Quantification of the Thyroid Scan (TS) and correlation to Multiparametric Ultrasounds (MPUS): A textbook case of nuclear molecular imaging

For decades, thyroid scintigraphy (TS) has been considered an interesting tool, especially in the field of hyperthyroidism. In recent years, TS has rapidly gained importance since it provides unique molecular information that cannot be obtained by any other modality. In fact, despite a limited 6 mm spatial resolution, it can highlight molecular and histo-functional changes that characterize most thyroid function disorders. However, to become such a powerful molecular image, the TS must be quantified. How much iodine is taken-up characterizes the Uptake (Up), while where iodine distributes characterizes the Spatial Targeting (ST). Methodology, results and limits of the thyroid Uptake are presented, including suppressed tests. Methods to determine the anatomical thyroid volume are revisited with special focus on planar scintigraphy. Recent developments in quantification make the ¹²³I-TS a new molecular imaging procedure. Since ¹²³I targets the sodium iodide symporter (NIS) and tracks the whole organification process, we derived a fundamental linear relationship between the TSH and the precocious (120–240 min) Uptake (p¹²³IUp). This relationship indicates whether the ¹²³I input follows the physiological TSH stimulation or is predictive of a non TSH-suppressible function, whatever the imaging pattern. This allows identification of toxic or compensated (TSH > 0.1 mU/L) Thyroid Functional Autonomy (TFA), even at baseline. Spatial Targeting, measured with the aid of computational algorithms, provides a reproducible Spatial Targeting Index (STI). This allows estimating a functional thyroid volume, that is likely more informative than the anatomical one. Most aspects of TS quantification and the interest to compare the structure (mostly MultiParametric US) and the function (molecular ¹²³I-TS) are presented.     

Archaeological records indicate a complex history of Pleistocene hunter-gatherer societies in Arabia

Paleolithic research on the Arabian Peninsula is still in its early stage. During the last decade, however, an increasing number of field projects were conducted and added significant data to the record. This development in addition to substantial paleoenvironmental research on Pleistocene climate and habitat changes creates a promising setting for research on human evolution in arid landscapes. Here I provide an overview of the main Paleolithic field projects conducted in Arabia and summarize their results.     

Ethyl nitrobenzoate: A novel scaffold for cholinesterase inhibition

A series of novel cholinesterase inhibitors containing nitrobenzoate core structure were synthesized by a facile and efficient method. The structure of the novel compounds were fully characterized and confirmed by analytical as well as spectroscopic methods. Compound indicated as 2f was found to possess the best cholinesterase inhibitory activities of all the evaluated compounds. Results suggest that 2f is a selective acetylcholinesterase inhibitor, although it also inhibits butyrylcholinesterase at higher concentration. Kinetics inhibition result suggest that 2f is a mixed-mode inhibitor of acetylcholinesterase. In addition, it was found to have low cytotoxicity. Molecular docking on compound 2f was carried out to rationalize the observed in vitro enzymatic assay results. Most importantly, the potential of nitrobenzoate derivatives as cholinesterase inhibitor was shown through this study. In summary, we discovered nitrobenzoates as a new scaffold that may eventually yield useful compounds in treatment of Alzheimer’s disease.     

Aberrant Tonic Inhibition of Dopaminergic Neuronal Activity Causes Motor Symptoms in Animal Models of Parkinson’s Disease

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Evaluation of nitrocatechol chalcone and pyrazoline derivatives as inhibitors of catechol-O-methyltransferase and monoamine oxidase

Literature reports that chalcones inhibit the monoamine oxidase (MAO) enzymes, mostly with specificity for the MAO-B isoform, while nitrocatechol compounds are established inhibitors of catechol–O-methyltransferase (COMT). Based on this, nitrocatechol derivatives of chalcone have been proposed to represent dual-target-directed compounds that may inhibit both MAO-B and COMT. Both these enzymes play key roles in the metabolism of dopamine and levodopa, and inhibitors are thus relevant to the treatment of Parkinson’s disease. The present study expands on the discovery of dual MAO-B/COMT inhibitors by synthesising additional nitrocatechol derivatives of chalcones which include heterocyclic derivatives, and converting them to the corresponding pyrazoline derivatives. The newly synthesised chalcone and pyrazoline compounds were evaluated as inhibitors of human MAO and rat COMT, and the inhibition potencies were expressed as IC₅₀ values. A pyrazoline derivative, compound 8b, was the most potent COMT inhibitor with an IC₅₀ value of 0.048 μM. This is more potent than the reference COMT inhibitor, entacapone, which has an IC₅₀ value of 0.23 μM. The results indicated that the pyrazoline derivatives (IC₅₀ = 0.048–0.21 µM) are more potent COMT inhibitors than the chalcones (IC₅₀ = 0.14–0.29 µM). Unfortunately, the chalcone and pyrazoline derivatives were weak MAO inhibitors with IC₅₀ values > 41.4 µM. This study concludes that the nitrocatechol derivatives investigated here are promising COMT inhibitors, while not being suitable as MAO inhibitors. Using molecular docking, potential binding modes and interactions of selected inhibitors with COMT are proposed.     

Synthesis and cholinesterase inhibitory activity of new 2-benzofuran carboxamide-benzylpyridinum salts

A series of benzofuran-2-carboxamide-N-benzyl pyridinium halide derivatives (6a-o) are synthesized as new cholinesterase inhibitors. The synthetic pathway involves the reaction of salicylaldehyde derivatives and ethyl bromoacetate, followed by hydrolysis and amidation with 3- and 4-picolyl amine. Subsequently, N-((pyridin-4-yl) methyl) benzofuran-2-carboxamide and substituted N-((pyridin-3-yl) methyl) benzofuran-2-carboxamides reacts with benzyl halides to afford target compounds (6a-o). The chemical structures of all derivatives were confirmed by spectroscopic methods. The studies reveal that some of the synthesized compounds are potent butyrylcholinesterase inhibitors with IC₅₀ values in the range of 0.054–2.7 µM. In addition, good inhibitory effects on Aβ self-aggregation are observed for 6h and 6k (33.1 and 46.4% at 100 µM, respectively).     

Health-risk market garden production linked to heavy metals in irrigation water in Benin

Heavy metals in the Benin market garden products: is irrigation water the first factor in question, and what is the level of health risk linked to the consumption of these vegetables? Such are the essential problems that this survey attempts to solve. Comparison of the level of lead (Pb), cadmium (Cd) and arsenic (As) pollution shows that all the vegetables taken from three market sites are differently contaminated, as well as their irrigation water and the soil. But establishing that water is the first factor responsible for the presence of heavy metals in market garden products is not so obvious. Otherwise, the health risk assessment revealed that the total daily exposure dose (DED) of Cd, namely 8.05 μg/kg/day, is high compared to the daily dose defined by the WHO, which is 1 μg/kg/day. Also, the ensuing quotient of danger (QD) is 8.05; such a value poses public health risks for the consumer.