorphisms are relevant in statin pharmacokinetics. Aim of this study was to investigate the genetic variability and haplotype profile of SLCO1B1 polymorphisms in Roma and Hungarian populations. Genotypes of 470 Roma and 442 Hungarian subjects for c.388A > G, c.521T > C and c.1498-1331T > C polymorphisms were determined by PCR-RFLP assay. Using these SNPs eight different haplotypes could be differentiated. RESULTS: Differences were found between Roma and Hungarians in SLCO1B1 388AA (24.5 vs. 45.5 %), GG (33.4 vs. 17.9 %) genotypes, AG + GG (75.5 vs. 54.5 %) carriers, in G allele frequency (0.545 vs. 0.362), respectively (p < 0.001). The most common SLCO1B1 haplotype was the ht8 (GTT) both in Roma (43.6 %) and in Hungarian (59.1 %) samples. The ht6 (GCT) was not present in Roma population samples Haplotype analyses showed striking differences between the Roma and Hungarian samples in ht4 (ATT, 37.2 % vs 20.8 %), ht5 (GCC, 1.15 % vs. 3.62 %) and ht8 (GTT, 43.6 % vs. 59.1 %) haplotypes (p < 0.01), respectively. Linkage disequilibrium analysis showed that the studied variants are in different linkage disequilibrium patterns depending on the ethnic origin. CONCLUSIONS: Similarly to Caucasians the 388G is the minor allele in Hungarians, however, in Roma the 388A was found to be the minor allele contrary to Indians (India). The minor allele frequency of 521T > C and 1498-1331T > C SNPs are almost three times higher in Romas than in Indians (Singapore and Gujarati, respectively). Observed allele frequency for 1498-1331T > C polymorphism reflects the measured average European rates in Hungarians. The results can be applied in population specific treatment algorithms when developing effective programs for statin therapy.

Clopidogrel resistance after renal transplantation.

BACKGROUND: Leading causes of mortality and morbidity after kidney transplantation are cardiovascular diseases. One of the fundamentals of their prevention is the inhibition of platelet aggregation. Resistance to anti-platelet agents is a well-established phenomenon; however, its causes are yet to be clarified. PATIENTS AND METHODS: Forty post-transplant patients, who received 75 mg clopidogrel q.d. as a prophylactic measure, were examined using optical aggregometry. Subsequently, logistic regression analysis was performed with 24 variables in order to expose possible causes of resistance. RESULTS: Sixty percent of patients (24) were resistant to clopidogrel therapy; effective thrombocyte inhibition could only be shown in 40% of them (16). Significant correspondence between resistance and variables could not be found. CONCLUSION: Clopidogrel resistance is expected to occur on a large scale in patients who underwent kidney transplant surgery. Thus, a key component of preventive therapy, which stresses the importance of discovering the cause of resistance so as to decrease mortality rates, is missing.

PARP-inhibitor treatment prevents hypertension induced cardiac remodeling by favorable modulation of heat shock proteins, Akt-1/GSK-3ß and several PKC isoforms.

Spontaneously hypertensive rat (SHR) is a suitable model for studies of the complications of hypertension. It is known that activation of poly(ADP-ribose) polymerase enzyme (PARP) plays an important role in the development of postinfarction as well as long-term hypertension induced heart failure. In this study, we examined whether PARP-inhibitor (L-2286) treatment could prevent the development of hypertensive cardiopathy in SHRs. 6-week-old SHR animals were treated with L-2286 (SHR-L group) or placebo (SHR-C group) for 24 weeks. Wistar-Kyoto rats were used as aged-matched, normotensive controls (WKY group). Echocardiography was performed, brain-derived natriuretic peptide (BNP) activity and blood pressure were determined at the end of the study. We detected the extent of fibrotic areas. The amount of heat-shock proteins (Hsps) and the phosphorylation state of Akt-1(Ser473), glycogen synthase kinase (GSK)-3ß(Ser9), forkhead transcription factor (FKHR)(Ser256), mitogen activated protein kinases (MAPKs), and protein kinase C (PKC) isoenzymes were monitored. The elevated blood pressure in SHRs was not influenced by PARP-inhibitor treatment. Systolic left ventricular function and BNP activity did not differ among the three groups. L-2286 treatment decreased the marked left ventricular (LV) hypertrophy which was developed in SHRs. Interstitial collagen deposition was also decreased by L-2286 treatment. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2(Thr183-Tyr185), Akt-1(Ser473), GSK-3ß(Ser9), FKHR(Ser256), and PKC ε(Ser729) and the level of Hsp90 were increased, while the activity of PKC α/ßII(Thr638/641), ζ/λ(410/403) were mitigated by L-2286 administration. We could detect signs of LV hypertrophy without congestive heart failure in SHR groups. This alteration was prevented by PARP inhibition. Our results suggest that PARP-inhibitor treatment has protective effect already in the early stage of hypertensive myocardial remodeling.

A quinazoline-derivative compound with PARP inhibitory effect suppresses hypertension-induced vascular alterations in spontaneously hypertensive rats.

AIMS: Oxidative stress and neurohumoral factors play important role in the development of hypertension-induced vascular remodeling, likely by disregulating kinase cascades and transcription factors. Oxidative stress activates poly(ADP-ribose)-polymerase (PARP-1), which promotes inflammation and cell death. We assumed that inhibition of PARP-1 reduces the hypertension-induced adverse vascular changes. This hypothesis was tested in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: Ten-week-old male SHRs and wild-type rats received or not 5mg/kg/day L-2286 (a water-soluble PARP-inhibitor) for 32 weeks, then morphological and functional parameters were determined in their aortas. L-2286 did not affect the blood pressure in any of the animal groups measured with tail-cuff method. Arterial stiffness index increased in untreated SHRs compared to untreated Wistar rats, which was attenuated by L-2286 treatment. Electron and light microscopy of aortas showed prominent collagen deposition, elevation of oxidative stress markers and increased PARP activity in SHR, which were attenuated by PARP-inhibition. L-2286 treatment decreased also the hypertension-activated mitochondrial cell death pathway, characterized by the nuclear translocation of AIF. Hypertension activated all three branches of MAP-kinases. L-2286 attenuated these changes by inducing the expression of MAPK phosphatase-1 and by activating the cytoprotective PI-3-kinase/Akt pathway. Hypertension activated nuclear factor-kappaB, which was prevented by PARP-inhibition via activating its nuclear export. CONCLUSION: PARP-inhibition has significant vasoprotective effects against hypertension-induced vascular remodeling. Therefore, PARP-1 can be a novel therapeutic drug target for preventing hypertension-induced vascular remodeling in a group of patients, in whom lowering the blood pressure to optimal range is harmful or causes intolerable side effects.

Comparison of minor bleeding complications using dabigatran or enoxaparin after cemented total hip arthroplasty.

BACKGROUND: Orally administered chemical thromboprophylactic agents for total hip replacement (THR) have become popular in recent years. Certain clinical trials suggest that the efficacy and the risk of major bleeding after administration of direct thrombin inhibitor dabigatran etexilate are equivalent to the clinical trial comparator, subcutaneous low-molecular-weight heparin enoxaparin. Our aim was to compare and evaluate the incidence of minor haemorrhagic and soft-tissue adverse effects of enoxaparin and dabigatran. MATERIALS AND METHODS: 122 patients who were treated by elective cemented primary THR were enrolled in our quasi-randomised study. Two groups were formed according to which perioperative thromboprophylactic agent was used: 61 patients in enoxaparin group versus 61 patients in dabigatran group. Thigh volume changes, calculated perioperative blood loss, area of haematoma, wound bleeding, duration of wound discharge and intensity of serous wound discharge on postoperative day 3 and day 7 were recorded. RESULTS: The duration and intensity of serous wound discharge differed significantly between the two groups. Duration of wound discharge after drain removal was 2.2 (±2.7) days in the dabigatran group and 1.2 (±1.9) days in the enoxaparin group (p < 0.05). Significant increase in serous discharge was found in the dabigatran group (p < 0.05) on third and seventh postoperative days compared to the enoxaparin group. CONCLUSION: Both thromboprophylactic agents were found to have appropriate antithrombotic effects after THR. However, dabigatran was associated with an increased incidence of prolonged serous wound discharge, which might cause longer hospitalization and might instigate the use of prolonged antibiotic prophylaxis.

[Experimental studies of microcirculatory changes in the bone]. / A csont mikrokeringési változásainak kísérletes vizsgálati lehetoségei.

INTRODUCTION/AIMS: Our aim was to characterize the periosteal microvascular reaction induced by the destruction of endosteal vasculature by reaming, and to monitor the time sequence of the events. We have also compared the microcirculatory effects of different implant materials that are most frequently employed in human endoprosthetics. MATERIALS AND METHODS: The right tibia of male Wistar rats was reamed by microsurgical means and implanted with titanium, steel-alloy or polyethylene nails. Intravital videomicroscopic examinations of the anteromedial and anterolateral surfaces of the tibial periosteum were performed to evaluate the changes in the overall vascular and capillary densities. Microscopic mechanical tests were used to assess the stability of the implants. In control groups, reaming without nailing was performed and the microvascular changes were examined 6 and 12 weeks after surgery. RESULTS: Reaming alone caused a significant increase in the vascular density of the anteromedial periosteum and a bilateral increase in capillary density. Vascular density at the anteromedial side was increased after all of the implant materials applied, while only polyethylene induced remarkable increases in the capillary and vascular densities at the anterolateral side. Furthermore, polyethylene did not bring about osseointegration. CONCLUSIONS: Enhanced periosteal angiogenesis could be demonstrated after 12 weeks following tibial reaming. The compensatory microvascular reactions evoked by destruction of endosteal microcirculation of long bones are not influenced by osseo-integrative implant materials, but materials of poor osseointegration properties induce considerable compensatory increases in the microvascular density of the periosteum.

[Vinpocetin in neurological diseases]. / Vinpocetin alkalmazása neurológiai kórképekben.

INTRODUCTION: Stroke is the third leading cause of death worldwide (following cardiovascular and cancer mortality) and associated with serious disability for the vast majority of patients. There is no salvage therapy for irreversibly damaged brain areas, improving the circulation of the surrounding hypoperfused areas may be associated with beneficial clinical effects. Cerebral hypoperfusion may play a role in the pathogenesis of other kind of neurological diseases, improvement of global circulation may have a preventive effect on these conditions. AIMS: The aim of our study was to review the experimental and clinical articles focusing on the role of vinpocetin in different neurological conditions. RESULTS: Vinpocetin appears to have several different mechanisms of action that allow for its antiinflammatory, antioxidant, vasodilating, antiepileptic and neuroprotective activities in experimental conditions. On the other hand, several meta-analysis of the existing studies in acute stroke examining short and long term fatality rates with vinpocetin was unable to assess efficacy. In chronic cerebrovascular patients, vinpocetin improves impaired hemorheologic variables, has significant vasodilating properties, improves endothelial dysfunction, neuroimaging studies showed selective increase in cerebral blood flow and cerebral metabolic rate, all of which are potentially beneficial in cerebrovascular disease and may improve cognitive functions. SUMMARY: Based on the above mentioned results, vinpocetin plays an important role both in basic research and in clinical management of different neurological diseases.

Regulation of kinase cascade activation and heat shock protein expression by poly(ADP-ribose) polymerase inhibition in doxorubicin-induced heart failure.

Cardiomyopathy is one of the most severe side effects of the chemotherapeutic agent doxorubicin (DOX). The formation of reactive oxygen species plays a critical role in the development of cardiomyopathies, and the pathophysiological cascade activates nuclear enzyme poly(ADP-ribose) polymerase (PARP), and kinase pathways. We characterized the effects of the PARP-inhibitor and kinase-modulator compound L-2286 in DOX-induced cardiac injury models. We studied the effect of the established superoxide dismutase-mimic Tempol and compared the effects of this agent with those of the PARP inhibitor. In the rat H9C2 cardiomyocytes, in which DOX-induced poly(ADP-ribosyl)ation, L-2286 protected them from the DOX-induced injury in a concentration-dependent manner. In the in vivo studies, mice were pretreated (for 1 week) with L-2286 or Tempol before the DOX treatment. Both the agents improved the activation of cytoprotective kinases, Akt, phospho-specific protein kinase C ϵ, ζ/λ and suppressed the activity of cell death promoting kinases glycogen synthase kinase-3ß, JNK, and p38 mitogen-activated protein kinase, but the effect of PARP inhibitor was more pronounced and improved the survival as well. L-2286 activated the phosphorylation of proapoptotic transcription factor FKHR1 and promoted the expression of Hsp72 and Hsp90. These data suggest that the mode of the cytoprotective action of the PARP inhibitor may include the modulation of kinase pathways and heat shock protein expression.

Puma deletion delays cardiac dysfunction in murine heart failure models through attenuation of apoptosis.

BACKGROUND: Puma (p53-upregulated modulator of apoptosis) is a proapoptotic Bcl-2 family protein that serves as a general sensor in response to pathological apoptotic stimuli. In previous work, we demonstrated that puma ablation protects the heart from reperfusion injury in a Langendorff setting. Consistent with this, downregulation of Puma in isolated cardiac myocytes prevented apoptosis induced by different proapoptotic agents. Here, we extended our research to investigate the role of Puma, a downstream mediator of p53, in the development of heart failure using Puma(-/-) mice. METHODS AND RESULTS: Mice underwent transverse aortic constriction, and the characteristics of cardiac remodeling were analyzed by echocardiography, histology, and gene expression at multiple time points after surgery. Four weeks after the operation, puma deletion attenuated pressure overload-induced apoptosis and fibrosis; however, it did not affect hypertrophy and angiogenesis and maintained functional performance (fractional shortening, 39% versus 25.2% in Puma(-/-) versus WT mice, respectively). Even at 12 weeks after transverse aortic constriction, Puma(-/-) mice displayed only slightly reduced contractility. In addition, transverse aortic constriction induced puma expression in a partially p53-dependent manner. To corroborate these findings, we studied another heart failure model in which heart-specific mdm4 deletion leads to p53 activation and dilated cardiomyopathy. In these mice, Puma was upregulated and its deletion rescued the cardiomyopathy phenotype. CONCLUSIONS: Our data indicate that Puma might be a critical component of the apoptotic signaling pathways that contribute to ventricular remodeling and heart failure. Therefore, Puma inactivation may serve as a preferential target to prevent heart failure induced by cellular stress.

Calcaneo-stop procedure for paediatric flexible flatfoot.

BACKGROUND: Flexible flatfoot is a frequent deformity found in children. The aim of this study is to evaluate the pedographic outcome of the percutaneous arthroereisis with the use of a screw through the sinus tarsi into the talus. MATERIALS AND METHODS: 43 calcaneo-stop procedures of 25 patients (18 bilateral, seven unilateral) were evaluated. Mean age at surgery was 10 years (7-14, SD 2.2) (SD: standard deviation), mean follow-up time was 9.7 months (3-19, SD 5.5). Patient satisfaction rate was recorded, the Meary's talus-first metatarsal angle was measured with lateral radiograms, and a dynamic pedographic assessment was also performed. RESULTS: Patient satisfaction rate was excellent for 33 feet of 19 children, good for eight feet of five children, and poor for either feet of one child. We did not observe any complications during or following the surgery.The mean rest heel valgus decreased from 13.4° (10°-17°, SD 1.5) to 2.8° (0°-6°, SD 1.7) post op. The Meary's angle improved from 160.2° (148°-177°, SD 6.8) to 175.9° (167°-179°, SD 3.5). By pedographic analysis, the area and the pressure-time integral (load amount, PTI) values increased on the lateral regions of the sole (except for the lesser toes) and decreased on the medial areas (except for the hallux). The relative contact time in the lateral midfoot increased from 63.8% (39.6-78.4%, SD 10.6) to 75.1% (50-86.1%, SD 9.4), and that in the lateral forefoot region from 81.2% (60.4-89.2%, SD 6.6) to 86.8% (78.1-97.1%, SD 4.8). CONCLUSION: The calcaneo-stop procedure is a simple and reliable method for the correction of severe flexible paediatric flatfoot. Our prospective, short-term results following the anterograde screw implantation into the talus correlate well with the results of similar or different arthroereisis methods. Further investigations are required to evaluate the long-term outcome of the screw calcaneo-stop method, including the conditions following implant removal.

Pathological femoral neck fracture caused by an echinococcus cyst of the vastus lateralis--case report.

BACKGROUND: Musculoskeletal hydatid cysts are rare, but being locally invasive, can potentially cause significant deformity or pathological fracture. CASE PRESENTATION: A 39 y.o. male presented to our orthopaedic outpatient clinic complaining of severe right hip pain, and inability to ambulate. Symptoms were not preceded by trauma. Subsequent imaging confirmed a large, 17 × 3 × 5 cm echinococcus cyst in the vastus lateralis, causing erosion of the proximal metaphysis of the femur. As a consequence the patient suffered a non-traumatic pathological intertrochanteric femur fracture. The patient was treated with an en-bloc excision of the lesion - the affected soft tissue envelope containing the large cyst - and as a second surgical step a cemented total hip replacement (THR) was implanted under the same anaesthetic. The manuscript reviews the literature regarding musculoskeletal hydatid disease.