Effect of iron supplementation on oxidative stress and antioxidant status in iron-deficiency anemia

This study was designed to measure the effect of iron supplementation on antioxidant status in iron-deficient anemia, including the time for hemoglobin normalization and at the time of filling of iron body stores. The extent of plasma lipid peroxidation was evaluated by measuring the levels of malondialdehyde and glutathione peroxidase (GSH-Px), and the activities of superoxide dismutase (SOD) and catalase in 63 patients with iron-deficiency anemia before and after 6 wk of iron supplementation and at the time when body iron stores are saturated. After 6 wk of iron supplementation, a significant decrease of oxidative stress was observed in the treated subjects relative to controls (p<0.05). No significant differences existed between treated patients at 6 wk and at the end of the study. The erythrocyte levels of catalase, SOD, and GSH-Px were significantly lower in treated patients relative to controls (p<0.05). These levels increased after 6 wk of supplementation (p<0.05) and showed no significant differences with those at the end of the study.     

Decrease of plasma taurine in Gaucher disease and its sustained correction during enzyme replacement therapy

Summary. Gaucher disease is caused by an autosomal-recessive deficiency of glucocerebrosidase. Cells of monocytic/macrophagic origin accumulate glucosylceramide. This leads to hepatosplenomegaly, bone destruction, thrombocytopenia and anemia. Enzyme replacement therapy (ERT) with macrophage-targeted glucocerebrosidase leads to normalization of these parameters. The way of macrophage activation in Gaucher disease is not known. Recently, the osmolytes taurine, betaine and inositol were identified as important regulators of macrophage function in liver. Therefore, the role of plasma taurine in Gaucher disease as a primarily macrophage-derived disease was studied. Fasting plasma levels were measured from blood samples of healthy control subjects (n = 29, m : f = 11 : 18, mean age 37 ± 3 years), from un-treated Gaucher patients (n = 16, m : f = 7 : 9, mean age 44 ± 4 years) and those treated for 37 ± 2 months (n = 54, m : f = 19 : 35, mean age 47 ± 2 years). Amino acid analysis was carried out in a BioChrom amino acid analyzer. In the untreated patients, plasma taurine was 45 ± 3 μM, as compared to the controls with a plasma taurine of 63 ± 4 μM (p < 0.01). The aver-age increase of plasma taurine during the first year of ERT was 18 ± 8 μM (n = 10). Patients treated for an average of 37 months (range 1–9 years of ERT) had a plasma taurine of 65 ± 4 μM (n = 54), which was not different from the controls. It is concluded that Gaucher patients show decreased plasma taurine levels and that therapy of Gaucher disease might correct this. It has to be established, whether decreased taurine availability is a cofactor of the permanent activation of glucosylceramide-storing monocytes/macrophages in this disease. Received January 25, 2000/Accepted January 31, 2000     

Response to orphaning in two Neotropical termites: shape Armitermes euamignathus and shape Embiratermes festivellus

In this paper we examine the potential of the termites Armitermes euamignathus Silvestri: 1901 and Embiratermes festivellus (Silvestri, 1901) (Isoptera, Termitidae, Nasutitermitinae) to produce neotenics experimentally. Three nests of the mound-building termite A. euamignathus, from the Brazilian cerrado, had their primary queens removed in August 1994. After 12 months, only one mound survived; it had a normal appearance. In this healthy, orphaned colony we found the primary king, six physogastric nymphoid female replacement reproductives, two ergatoid female replacement reproductives, 46 nymphs, several presoldiers, soldiers, workers, larvae and many eggs. These data show that neotenics in A. euamignathus may originate from both workers and nymphs, but nymphoids are produced in larger numbers. The biometric study of nymphs and nymphoids suggests that these brachypterous neotenics were derived from third instar nymphs after a single moult or from four instar nymphs after a reduction of wing bud length. A piece of an E. festivellus nest with some third instar nymphs, soldiers and workers was kept under laboratory conditions. After 12 months, the whole experimental subcolony was examined and appeared to contain two pigmented nymphoid females, two pigmented nymphoid males, only one larva, seven nymphs of the same instar, 148 workers, five soldiers and many eggs. These results also indicate the capacity of the termite E. festivellus to produce nymphoid neotenics. These neotenic females were laying eggs, but they were not physogastric after a year, unlike some nymphoids of the same species collected from natural colonies.     

Mutagenesis of histidine 26 demonstrates the importance of loop-loop and loop-protein interactions for the function of iso-1-cytochrome c.

In yeast iso-1-cytochrome c, the side chain of histidine 26 (His26) attaches omega loop A to the main body of the protein by forming a hydrogen bond to the backbone atom carbonyl of glutamic acid 44. The His26 side chain also forms a stabilizing intra-loop interaction through a hydrogen bond to the backbone amide of asparagine 31. To investigate the importance of loop-protein attachment and intra-loop interactions to the structure and function of this protein, a series of site-directed and random-directed mutations were produced at His26. Yeast strains expressing these variant proteins were analyzed for their ability to grow on non-fermentable carbon sources and for their intracellular production of cytochrome c. While the data show that mutations at His26 lead to slightly decreased intracellular amounts of cytochrome c, the level of cytochrome c function is decreased more. The data suggest that cytochrome c reductase binding is affected more than cytochrome c oxidase or lactate dehydrogenase binding. We propose that mutations at this residue increase loop mobility, which, in turn, decreases the protein's ability to bind redox partners.     

Tooth replacement rates in early chondrichthyans: a qualitative approach

The continuous replacement of teeth throughout their lifetime is a common characteristic of most chondrichthyans. This process was already present in the earliest representatives of the group. It has been well established that different species of extant sharks show rapid tooth replacement rates; however, some authors have suggested that in early chondrichthyans this rate might have been much slower. Here we present a qualitative approach to analyse tooth replacement rates in the Early Devonian shark Leonodus carlsi , the earliest tooth-bearing shark known to date. For this, we have examined 1,103 isolated teeth from Celtiberia, Spain. Our study provides strong evidences of an extremely slow dental replacement in this primitive chondrichthyan based on three independents analyses: (1) statistical analysis of the wear degree, demonstrating that teeth remain functional for a long period of time; (2) analysis of both the histological and the morphological features of the teeth cusps suggests that this chondrichthyan used a maturation process that optimizes its function, thus worn teeth show an efficient working shape that implies their teeth remained functional for a long time after being modelled by use; and (3) estimations of size increments between teeth (Δs) of the same dental family for some recent sharks whose rates of replacement were known prove that Δs is inversely proportional to the rate of replacement ( R ² = 0.8327). The estimated values of tooth replacement rates obtained from Δs for L. carlsi and for some Late Devonian cladoselachian sharks are significatively slower than those observed in current sharks.     

Deletion of sterol O-acyltransferase 2 (SOAT2) function in mice deficient in lysosomal acid lipase (LAL) dramatically reduces esterified cholesterol sequestration in the small intestine and liver

Sterol O-acyltransferase 2 (SOAT2), also known as ACAT2, is the major cholesterol esterifying enzyme in the liver and small intestine (SI). Esterified cholesterol (EC) carried in certain classes of plasma lipoproteins is hydrolyzed by lysosomal acid lipase (LAL) when they are cleared from the circulation. Loss-of-function mutations in LIPA, the gene that encodes LAL, result in Wolman disease (WD) or cholesteryl ester storage disease (CESD). Hepatomegaly and a massive increase in tissue EC levels are hallmark features of both disorders. While these conditions can be corrected with enzyme replacement therapy, the question arose as to what effect the loss of SOAT2 function might have on tissue EC sequestration in LAL-deficient mice. When weaned at 21 days, Lal^−/−:Soat2^+/+ mice had a whole liver cholesterol content (mg/organ) of 24.7 mg vs 1.9 mg in Lal^+/+:Soat2^+/+ littermates, with almost all the excess sterol being esterified. Over the next 31 days, liver cholesterol content in the Lal^−/−:Soat2^+/+ mice increased to 145 ± 2 mg but to only 29 ± 2 mg in their Lal^−/−:Soat2^−/− littermates. The level of EC accumulation in the SI of the Lal^−/−:Soat2^−/− mice was also much less than in their Lal^−/−:Soat2^+/+ littermates. In addition, there was a >70% reduction in plasma transaminase activities in the Lal^−/−:Soat2^−/− mice. These studies illustrate how the severity of disease in a mouse model for CESD can be substantially ameliorated by elimination of SOAT2 function.     

中华山蝠牙齿的脱换模式

笔者于1997年对中华山蝠(Nyctalus velutinus)牙齿的脱换模式进行了研究。共观察幼蝠200只次。中华山蝠初生仔共有22枚乳齿,齿式为2.1.2.0/3.1.2.0,各乳齿略向舌侧倾斜,除乳前臼齿齿冠不分叉外,其余乳齿齿冠均分为三叶。4d龄开始换齿,31d龄左右脱换完毕。乳齿的脱落顺序是:上颌,PM2→PM1→C1→I1→I2;下颌,I1→PM2.I2→I3→PM1→C1;恒齿萌生的顺序为:上颌,M1→PM2.C1→M2→PM1.M3→I1→I2,下颌,M1→I1.PM2→I2.M2→I3.PM1→C1→M3。     

Estradiol enhances cell-associated paraoxonase 1 (PON1) activity in vitro without altering PON1 expression

PON1 is a high density lipoprotein-associated enzyme that plays an important role in organophosphate detoxification and prevention of atherosclerosis. In vivo animal and human studies have indicated that estradiol (E2) supplementation enhances serum PON1 activity. In this study, we sought to determine if E2 directly up-regulates cell-associated PON1 activity in vitro and to characterize the mechanism of regulation. In vitro E2 treatment of both the human hepatoma cell line Huh7 and normal rat hepatocytes resulted in a 2- to 3-fold increase in cell-associated PON1 catalytic activity. E2 potently induced PON1 activity with average EC₅₀ values of 15 nM for normal hepatocytes and 68 nM for Huh7. The enhancement of PON1 activity by E2 was blocked by the estrogen receptor (ER) antagonist ICI 182,780 indicating that E2 was acting through the ER. The up-regulation of PON1 activity by E2 did not involve enhancement of PON1 mRNA or protein levels and did not promote secretion of PON1. Thus, E2 can enhance cell-associated PON1 activity in vitro without altering PON1 gene expression or protein level. Our data suggest that E2 may regulate the specific activity and/or stability of cell surface PON1.