Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia: it is not always as it is expected

Observation of Coincident arrhythmias is not uncommon but the co-existence of idiopathic verapamil sensitive left ventricular tachycardia (ILVT) with other arrhythmias is very rare. We hereby presented a 30 year old male patient with a history of frequent episodes of palpitations and sustained narrow complex tachycardia. During electrophysiologic study two arrhythmias, one with narrow complexes which was shown to be typical atrioventricular nodal re-entrant tachycardia and the other with wide QRS complexes and right bundle branch block and left axis morphology, compatible with ILVT, were inducible. Radiofrequency catheter ablation of both arrhythmias was done at two consecutive sessions. The patient has remained asymptomatic without antiarrhythmic therapy for the past six months.     

Contribution of basic residues of the autolysis loop to the substrate and inhibitor specificity of factor IXa

The autolysis loop (residues 143-154 in chymotrypsinogen numbering) plays a pivotal role in determining the macromolecular substrate and inhibitor specificity of coagulation proteases. This loop in factor IXa (FIXa) has 3 basic residues (Arg143, Lys147, and Arg150) whose contribution to the protease specificity of factor IXa has not been studied. Here, we substituted these residues individually with Ala in Gla-domainless forms of recombinant factor IX expressed in mammalian cells. All mutants exhibited normal amidolytic activities toward a FIXa-specific chromogenic substrate. However, Arg143 and Lys147 mutants showed a approximately 3- to 6-fold impairment in FX activation, whereas the Arg150 mutant activated factor X normally both in the absence and presence of factor VIIIa. By contrast, Arg143 and Lys147 mutants reacted normally with antithrombin (AT) in both the absence and presence of the cofactor, heparin. However, the reactivity of the Arg150 mutant with AT was impaired 6.6-fold in the absence of heparin and 33- to 70-fold in the presence of pentasaccharide and full-length heparins. These results suggest that Arg143 and Lys147 of the autolysis loop are recognition sites for FX independent of factor VIIIa, and Arg150 is a specific recognition site for AT that can effectively interact with AT only if the serpin is in the heparin-activated conformation.     

Synthesis of the first diethylenetriaminepentahydroxamic acid (DTPH) bifunctional chelating agent

Synthesis of a new pentahydroxamic acid bifunctional chelating agent (BCA), constructed on the aminoazaalkyl core of diethylenetriaminepentaacetic acid (DTPA), is reported. Rational modifications in the structure of DTPA, which could result in an enhancement of its chelation properties, add to the collection of diagnostic and therapeutic metals bound by this chelator, and might implement significant improvements in the in vivo behavior of this compound, are described. Further improvements in the stability of the ligand-metal complexes of DTPA may improve both diagnostic and therapeutic outcomes such as tumor-to-normal tissue ratios and target-delivered radioactivity. A combination of hydroxamate functions with the azaalkyl backbone of DTPA might be a suitable approach to generate such higher stabilities. This rationale may be justified by the well-known affinity of hydroxamates against different transition metals and favorable properties of DTPA as a versatile chelator. Thus, the N(4),N(alpha),N(alpha),N(epsilon),N(epsilon)-pentakis[[((N-hydroxy-N-methyl]carbonyl)methyl]-2, 6-diamino-4-azahexanoic hydrazide (5, DTPH) was designed and synthesized through a convergent synthesis and in 40.7% overall yield. Conjugation of this compound to the monoclonal antibody (MAb) Delta Ch2HuCC49, used as a model protein, was carried out to evaluate the efficiency of this molecule as a BCA. Radiolabeling of the DTPH-Delta CH2HuCC49 conjugate with lutetium-177 ((177)Lu) and biodistribution of the labeled conjugate in athymic nude mice, bearing LS174T human colon carcinoma xenografts, are reported.     

Host preference by Allothrombium pulvinum (Acari: Trombidiidae) larvae on aphids: Macrosiphum rosae,Aphis gossypii and Hyalopterus amygdali (Homoptera: Aphididae)

In this study aphid-plant association and its effect on host preference of parasitic Allothrombium pulvinum larvae was examined with multiple-choice tests. Host species selection, host size selection and superparasitism with mite larvae were studied with two-choice tests. Three aphid species were used: Macrosiphum rosae, Aphis gossypii and Hyalopterus amygdali. In multiple-choice tests, larvae of A. pulvinum showed no significant preference for any aphid-plant association when given M. rosae on rose, A. gossypii on cucumber and H. amygdali on apricot simultaneously. Two-choice tests showed that larval mites preferred H. amygdali to A. gossypii, but had no preference when offered a choice between A. gossypii and M. rosae or between H. amygdali and M. rosae. In host size selection and superparasitism tests, significantly more mites selected the larger host (M. rosae). Furthermore, parasitised H. amygdali were preferred to unparasitised ones. This revised version was published online in July 2006 with corrections to the Cover Date.     

Role of basic residues of the autolysis loop in the catalytic function of factor Xa

The autolysis loop of factor Xa (fXa) has four basic residues (Arg(143), Lys(147), Arg(150), and Arg(154)) whose contribution to protease specificity of fXa has not been examined. Here, we substituted these basic residues individually with Ala in the fX cDNA and expressed them in mammalian cells using a novel expression/purification vector system. Following purification to homogeneity and activation by the factor X activator from Russell viper venom, the mutants were characterized with respect to their ability to assemble into the prothrombinase complex to activate prothrombin and interact with target plasma fXa inhibitors, tissue factor pathway inhibitor (TFPI) and antithrombin. We show that all mutants interacted with factor Va with normal affinities and exhibited wild-type-like prothrombinase activities toward prothrombin. Lys(147) and Arg(154) mutants were inhibited by TFPI approximately 2-fold slower than wild type; however, both Arg(143) and Arg(150) mutants were inhibited normally by the inhibitor. The reactivities of Arg(143) and Lys(147) mutants were improved approximately 2-fold with antithrombin in the absence but not in the presence of heparin cofactors. On the other hand, the pentasaccharide-catalyzed reactivity of antithrombin with the Arg(150) mutant was impaired by an order of magnitude. These results suggest that Arg(150) of the autolysis loop may specifically interact with the activated conformation of antithrombin.     

Chemotactically directed redistribution of alpha-actinin precedes morphological polarization and reversal of polarity in human polymorphonuclear leucocytes (PMNs)

We have determined the temporal and spatial relationship between cell polarization and alpha-actinin localization by analysing the redistribution of alpha-actinin and F-actin in spherical PMNs developing polarity and in polarized cells reversing polarity following localized stimulation with chemotactic peptide using micropipettes. Initially spherical PMNs develop a one-sided accumulation of alpha-actinin before lamellipodia enriched in alpha-actinin are formed. In polarized cells, alpha-actinin is concentrated at the leading front. When polarity is reversed, alpha-actinin redistribution to the uropod precedes reversal of morphological polarity and formation of new lamellipodia at the uropod. Later, lamellipodia enriched in F-actin and alpha-actinin develop at the former uropod to form a new front. The data document that redistribution of alpha-actinin is a very early event in the development of polarity, which precedes formation of lamellipodia.     

Essential oil of one of the Iranian skullcaps

The hydro-distilled essential oil from dried aerial parts of one of widespread Iranian skullcaps, Scutellaria pinnatifida A. Hamilt. sap. alpina (Bornm.) Rech. grown in Khorassan province was analyzed by GC and GC/MS. Thirty components were characterized ing 93.8% of the total components detected. The major components of the oil were germacrene-D (39.7%) and beta-caryophyllene (15.0%).     

Selenium deficiency and hypothyroidism

Three female children presented with different clinical symptoms that could be related to impaired thyroid function. They underwent an accurate pediatric-endocrinologic diagnosis. Laboratory tests revealed no pathological findings, except latent hypothyroidism and selenium deficiency. Hypothyroidism was diagnosed by elevated basal TSH and by a pathological iv-TRH-stimulation test. After treating the children with sodium selenite orally for 4 wk, their metabolism had returned to normal and we saw a marked improvement of all clinical symptoms. For the first time, we have been able to describe hypothyroidism caused exclusively by selenium deficiency, the pathophysiology of which may be expressed as a malfunction of human 5′-deiodinases.     

Tissue distribution of puerarin and its conjugated metabolites in rats assessed by liquid chromatography–tandem mass spectrometry

Puerarin (an isoflavone C-glucoside from kudzu root) has been the focus of several studies investigating its potential effects on health benefits. In this study, we determined single dose tissue distribution of puerarin and its metabolites in order to examine whether they undergo selective uptake by specific organs. Puerarin was administered orally (50 mg/kg) to rats and the concentration of puerarin in tissue compartments was determined using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Puerarin was widely distributed in rat tissues with highest concentrations in lungs (799±411.6 ng/g wet tissues). In addition, we examined the excretion of puerarin into the bile. LC–MS/MS analysis of bile samples collected after infusing puerarin directly into the portal vein indicated that puerarin was excreted into the bile predominantly in the form of unconjugated puerarin. This report identifying puerarin in several organs including kidney and pancreas may explain its beneficial effects in diabetes.