Physicochemical evaluation of new tetrahydroacridine and iodobenzoic acid hybrids as the next step in the design of potential drugs for treating Alzheimer's disease.

Tacrine derivatives containing iodobenzoic acid were developed as a novel multitarget-directed ligand and find potential application in the treatment of Alzheimer's disease. The aim of this study is to perform a physicochemical profile of this series. Experimental log P and pKa values were determined and compared with those already calculated. The results indicated better values of the tested compounds than the values predicted using computer software. The stability report was obtained using the developed HPLC method. The stability assay in different environment conditions provided information about the photosensitivity of these compounds and a proper method for the storage of this series of compounds.

Indirect Radioiodination of DARPin G3 Using N-succinimidyl-Para-Iodobenzoate Improves the Contrast of HER2 Molecular Imaging.

Radionuclide molecular imaging of human epidermal growth factor receptor 2 (HER2) in breast and gastroesophageal cancer might be used to stratify patients for HER2-targeted therapy as well as monitor treatment response and disease progression. Designed ankyrin repeat proteins (DARPins) are small engineered scaffold proteins with favorable properties for molecular imaging. Herein we compared two methods for labeling the anti-HER2 DARPin (HE)3-G3, direct and indirect radioiodination. We hypothesized that the use of N-succinimidyl-para-iodobenzoate (SPIB) for radioiodination would facilitate the clearance of radiometabolites and improve the contrast of imaging. Both radiolabeled (HE)3-G3 variants preserved their binding specificity and high affinity to HER2-expressing cells. The specificity of tumor targeting in vivo was also demonstrated. A biodistribution comparison of [125I]I-(HE)3-G3 and [125I]I-PIB-(HE)3-G3, in mice bearing HER2 expressing SKOV3 xenografts, showed rapid clearance of [125I]I-PIB-(HE)3-G3 from normal organs and tissues and low accumulation of activity in organs with NaI-symporter expression. Both radiolabeled (HE)3-G3 variants had equal tumor uptake. Consequently, the indirect label provided higher tumor-to-blood and tumor-to-organ ratios compared with the direct label. Comparative Single Photon Emission Computed Tomography (SPECT)/CT imaging of HER2 expression in SKOV3 xenografts, using both radiolabeled DARPins, demonstrated the superior imaging contrast of the indirect label. Indirect radioiodination of (HE)3-G3 using SPIB could be further applied for SPECT and PET imaging with iodine-123 and iodine-124.

Drugs of abuse, cytostatic drugs and iodinated contrast media in tap water from the Madrid region (central Spain):A case study to analyse their occurrence and human health risk characterization.

This work analyses the presence of forty-eight emerging pollutants, including twenty-five drugs of abuse and metabolites, seventeen cytostatic drugs and six iodinated contrast media, in tap water from the Madrid Region. Analysis of the target compounds in the tap water was performed by means of (on-line or off-line) solid-phase extraction followed by analysis by liquid chromatography-tandem mass spectrometry. A preliminary human health risk characterization was undertaken for each individual compound and for different groups of compounds with a common mechanism of action found in tap water. The results of the study showed the presence of eight out of the twenty-five drugs of abuse and metabolites analysed, namely, the cocainics cocaine and benzoylecgonine, the amphetamine-type stimulants ephedrine, 3,4-methylenedioxymethamphetamine and methamphetamine, the opioid methadone and its metabolite 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine and, finally caffeine at concentrations ranging from 0.11 to 502 ng L(-1). Four out of the six analysed iodinated contrast media, namely, diatrizoate, iohexol, iomeprol and iopromide, were detected in at least one sample, with concentration values varying between 0.4 and 5 ng L(-1). Cytostatic compounds were not detected in any sample. Caffeine was the substance showing the highest concentrations, up to 502 ng L(-1), mainly in the drinking water sampling point located in Madrid city. Among the other drugs of abuse, the most abundant compounds were cocaine and benzoylecgonine, detected at concentrations ranging from 0.11 to 86 ng L(-1) and from 0.11 to 53 ng L(-1), respectively. Regarding iodinated contrast media, iohexol was the most ubiquitous and abundant compound, with a frequency of detection of 100% and concentrations from 0.5 to 5.0 ng L(-1) in basically the same range in all sampling points. Taking into account the results and types of treatment applied, ozonisation plus granular activated carbon filtration appears to be efficient in the removal of cocaine and benzoylecgonine. For the amphetamine-type stimulants, opioids and caffeine, ozonisation plus granular activated carbon filtration and ultrafiltration plus reverse osmosis showed higher removal efficiency than sand filtration. The human health risk characterization performed indicates that the lifetime consumption of the tap waters analysed has associated a negligible human health concern.

Vibrational and microbiological study on alkaline metal picolinates and o-iodobenzoates.

FT-IR and Raman experimental data were assigned to appropriate bond vibrations and used to compare the different electronic charge distributions in the aromatic rings and carboxylic anions of various lithium, sodium, potassium, rubidium and caesium o-iodobenzoates and picolinates. Then principal component analysis (PCA) was applied in order to attempt to distinguish the biological activities of these compounds according to selected band wavenumbers. The growth of the bacteria Escherichia coli and Bacillus subtilis and the yeasts Saccharomyces cerevisiae and Hansenula anomala under optimal growth conditions were measured after 24 hours of incubation by the classical plate method. The influence of the picolinates and o-iodobenzoates on the growth of these microorganisms, again after 24 hours of incubation, was also measured and compared to the effect of sodium benzoate, which was used as a reference material. In general, the o-iodobenzoates exhibited more activity against the microorganisms than the picolinates. A statistically significant linear correlation between the spectral data and the degree of influence of a given compound on microorganism growth was established. The correlation coefficients for the o-iodobenzoates were 0.696, -0.628, 0.693 and 0.755 for E. coli, B. subtilis, H. anomala and S. cerevisiae, respectively, and for the picolinates they were 0.818, 0.826, 0.821 and 0.877 for E. coli, B. subtilis, H. anomala and S. cerevisiae, respectively. Therefore, IR spectroscopy is shown to be a rapid and reliable analytical tool for preliminary estimation of the antimicrobial properties of newly synthesized compounds, that can be applied before microbial performance tests.

Excretion of iohexol and metrizoate in human breast milk.

Six lactating women undergoing contrast media examination had milk and blood taken to determine the rate and extent of excretion of iohexol (Omnipaque) (four mothers) and metrizoate (Isopaque) (two mothers). Blood samples were taken up to 45 minutes and milk samples up to 48 hours after the contrast medium injection. The excretion was low, reaching a maximum at 3 to 6 hours and showing a slow decay curve (t1/2 = 15 to 108 hours). One mother, who was weaning her baby, showed a different excretion pattern. The amount excreted during 24 hours was about 0.5 per cent of the weight adjusted maternal dose for both iohexol and metrizoate. It is not likely, that such a low dose of poorly absorbed drug would cause any adverse effects in the infant, unless it is hypersensitive to the drug already. The authors consider breast feeding to be acceptable for mothers receiving iohexol or metrizoate.

Correlation of computed tomography and nephrography in quantitative comparison of urographic contrast agents.

The use of computed tomography (CT) to estimate the differences in radiographic contrast obtainable with different contrast agents is discussed. A CT scanner was calibrated to measure the in vivo iodine concentration, and phantom studies were performed to derive the relationship between iodine concentration and resultant radiographic contrast in the kidneys. The technique is illustrated by a quantitative comparison of the nephrographic phase in dogs with two urographic contrast agents, sodium iothalamate and sodium ioxaglate.

[Quantiative determination of radiopaque contrast media by means of HPLC. I. Determination of diatrizoic acid, iothalamic acid and iodamide]. / Determinazione quantitativa di mezzi di contrasto radiologici mediante HPLC. Nota I - determinazione di acido diatrizoico, a cido iotalamico ed iodamide.

A rapid method for the quantitative analysis of radiopaque contrast media HPLC is described. Method can greatly help in solving problems of clinical and forensic interest.

[Chemical form of the radioactive excretion products after intravenous application of 125I-orthoiodohippurate to rats (author's transl)]. / Chemische Form der radioaktiven Ausscheidungsprodukte nach intravenöser Verabreichung von 125J-Orthojodhippuran an Ratten.

100 muCi 125I-Orthoiodohippurate were injected i. v. to 2 Wistar rats. Urine and faeces were analysed by means of thin-layer chromatography and high-pressure liquid chromatography. The combined metabolic balance resulted in the following findings: Rat 1: 15% 125I-Orthoiodobenzoic acid, 66% 125I-Orthoiodohippuric acid and 12,5% 125I-iodide. Rat 2: 18,5% 125I-Orthoiodobenzoic acid, 67,5% 125I-Orthoiodohippuric acid and 10,2% 125I-iodide.

A simple spectrophotometric method for measuring biliary ioglycamide (Biligram) concentration.

An extremely simple spectrophotometric method for measuring biliary ioglycamide (meglumine ioglycamate) concentration is described. It was validated by a radioactive technique.