Analysis of SAA1 gene polymorphisms in the Greek population: rheumatoid arthritis and FMF patients relative to normal controls. Homogeneous distribution and low incidence of AA amyloidosis.

OBJECTIVE: To address whether or not the rarity of amyloidosis in Greek patients with rheumatoid arthritis (RA) is related to specific alleles of single nucleotide polymorphisms (SNPs) in the 5'-flanking region and the exon 3 of the SSA1 gene. METHODS: The genotypes of the -13T/C SNP in the 5'-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 88 Greek patients with RA, 14 patients with familial Mediterranean fever (FMF) and 110 healthy controls. Linkage disequilibrium and haplotype frequencies involving -13T/C, 2995C/T and 3010C/T in these populations were tested and estimated, respectively. RESULTS: The genotypic distribution and allelic frequencies were similar in all groups tested. SNPs 2995 and 3010 were in linkage disequilibrium for all study populations (p < 0.05), whereas SNP -13 was not in linkage disequilibrium with either 2995 or 3010 (p > or = 0.05). Two major haplotypes presented in all patients with RA and FMF and controls: -13C; 2995T; 3010C (-13C; alpha) and -13C; 2995C; 3010T (-13C; beta). The -13T allele was linked with the gamma haplotype in Greek patients with RA and controls. The frequency of the -13T allele was found to be very rare in all groups tested. CONCLUSIONS: In conclusion, the rarity of the putative amyloidogenic -13T allele in Greek populations may be related to low prevalence of AA amyloidosis development in Greek RA patients.     

Crystalline morphology of block-copoly(oxypropylene/oxyethylene/oxypropylene) by small-angle X-ray and Raman scattering

Block-copoly(oxypropylene/oxyethylene/oxypropylene)s, with central-block lengths of 39 and 75 oxyethylene units and end-block lengths in the range 1 to 13 oxypropylene units, were investigated in their solid states by small-angle X-ray diffraction and low-frequency Raman spectroscopy, supplemented by differential scanning calorimetry. Low-frequency Raman transitions were assigned to longitudinal modes (LAM) of either unfolded or once-folded chains. The solid state comprised stacked monolayer lamellae in which the chains were usually tilted with respect to the lamellar end plane.     

The influence of molecular structure on the affinity and efficacy of some β-adrenoceptor agonists

Summary The affinity and efficacy of a number of sympathomimetic amines structurally related to prenalterol and the selective ₁-adrenoceptor agonist RO 363 were determined using a combination of radioligand binding and organ bath techniques. Affinity of the molecules (pK _D) was calculated from their ability to displace the radioligand [¹²⁵I]iodocyanopindolol ([¹²⁵I]CYP) from -adrenoceptor sites in left atrial (₁) and uterine (₂) membrane homogenates. These pK _D values were used to calculate efficacy from the positive inotropic and uterine relaxant responses elicited by the drugs in organ bath experiments. The drugs studied were either arylethanolamines i.e., (–)-isoprenaline (ISO), p-hydroxyisoprenaline (pOH-ISO), compounds XIV and XVI or aryloxypropanolamine-derivatives, i.e., oxymethylene-isoprenaline (OM-ISO), prenalterol and Compound XI which possessed ap-phenol or catechol ring and an isopropyl or a homoveratryl amine substituent. Only ISO, OM-ISO, pOH-ISO and Compound XVI were active as agonists in both tissue preparations. These drugs were partial agonists which exhibited a wide range of pD₂ values and did not display any marked selectivity for either -adrenoceptor subtype. Compound XI and prenalterol were inactive as agonists and together with the partial agonists behaved as competitive antagonists to ISO in the two preparations. All drugs tested displaced [¹²⁵I]CYP from -adrenoceptor sites, however, there was also a wide range of potency amongst the drugs.Analysis of the structure-affinity and structure-efficacy relationships indicated that removal of the 3-hydroxyl group from the catechol ring reduces both affinity and efficacy without altering the selectivity of the drug for either -adrenoceptor subtype. While aryloxypropanolamine derivatives have generally higher affinities than arylethanol-amines, especially at -adrenoceptor sites, their efficacies are generally reduced at both -adrenoceptors. The presence of a homoveratryl group in aryloxypropanolamines enhances slightly the affinity for ₁- and reduces affinity for ₂-adrenoceptors. With this amine group, efficacy is markedly reduced at ₂- as opposed to ₂-adrenoceptor sites.Thus for prenalterol, the small degree of cardioselectivity can be attributed to the oxymethylene group whilst its lack of agonist activity (i.e., efficacy) reflects a combined action of this group and the absence of the 3-hydroxyl group on the phenyl ring. In RO363 it can be deduced that the oxymethylene group, together with the homoveratryl substituent are responsible for the observed selective affinity of the drug for ₁- as opposed to ₂-adrenoceptors.     

Effect of endothelium on basal and α-adrenoceptor stimulated calcium fluxes in rat aorta

Summary The rate of unstimulated influx of Ca²⁺ into rat aorta smooth muscle, measured as uptake of ⁴⁵Ca, was inhibited in the presence of endothelium as compared to influx in the absence of endothelium. Efflux of ⁴⁵Ca from unstimulated prelabelled tissues was also reduced in the presence of endothelium. In normal physiological solution the rate of influx and efflux of Ca²⁺ stimulated by B-HT 920 (1 and 10 M), but not that stimulated by phenylephrine (30 nM and 1 M), was also reduced in the presence of endothelium. In the presence of the calcium entry blocker flunarizine (3 M), phenylephrine (1 M) stimulated efflux of Ca²⁺ was inhibited by the presence of endothelium. A correlation between inhibition of Ca²⁺ influx and modulation of -adrenoceptor agonist-induced contractions by endothelium could not be demonstrated, and methylene blue, an antagonist of endothelium mediated inhibition of B-HT 920 contractions, did not affect Ca²⁺ influx stimulated by the agonist. The effects of endothelium on Ca²⁺ influx and efflux are unlikely to be due to alterations by endothelium of diffusion of ⁴⁵Ca or the agonists in the vessel. The results demonstrate that an endothelial derived factor or factors can reduce calcium influx into smooth muscle cells and also modulate the release of calcium from cells, perhaps by affecting intracellular calcium pumping mechanisms. A reduction of calcium influx cannot be the sole explanation for the modulatory effect of endothelium on -adrenoceptor agonist-induced contractions but an effect on intracellular calcium metabolism may be important.     

A DPSIR Approach to Selected Cr(VI) Impacted Groundwater Bodies of Central Greece

Bulletin of Environmental Contamination and Toxicology - The holistic approach of Driver-Pressure-State-Impact-Response (DPSIR) methodology was applied to selected Cr(VI) impacted groundwater...     

Hormone levels of follicular fluids with and without oocytes in patients who received gonadotropin-releasing hormone analogues and gonadotropins in an in vitro fertilization program

Background Are follicles where no oocytes are retrieved empty follicles?Methods The levels of estradiol (E₂), progesterone (P), testosterone (T), cortisol (F), and prolactin (PRL) of follicular fluids (FF) aspirated individually from 34 randomly selected IVF patients in whom no oocytes were recovered were compared with the respective hormone levels of FF obtained from the same patients when oocytes were retrieved. Two FF without oocytes of a 35th patient in whom no oocytes were retrieved were analyzed.Results Hormones did not differ significantly in the paired samples, while in the two FF of the 35th woman they were in agreement with cystic follicles.Conclusions It is necessary to differentiate aspirated follicles where no oocytes are retrieved from the empty follicle syndrome, which was not observed in the IVF series studied and should be rare in IVF patients.