Effects of calcium ions and quinolinic acid on rat kidney mitochondrial kynurenine aminotransferase

At pH 6.4, rat kidney mitochondrial kynurenine aminotransferase activity is enhanced several-fold by the addition of CaCl2, apparently because Ca++ facilitates the translocation of [alpha]-ketoglutarate, one of the substrates, across the mitochondrial inner membrane. Chloride salts or Mg++, Mn++, Na+, K+, and NH4+ did not have this effect. At pH 6.8, the enzyme activity was near maximal even without added Ca++ but was strongly depressed by either of two calcium chelating agents, quinolinic acid (Q.A.) and ethyleneglycol-bis([beta]-aminoethyl ether)N,N'-tetraacetic acid (EGTA). These observations support the view that Ca++ is involved in regulating kidney mitochondrial translocation of [alpha]-ketoglutarate and that the reported interference of polycarboxylate anion translocation by Q.A. depends on the ability of that agent to chelate Ca++.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22280/1/0000719.pd

Platelet activating factor stimulates arachidonic acid release in differentiated keratinocytes via arachidonyl non-selective phospholipase A2

Platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is known to be present in excess in psoriatic skin, but its exact role is uncertain. In the present study we demonstrate for the first time the role of group VI PLA2 in PAF-induced arachidonic acid release in highly differentiated human keratinocytes. The group IVα PLA2 also participates in the release, while secretory PLA2s play a minor role. Two anti-inflammatory synthetic fatty acids, tetradecylthioacetic acid and tetradecylselenoacetic acid, are shown to interfere with signalling events upstream of group IVα PLA2 activation. In summary, our major novel finding is the involvement of the arachidonyl non-selective group VI PLA2 in PAF-induced inflammatory responses

Tetradecylthioacetic Acid Increases Hepatic Mitochondrial β-Oxidation and Alters Fatty Acid Composition in a Mouse Model of Chronic Inflammation

The administration of tetradecylthioacetic acid (TTA), a hypolipidemic and anti-inflammatory modified bioactive fatty acid, has in several experiments based on high fat diets been shown to improve lipid transport and utilization. It was suggested that increased mitochondrial and peroxisomal fatty acid oxidation in the liver of Wistar rats results in reduced plasma triacylglycerol (TAG) levels. Here we assessed the potential of TTA to prevent tumor necrosis factor (TNF) α-induced lipid modifications in human TNFα (hTNFα) transgenic mice. These mice are characterized by reduced β-oxidation and changed fatty acid composition in the liver. The effect of dietary treatment with TTA on persistent, low-grade hTNFα overexpression in mice showed a beneficial effect through decreasing TAG plasma concentrations and positively affecting saturated and monounsaturated fatty acid proportions in the liver, leading to an increased anti-inflammatory fatty acid index in this group. We also observed an increase of mitochondrial β-oxidation in the livers of TTA treated mice. Concomitantly, there were enhanced plasma levels of carnitine, acetyl carnitine, propionyl carnitine, and octanoyl carnitine, no changed levels in trimethyllysine and palmitoyl carnitine, and a decreased level of the precursor for carnitine, called γ-butyrobetaine. Nevertheless, TTA administration led to increased hepatic TAG levels that warrant further investigations to ascertain that TTA may be a promising candidate for use in the amelioration of inflammatory disorders characterized by changed lipid metabolism due to raised TNFα levels

Maintenance of the pectoralis muscle during hibernation in the big brown bat, Eptesicus fuscus

The relationship between pectoralis muscle mass and body mass is examined throughout the annual body mass cycle in Eptesicus fuscus in order to evaluate muscle maintenance during hibernation. E. fuscus undergoes large fluctuations in body mass during the year due to pregnancy, parturition, prehibernation fattening, and hibernation (Table 1). Parallel changes occur in pectoralis muscle mass and total pectoralis protein mass (Table 2). The strong correlation between log pectoralis mass and log body mass (Fig. 3) and the lack of correlation between pectoralis mass and forearm length (Fig. 1, 2) suggest that the seasonal variation in pectoralis muscle mass represents a compensatory response to changing body mass. In active bats this relationship closely resembles the compensatory response predicted by flight theory.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47128/1/360_2004_Article_BF00689733.pd

Scandinavian society for the study of diabetes Abstracts Seventh Meeting

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46039/1/125_2005_Article_BF01219478.pd

Development of a novel method for synthesis of β-lactams by the use of diazoacetamides

Due to the increase in antibacterial resistance, the world is in need of new, powerful antibacterial agents and synthetic methods to halter this trend. This study focused on broadening the scope of a new synthesis of β-lactams developed by Kaupang and Konradsen. The method uses carbenes generated from α-bromodiazoacetamides in an intramolecular C-H insertion reaction to generate the β-lactam moiety. With this new method, it could be possible to synthesize new β-lactam molecules. This creates an opportunity of discovering molecules with novel antibacterial properties beyond what is known today. The method was successfully applied in the syntheses of the diazoacetamides with a methyl, ethyl or isopropyl ester. Only the β-lactam with the ethyl ester was successfully synthesized from the diazoacetamides. Consequently, not enough data was available to determine how the product distribution in this synthetic step was affected by the ester. Additional focus of this thesis was on improving the synthesis of the diazoacetamides, due to a difficult purification and moderate yields. Several test reactions were conducted in order to develop a one-step synthesis of the diazoacetamides. A one-step reaction could avoid the problems in the original procedure, in addition to making the β-lactam formation more effective. The test reaction using 2,5-dioxypyrrolidin-1-yl 2-diazoacetate and methyl D-prolinate as reactants seems promising, but more work is necessary to develop the procedure further