18F-Mefway PET Imaging of Serotonin 1A Receptors in Humans: A Comparison with 18F-FCWAY

IntroductionThe purpose of this research is to evaluate the prospects for the use of 4-(trans-¹⁸F-fluoranylmethyl)-N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexane-1-carboxamide (¹⁸F-Mefway) in comparison to ¹⁸F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (¹⁸F-FCWAY) for the quantification of 5-HT_1A receptors in human subjects.MethodFive healthy male controls were included for two positron emission tomography (PET) studies: ¹⁸F-FCWAY PET after the pretreatment with 500 mg of disulfiram and two months later, ¹⁸F-Mefway PET without disulfiram. Regional time-activity curves (TACs) were extracted from nine cortical and subcortical regions in dynamic PET images. Using cerebellar cortex without vermis as reference tissue, in vivo kinetics for both radioligands were compared based on the distribution volume ratio (DVR) calculated by non-invasive Logan graphical analysis and area under the curve ratio of the TACs (AUC ratio).ResultAlthough the pattern of regional uptakes in the ¹⁸F-Mefway PET was similar to that of the ¹⁸F-FCWAY PET (highest in the hippocampus and lowest in the cerebellar cortex), the amount of regional uptake in ¹⁸F-Mefway PET was almost half of that in ¹⁸F-FCWAY PET. The skull uptake in ¹⁸F-Mefway PET was only 25% of that in ¹⁸F-FCWAY PET with disulfiram pretreatment. The regional DVR values and AUC ratio values for ¹⁸F-Mefway were 17—40% lower than those of ¹⁸F-FCWAY. In contrast to a small overestimation of DVR values by AUC ratio values (< 10%) in ¹⁸F-FCWAY PET, the overestimation bias of AUC ratio values was much higher (up to 21%) in ¹⁸F-Mefway PET.ConclusionAs ¹⁸F-Mefway showed lower DVR values and greater overestimation bias of AUC ratio values, ¹⁸F-Mefway may appear less favorable than ¹⁸F-FCWAY. However, in contrast to ¹⁸F-FCWAY, the resistance to in vivo defluorination of ¹⁸F-Mefway obviates the need for the use of a defluorination inhibitor. Thus, ¹⁸F-Mefway may be a good candidate PET radioligand for 5-HT_1A receptor imaging in human.     

Interleukin-18 and diabetic nephropathy: A review

The inflammatory response has an important role in the pathophysiology of diabetic nephropathy that is contributed to by inflammatory mediators such as interleukin-1 (IL-1), IL-6, IL-18, tumor necrosis factor-α, and macrophage chemotactic protein-1; however, the role of IL-18 seems to be more specific than other cytokines in the inflammatory process. IL-18 is expressed in renal tissue and is upregulated by several stimuli including hyperglycemia. The expression/urinary level of IL-18 is positively correlated with the progression of diabetic nephropathy and the urinary albumin excretion rate. In this review, we have focused on the molecular pathways modulating the relationship between IL-18 and diabetic nephropathy.     

A rare case of monosomy 18p: translocation between chromosomes 18 and 21

A rare case of monosomy 18p with molecular cytogenetic characterization of 18;21 whole arm translocation is presented. An 8-year-old gril with mental deficiency and growth deficiency was the child of a 45-year-old healthy mother and 50-year-old nonconsanguineous father with unremarkable prenatal history. She had a round face, flat nasal bridge, micrognathia and hypotonia. Cytogenetic studies revealed de novo 45,XX,del(18)t(18;21) karyotype, which was confirmed by fluorescence in situ hybridization (FISH).     

Interleukin-18 gene polymorphisms and rheumatoid arthritis: A meta-analysis

Interleukin-18 (IL-18) is a member of the IL-1 superfamily that enhances both innate and acquired immune responses. IL-18 is highly expressed in sera, synovial fluids and synovial tissues of patients with RA, and these IL-18 levels are correlated with RA disease activity, indicating an important role of IL-18 in the pathogenesis of RA. Several studies have examined the association of IL-18 gene polymorphisms with RA, but these studies have shown inconclusive and controversial results. To verify the association between IL-18 gene polymorphism and susceptibility to RA, we conducted a meta-analysis of all relevant reports cited in MEDLINE/PubMed before October 2012. A meta-analysis on the association between the IL-18 rs1946518 SNP and RA was performed for 2944 patients with RA and 2377 controls from 7 published studies and a meta-analysis on the association between the IL-18 rs187238 SNP and RA was performed for 1319 patients with RA and 1211 controls from 5 published studies. In addition, 2 studies involving 1873 RA patients and 1092 controls were considered in the meta-analysis of the association between the IL-18 rs360722 SNP and RA. No significant association was found between two IL-18 SNPs (rs1946518 and rs187238) and RA susceptibility in all subjects. In subgroup analysis stratified by ethnicity, there was still no significant association between these two IL-18 SNPs and RA susceptibility. However, the frequency of the T allele at rs360722 was found to be significantly lower in patients with RA compared with controls, although this finding was based on only 2 studies. The results of our meta-analysis suggest that IL-18 rs360722 SNP is only associated with RA susceptibility. However, due to only two studies included in our meta-analysis, large-scale well designed studies should be considered in future studies to confirm the exact role of IL-18 rs360722 SNP in RA susceptibility.     

Merkel cell carcinoma and 18FDG PET-CT: A case report

Merkel cell carcinoma (MCC) is a neuroendocrine skin tumor with an unpredictable evolution and high metastatic potential. It usually occurs in the elderly people with long-term sun exposure or weak immune systems. The avidity of MCCs for 18F-flourodeoxyglucose justifies the use of positron emission tomography for its staging.     

Lincomycin and Staphylococcal Infections: A Clinical Study of 18 Cases

Lincomycin, a chemically new antibiotic effective against Gram-positive organisms, was evaluated in vitro and tested clinically. In vitro testing indicated that lincomycin is especially effective against Staphylococcus aureus. Clinical testing showed that lincomycin was free of toxicity in a series of 18 cases of staphylococcal infection. Of particular interest was its pronounced effectiveness in nine cases of chronic osteomyelitis, one of which was of 15 years'' duration and unresponsive to all other forms of antibiotic and surgical treatment. The only side effect noted was loose stools in the occasional patient.     

A formal synthesis of 18-hydroxyestrone

A formal synthesis of $\text{dl}$-18-hydroxyestrone has been achieved by the preparation of $\text{dl}$-3-methanesulfonyloxy-13β,17β-dicarboxy-18--norestra-1,3,5(10)-triene anhydride, the dextrorotatory enantiomer of which is an intermediate in Barton's conversion of $\text{d}$-estrone to $\text{d}$-1β-hydroxyestrone (KC-6A).     

Microtubule structure at 18 A resolution

A model for the structure of microtubules at a resolution of 18 A (1 A = 0.1 nm) is described, based on X-ray fiber diffraction data from hydrated reassembled calf brain microtubules. The model was derived by an iterative solvent flattening refinement procedure, with initial phases based on those determined by electron microscopy. The major microtubule surface grooves are those defining the protofilaments, which form a hollow cylinder of maximum diameter 300 A. Strong electron density fluctuations in the microtubule wall are interpreted as evidence for a domain structure within the tubulin subunit. The arrangement of domains is such that the tubulin molecule could be quite flexible at the domain connections; thus, slight changes in this arrangement could account for the unusual polymorphism of tubulin assemblies.     

The O18 antigens (lipopolysaccharides) of Escherichia coli. Structural characterization of the O18A, O18A1, O18B and O18B1-specific polysaccharides.

The O-specific polysaccharide moieties (PS) of the O18A, O18A1, O18B, and O18B1 antigens (lipopolysaccharides, LPS) consist of L-rhamnose (Rha), N-acetyl-D-glucosamine, D-galactose, and D-glucose in different molar ratios. By using chemical fragmentation, methylation, as well as one- and two-dimensional NMR spectroscopy, the structures of these polysaccharides were found to be [formula: see text] In O18A-PS and O18A1-PS x = 2, whereas in O18B-PS and in O18B11-PS x = 3. In all four polysaccharides alpha-D-Galp (residue D) is substituted at O-3. This substituent L (residue E) is beta-D-GlcpNAc-(1 in O18A-PS and O18A1-PS and it is alpha-D-Glcp-(1 in O18B-PS and O18B1-PS. Whereas there is no further substituent on the main chain of the O18A and O18B polysaccharides, in O18A1-PS and O18B1-PS the alpha-D-GlcpNAc residue A is substituted with alpha-Glcp-(1 (residue F), which is linked to O-6 in O18A1-PS and to O-4 in O18B1-PS. These results show that the O18 antigen comprises a group of four related LPS (O18A and O18B, with their glucosylated forms O18A1 and O18B1). The results are discussed with respect to epitope definition and biochemical implications.     

A time-resolved fluoroimmunoassay for 18-oxocortisol and 18-hydroxycortisol. Development of a monoclonal antibody to 18-oxocortisol

Patients with primary aldosteronism and with glucocorticoid-suppressible aldosteronism excrete in the urine excessive amounts of the hybrid steroids 18-hydroxycortisol and 18-oxocortisol. The measurement of these steroids aids in the differential diagnosis of various adrenal disorders. We have produced mouse monoclonal antibodies against 18-oxocortisol and polyclonal antibodies against 18-hydroxycortisol and describe a time-resolved fluoroimmunoassay (TR-FIA) technique for the measurement of these steroids in the urine. We have also compared this assay with an ELISA technique for these compounds. We also describe the preparation of in-house Eu(III)-labeled avidin and an enhancement solution and compared to a commercially available Eu(III)-labeled streptavidin and enhancement solutions. The monoclonal antibodies against 18-oxocortisol are sensitive and have a high level of specificity. The TR-FIA technique using in-house prepared reagents or commercial ones were indistinguishable from each other, but at a significant saving. The TR-FIA technique was more sensitive and had a greater precision than the ELISA technique for both steroids.     

Leaf lipids of Ribes nigrum: a plant containing 16:3, alpha-18:3, gamma-18:3 and 18:4 fatty acids

The glycerolipid composition of Ribes nigrum (blackcurrant) leaves was determined. The total fatty acid composition was unusual in that alpha-linolenic acid (alpha-18:3) occurred together with cis-7,10,13-hexadecatrienoic acid (16:3) and lower amounts of stearidonic acid (18:4) and gamma-linolenic acid (gamma-18:3). Monogalactosyldiacylglycerol contained the highest proportion of 16:3 with less in digalactosyldiacylglycerol. gamma-18:3 and 18:4 were present in all lipids and 18:4 was always greater than gamma-18:3. The highest percentages of gamma-18:3 and 18:4 were in phosphatidylcholine, but phosphatidylglycerol was particularly low in these acids. In summary, the lipid composition was largely typical of 16:3 plants but there was a minor contribution typical of 18:4 plants. The possibility of three pathways for glycolipid biosynthesis is discussed.     

A 46, XY,del(18)(pter→pl 100:) Cebocephalic child from a 46, XX,t(12;18)(18pter→18pl 100 :: 12qter→12pter) normal parent

Summary A normal female with an 18p—chromosome but without any feature of the 18p—syndrome produced a cebocephalic child whose karyotype included an 18p—chromosome. Evidence is presented that the normal female is a nonreciprocal translocation heterozygote resulting from the short arm of one chromosome 18 becoming attached to the long arm of a chromosome 12.