Alpha-tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-alpha

Diabetes is a major risk factor for premature atherosclerosis, and oxidative stress appears to be an important mechanism. Previously, we showed that diabetic monocytes produce increased superoxide anion (O(2)(-)), and alpha-tocopherol (AT) supplementation decreases this. The aim of this study was to elucidate the mechanism(s) of O(2)(-) release and inhibition by AT under hyperglycemic (HG) conditions in monocytes. O(2)(-) release, protein kinase C (PKC) activity, and translocation of PKC-alpha and -betaII and p47phox were increased in THP-1 cells (human monocytic cell line) under HG (15 mmol/l glucose) conditions, whereas AT supplementation inhibited these changes. AT, NADPH oxidase inhibitors (apocynin and diphenyleneiodonium chloride [DPI]), and an inhibitor to PKC-alpha and other isoforms (2,2',3,3',4,4'-hexahydroxy-1,1'-biphenyl-6,6'-dimethanol dimethyl ether [HBDDE]) but not PKC-beta II (LY379196) decreased O(2)(-) release and p47phox translocation. Antisense oligodeoxynucleotides to PKC-alpha and p47phox but not to PKC-betaII inhibited HG-induced O(2)(-) release and p47phox translocation in THP-1 cells. Under HG conditions, reactive oxygen species release from monocytes was not inhibited by agents affecting mitochondrial metabolism but was inhibited in human endothelial cells. We conclude that under HG conditions, monocytic O(2)(-) release is dependent on NADPH oxidase activity but not the mitochondrial respiratory chain; HG-induced O(2)(-) release is triggered by PKC-alpha, and AT inhibits O(2)(-) release via inhibition of PKC-alpha.     

Cocoa products decrease low density lipoprotein oxidative susceptibility but do not affect biomarkers of inflammation in humans

Flavonoids and related polyphenolics with antioxidant and anti-inflammatory activities may play a role in the prevention of cardiovascular disease by decreasing oxidative stress and inflammation. We wished to determine the effects of cocoa extract supplementation on markers of oxidative stress and inflammation. Healthy subjects (n = 25) were studied at baseline, after cocoa supplementation (36.9 g of dark chocolate bar and 30.95 g of cocoa powder drink) for 6 wk and after a 6-wk washout period. Fasting blood and early morning urine were collected at the three time points. Two indices of flavonoid intake, total phenols and oxygen radical absorbance capacity of plasma, were measured after an overnight fast. Neither was affected by supplementation. Measures of oxidative stress included copper-catalyzed LDL oxidation kinetics and urinary F(2) isoprostanes. LDL oxidizability was lower after chocolate supplementation as evidenced by a longer lag time (P < 0.05) of conjugated diene formation (101.0 +/- 20.7 min) compared with baseline (91.3 +/- 18.0 min) and washout (96.4 +/- 7.5 min) phases. There was no effect of chocolate on urinary F(2) isoprostane levels or on markers of inflammation including the whole-blood cytokines, interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha, high sensitivity C-reactive protein and P-selectin. In conclusion, cocoa products supplementation in humans affects LDL oxidizability, but not urinary F(2) isoprostanes or markers of inflammation.     

Alcoholic extract of 'Bacopa monniera' reduces the in vitro effects of morphine withdrawal in guinea-pig ileum

The effect of the alcoholic extract of the whole plant of Bacopa monniera (Scrophulariaceae) on morphine withdrawal was evaluated in vitro in guinea-pig ileum. After a 4 min in vitro exposure to morphine, addition of naloxone induced a strong contraction. Addition of various concentrations of the alcoholic extract of B. monniera (100-1000 microg/ml) 15 min before exposure to morphine reduced the naloxone-induced contraction in a dose-dependent manner. The results suggest that B. monniera extract may be useful in reducing the withdrawal symptoms induced by morphine.     

Antioxidants and vitamins to reduce cardiovascular disease

Cardiovascular disease is the leading cause of morbidity and mortality in Western populations. Several lines of evidence support the role of oxidative stress in atherogenesis. Dietary micronutrients with antioxidant properties and vitamins have also been shown to have a benefit with regards to cardiovascular disease. The most persuasive evidence relates to alpha tocopherol and folate and vitamin B₁₂. Although the evidence is mounting for supplementation with alpha tocopherol and folate and B₁₂ for secondary prevention of cardiovascular disease, no clear consensus can be reached for primary prevention of cardiovascular disease. This will have to await results of ongoing clinical trials.     

Microdrilling of digital calcinosis

Soft tissue calcification may be an unspecific local response or cause pain and present as part of a complex underlying disease. It can be exquisitely painful when located in the pulp of the digits. In this paper we describe a new minimally invasive technique for the treatment of finger calcinosis in patients with CREST syndrome (calcinosis, Raynaud’s phenomenon, esophageal hypomotility, sclerodactyly, telengectasia). A rose head or micropoint burr on a minidriver or microaire system is used to disrupt the calcific deposit. Healing is usually rapid. Received: 10 December 1997 / Accepted: 5 May 1998     

Hb Regina or alpha 2 beta 2 96(FG3)Leu----Val: a high oxygen affinity variant discovered by cation-exchange HPLC

Results are reported of studies of the hemoglobin from one member of a Canadian family with a mild erythrocytosis. This variant, which accounted for about 40% of the hemoglobin, could be separated from Hb A and Hb A2 by cation-exchange chromatography. Micro methodology allowed the characterization of a Leu----Val replacement at position beta 96(FG3). Hb Regina has an increased oxygen affinity, which adequately explains the hematological observations.     

Protective effect of propyl gallate against myocardial oxidative stress-induced injury in rat

This study was designed to investigate the effect of chronic administration of propyl gallate on myocardial oxidative stress-induced injury. Propyl gallate was administered orally to Wistar albino rats (150-200 g) in three different doses, by gastric gavage (250 mg kg(-1) (P1), 500 mg kg(-1) (P2) and 750 mg kg(-1) (P3)), 6 days a week for 5 weeks. At the end of this period, all the rats, except the normal untreated rats that served as the control group, were administered isoproterenol (ISO), 85 mg kg(-1) subcutaneously, for 2 consecutive days to induce myocardial injury. After 48 h, rats (n = 6 per group) were anaesthetized with anaesthetic ether, sacrificed and the hearts were harvested for the estimation of thiobarbituric acid reactive substances (TBARS), endogenous antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD) and catalase) and for the assessment of histological changes. In the P2 BL group (BL = baseline), there was a significant (P < 0.001) rise in baseline TBARS and SOD when compared with the saline-treated group, while no such changes were observed in the other baseline-treated groups. However, there was a significant (P < 0.001) increase in TBARS and endogenous anti-oxidants (GSH, SOD and catalase) in the P2 ISO and P3 ISO groups, when the hearts were subjected to in-vivo myocardial oxidative stress-induced injury. We observed no such changes in the P1 ISO group. This study showed that propyl gallate modulates the levels of endogenous antioxidants present at the myocardial site. Whether these modifications are a result of direct interference at this site or a remote effect is not immediately clear. In conclusion, from the results it could be stated that chronic administration of 500 mg kg(-1) of propyl gallate offers significant protection against myocardial oxidative stress-induced injury.     

In vivo micronucleus assay and GST activity in assessing genotoxicity of plumbagin in Swiss albino mice

Information available on the mutagenicity of a large number of indigenous drugs commonly employed in the Siddha and Ayurveda systems of medicine is scanty. In this context, the current investigation on plumbagin, 5-hydroxy-2methyl-1,4-napthoquinone, an active principle in the roots of Plumbago zeylanica used in Siddha and Ayurveda for various ailments, was carried out; 16 mg/kg b.w. (LD(50)) was fixed as the maximum dose. Subsequent dose levels were fixed as 50% and 25% of LD(50) amounting to 8 mg and 4 mg/kg b.w., respectively, and given orally for 5 consecutive days in 1% Carboxyl Methyl Cellulose (CMC) to Swiss albino mice weighing 25-30 g. The micronucleus assay was done in mouse bone marrow. Plumbagin was found to induce micronuclei at all the doses studied (4 mg/kg, 8 mg/kg, 16 mg/kg b.w.), and it proves to be toxic to bone marrow cells of Swiss albino mice. Animal treated with cyclophosphamide (40 mg/kg b.w.) served as positive control. In addition, glutathione S-transferase (GST) activity was observed in control, plumbagin (4 mg, 8 mg, 16 mg/kg b.w., respectively), and genotoxin-treated experimental group of animals. No significant change in GST activity was observed with plumbagin dose of 4 mg/kg b.w., whereas GST activity was significantly inhibited by higher doses of plumbagin (8 mg and 16 mg/kg b.w.) and cyclophosphamide.