salicylates and 3-5-diisopropylsalicylic-acid

Transjugular intrahepatic portosystemic shunt (TIPS) is nowadays the benchmark treatment of severe portal hypertension complications. However, besides usual contraindication to the procedure (namely recurrent hepatic encephalopathy, severe liver dysfunction, right heart failure and/or pulmonary hypertension), TIPS appears regularly unfeasible due to abnormal and/or distorted anatomy. In this situation, the only non-surgical approaches to treat severe portal hypertension consist in the creation of an intrahepatic portocaval shunt from percutaneous (direct intrahepatic portocaval shunt - DIPS) or transjugular route (transjugular transcaval intrahepatic portosystemic shunt - TTIPS). These procedures have been rapidly adopted in patients with Budd-Chiari syndrome but are only poorly reported in patients with cirrhosis and without BCS. Considering the broadening landscape of TIPS indication in patients with cirrhosis within the last ten years, we aimed to describe the techniques, safety and efficacy of DIPS and TTIPS procedures as an alternative to TIPS in case of unfavourable anatomy.

Topics: Budd-Chiari Syndrome; Humans; Hypertension, Portal; Liver Cirrhosis; Portasystemic Shunt, Transjugular Intrahepatic; Salicylates; Treatment Outcome

Topics: Budd-Chiari Syndrome; Endovascular Procedures; Humans; Portasystemic Shunt, Transjugular Intrahepatic; Retrospective Studies; Salicylates; Treatment Outcome

Majority of iodine found in dairy milk comes from the diet and teat disinfection products used during milking process. The objective of this study was to evaluate the effects of 4 iodine-based teat dips on milk iodide concentrations varying in iodine level (0.25% vs. 0.5%, w/w), normal low viscosity dip versus barrier dip, and application method (dip vs. spray) to ensure safe iodine levels in dairy milk when these products are used. The iodine exposure study was performed during a 2-wk period. The trial farm was purged of all iodine-based disinfection products for 21 d during a prestudy "washout period," which resulted in baseline milk iodide range of 145 to 182 ppb. During the experiment, iodine-based teat dips were used as post-milking teat disinfectants and compared to a non-iodine control disinfectant. Milk iodide residue levels for each treatment was evaluated from composited group samples. Introduction of different iodine-based teat disinfectants increased iodide residue content in milk relative to the control by between 8 and 29 μg/L when averaged across the full trial period. However, residues levels for any treatment remained well below the consumable limit of 500 μg/L. The 0.5% iodine disinfectant increased milk iodide levels by 20 μg/L more compared to the 0.25% iodine. Compared to dip-cup application, spray application significantly increased milk iodide residue by 21 μg/L and utilized approximately 23% more teat dip. This carefully controlled study demonstrated an increase in milk iodide concentrations from iodine disinfectants, but increases were small and within acceptable limits.

Topics: Animals; Diet; Disinfectants; Disinfection; Female; Food Contamination; Humans; Iodides; Iodine; Mammary Glands, Animal; Milk; Salicylates

The purpose of these experiments was to (1) assess differences in mastitis pathogen strain sensitivities to teat disinfectants (teat dips), and (2) determine the optimum time for premilking teat dips to remain in contact with teat skin to reduce pathogen loads on teat skin. Two experiments were conducted using the excised teat model. In experiment 1, the differences in mastitis pathogen strain sensitivities to 4 commercially available dips (dip A: 1% H2O2; dip B: 1% chlorine dioxide; dip C: 1% iodophor; and dip D: 0.5% iodophor) were evaluated. Four strains of 11 common mastitis pathogens (Staphylococcus aureus, Streptococcus agalactiae, Mycoplasma bovis, Streptococcus dysgalactiae, Streptococcus uberis, Escherichia coli, Staphylococcus chromogenes, Staphylococcus epidermidis, Staphylococcus hyicus, Staphylococcus xylosus, and Staphylococcus haemolyticus) were tested. In experiment 2, the percentage log reduction of mastitis pathogens (Escherichia coli, Streptococcus uberis, Streptococcus dysgalactiae, Klebsiella species, Staphylococcus chromogenes, Staphylococcus haemolyticus, Staphylococcus xylosus, and Staphylococcus epidermidis) on teat skin with 3 commercially available teat dips: dip A; dip D; and dip E: 0.25% iodophor, using dip contact times of 15, 30, and 45 s, was evaluated. Experiment 1 results indicated significant differences in strain sensitivities to dips within pathogen species: Staphylococcus aureus, Staphylococcus chromogenes, and Streptococcus uberis. Species differences were also found where Mycoplasma bovis (97.9% log reduction) was the most sensitive to tested teat dips and Staphylococcus haemolyticus (71.4% log reduction) the most resistant. Experiment 2 results indicated that contact times of 30 and 45 s were equally effective in reducing recovered bacteria for dips D and E and were also significantly more effective than a 15-s contact time. No differences were seen in recovered bacteria between tested contact times after treatment with dip A. It can be concluded that different mastitis pathogen species and strains within species may possess different sensitivities to teat dips, which may have implications in selection of teat dips on dairies. Furthermore, a 30-s premilking dip contact time for iodophors and 15 s for H2O2 dips may be optimal in reducing pathogen load in the shortest amount of time. A reduction in premilking teat dip contact time may improve milking parlor efficiency.

Topics: Animals; Anti-Infective Agents, Local; Bacterial Load; Cattle; Chlorine Compounds; Escherichia coli; Female; Hydrogen Peroxide; Mammary Glands, Animal; Mastitis, Bovine; Oxides; Salicylates; Skin; Species Specificity; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Streptococcal Infections; Streptococcus; Streptococcus agalactiae; Time Factors

Currently, the bone-repair biomaterials market is dominated by high modulus metals and their alloys. The problem of stress-shielding, which results from elastic modulus mismatch between these metallic materials and natural bone, has stimulated increasing research into the development of polymer-ceramic composite materials that can more closely match the modulus of bone. In this study, we prepared poly(L: -lactic acid)/hydroxyapatite/poly(epsilon-caprolactone) (PLLA/HA/PCL) composites via a four-step process, which includes surface etching of the fiber, the deposition of the HA coating onto the PLLA fibers through immersion in simulated body fluid (SBF), PCL coating through a dip-coating process, and hot compression molding. The initial HA-coated PLLA fiber had a homogeneous and continuous coating with a gradient structure. The effects of HA: PCL ratio and molding temperature on flexural mechanical properties were studied and both were shown to be important to mechanical properties. Mechanical results showed that at low molding temperatures and up to an HA: PCL volume ratio of 1, the flexural strain decreased while the flexural modulus and strength increased. At higher mold temperatures with a lower viscosity of the PCL a HA: PCL ratio of 1.6 gave similar properties. The process successfully produced composites with flexural moduli near the lower range of bone. Such composites may have clinical use for load bearing bone fixation.

Topics: Biocompatible Materials; Biomimetics; Caproates; Ceramics; Durapatite; Hot Temperature; Lactic Acid; Lactones; Polyesters; Polymers; Salicylates; Temperature; Viscosity

The coordination complexes (DIP)(2)Ru(CH(3)bpyCOOH) and (DIP)(2)Ru(COOHbpyCOOH), where DIP and bpy are diphenylphenanthroline and bispyridine, have been recently proposed as fluorescent markers of nuclear DNA (Musatkina et al., J. Inorg. Biochem. 101:1086-1089, 2007), but no DNA binding investigation and no quantitative fluorescence evaluations had been done. Both complexes, as well as the smaller ones with bpy's in place of DIP's, have been investigated here by spectroscopic DNA titrations (UV-vis absorption, fluorescence, circular dichroism) and by in vitro cellular studies (flow cytometry and fluorescence imaging). Contrary to previous reports, neither the carboxylic function nor the more extended DIP ligand ensures any appreciable binding to DNA. This is clearly illustrated by the appearance of an isosbestic point of a second kind and by the proportionality of the fluorescence maximum intensity to the absorbance at the excitation wavelength. Above all, the lack of enhanced fluorescence in the presence of DNA definitively rules out the use of such complexes as DNA markers. Moreover, there is no detectable nuclear uptake. However, the fluorescent complexes with the DIP ligands, especially (DIP)(2)Ru(CH(3)bpyCOOH), are massively incorporated into the cytoplasm while preserving cell integrity, which could suggest other types of biological application.

Topics: Absorption; Circular Dichroism; Coordination Complexes; DNA; Fluorescence; Ligands; Salicylates; Spectrum Analysis

Gamma radiation is known to induce cell death in several organs. This damage is associated with endonuclease-mediated DNA fragmentation; however, the enzyme that produces the latter and is likely to cause cell death is unknown. To determine whether the most abundant cytotoxic endonuclease DNase I mediates gamma-radiation-induced tissue injury, we used DNase I knockout mice and zinc chelate of 3,5-diisopropylsalicylic acid (Zn-DIPS), which, as we show, has DNase I inhibiting activity in vitro. The study demonstrated for the first time that inactivation or inhibition of DNase I ameliorates radiation injury to the white pulp of spleen, intestine villi and bone marrow as measured using a quantitative TUNEL assay. The spleen and intestine of DNase I knockout mice were additionally protected from radiation by Zn-DIPS, perhaps due to the broad radioprotective effect of the zinc ions. Surprisingly, the main DNase I-producing tissues such as the salivary glands, pancreas and kidney showed no effect of DNase I inactivation. Another unexpected observation was that even without irradiation, DNA fragmentation and cell death were significantly lower in the intestine of DNase I knockout mice than in wild-type mice. This points to the physiological role of DNase I in normal cell death in the intestinal epithelium. In conclusion, our results suggested that DNase I-mediated mechanism of DNA damage and subsequent tissue injury are essential in gamma-radiation-induced cell death in radiosensitive organs.

Topics: Animals; Bone Marrow; Chelating Agents; Deoxyribonuclease I; DNA Fragmentation; Enzyme Activation; Enzyme Inhibitors; Gamma Rays; Gene Knockout Techniques; Ileum; Jejunum; Mice; Radiation Injuries, Experimental; Rats; Salicylates; Spleen; Survival Analysis; Whole-Body Irradiation; Zinc

Novel lipophilic platinum(II) complexes (LSPt-1-3), containing 3,5-diisopropylsalicylate (DIPS) as a leaving group and 2NH(3) or 1R,2R-diaminocyclohexane or (4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane as the carrier, have been synthesized, characterized and evaluated in vitro and in vivo. The octanol/water distribution coefficient of the complexes has also been measured. The results showed that the complexes achieved a typical square planar and the octanol/water distribution coefficient logP was 4.27, 4.37 and 4.31. The complexes were tested by SRB method to be more cytotoxic than Carboplatin, Oxaliplatin and Eptaplatin against 3AO, A549, NCI-H460 and SGC-7901 human cancer cell lines. Among complexes, LSPt-2 was much more effective than Carboplatin and Oxaliplatin in treating the NCI-H460 non-small-cell lung tumor-bearing mice. Its optimal activity was 38.8% (T/C) at a dose of 30 mg/kg following i.p. administration. LD(50) for the complex was found to be 230.9 mg/kg. LSPt-2 exhibited great anticancer activity, good lipophilic ability and low toxicity and therefore, it is a promising candidate for effective and stable pharmaceutical liposomal platinum anticancer drug.

Topics: Animals; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Lethal Dose 50; Magnetic Resonance Spectroscopy; Mice; Platinum Compounds; Salicylates; Spectrometry, Mass, Fast Atom Bombardment; Spectrophotometry, Ultraviolet

The purpose of this study was to identify the low molecular mass complexes formed between copper(II) and 3,5-diisopropylsalicylic acid (Dips) in physiological conditions. Copper(II)-Dips complex equilibria were determined using glass electrode potentiometry and their solution structures checked by UV-visible (UV-vis) spectrophotometry. Because of the low solubility of Dips in water, the equilibria were investigated in different water/ethanol mixtures. Formation constants were extrapolated to 100% water and then compared with the values obtained for the other anti-inflammatory drugs previously studied. Given the prime role of histidine as the copper(II) ligand in blood plasma, copper(II)-histidine-Dips ternary equilibria were studied under similar experimental conditions. Computer simulations of copper(II) distribution relative to different biofluids, gastrointestinal (g.i.) fluid and blood plasma, show that like salicylic and anthranilic acids, Dips favors g.i. copper absorption, but cannot exert any significant influence on plasma copper distribution. Moreover, Dips can mobilize increasing fractions of copper(II) as the pH decreases. In conclusion, Dips seems to correspond to the notion of *OH-inactivating ligand (OIL) as determined for anthranilic acid.

Topics: Anti-Inflammatory Agents; Computer Simulation; Copper; Histidine; Hydroxides; Ligands; Potentiometry; Salicylates

We examined the influence of 3,5-diisopropylsalicylic acid (3,5-DIPS) and calcium(II)3 (3,5-diisopropylsalicylate)6 (H2 O)6 [Ca(II)3 (3,5-DIPS)6 ], a new activator of calcium-dependent calmodulin-triggered nitric oxide synthase, on thrombin-induced platelet P-selectin expression. Citrated whole blood samples were incubated with either ethanol vehicle, 3,5-DIPS, or Ca(II)3 (3,5-DIPS)6. These whole blood samples were also co-incubated with thrombin receptor activating peptide (TRAP) or adenosine diphosphate (ADP), to up-regulate P-selectin (CD62P) on platelets. Both TRAP and ADP up-regulated P-selectin on platelets compared with platelets in whole blood samples that were not incubated with either platelet activator. Co-incubation of whole blood samples with TRAP, ADP together with 3,5-DIPS, or Ca(II)3 (3,5-DIPS)6 revealed that Ca(II)3 (3,5-DIPS)6 caused a decrease in platelet P-selectin expression for TRAP, ADP, and no-activator co-incubated samples of whole blood. Incubation of platelets with 3,5-DIPS also caused a decrease in ADP-induced up-regulation of P-selectin but failed to affect TRAP or no-activator-treated platelets. Incubation of whole blood with Ca(II)3 (3,5-DIPS)6 induced some hemolysis. We found that hemolysis increases basal P-selectin expression on platelets. We therefore conclude that Ca(II)3 (3,5-DIPS)6 decreased not only basal, but also hemolysis-induced P-selectin expression on platelets. In contrast, incubation of haemolysed whole blood with SIN-1 (standard nitric oxide-releasing drug) had no effect on P-selectin expression. In summary, Ca(II)3 (3,5-DIPS)6, a new calmodulin-dependent nitric oxide synthase activator, decreases P-selectin expression of human platelets in response to thrombin receptor activation. Improved calcium-dependent calmodulin activators may become useful drugs for the treatment of disorders associated with platelet activation, and P-selectin may decrease expression due to hemolysis.

Topics: Adenosine Diphosphate; Adult; Blood Platelets; Calcium; Calmodulin; Cross-Sectional Studies; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Flow Cytometry; Humans; In Vitro Techniques; Male; Molsidomine; Nitric Oxide Synthase; omega-N-Methylarginine; P-Selectin; Peptide Fragments; Platelet Aggregation Inhibitors; Salicylates

Interaction between anti-inflammatory drugs and reactive oxygen metabolites must be considered in the course of pharmacological studies intended to develop new compounds. Effects of indomethacin, aspirin, and 3,5-diisopropylsalicylic acid (3,5-DIPS) and their copper complexes on PMNL oxidative metabolism and the evolution of an acute inflammatory reaction were studied in the rat. Experiments were performed in vitro by assessment of superoxide generation and reduction of chemiluminescence by PMNLs incubated or not (control) in medium containing various concentrations of these compounds. A dose-related decrease of these parameters was observed, however, copper complexes were found to be more effective than their parent drugs or Cu gluconate. Copper complexes were also more effective anti-inflammatory agents than their parent ligands or Cu gluconate when the volume of exudate and number of exudate PMNLs were assessed after induction of pleurisy in rats by injection of isologous serum. It is concluded that modulation of the PMNL oxidative burst by copper complexes offers an accounting for the anti-inflammatory activity of these compounds.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Copper; Free Radical Scavengers; In Vitro Techniques; Indomethacin; Luminescent Measurements; Male; Neutrophils; Oxidation-Reduction; Pleurisy; Rats; Rats, Inbred Strains; Salicylates; Superoxides

Topics: Hearing Tests; Humans; Noise; Salicylates

Topics: Animals; Cattle; Gamma Rays; Hexachlorocyclohexane; Isomerism; Salicylates

Topics: Animals; Arsenic; Hexachlorocyclohexane; Salicylates; Ticks

Topics: Animals; DDT; Diptera; Ethyl Chloride; Salicylates; Sheep; Ticks

Topics: Animals; Arsenic; Cattle; Hexachlorocyclohexane; Insecticides; Pest Control; Salicylates; Ticks

Topics: Animals; Arsenic; Arsenicals; Derris; Ixodes; Salicylates; Sheep

Topics: Animals; Asteraceae; DDT; Diptera; Ethyl Chloride; Salicylates; Sheep