Borylation directed borylation of N-alkyl anilines using iodine activated pyrazaboles.

Doubly electrophilic pyrazabole derivatives (pyrazabole = [H2B(µ-C3N2H3)]2) combined with one equiv. of base effect the ortho-borylation of N-alkyl anilines. Initial studies found that the bis(trifluoromethane)sulfonimide ([NTf2]-) pyrazabole derivative, [H(NTf2)B(µ-C3N2H3)]2, is highly effective for ortho-borylation, with this process proceeding through N-H borylation and then ortho C-H borylation. The activation of pyrazabole by I2 was developed as a cheaper and simpler alternative to using HNTf2 as the activator. The addition of I2 forms mono or ditopic pyrazabole electrophiles dependent on stoichiometry. The ditopic electrophile [H(I)B(µ-C3N2H3)]2 was also effective for the ortho-borylation of N-alkyl-anilines, with the primary C-H borylation products readily transformed into pinacol boronate esters (BPin) derivatives. Comparison of borylation reactions using the di-NTf2-and the diiodo-pyrazabole congeners revealed that more forcing conditions are required with the latter. Furthermore, the presence of iodide leads to competitive formation of side products, including [HB(µ-C3N2H3)3BH]+, which are not active for C-H borylation. Using [H(I)B(µ-C3N2H3)]2 and 0.2 equiv. of [Et3NH][NTf2] combines the higher yields of the NTf2 system with the ease of handling and lower cost of the iodide system generating an attractive process applicable to a range of N-alkyl-anilines. This methodology represents a metal free and transiently directed C-H borylation approach to form N-alkyl-2-BPin-aniline derivatives.

The effects of conjugated linoleic acid supplementation on immune function in healthy volunteers.

OBJECTIVE: To assess the effects of dietary supplementation using two isomeric blends of conjugated linoleic acid (CLA) on immune function in healthy human volunteers. DESIGN: Double-blind, randomised, placebo-controlled intervention trial. SUBJECTS AND INTERVENTION: A total of 55 healthy volunteers (n=20 males, n=35 females) were randomised into one of three study groups who received 3 g/day of a fatty acid blend containing a 50:50 cis-9, trans-11: trans-10, cis-12 CLA isomer blend (2 g CLA), and 80:20 cis-9, trans-11: trans-10, cis-12 (80:20) CLA isomer blend (1.76 g CLA) or linoleic acid (control, 2 g linoleic acid) for 8 weeks. RESULTS: Supplementation with the 80:20 CLA isomer blend significantly (P< or =0.05) enhanced PHA-induced lymphocyte proliferation. CLA decreased basal interleukin (IL)-2 secretion (P< or =0.01) and increased PHA-induced IL-2 and tumor necrosis factor alpha (TNF(alpha)) production (P< or =0.01). However, these effects were not solely attributable to CLA as similar results were observed with linoleic acid. CLA supplementation had no significant effect on peripheral blood mononuclear cells IL-4 production, or on serum-soluble intercellular adhesion molecule-1 (sICAM-1) or plasma prostaglandin E2 (PGE2) or leukotreine B4 (LTB4) concentrations. CONCLUSIONS: This study shows that CLA supplementation had a minimal effect on the markers of human immune function. Furthermore, supplementation with CLA had no immunological benefit compared with linoleic acid.

Conjugated linoleic acid: a novel therapeutic nutrient?

Conjugated linoleic acid (CLA) refers to a group of fatty acid isomers of linoleic acid. Recent research shows that CLA affects body composition, lipoprotein metabolism, inflammationand carcinogenesis. Therefore, CLA may have potential as a therapeutic nutrient with respect to many common diseases, including obesity, atherosclerosis, chronic inflammatory diseases and cancer. Animal studies show that CLA is a potent anti-adipogenic nutrient, reducing adipose tissue mass and increasing lean mass. However, the effect of CLA on body composition in human subjects has been less spectacular. Several studies have demonstrated that CLA significantly improves plasma cholesterol and triacylglycerol metabolism in a number of animal models. These studies also showed that CLA inhibits the progression and pathogenesis of atherosclerosis. Whilst CLA has also been shown to improve triacylglycerol metabolism in human subjects, it has not been determined whether CLA affects atherogenesis. Animal models show that CLA-rich diets modulate the inflammatory response and preliminary trials with human subjects show that CLA affects the cell-mediated immune response. The molecular basis of the health effects of CLA has not been elucidated, but it is probable that CLA mediates its effect in a number of ways including altered eicosanoid or cytokine metabolism and/orby a direct effect of dietary fats on gene transcription. Most of our knowledge is based on in vitro and animal studies; the challenge is to define the nature and molecular basis of any health effects of CLA in human subjects.

Review of a mobile accident and emergency unit at a rock concert.

On Saturday 16th May 1992, an outdoor Rock concert was held at a rural location located between two hospitals which are fourteen miles apart. It was attended by over 50,000 people. A mobile accident and emergency unit (MAEU), was staffed by two doctors and five nurses. The facilities, demands and injury pattern are reviewed, and recommendations for future events are made.

Increased intake of fruit and vegetables and a low-fat diet, with and without low-fat plant sterol-enriched spread consumption: effects on plasma lipoprotein and carotenoid metabolism.

BACKGROUND: Regular intake of plant sterol (phytosterol)-enriched foods enhances the cholesterol lowering effect of diets. One side effect associated with plant sterol consumption is a modest reduction in plasma carotenoid concentrations. This study investigated the effect of consuming a low-fat National Cholesterol Education Programme (NCEP) Step 1 diet, including a low-fat plant sterol ester (PSE)-enriched spread on cholesterol metabolism to determine if specific dietary advice to increase daily fruit and vegetable intake could prevent reduced plasma carotenoid concentrations. MATERIALS AND METHODS: In this randomised, crossover double-blind trial, 48 hypercholesterolaemic men received 21 g day(-1) of a low-fat PSE-enriched spread or placebo for 3 weeks, interrupted by 3 weeks washout. Individuals also adhered to a NCEP Step 1 diet and repeated 3-day food diaries monitored adherence. Specific advice was provided to increase dietary fruit and vegetable intakes. Fasting blood samples were collected at pre- and post-intervention for lipoprotein and carotenoid analysis. RESULTS: Plasma total and low-density lipoprotein (LDL) cholesterol concentrations were significantly (P <0.05) reduced, by 4.6 and 7.1%, respectively, after the PSE-enriched low-fat spread. Plasma apo B concentrations were significantly (P <0.0005) lower after the PSE spread. PSE consumption was also associated with significantly (P <0.05) lower total plasma beta-carotene concentrations, but this change was not significant after lipid standardisation. PSE consumption had no effect on retinol, alpha-carotene, gamma-tocopherol, alpha-tocopherol, lutein, zeaxanthin, beta-crypyoxanthin or lycopene concentrations. CONCLUSION: Dietary advice to increase daily fruit and vegetable consumption may be effective in preventing a reduction in plasma carotenoid concentrations previously associated with PSE consumption. Further, PSE incorporated in a low-fat spread and consumed as part of a NCEP Step 1 diet are effective in reducing total and LDL cholesterol.

Effect of postprandial lipaemia and Taq 1B polymorphism of the cholesteryl ester transfer protein (CETP) gene on CETP mass, activity, associated lipoproteins and plasma lipids.

A large number of studies in recent years have investigated the effects of hyperlipidaemias and diabetes on cholesteryl ester transfer protein (CETP) on neutral lipid transfer activity and plasma lipids. There has been an ongoing debate as to whether CETP is pro- or anti-atherogenic as it provides a mechanism for the transfer of cholesterol from the cardioprotective HDL subfraction to the potentially atherogenic LDL subfraction. This study was designed to investigate whether there was significant variability of CETP mass and activity in a large normolipidaemic population and whether there is an association between CETP and plasma lipoprotein composition. The presence of a known polymorphism of CETP gene (Taq 1B) was investigated to see if there was any association between this polymorphism and CETP mass and activity, and plasma lipids. There was significant (P < 0.0001) increase in CETP mass and activity in plasma postprandially at 6 h. Using multiple stepwise regression analysis there was significant association with fasting CETP mass and activity (beta = 0.055; P = 0.002) and triacylglycerol-rich lipoprotein (beta = 0.013; P = 0.005) and postprandial CETP mass (beta = 0.254; P = 0.007). Repeated-measures analysis showed a strong association between the absence of Taq 1B polymorphism and low CETP mass and elevated HDL- and HDL2-cholesterol and HDL-phospholipid concentrations than did those who were homozygous or heterozygous for the presence of the restriction site.

Postprandial factor VII metabolism: the effect of the R353Q and 10 bp polymorphisms.

Elevated levels of coagulation factor VII activity (FVIIc) are associated with increased risk of CHD. FVIIc is strongly determined by two polymorphisms (R353Q and 0/10 base pairs (bp)) and plasma triacylglycerol (TAG) concentrations. The Q and 10 bp polymorphisms show strong linkage disequilibrium and have been associated with lower levels of fasting FVII, but there has been little investigation of the effect of these genotypes on the postprandial FVII metabolism. The present study demonstrated that fasting activated factor VII (FVIIa) and factor VII antigen (FVIIag) levels were significantly lower in the heterozygotes carrying the Q and 10 bp alleles (n 12), than in the R/0 bp homozygotes (n 12) (43.0 (SE 4.8) v. 23.9 (SE 6.5) mU/ml and 85.7 (SE 5.4) v. 71.6 (SE 7.5)% respectively). During postprandial lipaemia there was a significant increase in FVIIa in R/0 bp homozygotes but not in the heterozygotes carrying the Q and 10 bp alleles. The proportion of FVIIa (FVIIa:FVIIag) increased in the homozygotes but not in the heterozygotes (2.04 (SE 0.35) v. 1.20 (SE 0.26) respectively). Therefore possession of the relatively common Q and 10 bp alleles is not associated with postprandial activation of FVII, which may in turn have a protective effect against CHD.