Mitro-aortic pathology: a point of view for a fully transcatheter staged approach

Severe aortic valve stenosis (AVS) and mitral valve regurgitation (MVR) often coexist. Although a fully percutaneous treatment for the two conditions, by means of transcatheter aortic valve implantation (TAVI) followed by MitraClip, can be appealing in selected high-risk candidates, critical and strategical reasoning should be applied. In a 3-year period we have developed a single-centre experience of 14 patients who were managed with a staged percutaneous approach to treat severe AVS and MVR. The average interval from TAVI to MitraClip repair was 101 ± 12 days. Success for TAVI was 100% and 92.9% (13/14) for MitraClip. At late follow-up, 3 patients developed MVR 3+. Estimated 1?year survival was 66.5%. Freedom from 1?year endpoint (death, stroke, major bleeding, myocardial infarction, and cardiac re-hospitalisation) was 57.9%.In our view, a fully transcatheter approach for mitro-aortic pathology is feasible and should be performed only as a staged procedure in those patients that remain symptomatic, in spite of successful TAVI. It should be emphasised that although the periprocedural success rate is satisfactory, follow-up mortality and re-hospitalisation rates remain high, even at mid-term follow-up. This most probably results from the advanced clinical picture at time of referral for treatment.     

Role of Hsp70 ATPase Domain Intrinsic Dynamics and Sequence Evolution in Enabling its Functional Interactions with NEFs

Catalysis of ADP-ATP exchange by nucleotide exchange factors (NEFs) is central to the activity of Hsp70 molecular chaperones. Yet, the mechanism of interaction of this family of chaperones with NEFs is not well understood in the context of the sequence evolution and structural dynamics of Hsp70 ATPase domains. We studied the interactions of Hsp70 ATPase domains with four different NEFs on the basis of the evolutionary trace and co-evolution of the ATPase domain sequence, combined with elastic network modeling of the collective dynamics of the complexes. Our study reveals a subtle balance between the intrinsic (to the ATPase domain) and specific (to interactions with NEFs) mechanisms shared by the four complexes. Two classes of key residues are distinguished in the Hsp70 ATPase domain: (i) highly conserved residues, involved in nucleotide binding, which mediate, via a global hinge-bending, the ATPase domain opening irrespective of NEF binding, and (ii) not-conserved but co-evolved and highly mobile residues, engaged in specific interactions with NEFs (e.g., N57, R258, R262, E283, D285). The observed interplay between these respective intrinsic (pre-existing, structure-encoded) and specific (co-evolved, sequence-dependent) interactions provides us with insights into the allosteric dynamics and functional evolution of the modular Hsp70 ATPase domain.     

A trophic effect of epidermal growth factor (EGF) on rat colonic mucosa in organ culture

The development of an organ-culture system for rat colonic mucosa has enabled a direct assessment of the effect of epidermal growth factor (EGF) on cell division. An augmented mitotic index (AIm) has been employed to identify changes in cell proliferation. Explants of colonic mucosa from four animals were maintained in a medium containing serum for five days. On the fifth day of culture, half of the explants received fresh medium containing EGF (40 ng/ml) and the remainder (controls) fresh medium only. At 6, 12, 24 and 48 hr thereafter groups of both experimental and control explants received the metaphase-arresting drug vincristine (4 micrograms/ml) for 3 hr prior to fixation. The proportions of vincristine-arrested metaphases within the explants were determined. Analysis of the data indicates that when serum is present exogenous EGF exerts a trophic effect which increases with time (P less than 0.001). In a second experiment colonic explants from four animals were maintained for five days in a serum-free medium and were then divided into groups, each of which received one of a range of concentrations of EGF. The AIm was determined for each group after 36 hr. It was found that increasing concentrations of EGF produce a small but significant increase in cell proliferation (P less than 0.01). This effect, however, was less pronounced than that seen when serum was present. These results suggest that EGF has a trophic action on the colon and interacts with additional factors found in serum.     

Intracellular microelectrode measurements in small cells evaluated with the patch clamp technique.

Microelectrode penetration of small cells leads to a sustained depolarization of the resting membrane potential due to a transmembrane shunt resistance (Rs) introduced by the microelectrode. This has led to underestimation of the resting membrane potential of various cell types. However, measurement of the fast potential transient occurring within the first few milliseconds after microelectrode penetration can provide information about pre-impalement membrane electrophysiological properties. We have analyzed an equivalent circuit of a microelectrode measurement to establish the conditions under which the peak of the impalement transients (Ep) approaches the pre-impalement resting membrane potential (Em) of small cells most closely. The simulation studies showed that this is the case when the capacitance of the microelectrode is low and the membrane capacitance of the cell high. In experiments performed to assess the reliability of Ep as a measure of Em, whole-cell patch clamp measurements were performed in the current clamp mode to monitor, free from the effects of Rs, Em in cultured human monocytes. Microelectrode impalement of such patch clamped cells and measurement of Ep made it possible to detect correlation between Ep and Em and showed that for small cells such as human monocytes Ep is on average 6 mV less negative than the resting membrane potential.     

Asplenetin,a flavone and its glycoside from Launaea asplenifolia

A new flavone, asplenetin, has been isolated from Launea asplenifolia and characterized as 5,7,3′,4′,5′-pentahydroxy-3-(3-methylbutyl)flavone. Its glycoside, asplenetin 5-O-neohesperidoside, is also reported.     

Racial and other characteristics of human T cell leukemia/lymphoma (HTLV-I) and AIDS (HTLV-III) in Trinidad.

Adult T cell leukaemia/lymphoma was first recognised as a clinical entity in southwest Japan. Subsequently the Caribbean has been found to be another area where the disease is endemic, and sporadic cases have been identified in different parts of the world. The human T cell leukaemia/lymphoma virus (HTLV-I) is causally related to adult T cell leukaemia/lymphoma. A subgroup of HTLV, designated HTLV-III, has recently been isolated from many patients with the acquired immunodeficiency syndrome (AIDS) and preAIDS, and there is now evidence that this variant is the primary cause of AIDS. This is the first report from Trinidad to describe 12 cases of adult T cell leukaemia/lymphoma and 14 of AIDS. All were in patients of African descent. No cases were seen in subjects of East Indian descent, who, like those of African descent, comprise as much as 40% of the population. West Indians of African descent may have increased susceptibility to infection with both HTLV-I and HTLV-III.     

Secretin-stimulated insulin release in vivo in European eels, Anguilla anguilla L

Plasma insulin and glucose responses to a secretin-like factor, extracted from pike intestines, have been investigated in vivo in European eels, Anguilla anguilla L. Intra-arterial injection of pike secretin elicited a dose-related, significant increase of plasma insulin after 30 min at 100 and 250 μgkg^-1 body weight, but was without effect at 40μgkg^-1. Plasma glucose levels, however, remained unchanged over this dose range. These results suggest that hormonal factors of gastrointestinal origin may modify pancreatic endocrine function in teleost fish.     

A Simple and Widely Applicable Method for Preparing Homogeneous and Stable Quality Control Samples in Water Microbiology

Test strains suspended in skim milk, quickly frozen in dry ice-ethanol, and stored at - 70°C can be used as quality control samples that are immediately available by quickly thawing at 37°C. The samples remain homogeneous and stable for at least 1 year, except for Aeromonas hydrophila, which decreases 20 to 30% in 1 year.     

Effect of Axial Ligand Length on Biological and Anticancer Properties of Axially Disubstituted Silicon Phthalocyanines

In this study, three new axially disubstituted silicon phthalocyanines ( SiPc1–3 ) and their quaternized phthalocyanine derivatives ( QSiPc1–3 ) were prepared and characterized. The biological properties (antioxidant, antimicrobial, antibiofilm, and microbial cell viability activities) of the water-soluble silicon phthalocyanines were examined, as well. A 1 % DMSO diluted with pure water was used as a solvent in biological activity studies. All the compounds exhibited high antioxidant activity. They displayed efficient antimicrobial and antimicrobial photodynamic therapeutic properties against various microorganisms, especially Gram (+) bacteria. Additionally, they demonstrated high antibiofilm activities against S. aureus and P. aeruginosa. In addition, 100 % bacterial reduction was obtained for all the studied phthalocyanines against E. coli viable cells. Besides, the DNA cleavage and binding features of compounds ( QSiPc1–3 ) were studied using pBR322 DNA and CT-DNA, respectively. Furthermore, the human topoisomerase I enzyme inhibition activities of compounds QSiPc1 – 3 were studied. Anticancer properties of the water-soluble compounds were investigated using cell proliferation MTT assay. They exhibited anticarcinogenic activity against the human colon cancer cell line (DLD-1). Compounds QSiPc1 and QSiPc3 displayed a high anticarcinogenic effect on the DLD-1 cell line. The obtained results indicated that all the studied compounds may be effective biological agents and anticancer drugs after further investigations.