The redox status of human breast cancer cell lines (MCF-7 and MDA-MB231) treated with novel dinuclear berenil-platinum(II) complexes.

This study compared the effects of cisplatinum and novel berenil-platinum(ll) complexes on the redox status of breast cancer cells that were estrogen receptor-positive (MCF-7) or estrogen receptor-negative (MDA-MB231). Both cell lines were treated with cisplatinum or the following berenil-platinum(ll) complexes: Pt2(isopropylamine)4(berenil)2, Pt2(piperidine)4(berenil)2, Pt2(2-picoline)4(berenil)2, Pt2(3-picoline)4(berenil)2, and Pt2(4-picoline)4(berenil)2. Changes in levels of reactive oxygen species, levels and activities of antioxidants, and lipid peroxidation products levels were measured. All investigated compounds enhanced ROS generation, reduced the activity of antioxidant enzymes (e.g., glutathione peroxidase and glutathione reductase), and decreased levels of small-molecule antioxidants (GSH, vitamins E and A). Such conditions are conducive to generating oxidative stress and phospholipids peroxidation. Cellular phospholipids in MCF-7 cells were most sensitive to the Pt2(isopropylamine)4(berenil)2 complex, whereas MDA-MB231 cells were not particularly sensitive to any berenil-platinum(ll) complex. These findings will facilitate future anticancer drug design strategy for breast cancer pharmacotherapy.

Lipid peroxidation products as potential bioindicators of Lyme arthritis.

Lipid peroxidation products, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) and [Formula: see text], were determined in the plasma and urine of patients with Lyme arthritis and healthy people. The group consisted of 19 patients with Lyme arthritis (mean age 47 years) and the control group consisted of 16 healthy individuals (mean age 38 years). Diagnosis of Lyme disease was confirmed by epidemiological anamnesis, clinical manifestation of arthritis and serological examinations. Lipid peroxidation was estimated by the measurement of aldehydes (MDA and 4-HNE, determined by high-performance liquid chromatography [HPLC]) and prostaglandin derivatives (8 - isoPGF(2a), determined by liquid chromatography/mass spectrometry [LC/MS]). MDA and 4-HNE levels were increased about 2-4-fold in the plasma, while in the urine, the increases were about 2-fold. More significant increases were noted for the 8 - isoPGF(2a) total plasma level, which was enhanced over 4-fold, and for the urine 8 - isoPGF(2a) level, which was increased over 8-fold. The 8 - isoPGF(2a) total plasma level consists of free and esterified form. During infection, the ratio of free to esterified form is significantly smaller compared to healthy people. The ratio of free to esterified form of 8 - isoPGF(2a) may be a useful indicator of Lyme arthritis. Moreover, the complementarities of three lipid peroxidation product levels may be helpful in the diagnosis of Lyme arthritis.

Phospholipidomic Analysis Reveals Changes in Sphingomyelin and Lysophosphatidylcholine Profiles in Plasma from Patients with Neuroborreliosis.

In recent years, the number of patients suffering from Lyme Disease (LD) has significantly increased. The most dangerous manifestation of LD is neuroborreliosis associated with invasion of the central nervous system by Borrelia burgdorferi. Phospholipids (PL) and their metabolites are involved in inflammation, which plays a dominant, but still unclear, role in the pathogenesis of neuroborreliosis. We analyzed the plasma PL profiles of neuroborreliosis patients (n = 8) and healthy volunteers (n = 8) using a lipidomic approach. Significant increases in the lysophosphatidylcholines LysoPtdCho 16:0 and LysoPtdCho 18:2 were observed. The plasma of neuroborreliosis patients appeared to have an increased relative abundance of sphingomyelin CerPCho d18:1/24:1 and a decrease in CerPCho d18:0/18:0. Principal components analysis of the relative abundances of all PL class species distinguished between neuroborreliosis patients and healthy subjects. This is the first report comparing PL classes and their molecular species in neuroborreliosis patients and healthy subjects.

Bi-directional CB1 receptor-mediated cardiovascular effects of cannabinoids in anaesthetized rats: role of the paraventricular nucleus.

The activation of cannabinoid CB1 receptors decreases and increases blood pressure (BP) in anaesthetized and conscious rats, respectively. The aim of our study was to check the possible involvement of CB1 receptors in the paraventricular nucleus of the hypothalamus (PVN) in the cardiovascular effects of cannabinoids in rats. Methanandamide (metabolically stable analogue of the endocannabinoid anandamide) and the synthetic cannabinoid receptor agonist CP55940 were microinjected into the PVN of urethane-anaesthetized rats twice (S1 and S2, 20 min apart). Receptor antagonists were administered intravenously (i.v.) 5 min before S1. Methanandamide and CP55940 decreased blood pressure by 15 - 20%. The CB1 receptor antagonist AM251 reversed the depressor effect into a pressor response of 20 - 30%. The pressor effect of CP55940 observed in the presence of AM251 i.v. was reduced by AM251 given additionally into the PVN but not by the i.v. injection of the CB2 antagonist SR144528 or the vanilloid TRPV1 antagonist ruthenium red. In the presence of the peripherally restricted CB1 receptor antagonist AM6545, CP55940 given into the PVN increased BP by 40%. AM6545 reversed the decrease in BP induced by CP55940 i.v. into a marked increase. Bilateral chemical lesion of the PVN by kainic acid abolished all cardiovascular effects of CP55940 i.v. In conclusion, the cannabinoid CP55940 administered to the PVN of urethane-anaesthetized rats can induce depressor and pressor effects. The direction of the response probably depends on the sympathetic tone. The centrally induced hypertensive response of CP55940 can, in addition, be masked by peripheral CB1 receptors.

Antioxidant properties of black tea in alcohol intoxication.

Food ingredients such as alcohol may modify cellular redox state. Ethanol metabolism is accompanied by generation of free radicals that can damage cell components especially when antioxidant mechanisms are no able to neutralize them. However black tea is a source of polyphenol antioxidants that may enhance cellular antioxidant abilities. The aim of this study was to investigate the effect of black tea on antioxidant abilities of the liver, blood serum and brain of 12-months old rats sub-chronically (for 28 days) intoxicated with ethanol. Administration of black tea alone caused increase in the activity and concentration of antioxidant parameters more extensively in the liver and serum than in the brain. Alcohol caused decrease in the liver glutathione peroxidase and reductase and catalase activity but increase in activity of superoxide dismutase. Moreover, decrease in the level of non-enzymatic antioxidants, such as reduced glutathione, vitamin C, A and E and beta-carotene was observed. The activity of serum glutathione peroxidase and reductase decreased while superoxide dismutase activity was not changed. The level of non-enzymatic antioxidants in serum was also decreased. However brain activity/level of all examined antioxidants enzymatic as well as non-enzymatic was decreased after ethanol intoxication. Black tea considerably prevented antioxidant parameters against changes caused by ethanol. These results indicate beneficial antioxidant effect of black tea regarding all examined tissues, but especially the liver.

[Pertrochanteric fractures of the femur in patient with thrombophlebic crural ulcerations of the legs in the course of 50 years]. / Przezkretarzowe zlamanie kosci udowej u chorej z piecdziesiecioletnimi owrzodzeniami zylakowatymi obu podudzi.

The authors present a case of 75-year old female, who has suffered from venous insufficiency crural ulcerations and lost hope for any relief for 50 years. Hospitalisation for a femur fracture has been a turning point. The patient learnt that modern medicine can treat disease that she suffered from for most of her life.

Effects of dinuclear berenil-platinum(II) complexes on fibroblasts redox status.

PURPOSE: Platinum(II) complex anticarcinogenic mechanisms are associated with changes in the cellular redox status of cancer as well as healthy cells. Therefore, the goal of the present study was to investigate oxidative modifications in cellular components following fibroblast exposure to novel dinuclear berenil-platinum(II) complexes. MATERIAL AND METHOD: ROS levels, antioxidant parameters level/activity, and damage to DNA, lipids, and proteins, including pro-apoptotic and anti-apoptotic factors in human skin fibroblasts following berenil-platinum(II) complex treatments i.e. Pt2(isopropylamine)4(berenil)2, Pt2(piperazine)4(berenil)4, Pt2(2-picoline)4(berenil)2, Pt2(3-picoline)4(berenil)2, and Pt2(4- picoline)4(berenil)2 were examined. RESULTS: Treatment of fibroblasts with platinum(II) complexes has shown that all compounds enhance total ROS and superoxide anion generation as well as change the activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase and decrease in the level of non-enzymatic antioxidants (GSH, vitamin C, E and A). Such a situation is conducive to oxidative stress formation and oxidative modifications of cellular macromolecules and to increase in the expression of proapoptotic proteins. Pt2(isopropylamine)4(berenil)2 elicited the most damage, which resulted in oxidative modification of cellular components. The therapeutic use of this complex would cause considerable side effects in patients, therefore the agent lacks drug potential; however Pt2(piperazine)4(berenil)2 and Pt2(2-picoline)4(berenil)2 exhibited reduced redox and increased apoptotic profiles compared to cisplatin. CONCLUSION: Results of this paper and preliminary data show that Pt2(2-picoline)4(berenil)2 is less dangers than cisplatin to fibroblasts and more disruptive than cisplatin to breast cancer cell metabolism, and therefore it is a promising candidate for use in future anticancer drug strategies.

Effect of sweet grass extract against oxidative stress in rat liver and serum.

Ethanol metabolism is accompanied by generation of free radicals which can damage the cell components. However, sweet grass is a source of coumarin and its derivatives have emerged as a promising group of antioxidant compounds. The aim of this study has been to investigate the influence of sweet grass on oxidative stress formation in the liver and serum of rats intoxicated with ethanol. Alcohol intoxication led to a decrease in the superoxide dismutase, catalase, glutathione peroxidase and reductase activity in the blood serum as well as in the liver, but not in the glutathione reductase activity. The decrease in the antioxidant abilities of the examined tissues after ethanol intoxication resulted in enhanced lipid peroxidation measured as malondialdehyde and 4-hydroxynonenal levels. The metabolic consequence of oxidative modifications of lipids was damage of the liver cells membrane and an increase in its permeability appeared as a leakage of alanine aminotransferase and aspartate aminotransferase into the blood. Administration of sweet grass to the ethanol-intoxicated rats remarkably prevented the significant increase in concentrations of all measured lipid peroxidation products as well as the damage of the liver cell membrane. These results indicate beneficial antioxidant effect of the sweet grass on the liver of rats intoxicated with ethanol.

Antioxidative properties of black tea.

BACKGROUND: Black tea, obtained by tea leaves fermentation, is an oxidized product and contains mainly multimeric polyphenols, whose biological activity is not well documented. This paper reviews the available literature on the effects of black tea on health with a focus on its antioxidative activity. METHODS: A review of the different issues and studies relating to composition, manufacturing, and antioxidative effects of black tea and its components in vitro as well as in vivo is presented. RESULTS: It is generally believed that polyphenols such as theaflavins and thearubigins as well as catechins as major constituents of black tea are mainly responsible for antioxidant actions. Antioxidative properties of black tea are manifested by its ability to inhibit free radical generation, scavenge free radicals, and chelate transition metal ions. Black tea, as well as individual theaflavins, can influence activation of transcription factors such as NFkappaB or AP-1. Theaflavins have been also proved to inhibit the activity of prooxidative enzymes such as xanthine oxidase or nitric oxide synthase. CONCLUSIONS: Black tea consumed throughout the world is believed to be not only a popular beverage but also an antioxidative agent available in everyday life.

[Own experience in Partridge fixation method]. / Wlasne doswiadczenia w zastosowaniu metody zespalania wedlug Partridge'a.

A series of 34 patients (21 males, 13 females aged 16 to 85 years) served to assess Partridge fracture stabilization method. The method was employed always with some other mode of fixation. Twenty-eight patients had primary long bone shaft fracture, in 6 cases refracture occurred in the course of treatment with different method or resulted from intraoperative complication. In authors' opinion Partridge method is best combined with intramedullar fixation, extends indications for the latter and is recommended in atypical surgical situations. Good clinical results were achieved and no bony union disturbances were observed.