Acaricides containing zein nanoparticles: A tool for a lower impact control of the cattle tick Rhipicephalus microplus.

Nanoformulations containing zein nanoparticles (ZN) can promote the stability and protection of molecules with acaricidal activity. The present study sought to develop nanoformulations with ZN associated with cypermethrin (CYPE) + chlorpyrifos (CHLO) + a plant compound (citral, menthol or limonene), characterize them, and verify their efficacy against Rhipicephalus microplus ticks. Additionally, we aimed to assess its safety in nontarget nematodes found in soil at a site subjected to contamination by acaricides.

Proposed Tandem Effect of Physical Activity and Sirtuin 1 and 3 Activation in Regulating Glucose Homeostasis.

Sirtuins (SIRTs) are seven nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylases enzymes (SIRT1-7) that play an important role in maintaining cellular homeostasis. Among those, the most studied are SIRT1 and SIRT3, a nuclear SIRT and a mitochondrial SIRT, respectively, which significantly impact with an increase in mammals' lifespan by modulating metabolic cellular processes. Particularly, when activated, both SIRT1 and 3 enhance pancreatic β-cells' insulin release and reduce inflammation and oxidative stress pancreatic damage, maintaining then glucose homeostasis.

Intracellular accumulation of a mild-denatured monomer of the human PrP fragment 90-231, as possible mechanism of its neurotoxic effects.

Because of high tendency of the prion protein (PrP) to aggregate, the exact PrP isoform responsible for prion diseases as well as the pathological mechanism that it activates remains still controversial. In this study, we show that a pre-fibrillar, monomeric or small oligomeric conformation of the human PrP fragment 90-231 (hPrP90-231), rather than soluble or fibrillar large aggregates, represents the neurotoxic species. In particular, we demonstrate that monomeric mild-denatured hPrP90-231 (incubated for 1 h at 53 degrees C) induces SH-SY5Y neuroblastoma cell death, while, when structured in large aggregates, it is ineffective.

Conformation dependent pro-apoptotic activity of the recombinant human prion protein fragment 90-231.

The transition of prion protein from a mainly alpha-structured isoform (PrPC) to a beta sheet-containing protein (PrPSc) represents a major pathogenetic mechanism in prion diseases. To study the role of PrP structural conformation in prion-dependent neurodegeneration, we analysed the neurotoxicity of PrP in alpha and beta conformations, using a recombinant protein encompassing amino acids 90-231 of the human PrP (hPrP90-231). Using controlled thermal denaturation (53 degrees C, 1h) we converted hPrP90-231 in a structural isoform displaying PrPSc-related characteristics: high beta sheet content, increased aggregability and a slight increase in the resistance to protease K.

Pyrimido [4,5,6-kl] acridines, a new class of potential anticancer agents. Synthesis and biological evaluation.

A series of 3-(aminoalkyl)-2,7-dihydro-6-nitropyrimido [4,5,6-kl] acridin-2-ones 3, strictly related to the pyrazoloacridines 1, have been synthesized. Thus, the reaction of the suitable 1-(aminoalkyl)amino-9, 10-dihydro-9-imino-4-nitroacridine 2 with ethyl chloroformate afforded the pyrimidoacridines 3a-f. By hydrolysis in hydrobromic acid of the 10-methoxy derivatives 3d-f, the 10-hydroxy derivatives 3g-i were obtained.

Synthesis and biological evaluation of mono- and bis-[(alkylamino)alkylamino] substituted thienopyridopyridazines, a new class of potential antitumor agents.

A new class of potential antitumor agents, provided with thieno[2',3':5,6]pyrido[2,3-d]pyridazin-9(4H)-one nucleus as chromophore, was synthesized. Thus, the suitable amines were reacted, in different conditions, with 5,8-dichlorothieno[2',3':5,6]pyrido[2,3- d]pyridazin-9(4H)-one (5) to afford the 8-alkylamino derivatives 6a-f, the 5-alkylamino derivatives 7a-f, and the 5,8-bis-alkylamino derivatives 8a,b. Selected compounds were evaluated for cytotoxic potency in vitro against the human colon adenocarcinoma HT 29 cell line and studied in DNA binding assays.

Adolescent schizophrenia: a methodologic review of the current neuroimaging and neuropsychologic literature.

This paper reviews all relevant articles that reported structural neuroimaging or neuropsychological data in adolescent patients with schizophrenia. These papers were subsequently examined from a methodological perspective. Few papers have been written that have examined whether adolescent schizophrenia is associated with structural neuroimaging abnormalities or cognitive dysfunction.

Synthesis of (dialkylamino)alkyl-disubstituted pyrimido[5,6,1- de]acridines, a novel group of anticancer agents active on a multidrug resistant cell line.

A series of pyrimidoacridine derivatives with two basic side chains, 7a-e, was synthesized, as potential antitumor drugs, starting from 2-[2-(dimethylamino)ethyl]-6-chloropyrimido[5,6,1-de]acridine-1,3, 7- trione (6) and a suitable (alkylamino)alkylamine. The products 6 and 7a-e showed significant cytotoxic activity in vitro against L1210 leukemia. Compounds 7a,d were 2 orders of magnitude more cytotoxic than ametantrone.

Dynamics of hydrogen atoms in superoxide dismutase by quasielastic neutron scattering.

The low energy dynamic of the enzyme Cu,Zn superoxide dismutase have been investigated by means of quasielastic neutron scattering in the temperature range 4-320 K. Below 200 K the scattering is purely elastic, while above this temperature a pronounced decrease in the elastic intensity is observed, together with the onset of a small quasielastic component. This behavior is similar to that previously observed in other more flexible globular proteins, and can be attributed to transitions between slightly different conformational substates of the protein tertiary structure.

Water dynamics in charged and uncharged polysaccharide gels by quasi-elastic neutron scattering.

Using a microeV neutron spectrometer we have studied the mobility of water in gels formed by two polysaccharides: agarose and hyaluronic acid. Agarose is a nearly uncharged polysaccharide; its gels are fairly stiff, quasi-random networks of fibre bundles. Hyaluronic acid is a highly charged polysaccharide capable of retaining large amounts of water in entangled meshworks with unusual rheological properties.

Synthesis of 9,10-anthraquinone monoalkylaminoalkylhydrazones as potential antitumor drugs.

In the constant search for new compounds endowed with antitumor activity we have synthesized a series of anthraquinone hydrazones, which can bee seen either as opened-cycle modified anthrapyrazoles or as chromophore-modified anthracenediones. Seven 9,10-anthraquinone monoalkylaminoalkylhydrazones (3c-i) were synthesized from 10,10-dibromoanthrone (4) and a suitable N-alkylhydrazine. The hydrazones were converted into hydrochlorides and tested for their cytotoxic activity against L1210 murine leukemia cells.

Synthesis of 7-oxo-7H-benzo[e]perimidine-4-carboxamides as potential antitumor drugs.

A series of 7-oxo-7H-benzo[e]perimidine-4-carboxamides (4a-f) was synthetized from the corresponding acid (3) and the suitable amines by the "mixed anhydride" method. The amide derivatives were tested for antitumor activity against P 388 leukemia "in vivo". Only the N-[2-(diethylamino)ethyl]-7-oxo-7H-benzo[e]perimidine-4-carboxa mid e (4b) shows borderline antineoplastic activity.

Pyrimidoacridine derivatives as potential antitumor agents.

A series of some N-alkylaminoalkyl derivatives of pyrimido[5,6,1-d,e]acridine-1,3,7-trione (3) was synthesized as new potential antitumor drugs, starting from the suitable 9,10-dihydro-9-oxo-4-acridinecarboxamides and using phosgene as cyclizing agent. 1-(9,10-dihydro-9-oxo-4-acridinecarbonyl)-3-alkyl-2-imidazolido nes were also obtained as side products. The final products 3 and some carboxamides were tested "in vitro" against L 1210 leukemia and "in vivo" against P388 leukemia.

Human erythrocyte contains a factor that stimulates the peptidase activities of multicatalytic proteinase complex.

A novel biological factor that stimulates the peptidase activities of multicatalytic proteinase complex (MPC) has been identified and partially purified from human erythrocytes. The stimulatory factor enhances trypsin-like, chymotrypsin-like and peptidyl-glutamyl peptide hydrolyzing activity of MPC in a dose related manner. At saturating concentration of the stimulatory factor, MPC increases the activity to a different extent (10 to 56 fold) depending on the substrate used to assay the enzyme.

Multicatalytic and 26 S ubiquitin/ATP-stimulated proteases in maturing rabbit red blood cells.

Rabbit red blood cells of various ages were separated on Percoll gradients and the activities of two large cytosolic proteases were measured. Both the multicatalytic protease (MCP), assayed by hydrolysis of fluorigenic peptides, and the 26 S ubiquitin/ATP-stimulated protease, assayed by degradation of ubiquitin-lysozyme conjugates, declined 3-fold or less during maturation of rabbit reticulocytes to erythrocytes. The ability of MCP to hydrolyze three classes of peptides decreased in parallel indicating that the 20 S protease is not significantly remodeled during red blood cell maturation.

Isolation of two high-molecular-mass proteinases from human erythrocytes.

Two forms of a neutral--alkaline high-molecular-mass proteinase (termed A1 and A2) have been purified from human erythrocytes by a procedure including a DEAE-cellulose batchwise treatment of erythrocyte cytosol, gel filtration and DEAE-cellulose chromatography. Both enzymes show distinctive properties of multicatalytic proteinases. They have an apparent molecular mass of 700 kDa and are composed by eight major subunits (23-32 kDa).

Purification of human erythrocyte proteolytic enzyme responsible for degradation of oxidant-damaged hemoglobin. Evidence for identifying as a member of the multicatalytic proteinase family.

Exposure of human red cells to oxidants such as phenylhydrazine, 2,4-dimethylphenylhydrazine and 4-hydrazinobenzoic acid stimulates the proteolysis of hemoglobin as evidenced by the increase in the rate of the free alanine and acid soluble amino groups released. An enzyme responsible for proteolytic degradation of oxidized hemoglobin, was purified from cytosolic fraction of erythrocytes by a DEAE-batch procedure followed by gel-filtration and ion-exchange chromatography. The final enzyme preparation produces a single band in non-denaturing polyacrylamide gel electrophoresis, and eight different bands of 23-32 kDa when subjected to polyacrylamide gel electrophoresis under denaturing conditions.

Changes of a high molecular mass proteinase activity during Bufo bufo development.

1. A chymotrypsin-like proteolytic activity was found both in unfertilized eggs and in embryos of Bufo bufo. 2.

Fragmentation of human hemoglobin by oxidative stress produced by phenylhydrazine.

Exposure of purified human hemoglobin to phenylhydrazine induces the oxidation of hemoglobin and the generation of acid soluble peptides. The extent of protein fragmentation depends on the concentration of phenylhydrazine, incubation time and temperature. The fragments, excluded by gel filtration chromatography on Sephadex G-15, are partially degraded by leucine aminopeptidase and are totally converted to amino acids by acid hydrolysis.

Proteolysis in human erythrocytes is triggered only by selected oxidative stressing agents.

Human erythrocytes have been treated with different agents producing oxidative stress. Diamide, tetrathionate, chromate, cystamine and iodate preferentially influenced the cellular redox state by oxidation of free and protein thiol groups leaving the redox state of hemoglobin virtually unaffected. None of these compounds was able to stimulate the proteolysis.

Preliminary studies on the effect of glutathione S-transferase from Providencia stuartii on the antimicrobial activity of different antibiotics.

Glutathione S-transferase has been isolated and purified from a Providencia stuartii CH 114 strain. The effect of the enzyme on the antimicrobial activity of amikacin, cefotaxime, cephalexin, ampicillin, nalidixic acid, and ofloxacin was tested. The efficiency of all antibiotics tested, except nalidixic acid and ofloxacin, is relevantly decreased by the presence of glutathione S-transferase in the medium culture, as proved by the increased value of MIC.

Irreversible inactivation of calcium-dependent proteinases from rat liver by biological disulfides.

The effect of low-molecular-mass biological disulfides and their related reduced compounds on the activity of two calcium-dependent neutral proteinases (calpains) from rat liver has been investigated. L-Cystine and L-cystamine bring about the inactivation of both enzymes, while the related reduced compounds L-cysteine and L-cysteamine are without effect. Calpain II is more sensitive to the inactivating effect of glutathione disulfide in comparison with calpain I.