Comparison of technetium-99m IgG with technetium-99m red blood cells labeling in cardiac blood-pool scintigraphy: a preliminary study

This first clinical prospective study was conducted to use of technetium-99m immunoglobulin G ((99m)Tc-IgG) as compared with autologous (99m)Tc-red blood cells (RBC) in gated blood pool ventriculography. We studied 12 patients who referred to us for a possible diagnosis of liver hemangioma or infection. Six patients underwent gated planar blood pool (GPBP) acquisition using (99m)Tc-RBC and 6 GPBP acquisition using (99m)Tc-IgG. The use of (99m)Tc-IgG in cardiac blood pool studies provided comparable images to (99m)Tc-RBC. In conclusion, (99m)Tc-IgG, which is readily available and needs only a single injection, may be an attractive alternative to (99m)Tc-RBC for the estimation of various cardiac function parameters like left ventricular function.     

Interaction of W-substituted analogs of cyclo-RRRWFW with bacterial lipopolysaccharides: the role of the aromatic cluster in antimicrobial activity

The activity of cyclo-RRRWFW (c-WFW) against Escherichia coli has been shown to be modulated by the aromatic motif and the lipopolysaccharides (LPS) in the bacterial outer membrane. To identify interaction sites and to elucidate the mode of c-WFW action, peptides were synthesized by the replacement of tryptophan (W) with analogs having altered hydrophobicity, dipole and quadrupole moments, hydrogen-bonding ability, amphipathicity, and ring size. The peptide activity against Bacillus subtilis and erythrocytes increased with increasing hydrophobicity, whereas the effect on E. coli revealed a more complex pattern. Although they had no effect on the E. coli inner membrane even at concentrations higher than the MIC, peptides permeabilized the outer membrane according to their antimicrobial activity pattern, suggesting a major role of LPS in peptide transport across the wall. For isothermal titration calorimetry (ITC) studies of peptide-lipid bilayer interaction, we used POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-choline), either alone or in mixtures with 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPG), to mimic the charge properties of eukaryotic and bacterial membranes, respectively, as well as in mixtures with lipid A, rough LPS, and smooth LPS as models of the outer membrane of E. coli. Peptide accumulation was determined by both electrostatic and hydrophobic interactions. The susceptibility of the lipid systems followed the order of POPC-smooth LPS > POPC-rough LPS > POPC-lipid A = POPC-POPG > POPC. Low peptide hydrophobicity and enhanced flexibility reduced binding. The influence of the other properties on the free energy of partitioning was low, but an enhanced hydrogen-bonding ability and dipole moment resulted in remarkable variations in the contribution of enthalpy and entropy. In the presence of rough and smooth LPS, the binding-modulating role of these parameters decreased. The highly differentiated activity pattern against E. coli was poorly reflected in peptide binding to LPS-containing membranes. However, stronger partitioning into POPC-smooth LPS than into POPC-rough LPS uncovered a significant role of O-antigen and outer core oligosaccharides in peptide transport and the permeabilization of the outer membrane and the anti-E. coli activity of the cyclic peptides.     

Cloning and Expression of the Allergen Cro s 2 Profilin from Saffron (Crocus sativus)

BackgroundProfilin is a panallergen that is recognized by IgE in allergic patients. Allergy to saffron (Crocus sativus) pollen has been described in people exposed to its pollen. Saffron contains a profilin that may cause allergic reactions in atopic subjects. The aim of this study was to describe the cloning, expression and purification of saffron profilin from pollen.MethodsCloning of saffron profilin was performed by polymerase chain reaction using specific primers from saffron pollen RNA. Expression was carried out in Escherichia coli BL21 (DE3) using a vector pET-102- TOPO. A recombinant fusion protein was expressed and the recombinant profilin was purified by metal precipitation. Immunological characterization was performed by immunoblotting experiments.ResultsThe 34 kDa- recombinant saffron profilin, Cro s 2, as a fusion protein was purified. Immunoblotting tested with the sera of allergic patients showed a specific reaction with the recombinant Cro s 2 band.ConclusionsThe sequence of Cro s 2 showed a high degree of identity and similarity to other plant profilins and the recombinant saffron profilin, Cro s 2, may be used for target-specific diagnosis and structural analyses and investigation of cross reactivity of Cro s 2 with other plant profilins.     

Production, quality control and pharmacokinetic studies of Ho-EDTMP for therapeutic applications

¹⁶⁶Ho-EDTMP is a major therapeutic agent which is widely used in bone palliation therapy. In this study, a ¹⁶⁶Ho-EDTMP complex was prepared successfully using an in-house synthesized EDTMP ligand and ¹⁶⁶HoCl₃. Ho-166 chloride was obtained by thermal neutron irradiation (1 × 10¹³ ncm⁻²s⁻¹) of natural Ho(NO₃)₃ samples (specific activity = 3–5 GBq/mg), dissolved in acidic media. The radiochemical purity of ¹⁶⁶Ho-EDTMP was checked by ITLC (>99%) and stability studies in presence of human serum and final preparation were performed. The biodistribution of ¹⁶⁶Ho-EDTMP and ¹⁶⁶HoCl₃ in wild-type rats was checked by scarification. SPECT imaging of ¹⁶⁶Ho-EDTMP was also performed in wild-type rats. A comparative accumulation study for ¹⁶⁶Ho-EDTMP and ¹⁶⁶HoCl₃ was performed for vital organs up to 48h. Significant bone accumulation (>70%) of the tracer in 48h was observed.     

Correlation between ABO blood groups, major risk factors, and coronary artery disease

To investigate a possible association of ABO blood groups with coronary artery disease in well-documented patients, we designed a cross-sectional study of 2026 patients, known case of coronary artery disease in angiography, who underwent coronary artery bypass graft at Tehran Heart Center, with regard to coronary artery disease major risk factors as well as ABO blood groups. Analysis did not show any significant difference between the frequency of ABO blood groups in coronary artery disease patients compared to the Iranian general population. In addition, frequency of cardiac risk factors was similar in coronary artery disease patients with different blood groups. Therefore, these finding suggest that there is no correlation between various ABO blood groups and development of coronary artery disease. Moreover, the prevalence of major risk factors was equal in patients with different blood groups, and blood groups had no impact on development of premature coronary artery disease in individual subjects.     

Eicosapentaenoic acid versus docosahexaenoic acid in mild-to-moderate depression: A randomized,double-blind,placebo-controlled trial

Controversy exists as to whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) or both are responsible for the efficacy of n-3 polyunsaturated fatty acids in depression. We conducted a single-center, randomized, double-blind, placebo-controlled, multi-arm, parallel-group trial, comparing the efficacy of EPA versus DHA as adjuvants to maintenance medication treatments for mild-to-moderate depression. Eighty-one mild-to-moderately depressed outpatients were randomly assigned to receive either 1 g/d of EPA or DHA or placebo (coconut oil) for 12 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS) final score in the modified intention-to-treat population, which comprised of all randomized patients with at least 1 post-randomization observation (n=62; 61.3% female; mean age 35.1±1.2 years). Allocated treatments were well tolerated. Although there was no significant difference between groups at baseline, patients in the EPA group showed a significantly lower mean HDRS score at study endpoint compared with those in the DHA (p<0.001) or placebo (p=0.002) groups. Furthermore, response to treatment (defined as a ≥50% decrease from the baseline HDRS score) was only observed in 6 patients receiving EPA, while no one in any of DHA or placebo groups responded to treatment. Overall, these data suggest greater efficacy of EPA compared to DHA or placebo as an adjunctive treatment in mild-to-moderate depression. However, further, randomized controlled trials are needed to support these findings.     

RalA signaling pathway as a therapeutic target in hepatocellular carcinoma (HCC)

Ral (Ras like) leads an important proto‐oncogenic signaling pathway down‐stream of Ras. In this work, RalA was found to be significantly overactivated in hepatocellular carcinoma (HCC) cells and tissues as compared to non‐malignant samples. Other elements of RalA pathway such as RalBP1 and RalGDS were also expressed at higher levels in malignant samples. Inhibition of RalA by gene‐specific silencing caused a robust decrease in the viability and invasiveness of HCC cells. Additionally, the use of geranyl–geranyl transferase inhibitor (GGTI, an inhibitor of Ral activation) and Aurora kinase inhibitor II resulted in a significant decrease in the proliferation of HCC cells. Furthermore, RalA activation was found to be at a higher level of activation in HCC stem cells that express CD133. Transgenic mouse model for HCC (FXR‐Knockout) also revealed an elevated level of RalA‐GTP in the liver tumors as compared to background animals. Finally, subcutaneous mouse model for HCC confirmed effectiveness of inhibition of aurora kinase/RalA pathway in reducing the tumorigenesis of HCC cells in vivo. In conclusion, RalA overactivation is an important determinant of malignant phenotype in differentiated and stem cells of HCC and can be considered as a target for therapeutic intervention.