A single dose of dietary nitrate supplementation protects against endothelial ischemia-reperfusion injury in early postmenopausal women.

The onset of menopause and accompanying changes to ovarian hormones often precedes endothelial dysfunction in women. In particular, accelerated impairments in macrovascular and microvascular function coincide with the loss of estrogen, as does impaired endothelial responses to ischemia-reperfusion (IR) injury. In healthy, early postmenopausal women (n = 12; 3.9 ± 1.5 years since menopause) we tested the hypothesis that acute dietary nitrate (NO3-) supplementation would improve endothelial function and attenuate the magnitude of endothelial dysfunction following whole-arm IR in comparison with placebo. In this randomized, double-blind, placebo-controlled, crossover study we tested participants before and after NO3--rich (BRnitrate) and NO3--depleted (BRplacebo) beetroot juice (BR) consumption, as well as following IR injury, and 15 min after IR to assess recovery. Analyses with repeated-measures general linear models revealed a condition × time interaction for brachial artery flow-mediated dilation (FMD; P = 0.04), and no interaction effect was found for the near-infrared spectroscopy-derived reperfusion slope (P = 0.86). Follow-up analysis showed a significant decline in FMD following IR injury with BRplacebo in comparison with all other timepoints (all, P < 0.05), while this decline was not present with BRnitrate (all, P > 0.05). Our findings demonstrate that a single dose of dietary NO3- minimizes IR-induced macrovascular endothelial dysfunction in healthy, early postmenopausal women, but does not improve resting macrovascular and microvascular function. Trial registration number: NCT03644472. Novelty: In healthy, early postmenopausal women, a single dose of NO3--rich BR can protect against IR-induced endothelial dysfunction. This protection may be due to nitric oxide bioactivity during IR rather than improved endothelial function prior to the IR protocol per se.

Cost-effectiveness of lenalidomide plus dexamethasone vs. bortezomib plus melphalan and prednisone in transplant-ineligible U.S. patients with newly-diagnosed multiple myeloma.

OBJECTIVE: To conduct a cost-effectiveness assessment of lenalidomide plus dexamethasone (Rd) vs bortezomib plus melphalan and prednisone (VMP) as initial treatment for transplant-ineligible patients with newly-diagnosed multiple myeloma (MM), from a U.S. payer perspective. METHODS: A partitioned survival model was developed to estimate expected life-years (LYs), quality-adjusted LYs (QALYs), direct costs and incremental costs per QALY and LY gained associated with use of Rd vs VMP over a patient's lifetime. Information on the efficacy and safety of Rd and VMP was based on data from multinational phase III clinical trials and a network meta-analysis. Pre-progression direct costs included the costs of Rd and VMP, treatment of adverse events (including prophylaxis) and routine care and monitoring associated with MM. Post-progression direct costs included costs of subsequent treatment(s) and routine care and monitoring for progressive disease, all obtained from published literature and estimated from a U.S. payer perspective. Utilities were obtained from the aforementioned trials. Costs and outcomes were discounted at 3% annually. RESULTS: Relative to VMP, use of Rd was expected to result in an additional 2.22 LYs and 1.47 QALYs (discounted). Patients initiated with Rd were expected to incur an additional $78,977 in mean lifetime direct costs (discounted) vs those initiated with VMP. The incremental costs per QALY and per LY gained with Rd vs VMP were $53,826 and $35,552, respectively. In sensitivity analyses, results were found to be most sensitive to differences in survival associated with Rd vs VMP, the cost of lenalidomide and the discount rate applied to effectiveness outcomes. CONCLUSIONS: Rd was expected to result in greater LYs and QALYs compared with VMP, with similar overall costs per LY for each regimen. Results of this analysis indicated that Rd may be a cost-effective alternative to VMP as initial treatment for transplant-ineligible patients with MM, with an incremental cost-effectiveness ratio well within the levels for recent advancements in oncology.

UGT1A1 gene variants and clinical risk factors modulate hyperbilirubinemia risk in newborns.

OBJECTIVE: To study the contribution of UGT1A1 gene variants and clinical risk factors in modulating hyperbilirubinemia risk in newborns. STUDY DESIGN: Seven UGT1A1 gene variants and clinical risk factors were studied in 113 hyperbilirubinemia cases and 218 control newborns. Hyperbilirubinemia was defined as the total serum bilirubin levels >95th percentile of the American Academy of Pediatrics nomogram. The study population included term (37 to 41 weeks) newborns below 2 weeks of age. RESULT: UGT1A1 gene variants, namely, c.211G>A, g.-3279T>G, TATA box polymorphism and CAT insertion were identified as independent molecular risk factors for neonatal hyperbilirubinemia, whereas c.686C>A, c.1091C>T and c.1456T>G were not detected in study cohort. Among clinical risk factors, excessive weight loss, sepsis and ABO incompatibility emerged as independent risk factors. Co-expression of UGT1A1 variants and clinical risk factors further accentuated the risk of neonatal hyperbilirubinemia. CONCLUSION: Multiple risk factors, whether genetic or clinical, are instrumental in modulating hyperbilirubinemia risk in newborns. Disordered bilirubin conjugation through interactions of UG1TA1 gene variants contributes to the clinical phenotype of neonatal hyperbilirubinemia.

Spinal cord stimulation to abort painful spasms of atypical stiff limb syndrome.

Stiff limb syndrome (SLS) is a rare chronic condition which can result in significant debility. We report the case of a 44-year-old man suffering from severe painful spasms in his right leg with a diagnosis of SLS. He had been initially treated for his pain with a spinal cord stimulator but presented with exacerbation of pain secondary to a lead fracture for which he underwent revision of the stimulator. Postoperative programming unexpectedly resulted in not only control of his pain but also an ability to abort his spasmodic episodes related to SLS. To our knowledge, spinal cord stimulation has not been previously used for SLS and our report opens up another avenue for this rare condition. We provide a brief overview of SLS and propose an underlying mechanism for the observed phenomenon.

Quality of ready to serve tilapia fish curry with PUFA in retortable pouches.

UNLABELLED: Studies on the physical, chemical, and microbiological qualities of fresh tilapia meat revealed its suitability for the preparation of ready to eat fish curry packed in retort pouches. Studies on the fatty acid profile of tilapia meat suggest fortification with polyunsaturated fatty acid (PUFA) to increase the nutritional value. Based on the commercial sterility, sensory evaluation, color, and texture profile analysis F(0) value of 6.94 and cook value of 107.24, with a total process time of 50.24 min at 116 °C was satisfactory for the development of tilapia fish curry in retort pouches. Thermally processed ready to eat south Indian type tilapia fish curry fortified with PUFA was developed and its keeping quality studied at ambient temperature. During storage, a slight increase in the fat content of fish meat was observed, with no significant change in the contents of moisture, protein, and ash. The thiobarbituric acid (TBA) values of fish curry significantly increased during storage. Fish curry fortified with 1% cod liver oil and fish curry without fortification (control) did not show any significant difference in the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), during thermal processing and storage. Sensory analysis revealed that fortification of fish curry with cod liver oil had no impact on the quality. Tilapia fish curry processed at 116 °C and F(0) value of 7.0 (with or without fortification of cod liver oil) was fit for consumption, even after a period of 1-y storage in retort pouch. PRACTICAL APPLICATION: Tilapia is a lean variety of fish with white flesh and therefore an ideal choice as raw material for the development of ready to serve fish products such as fish curry in retort pouches for both domestic and international markets. Ready to eat thermal processed (116 °C and F(0) value of 7.0) south Indian type tilapia fish curry enriched with PUFA and packed in retort pouch was acceptable for consumption even after a storage period of 1 y at ambient temperature.

Acute toxicity and diuretic studies of Rungia repens aerial parts in rats.

Ethanolic extract of Rungia repens aerials parts (300 and 600 mg/kg p.o) showed diuretic activity in rats. The acute toxicity, orally evaluated in mice, was found to be higher than 3000 mg/kg.

Effect of Mesua ferrea Linn. flower extract on Salmonella.

Based on its traditional uses in folk medicine, the whole flower extract of Mesua ferrea Linn. was tested for its in vitro antimicrobial efficacy against five different strains of Salmonella spp. All the strains were found to be highly sensitive to the extract, MIC of the extract against each organism being 50 microg/ml. The extract was tested in vitro for its mode of antibacterial activity against S. Typhimurium NCTC 74 and it was found to be bactericidal in action. In vivo studies of this extract offered significant protection to Swiss albino mice at doses approximately 2 and 4 mg/mouse when challenged with 50 median lethal dose of S. Typhimurium NCTC 74. Further, the extract caused statistically significant reduction in viable count of the strain in liver, spleen and heart blood of challenged mice.

The theaflavin fraction is responsible for the facilitatory effect of black tea at the skeletal myoneural junction.

The effect of various fractions of black tea [(Camellia Sinensis) (L) O. Kuntze (Theaceae)] on the function of mammalian skeletomotor apparatus was studied. The theaflavin fraction (Tfs) produced a concentration- dependent facilitation of indirect twitch responses of the rat phrenic nerve diaphragm preparation and the facilitation was dependent on the amount of calcium present in the bathing fluid. Nifedipine reduced the facilitatory effect of Tfs as a function of its concentration. Tfs failed to produce facilitation when the twitch height was reduced to about 50% of the control value in presence of magnesium chloride. Tfs completely antagonized the submaximal paralytic effect of d- tubocurarine and decamethonium bromide. Tfs did not have any effect on direct twitch responses or on acetylcholine (Ach) and potassium chloride (KCl) induced contractures of denervated diaphragm. The results revealed that the site of action of Tfs is on the contractile mechanism of the voluntary muscle and point to a critical role of calcium in the mechanism of action of Tfs. N omega-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, antagonized both the facilitatory and inhibitory effects on indirect twitch responses of rat diaphragm induced by L-arginine and Tfs when the phrenic nerve was stimulated at 5 Hz and 50 Hz respectively. The thearubigin (Trs) fraction of black tea and the aqueous part which is completely devoid of Tfs, did not potentiate the twitch responses. The findings suggest that Tfs have a potentiating effect on the contractile mechanism of skeletal muscle and that calcium and nitric oxide may modulate this action of Tfs.

Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning?

Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg i.p.) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects.

Antibacterial potentiality of Mesua ferrea Linn. flowers.

The antibacterial efficacy of the methanol extract of whole flowers of Mesua ferrea Linn. was studied against various strains of bacteria. It could inhibit a large number of Gram-positive and Gram-negative bacteria at concentration ranges of 100 to 50 microg/ml, or even lower, as against vibrios and Escherichia coli. In in vivo tests, used at concentrations of 100 and 200 microg/g of body weight, it offered significant protection to Swiss strain of albino mice when challenged with 50 MLD of a virulent strain Sulmonella typhimurium ATCC 6539. Mortality in mice due to these two dosages of the extract alone was insignificant. The extract at 200 microg/g body weight dosage, could significantly reduce the viable count of the strain Sulmonella typhimurium ATCC 6539 in liver, spleen and heart blood of the extract treated challenged mice.

Evaluation of antitussive activity of Lagerstroemia parviflora leaf extract.

The methanol extract of the leaves of Lagerstroemia parviflora Roxb was investigated for its effect on a cough model induced by sulfur dioxide gas in mice. It exhibited significant antitussive activity when compared with the control in a dose-dependent manner. The L. parviflora extract (100, 200, 300 mg/kg) showed maximum inhibition of cough reflex at 90 min after drug administration and the antitussive activity was comparable to that of codeine phosphate, a standard antitussive agent.

Single megadose vitamin A supplementation of Indian mothers and morbidity in breastfed young infants.

BACKGROUND AND OBJECTIVE: In developing countries low maternal vitamin A stores combined with increased demands of pregnancy and lactation may lead to its deficiency in breastfed infants. This study evaluates the effects of maternal supplementation with a high dose of vitamin A on the serum retinol levels of exclusively breastfed infants, and their morbidity in the first six months of life. SETTING: Hospital based. STUDY DESIGN: Randomised controlled trial. SUBJECTS AND METHODS: Mothers of the test group (n=150) were orally supplemented with a single dose of retinol (209 micro mol) soon after delivery and were advised exclusive breastfeeding for six months. Before supplementation retinol levels were estimated in the mothers' and newborns' blood, and in colostrum. On follow up, breastmilk and infants' serum retinol contents were assessed monthly for six months. Retinol level <0.7 micro mol/l indicated vitamin A deficiency. Morbidity patterns like vitamin A deficiency, diarrhoea, febrile illnesses, acute respiratory infection, measles, and ear infection were also studied and compared between the two groups. RESULTS: Presupplement mean maternal serum retinol levels were 0.98 and 0.92 micro mol/l and mean breastmilk levels were 3.85 and 3.92 micro mol/l in the test and control groups respectively (p>0.05). Mean cord blood retinol levels were also comparable (0.68 v 0.64 micro mol/l). After supplementation, the test group showed a rise in mean breastmilk retinol content (12.08 v 2.96 micro mol/l) which remained significantly higher for four months. The infants' mean serum retinol level, initially 322.06% of the baseline value, was significantly higher for five months. In the control group, significant numbers of mothers and infants showed deficient breastmilk and serum retinol throughout the follow up (p<0.01). Decreased incidence and duration of various diseases were also found in the test group suggesting lesser morbidity. CONCLUSION: Maternal supplementation with single megadose vitamin A is an effective strategy for vitamin A prophylaxis of exclusively breastfed infants of 0-6 months.

Oxidative stress and antioxidant status in type 1 diabetes mellitus.

OBJECTIVES: To test the hypothesis that type 1 diabetes is associated with increased oxidative stress and/or antioxidant status by investigating concentrations of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) in urine and plasma and malondialdehyde (MDA) in plasma as indicators of lipid peroxidation in vivo, and antioxidant status in diabetic subjects compared with healthy control subjects. DESIGN AND SUBJECTS: Thirty-eight subjects with type 1 diabetes mellitus and 41 healthy age- and sex-matched control subjects were included in the study. Blood and urine samples were obtained and analysed for 8-iso-PGF2alpha with a newly developed radioimmunoassay, as well as for MDA, total antioxidant capacity (TAOC) and serum tocopherol levels. RESULTS: None of the variables of lipid peroxidation showed any significant difference between the two groups. Similarly, there were no significant correlations between the levels of 8-iso-PGF2alpha or MDA, and degree of glycemic control (HbA1c). Total antioxidant capacity in plasma was 16% lower amongst the subjects with type 1 diabetes than in the control group (P < 0.0005). Lipid corrected levels of alpha-tocopherol in serum were significantly increased in type 1 diabetic subjects (P < 0.05), as were gamma-tocopherol levels (P < 0.005). CONCLUSIONS: In spite of lower total antioxidant defence, our results do not support the oxidative stress hypothesis for type 1 diabetes mellitus. The higher tocopherol levels suggest that no vitamin E supplementation is necessary for subjects with type 1 diabetes mellitus.

Propofol (Diprivan-EDTA) counteracts oxidative injury and deterioration of the arterial oxygen tension during experimental septic shock.

PURPOSE: Human septic shock can be replicated in the endotoxaemic pig. Endotoxaemia causes a multitude of events, including reduced PaO(2) and increased lipid peroxidation. This study was designed to evaluate the possible effects of a commonly used anaesthetic drug with known antioxidant properties (propofol) during porcine endotoxaemia. METHODS: Ten pigs were anaesthetised and given a 6 h E. coli endotoxin infusion. The animals received, randomly, a supplementary continuous infusion of propofol emulsion (containing 0.005% EDTA) or the corresponding volume of vehicle (controls). Pathophysiologic responses were determined. Non-enzymatic (by measuring plasma 8-iso-PGF(2 alpha) and enzymatic (by measuring plasma 15-keto-dihydro-PGF(2 alpha)) lipid peroxidations were evaluated. Plasma levels of the endogenous antioxidants alpha- and gamma-tocopherols, were also analysed. RESULTS: Endotoxaemia increased plasma levels of 8-iso-PGF(2 alpha) (1st-4th h) and 15-keto-dihydro-PGF(2 alpha) (1st-4th h) significantly more in controls than in the propofol+endotoxin group. PaO(2) was significantly less affected by endotoxin in the propofol treated animals (2nd-4th h). Mean arterial pressure (4th-6th h) and systemic vascular resistance (6th h) were reduced significantly more by endotoxin among the propofol-treated animals. Vitamin E (alpha-tocopherol) increased in all animals, significantly more in the propofol+endotoxin group (1/2-6th h) than in the control group. CONCLUSIONS: Propofol reduced endotoxin-induced free radical mediated and cyclooxygenase catalysed lipid peroxidation significantly. The implication is that propofol counteracts endotoxin-induced deterioration of PaO(2).

A diet containing rapeseed oil-based fats does not increase lipid peroxidation in humans when compared to a diet rich in saturated fatty acids.

OBJECTIVE: To compare the effects of a rapeseed oil-based diet containing an increased proportion of easily oxidised polyunsaturated fatty acids such as alpha-linolenic acid with a diet rich in saturated fatty acids on the degree of lipid peroxidation in the human body. DESIGN: A randomised cross-over study. SUBJECTS AND INTERVENTIONS: Nineteen healthy moderately hyperlipidemic subjects (six women and 13 men, age 50+/-8 y and body mass index (BMI) 24.5+/-2.6 kg/m(2)) were given a rapeseed oil-based diet (RO) and a control diet (SAT) rich in saturated fatty acids during two consecutive 4 week periods separated by a 4 week wash-out period. Biomarkers of lipid peroxidation and antioxidants were analysed in plasma and urine. RESULTS: No significant differences in plasma or urinary levels of free 8-iso-prostaglandin F(2alpha), plasma total 8-iso-prostaglandin F(2alpha) plasma hydroperoxides or plasma malondialdehyde were observed between the RO and SAT diets (P=0.14-0.95). A higher concentration of serum gamma-tocopherol was detected after the RO diet compared to the SAT diet (P<0.001), whereas the serum alpha-tocopherol concentration and plasma antioxidative capacity did not differ between the two test diets. The total cholesterol, LDL cholesterol and LDL/HDL ratio were lower after the RO diet compared to the SAT diet (P<0.001), while HDL cholesterol and total triglyceride levels were similar after the two diets. CONCLUSION: These results suggest that a rapeseed oil-based diet rich in alpha-linolenic acid does not seem to increase the degree of lipid peroxidation in plasma and urine compared to a diet rich in saturated fats. This is possibly due to a sufficient content of antioxidants in the rapeseed oil diet to increase circulating concentrations of antioxidants that may protect unsaturated fatty acids from oxidation. SPONSORSHIP: Swedish Council for Forestry and Agricultural Research and Foundation for Geriatric Research.

Advances in cancer therapy with plant based natural products.

Natural Products have long been a fertile source of cure for cancer, which is projected to become the major causes of death in this century. However, there is a continuing need for development of new anticancer drugs, drug combinations and chemotherapy strategies, by methodical and scientific exploration of enormous pool of synthetic, biological and natural products. There are at least 250,000 species of plants out of which more than one thousand plants have been found to possess significant anticancer properties. While many molecules obtained from nature have shown wonders, there are a huge number of molecules that still either remains to be trapped or studied in details by the medicinal chemists. The article reviews many such structures and their related chemistry along with the recent advances in understanding mechanism of action and structure-function relationships of nature derived anti-cancer agents at the molecular, cellular and physiological levels. Taxol, one of the most outstanding agents, has been found beneficial in treatment of refractory ovarian, breast and other cancers. Another prominent molecule includes Podophyllotoxin. Synthetic modification of this molecule led to the development of Etoposide, known to be effective for small cell cancers of the lungs and testes. Camptothecin isolated from Camptotheca acuminata also have been extensively studied. Other important molecules discussed include Vincristine, Vinblastine, Colchicine, Ellipticine and Lepachol along with Flavopiridol, a semi-synthetic analogue of the chromone alkaloid Rohitukine from India, a pyridoindole alkaloid from leaves of Ochrosia species and many more. The review also deals with the lesser-known plants of sub-Himalayan region.

Physiological concentrations of dopamine inhibit the proliferation and cytotoxicity of human CD4+ and CD8+ T cells in vitro: a receptor-mediated mechanism.

OBJECTIVE: Dopamine, a catecholamine neurotransmitter, influences growth and proliferation of lymphocytes. Pharmacological doses of dopamine have been shown to modulate T cell functions significantly, but no information is available on the effect of physiological concentrations of circulating dopamine on CD4+ and CD8+ T cell functions. This information may be of importance since significantly elevated plasma dopamine levels were observed in humans during uncoping stress, and suppression of T cell functions during stress is a well-known phenomenon. However, the mechanism inducing the suppression of T cell functions during stress is not yet clear. In the present investigation, we evaluated the effect of the dopamine level attained in the plasma of individuals with uncoping stress on the proliferation and cytotoxicity of CD4+ and CD8+ T cells in vitro. METHODS: T cell subpopulations were separated by panning. The effect of dopamine on IL-2-induced cell proliferation in vitro was evaluated by [3H]thymidine incorporation and cytotoxicity by 51Cr release, receptors by radioligand binding, cAMP by an assay kit and apoptosis by DNA fragmentation. RESULTS: At these elevated physiological concentrations, dopamine was found to inhibit significantly the proliferation and cytotoxicity of CD4+ and CD8+ T cells in vitro. This dopamine-mediated inhibition of proliferation was more marked on CD8+ T cells than on CD4+ T cells. The underlying mechanism was found to be D1 class of dopamine-receptor-mediated stimulation of intracellular cAMP. CONCLUSION: Results may be of significance to understand the role of peripheral dopamine in human neuroimmune communication in terms of physiological homeostasis in health and disease.

Raised levels of F(2)-isoprostanes and prostaglandin F(2alpha) in different rheumatic diseases.

OBJECTIVE: To evaluate oxidative injury and inflammatory status in various rheumatic diseases by measuring the levels of isoprostanes and prostaglandins in serum and synovial fluid. METHODS: The concentrations of 8-iso-PGF(2alpha) (F(2)-isoprostane indicating oxidative injury) and 15-keto-dihydro-PGF(2alpha) (a major metabolite of prostaglandin F(2alpha)) were measured in both serum and synovial fluid aspirated from 26 patients with various arthritic diseases, including rheumatoid arthritis (RA), reactive arthritis (ReA), psoriatic arthritis (PsA), and osteoarthritis (OA). These prostaglandin derivatives were also measured in serum samples collected from 42 healthy control subjects. RESULTS: Overall, serum levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) were much higher in patients with arthritic diseases than in the healthy control subjects. The levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) in synovial fluid aspirated from knee joints were also high and varied among various types of arthritic patients. Although the synovial fluid level of these prostaglandin derivatives was sometimes higher than in the corresponding serum sample, this was not a consistent finding. Overall, there was no correlation between serum and synovial fluid levels of 8-iso-PGF(2alpha), or between serum and synovial fluid levels of 15-keto-dihydro-PGF(2alpha). However, a strong relation was found between the levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha,) in both serum (r(s)=0.53, p<0.001) and synovial fluid (r(s)=0.62, p<0.001). CONCLUSIONS: These data suggest that both free radical mediated oxidative injury and cyclo-oxygenase dependent inflammatory responses are closely correlated in various types of arthritis.

Vitamin E reduces lipid peroxidation in experimental hepatotoxicity in rats.

BACKGROUND AND AIMS: Lipid peroxidation is believed to be involved in the pathophysiology of a number of diseases and in the process of aging. This study investigates the effects of dietary supplementation with vitamin E (20 g/kg diet of all-rac-alpha-tocopheryl succinate for 3 weeks) on both non-enzymatic and enzymatic lipid peroxidation in experimental rats with carbon tetrachloride (CCl4)-induced hepatotoxicity (2.5 mL/kg body). METHODS: Plasma, urine and liver samples from control rats (n = 6), CCl4-treated rats (n = 6), and rats supplemented with vitamin E prior to CCl4 treatment (n = 8) were collected. Non-enzymatic lipid peroxidation induced by free radicals was investigated by measurement of a major F2-iso-prostane, 8-iso-prostaglandin F2 alpha (8-iso-PGF2 alpha). Cyclooxygenase-catalyzed enzymatic lipid peroxidation was measured with a major PGF2 alpha metabolite, 15-keto-13,14-dihydro-prostaglandin F2 alpha (15-K-DH-PGF2 alpha). Malondialdehyde and antioxidants in plasma were also quantified. RESULTS: CCl4 treatment alone resulted in significantly higher levels of plasma, urinary and liver 8-iso-PGF2 alpha, and of plasma and urinary 15-K-DH-PGF2 alpha compared to controls. Rats supplemented with vitamin E prior to CCl4 treatment had significantly lower levels of urinary and liver 8-iso-PGF2 alpha, urinary 15-K-DH-PGF2 alpha, and plasma malondialdehyde than rats treated with CCl4 alone. However, plasma 8-iso-PGF2 alpha and plasma 15-K-DH-PGF2 alpha were not affected by vitamin E supplementation. CONCLUSION: Thus, both non-enzymatic and enzymatic lipid peroxidation during experimental hepatic oxidative injury were suppressed by dietary vitamin E supplementation in rats.

Conjugated linoleic acid induces lipid peroxidation in men with abdominal obesity.

Conjugated linoleic acid (CLA) has been shown in experimental studies to have chemoprotective properties, and may decrease the deposition of body fat. CLA is prone to oxidation, and it has been suggested that increased lipid oxidation may contribute to the anti-tumorigenic effects of this agent. The present study investigates the urinary levels of 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)), a major isoprostane, and of 15-oxo-dihydro-PGF(2alpha), a major metabolite of PGF(2alpha), as indicators of non-enzymic and enzymic arachidonic acid oxidation respectively after dietary supplementation with CLA in middle-aged men (mean age 53 years) with abdominal obesity for 1 month in a randomized controlled trial. Significant increases in the levels of both 8-iso-PGF(2alpha) and 15-oxo-dihydro-PGF(2alpha) in urine (P<0. 0001 and P=0.0013 respectively) were observed after 1 month of daily CLA intake (4.2 g/day) as compared with the control group. The lipid peroxidation parameters had returned to their basal levels at 2 weeks after the cessation of CLA intake, and remained at the same levels for a further 2 weeks until the end of the study. CLA had no effect on serum alpha-tocopherol and gamma-tocopherol levels, or on the urinary levels of 2,3-dinor-thromboxane B(2). Thus CLA may induce both non-enzymic and enzymic lipid peroxidation in vivo in middle-aged men with abdominal obesity, without any side effects. The consequences of the increased lipid peroxidation after CLA supplementation are unknown.