Loss of Ascorbic Acid from Injured Feline Spinal Cord

Feline spinal cord contains 0.97 mM ascorbic acid, as measured by the dinitrophenylhydrazine method. Greater than 90% is maintained in the reduced form. When functioning normally, the CNS conserves its ascorbic acid with a turnover rate of 2% per h. Following contusion injury severe enough to produce paraplegia, ascorbic acid is rapidly lost from injured spinal tissue. Thus, ascorbic acid is decreased 30% by 1 h and 50% by 3 h following injury. Oxidized ascorbic acid is increased at 1, but not 3, h following impact. As a consequence of its many functions in CNS, loss of ascorbic acid may contribute to derangements in spinal cord function following injury.     

Induction of chromosomal aberrations in human lymphocytes by the antitumour alkylating agent homo-aza-steroidal ester of p-bis(2-chloroethyl)aminophenoxy acetic acid, in vitro

The clastogenic activity of the antineoplastic alkylating agent 3β-hydroxy-13-amino-13,17-seco-5-androstan-17-oic- 13,17-lactam-p-bis (2-chloroethyl) aminophenoxy acetic acid (NSC 294859) and its congeners was studied in human lymphocyte cultures in vitro. Cells were exposed to several concentrations of the drugs for 24 h. It was found that NSC 294859 reduces the mitotic index and causes chromosome- as well as chromatid-type aberrations in a dose-dependent way. From its congeners, the alkylating agent (p-bis (2-chloroethyl) aminophenoxy acetic acid) induces the same phenomena but to a lesser extent, while the modified steroid (3β-hydroxy-13-amino-13,17-seco-5-androstan-17-oic-13,17-lactam) causes cytogenetic damages at the control level. These results favour the assumption that the antitumor activity of NSC 294859 is mainly based on its cytogenetic effects.     

Electrocardiographic alterations induced by AGEPC in Wistar rats in relation to its hypotensive and hematologic effects

AGEPC administration into Wistar rats caused no remarkable thrombocytopenia, slight decrease of the percent count of PMNs in whole blood accompanied by anequal leukocytopenia and a transient increase in hematocrit, due to fluid extraversion. Apart from the dramatic fall in blood pressure caused by AGEPC, relatively sinus bradycardia was recorded at doses over 6 micrograms/kg b.w. S-T segment elevation, mainly evident in II, III and AVF leads, was also recorded within the first minutes after AGEPC administration, at doses over 1 microgram/kg b.w. At lethal doses, various degrees of A-V block resulting in complete A-V block with idioventricular rhythm, or injury pattern resulting in ventricular fibrillation or ventricular flutter, were recorded. At sublethal doses no arrhythic manifestations were recorded, while S-T segment elevation upward inversion became gradually normal.     

Evaluation of aldose reductase inhibition and docking studies of some secondary metabolites, isolated from Origanum vulgare L. ssp. hirtum

Five polar constituents of Origanum vulgare L. ssp. hirtum were investigated for their ability to inhibit aldose reductase (ALR2), the first enzyme of the polyol pathway implicated in the secondary complications of diabetes. The most active compound was found to be lithospermic acid B. Caffeic acid was inactive as it showed no inhibitory activity against the enzyme. The order of the inhibitory activity of the remaining compounds was: rosmarinic acid >12-hydroxyjasmonic acid 12-O-beta-glucopyranoside > p-menth-3-ene-1,2-diol 1-O-beta-glucopyranoside. Docking studies have been undertaken to gain insight into the binding mode of the investigated compounds at the active site of ALR2. The predicted hydrogen bonding and hydrophobic interactions may explain the observed inhibitory activity.     

Isolation and identification of hydroxyl-platelet-activating factor from natural sources

Platelet-activating factor (PAF), a potent inflammatory mediator that has previously been detected in elevated levels in inflamed gingival tissues, in gingival crevicular fluid (GCF) and in saliva, is implicated in periodontal disease. The biologically active phospholipid detected in gingival crevicular fluid is a hydroxyl-PAF analogue. In a preliminary study this bioactive molecule was detected for the first time in human blood derived from volunteers with chronic periodontitis as well as from periodontally healthy volunteers. Compounds isolated from natural sources as well as synthetic ones have been reported as biologically active lipids with physiological importance based on the fact that they induce platelet aggregation with EC50 values ranging from 100 to 0.01 microM through interaction with G-protein-coupled receptors like the PAF receptor, leading to altered signal transduction. In this study, the existence of hydroxyl-PAF analogue in human blood was further studied as well as its distribution in plasma and in blood components. The existence of hydroxyl-PAF analogue was also investigated in samples from rabbit blood hen's egg yolk. The hydroxyl-PAF analogue was purified by high-performance liquid chromatography, detected by biological assays and identified by electrospray MS analysis. Quantitative determination of PAF and hydroxyl-PAF analogue (expressed as PAF-like activity) showed a statistically significant increase in the ratio of plasma hydroxyl-PAF analogue levels to plasma PAF levels in volunteers with periodontitis. Moreover, hydroxyl-PAF analogue was also detected in rabbit blood and hen's egg yolk samples. These data support that this bioactive lipid may play a role in oral inflammation and suggest PAF as a member of a lipid molecule family with different structures and from different sources which share the same or similar biological activities, apparently with different physiological roles in human and animals.     

Pyrrolylbenzothiazole Derivatives as Aldose Reductase Inhibitors

Abstract

2,2-Dimethyl-4-hydroxy-4-androstene-3,17-dione (4) has been synthesized and has been shown to be a powerful competitive inhibitor of aromatase (K_i = 11.4nM). However, compound 4 does not cause time-dependent loss of enzyme activity, in contrast to the unmethylated parent compound, 4-OHA.     

Substituted derivatives of indole acetic acid as aldose reductase inhibitors with antioxidant activity: structure-activity relationship

Although multiple biochemical pathways are likely to be responsible for the pathogenesis of diabetic complications, substantial evidence suggests a key role for the polyol pathway and oxidative stress initiated by hyperglycemia. Thus aldose reductase, the first enzyme of the polyol pathway, has been identified as a potential target of pharmacological intervention to prevent diabetic complications. Aldose reductase inhibitors endowed with antioxidant activity would be dually beneficial. The aim of the study was to evaluate the structure-activity relationship of commercially available indole derivatives supported by the molecular modeling of their interaction with the enzyme aldose reductase from the viewpoint of the inhibitory effect on the enzyme and their antioxidant activity. The partially purified aldose reductase was prepared from rabbit eye lenses. In vitro inhibiton of the aldose reductase was determined by a conventional method. Antioxidant action of the compounds was documented in a DPPH test. Marked differences were recorded in the aldose reductase inhibition activities of 1- and 3-indole acetic acid derivatives. The interaction energies of the inhibitor vs. enzyme-NADP(+) complexes, calculated by computer aided molecular modeling, were in agreement with the higher inhibitory efficacy of 1-indole acetic acid in contrast with 3-indole acetic acid. The more efficient 1-indole acetic acid was proved to create stronger electrostatic interaction with NADP(+). However, the order of the antioxidant activities of the compounds studied was not in agreement with that of the inhibitory efficacies.     

Homology modeling, simulation and molecular docking studies of catechol-2, 3-Dioxygenase from Burkholderia cepacia: Involved in degradation of Petroleum hydrocarbons

Catechol 2, 3-dioxygenase is present in several types of bacteria and undergoes degradation of environmental pollutants through an important key biochemical pathways. Specifically, this enzyme cleaves aromatic rings of several environmental pollutants such as toluene, xylene, naphthalene and biphenyl derivatives. Hence, the importance of Catechol 2, 3-dioxygenase and its role in the degradation of environmental pollutants made us to predict the three-dimensional structure of Catechol 2, 3-dioxygenase from Burkholderia cepacia. The 10ns molecular dynamics simulation was carried out to check the stability of the modeled Catechol 2, 3- dioxygenase. The results show that the model was energetically stable, and it attains their equilibrium within 2000 ps of production MD run. The docking of various petroleum hydrocarbons into the Catechol 2,3-dioxygenase reveals that the benzene, O-xylene, Toluene, Fluorene, Naphthalene, Carbazol, Pyrene, Dibenzothiophene, Anthracene, Phenanthrene, Biphenyl makes strong hydrogen bond and Van der waals interaction with the active site residues of H150, L152, W198, H206, H220, H252, I254, T255, Y261, E271, L276 and F309. Free energy of binding and estimated inhibition constant of these compounds demonstrates that they are energetically stable in their binding cavity. Chrysene shows positive energy of binding in the active site atom of Fe. Except Pyrene all the substrates made close contact with Fe atom by the distance ranges from 1.67 to 2.43 Å. In addition to that, the above mentioned substrate except pyrene all other made π-π stacking interaction with H252 by the distance ranges from 3.40 to 3.90 Å. All these docking results reveal that, except Chrysene all other substrate has good free energy of binding to hold enough in the active site and makes strong VdW interaction with Catechol-2,3-dioxygenase. These results suggest that, the enzyme is capable of catalyzing the above-mentioned substrate.     

Biological activity of lipids of pine pollen on platelet aggregation in correlation with the platelet activating factor

Pollen lipids of a pine species were separated by thin layer chromatography systems. The purified neutral and polar lipid classes were examined for their possible platelet aggregation activity and for their effect on Platelet Activating Factor activity. The lipid fraction comigrating on thin layer chromatography with glycerylether standards was shown to have a remarkable inhibition of Platelet Activating Factor activity on washed rabbit platelets in a concentration of 4.5.10(-6) M. At a ten fold higher concentration these lipids also induced platelet aggregation.     

Capacity Fade Mechanism of Li4Ti5O12 Nanosheet Anode

Zero‐strain and long‐term stability of nanoscale lithium titanate (LTO) anode materials make possible the fabrication of exceptionally stable lithium ion batteries. But one issue must be considered that of nanostructure‐induced relaxation in 2D LTO nanosheets which profoundly modifies their Li storage properties and structural stability. Excessively intercalated Li ions at both 8a and 16c sites trigger nucleation of the relaxed LTO structure in the near‐surface region, which impedes Li‐ion diffusion and causes the increasing polarization of LTO nanosheet electrodes. Nuclei of relaxed LTO then undergo isotropic growth along the 3D Li‐ion pathways in LTO to completely convert near‐surface regions into relaxed LTO. With increasing population of trapped Li ions, the enhanced conductivity due to Ti⁴⁺/Ti³⁺ reduction gradually eliminates the raised polarization. In the meantime, spontaneous electrolyte/LTO reduction to form the solid electrolyte interphase starts playing a major role in capacity loss once the transformation of near‐surface region into relaxed LTO becomes saturated. Elucidation of these fundamental intercalation‐induced surface structure transformations contribute greatly into the design of highly performing 2D nanoscaled LTO and other electrode materials.