The comparison of the relaxant effects of two methoxylated flavones in rat aortic rings

The vascular effect of salvigenin (6-hydroxyapigenin 6,7,4' -trimethyl ether), a natural flavone, was investigated in comparison with another flavone, 6-hydroxyluteolin 6,7,3',4' -tetramethyl ether in rat aortic rings. Cumulative addition of their increasing concentrations (10(-9)-10(-4)M) produced graded relaxations on rings precontracted with noradrenaline (10(-6) M) and KCl (40 mM). The maximal relaxations induced by flavones were similar, however, based on their pEC50 values salvigenin displayed a higher potency than 6-hydroxyluteolin 6,7,3',4'-tetramethyl ether. Endothelium removal markedly reduced the relaxations to salvigenin while the responses to 6-hydroxyluteolin 6,7,3',4'-tetramethyl ether were partially affected. In addition, a significant decrease was observed in maximal responsiveness and sensitivity to flavones in the presence of L-NOARG, a NO synthase inhibitor. The cyclooxygenase inhibitor indomethacin significantly inhibited the relaxations to salvigenin, but not altered the responses to 6-hydroxyluteolin 6,7,3',4'-tetramethyl ether. Our results provide evidence that salvigenin is an effective flavone in causing vasorelaxation which appears to be mediated by endothelium derived NO and prostacyclin. Whereas, the other flavone, 6-hydroxyluteolin 6,7,3',4'-tetramethyl ether induced relaxant responses are partially endothelium, presumably NO mediated.     

Sarcoidosis (after cosmetic intervention)

The authors' report a case of a 26-year-old female. In 1996, and 1997 she underwent cosmetic lip augmentations (polymethyl methacrylate and silicone). After a six-year symptom free period sudden swelling of the lips developed and red-brown papules and subcutaneous nodules appeared in the scars of various body parts ( permanent make-up, tattoos, umbilical piercing). The clinical features, radiological signs and histology proved the diagnosis of systemic sarcoidosis. Systemic corticosteroid treatment was introduced. After 4 months of treatment the pulmonary and clinical symptoms showed regression. To be able to suspend the systemic treatment the silicone implant was removed.     

Role of poly(ADP-ribose) polymerase activation in diabetic neuropathy

Oxidative and nitrosative stress play a key role in the pathogenesis of diabetic neuropathy, but the mechanisms remain unidentified. Here we provide evidence that poly(ADP-ribose) polymerase (PARP) activation, a downstream effector of oxidant-induced DNA damage, is an obligatory step in functional and metabolic changes in the diabetic nerve. PARP-deficient (PARP(-/-)) mice were protected from both diabetic and galactose-induced motor and sensory nerve conduction slowing and nerve energy failure that were clearly manifest in the wild-type (PARP(+/+)) diabetic or galactose-fed mice. Two structurally unrelated PARP inhibitors, 3-aminobenzamide and 1,5-isoquinolinediol, reversed established nerve blood flow and conduction deficits and energy failure in streptozotocin-induced diabetic rats. Sciatic nerve immunohistochemistry revealed enhanced poly(ADP-ribosyl)ation in all experimental groups manifesting neuropathic changes. Poly(ADP-ribose) accumulation was localized in both endothelial and Schwann cells. Thus, the current work identifies PARP activation as an important mechanism in diabetic neuropathy and provides the first evidence for the potential therapeutic value of PARP inhibitors in this devastating complication of diabetes.     

Cardiovascular effects of selective serotonin reuptake inhibitor antidepressants

This paper reviews the cardiovascular effects of fluoxetine and other selective serotonin reuptake inhibitors comparing with those of tricyclic antidepressants. The authors survey the electrophysiological mechanisms and the recent data referring on drug's actions on different ionic currents/channels. The paper primarily focuses on preclinical data, showing various effects of fluoxetine and citalopram on cardiac and smooth muscle preparations and on cardiac ionic currents. At concentrations of 0.5-50 microM, fluoxetine and citalopram exhibit depressant effects on Ca(2+)- and Na(+)-dependent electrophysiological parameters of different cardiac preparations and on cardiac Ca2+ current. At concentrations of 0.1-10 microM, fluoxetine and citalopram elicit relaxation of both vascular and intestinal smooth muscles. These results provide evidence for inhibition of cardiac Na+, Ca2+ and more recently K+ channels by fluoxetine and citalopram at concentrations close to therapeutic level. The inhibition of cardiac Ca2+, Na+ and K+ and vascular Ca2+ channels by fluoxetine and citalopram may explain most cardiovascular side effects observed occasionally with the drugs during the chronic treatment. The inhibitory effects on cardiac Ca2+, Na+ and K+ channels of fluoxetine and citalopram may result in antiarrhythmic/proarrhythmic actions. Thus fluoxetine, citalopram and other selective serotonin reuptake inhibitors similarly to tricyclic antidepressants, may exhibit cardiovascular depressant effects. The paper summarizes drug interactions that may lead risk of arrhythmia and vascular side effects. Taking all these into consideration, in depressed patients having also cardiac or liver disorders, these antidepressants should be also more rigorously applied.     

Incidence of risk factors in parents with acute myocardial infarction at young age and in their children

INTRODUCTION: The preliminaries of the cardiovascular diseases can be traced back to the childhood. The authors tried to find relationship between parents with early onset myocardial infarction (AMI) and incidence of risk factors for ischemic heart disease in their children as compared to respective data for families with no incidence of myocardial infarction. METHODS: The study population consisted of 38 persons with early onset AMI myocardial infarction (age < 55 y) and their 66 children, and 38 adult control subjects and their 33 children. In each person arterial blood pressure, body weight, body height, waist circumference were recorded and body mass index (BMI: kg/m2) was calculated. Eating habits and life style practices were recorded in a questionnaire in the case of each participant. Laboratory variables were determined in the blood sera as follows, glucose, triglycerides (Tg), total cholesterol (T-C), HDL-cholesterol, LDL-cholesterol, apolipoprotein-A, apolipoprotein-B, and lipoprotein (a). The atherogenic index (LDL-C/HDL-C) (LDL-cholesterol/HDL-cholesterol) was also calculated. STATISTICAL EVALUATION: Data were evaluated statistically using the SPSS for Windows 9. RESULTS: According to the mean BMI values all groups of parents belonged to the overweight category. The mean cholesterol levels of all adults were in the borderline high category. In males with early onset myocardial infarction sera concentrations of HDL-cholesterol and apolipoprotein-A were significantly lower, whereas triglyceride and atherogenic index were significantly higher than respective data for control parents. In all groups of parents, fasting mean serum glucose concentrations were higher than the reference value, serum total-cholesterol concentrations were in the borderline high category. In the daughter of the parents with early onset myocardial infarction had a higher atherogenic index than that of controls. Eating habits did not essentially differ between case vs. control families. Consumption of milk, dairy products, fruit and vegetables was insufficient in each group. Incidences of smoking for parents and children were 55% and 35% in the myocardial infarction group and 44% and 37% in the control group, respectively. Physical activity was completely insufficient in each group studied. CONCLUSION: Since no considerable differences were seen between the case vs control families in the parameters tested, therefore it is presumed that the offspring born to parents with or without early onset myocardial infarction are at equal risk to develop cardiovascular diseases unless lifestyle practices are profoundly changed.     

Herbal remedies of Solidago--correlation of phytochemical characteristics and antioxidative properties

In this study the correlation of phytochemical characteristics and antioxidative properties of classical herbal tea extracts-Infusum solidaginis, Decoctum solidaginis, Maceratum solidaginis-and tinctures prepared by various concentration of ethanol (40, 70, 96% v/v) have been examined for the release of flavonoids and their antioxidant activity. Quantitative and composition determination of flavonoids were carried out by spectrophotometry, high-performance liquid chromatography and capillary electrophoresis, respectively. Hydrogen-donating ability and reducing power properties were used to define in vitro radical scavenging activity of Solidago extracts, but integral antioxidative capacity was determined by luminometry (Photochem), calculating the ascorbic acid equivalents. Chlorogenic acid, quercetin-3-O-beta-D-rutinoside, quercetin-3-O-beta-D-galactoside, quercetin-3-O-beta-D-glucoside, quercetin-3-O-beta-D-rhamnoside, kaempferol-3-O-alpha-L-rhamnoside and quercetin were confirmed by retention times and UV spectra. Based on the dissolution rate, variance of flavonoid release and ascorbic acid equivalents it was concluded, that Tinctura solidaginis (70% v/v ethanol) and Infusum solidaginis are the most appropriate preparations.     

M-CSF targeting into LCL nucleus behaves as a malignancy promotor

Objective: To investigate the functions of nM-CSF in malignant cells. Methods: recombinant M-CSF was targeted into cell nucleus by employing a eukaryotic expression plasmid vector pCMV/myc/nuc. The constructed plasmid was transfected into cells of EBV transformed lymphoblastoid cell line (LCL). RT-PCR, Western blot and immunofluorescent staining showed that recombinant M-CSF was localized into LCL cell nucleus. The transgenic cells showed elevated proliferation potential, enhanced resistance to apoptosis and increased ability of in vitro migration. Conclusion: Nucleus presenting M-CSF might act as a promoting factor in the processes of cellmalignancy.