Inhibitory effect of the flavonoid silymarin on the erythrocyte hemolysis induced by phenylhydrazine

The flavonoid silymarin, which is used as a therapeutical agent in the treatment of liver diseases, can inhibit the hemolysis and lipid peroxidation induced by phenylhydrazine on erythrocytes obtained from rats treated with the flavonoid. This effect is ascribed to the antioxidant properties as a free radical scavenger exhibited by the flavonoid. Silymarin failed to inhibit the glutathione depletion induced by phenylhydrazine on erythrocytes. It is proposed that the flavonoid acts at the membrane level of the cell avoiding the lipid peroxidative and fluidizing effect of phenylhydrazine.     

Cyclo(His-Pro) up-regulates heme oxygenase 1 via activation of Nrf2-ARE signalling

Paraquat (1,1'-dimethyl-4,4'-bipyridinium), a widely used non-selective herbicide, is a redox cycling agent with adverse effects on dopamine systems. Epidemiological data have shown that exposure to paraquat is one of the several risk factors for Parkinson's disease. We have already shown that cyclo(His-Pro), an endogenous cyclic dipeptide produced by the cleavage of the thyrotropin releasing hormone, has a cytoprotective effect through a mechanism involving Nrf2 activation that decreases production of reactive oxygen species and increases glutathione synthesis. Using primary neuronal cultures and PC12 cells as targets of paraquat neurotoxicity, we addressed whether and how cyclo(His-Pro) causes cellular protective response against paraquat-mediated cell death. We found that cyclo(His-Pro) attenuated reactive oxygen species production, and prevented glutathione depletion by up-regulating Nrf2 gene expression, triggering its nuclear accumulation and activating the expression of heme oxygenase1. These protective effects were abolished by RNA interference-mediated Nrf2 knock down whereas were unaffected by RNA interference-mediated Keap1 knock down. Inhibition of heme oxygenase activity decreased cyclo(His-Pro)-induced neuroprotection. These results suggest that cyclo(His-Pro), acting as a selective activator of the brain modulable Nrf2 pathway, may be a promising candidate as neuroprotective agent that act through induction of phase II genes.     

A new mutant class of soybean lacks urease in leaves but not in leaf-derived callus or in roots

Summary We reported earlier the recovery of two classes of soybean urease mutants in soybean (Glycine max L. Merr. cv. Williams). Class I mutants lack the embryo-specific urease while class II mutants lack the activities of both urease isozymes, the embryo-specific and the ubiquitous urease, the latter found in all tissues examined. We report here the recovery of a true-breeding mutant, aj3, which represents the third phenotypic class: normal levels of embryo-specific urease and little or no ubiquitous urease. Unlike class II mutant plants which lack urease in all tissue, aj3 lacks urease activity only in leaves (ca. 2% normal activity); its roots have near normal urease activity. Callus derived from leaves of aj3 has 14% to 40% the urease activity of Williams 82 callus. This partial reduction in urease activity in aj3 callus is sufficient to reduce growth with urea as sole nitrogen source and to confer resistance to 50 mM urea added to callus maintenance medium. Leaves of aj3 produce more than 40 times the urease antigen expected from their urease activity. The aj3 trait is due to a single recessive lesion which is not allelic with lesions at theEu2, Eu3 (class II) orEu1 (class I) loci. We designate the aj3 genotype aseu4/eu4.     

Meclofenamate increases ventilation in lambs

To investigate the effects of the prostaglandin synthetase inhibitor, meclofenamate, on postnatal ventilation, we studied 11 unanaesthetised, spontaneously-breathing lambs at an average age of 7.9 +/- 1.1 days (SEM; range 5-14 days) and an average weight of 4.9 +/- 0.5 kg (range 3.0-7.0 kg). After a 30-min control period we infused 4.23 mg/kg meclofenamate over 10 min and then gave 0.23 mg/h per kg for the remainder of the 4 h. Ventilation increased progressively from a control value of 515 +/- 72 ml/min per kg to a maximum of 753 +/- 100 ml/min per kg after 3h of infusion (P less than 0.05) due to an increased breathing rate; the effects were similar during both high- and low-voltage electrocortical activity. There were no significant changes in tidal volume, heart rate, blood pressure, arterial pH or PaCO2, the increased ventilation resulted from either an increase in dead space ventilation or an increase in CO2 production. This study indicates that meclofenamate causes an increase in ventilation in lambs but no changes in pH of PaCO2. The mechanism and site of action remain to be defined.     

The cytotaxonomy ofEmilia spp. (Asteraceae: Senecioneae) occurring in Brazil

Analysis of several populations in a large part of the distribution area of the genusEmilia in Brazil has revealed only two species: the diploidE. sonchifolia and the tetraploidE. fosbergii. The more widely reportedE. coccinea was not found. They show a karyotype constancy in morphology and chromosome number (2n = 10 and 2n = 20, respectively), C-banding pattern and number of secondary constrictions. Some indications were found thatE. fosbergii may be an allopolyploid and that its ancestors had different genome sizes.     

Aromatic l-Amino Acid Decarboxylase Activity of the Rat Retina Is Modulated In Vivo by Environmental Light Maria Hadjiconstantinou

Aromatic L-amino acid decarboxylase (AAAD) activity of rat retina is low in animals placed in the dark. When the room lights are turned on, activity rises for almost 3 h and reaches values that are about twice the values found in the dark. A study of the kinetics of the enzyme revealed that the apparent Km values for L-3,4-dihydroxyphenylalanine and pyridoxal-5'-phosphate were unchanged in light- and dark-exposed animals, whereas the Vmax increased in the light. Treating the animals with cycloheximide before exposure to light prevented the increase of enzyme activity. Immunotitration with antibodies to AAAD suggested that more enzyme molecules are present in the light than in the dark. When the room lights are turned off AAAD activity drops rapidly at first and then more slowly, suggesting that at least two processes are responsible for the fall of enzyme activity. Exposure to short periods of dark followed by light results in a rapid increase of AAAD activity. Mixing homogenates from light- and dark-exposed rats results in activity values that are less than expected, suggesting the presence of an endogenous inhibitor(s). These studies demonstrate that AAAD activity is modulated in vivo.     

1H NMR investigation of reduced copper-cobalt superoxide dismutase

Human copper-cobalt superoxide dismutase in the reduced form has been investigated through ¹H NMR techniques. The aim is to monitor the structural properties of this derivative and to compare them with those of reduced and oxidized native superoxide dismutases. The observed signals of the cobalt ligands have been assigned as well as the signals of the histidines bound to copper(I). The latter signals experience little pseudocontact shifts which allow a rough orientation of the magnetic susceptibility tensor in the molecular frame. The connectivities indicate that, although the histidine bridge is broken in the reduced form, the interproton distances between ligands of both ions are essentially the same.Abbreviations WEFT water eliminated Fourier transform - NOE nuclear Overhauser effect - NOESY NOE spectroscopy - COSY correlation spectroscopy - TOCSY total correlation spectroscopy - SOD superoxide dismutase - E₂Co(II)SOD SOD with empty copper site (E=empty) and with cobalt(II) in the Zinc(II) site Offprint requests to: I. Bertini     

Effects of progesterone and estradiol-17 beta on uterine secretion of prostaglandin F2 alpha in response to oxytocin in ovariectomized ewes

Twenty ovariectomized ewes were used in an experiment designed to examine the interaction of progesterone, estradiol, and oxytocin in the regulation of uterine secretion of prostaglandin F2 alpha (PGF2 alpha). All ewes underwent a steroid pretreatment that mimicked the changes in progesterone and estradiol which occur during the six days immediately prior to estrus. After pretreatment, ewes were randomly assigned to 1 of 4 treatment groups: 1) control (n = 4); 2) estradiol-17 beta (n = 6); 3) progesterone (n = 4); and 4) progesterone and estradiol-17 beta (n = 6). Progesterone was injected twice daily for 15 days. The dose of progesterone varied with day postestrus in a manner designed to simulate endogenous luteal secretion of progesterone. Estradiol-17 beta was administered in s.c. Silastic implants. The implants maintained circulating concentrations of estradiol at 3 pg/ml. On Days 5, 10, and 15 of treatment, ewes were injected with oxytocin (10 IU in 1.0 ml saline, i.v.). Jugular venous blood samples were collected beginning one-half hour prior to and continuing for 2 hours post-oxytocin injection for quantification of 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM). No changes in concentration of PGFM following injection of oxytocin were observed on Day 5 or 10 in any treatment group. Concentrations of PGFM increased following injection of oxytocin on Day 15 only in groups receiving progesterone. Both the area under the PGFM response curve (p = 0.08) and peak response (p = 0.06) were greater in ewes treated with progesterone and estradiol-17 beta than in those receiving progesterone alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased Resistance Against Oxidative Stress Is Observed During A Short Period of Renal Reperfusion After A Temporal Ischaemia

Reperfusion of rat kidney submitted to temporal ischaemia induces a decrease in glutathione content. Lipid peroxidation is not detected in kidney homogenates but microsomes obtained after periods of reperfusion longer than 60 minutes show increased malondialdehyde values correlated with high oxygen consumption and superoxide free radical generation. Microsomes obtained from kidneys submitted to 15 or 60 minutes of reperfusion are resistant to NADPH-induced lipid peroxidation but after 120 minutes of reperfusion an increased lipid peroxidative response is observed. Although the mechanism of the protection found in microsomes against the induction of oxidative stress in the first 60 minutes of reperfusion is unknown, it is postulated that this subcellular fraction plays an important role in the oxidative stress observed after longer periods of reperfusion.