Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part III. Apigenin, baicalelin, kaempherol, luteolin and quercetin

Flavonoids are found universally in plants and act as free radical scavenging and chelating agents with antiinflammatory, antiischemic, vasodilating and chemoprotective properties. In this study, the antilipoperoxidative and cytoprotective effects of apigenin, baicalein, kaempferol, luteolin and quercetin against doxorubicin-induced oxidative stress were investigated in isolated rat heart cardiac myocytes, mitochondria and microsomes. After preincubation of cardiomyocytes with the test compounds for 1 h the cardiomyocytes were treated with the toxic agent, doxorubicin (100 micro M for 8 h). Cardiomyocyte protection was assessed by extracellular LDH and cellular ADP and ATP production. Cytoprotection was concentration dependent for baicalein > luteolin congruent with apigenin > quercetin > kaempferol. All test compounds had signi fi cantly better protective effects than dexrazoxan, an agent currently used for adjuvant therapy during anthracycline antibiotic therapy. In microsomes/mitochondria the IC(50) values of lipid peroxidation inhibition for quercetin, baicalein, kaempferol, luteolin, and apigenin were 3.1 +/- 0.2/8.2 +/- 0.6, 3.3 +/- 0.3/9.6 +/- 0.5, 3.9 +/- 0.3/10.1 +/- 0.8, 22.9 +/- 1.7/18.2 +/- 0.7, and 338.8 +/- 23.1/73.1 +/- 6.4 mM, respectively. The antilipoperoxidative activity of apigenin differed from its cytoprotective effects, but correlated with the free radical scavenging of 2,2-diphenyl-1-picrylhydrazyl radical and half peak oxidation potential (E(p/2)). Apigenin was the least effective of the flavonoids studied in all models except the cardiomyocyte model where its cardiomyocyte cytoprotective effect was comparable to other compounds.     

Changes in antioxidant,inflammatory and metabolic markers during 1 week cultivation of human skin explants

Human skin explant (HSE) seems to be a useful model for dermatological/cosmetic testing. HSE prepared from donor superfluous skin from plastic surgery operations is cheap and easily obtainable compared to reconstructed models. The HSE use, however, may be limited by the degeneration processes during cultivation. The aim was to monitor changes in metabolic activity and selected apoptotic, inflammatory and antioxidant parameters during 7 day cultivation. The significant changes were found in the superoxide dismutase‐2 level from day 5, glutathione S‐reductase level from day 6, metabolic activity and fibulin‐5 level from day 4, cyclooxygenase‐2, interleukin‐6 and interleukin‐10 from day 1 to 2. Other selected markers (lipid peroxidation products and glutathione level, glutathione S‐transferase, catalase, superoxide dismutase and glutathione S‐reductase activity, glutathione peroxidase and glutathione S‐reductase levels) were not modified significantly due to high inter‐individual variability of skin donors. The HSE microstructure as well as cytokeratin‐10 and proliferation marker Ki67 expression was also only minimally affected during cultivation. Collectively, the results demonstrate that HSE represents a good model for short‐term studies focused on the physical and chemical agent toxicity, protective potential of compounds or metabolic biotransformation. However, reduced metabolic activity, increased inflammation and the high inter‐individual variability and sensitivity of donors have to be taken into consideration.     

Right ventricular perforation with an ICD defibrillation lead managed by surgical revision and epicardial leads--case reports.

The authors present two cases of patients with perforation of the right ventricular wall by the implantable cardioverter defibrillator (ICD) lead. The complication was resolved by cardiosurgical revision and epicardial leads stitched onto the diaphragmatic wall of the heart. The perforation was identified by electrical parameter changes of the leads, echocardiography, and computed tomography. Both patients had satisfactory values of electrical parameters and ICD function with epicardial leads. The importance of regular follow-up and a check of the lead parameters are emphasized.     

PKD2 mutations in a Czech population with autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous and caused by mutations in at least three different loci. Based on linkage analysis, mutations in the PKD2 gene are responsible for approximately 15% of the cases. PKD2-linked ADPKD is supposed to be a milder form of the disease, its mean age of end-stage renal failure (ESRF) approximately 20 years later than PKD1. METHODS: We screened all coding sequences of the PKD2 gene in 115 Czech patients. From dialysis centres in the Czech Republic and from the Department of Nephrology of the General Hospital in Prague, we selected 52 patients (29 males, 23 females), who reached ESRF after the age of 63, and 10 patients (three males, seven females) who were not on renal replacement therapy at that age. The age of 63 was used as the cut-off because it is between the recently published ages of onset of ESRF for PKD1 and PKD2. From PKD families we also selected 53 patients (26 males, 27 females) who could be linked to either the PKD1 or PKD2 genes by linkage analysis. An affected member from each family was analysed by heteroduplex analysis (HA) for all 15 coding regions. Samples exhibiting shifted bands on gels were sequenced. RESULTS: We detected 22 mutations (six new mutations)-14 mutations in 62 patients (23%) with mild clinical manifestations, eight in 53 families (15%) with possible linkage to both PKD genes. As the detection rate of HA is approximately 70-80%, we estimate the prevalence of PKD2 cases in the Czech ADPKD population to be 18-20%. We identified nonsense mutations in eight patients (36.5%), frameshifting mutations in 12 patients (54.5%) and missense mutations in two patients (9%). CONCLUSION: In this study in the Czech population we identified 22 mutations (six of which were new mutations). The prevalence of PKD2 cases was 18-20% and the mean age of ESRF was 68.3 years. An at-least weak hot spot in exon 1 of the PKD2 gene was found.     

A mutational hot spot induced by N-hydroxy-aminofluorene in dihydrofolate reductase mutants of Chinese hamster ovary cells

Eighteen mutants deficient in dihydrofolate reductase (DHFR)activity were induced with 0.5 µM N-hydroxy-aminofluorenein four separate experiments. This carcinogen dose killed     

Cost of digging is determined by intrinsic factors rather than by substrate quality in two subterranean rodent species

Searching for food by extensive digging is one of the most important aspects of life of subterranean rodents. We studied the effect of extrinsic (substrate quality) and intrinsic factors (sex and body mass) upon the cost of burrowing, expressed as digging metabolic rate (DMR) in two African mole-rat species (Bathyergidae, Rodentia) with distinct social structures. The sexually dimorphic giant mole-rat (Fukomys mechowii) is a highly social species, whereas the almost monomorphic silvery mole-rat (Heliophobius argenteocinereus) is a solitary bathyergid. Burrowing in F. mechowii was more costly (DMR was greater) than in H. argenteocinereus, but there was no difference in burrowing speed between both species. DMR within a particular species was dependent upon body mass, but independent of sex. Different substrate quality had no effect upon DMR in either species, yet it affected burrowing speed. We conclude that less effective digging in F. mechowii can be compensated by the joint workforce of other family members. Alternatively, H. argenteocinereus, being a more effective digger, can afford a solitary way of life.     

Clonal Distribution of Invasive Pneumococci, Czech Republic, 1996�C2003

We conducted surveillance on invasive pneumococci isolated from adults in the Czech Republic during 1996–2003. The 7 most prevalent serotypes were characterized. Coverage with the 7-valent pneumococcal conjugate vaccine was low. Our observations confirm that detection methods may have modified the expected effect of this vaccine.     

Soluble leptin receptor and leptin levels in pregnant women before and after delivery

Soluble leptin receptor is an extracellular domain of the leptin receptor that serves as the main leptin-binding protein and may play a role in the regulation of leptin tissue effects. The aim of our study was to assess serum concentrations of leptin, soluble leptin receptor, and other hormones involved in the regulation of leptin secretion in pregnant women before and after delivery. Serum leptin, cortisol, and tumor necrosis factor alpha (TNF-alpha) concentrations in 19 pregnant women before delivery were significantly higher than in healthy nonpregnant women (33.3+/-21.0 vs. 7.9+/-3.5 ng/mL, 1068.9+/-442.2 vs. 546.6+/-165.3 nmol/L, 4.4+/-1.1 vs. 3.4+/-1.2 ng/mL, respectively). In contrast, no differences between these groups were found in soluble leptin receptor levels. Delivery significantly decreased serum leptin and cortisol levels and increased soluble leptin receptor levels (12.3+/-9.1 ng/mL, 749.6+/-205.3 nmol/L, 23.3+/-7.9 U/mL, respectively). Soluble leptin receptor levels after delivery became higher than in the control group. We conclude that serum leptin and serum soluble leptin-receptor levels are significantly affected by pregnancy and delivery. The regulation of leptin levels in this group of patients appears to be distinct and independent of soluble leptin-receptor levels.