Quantification of Myocardial Blood Flow with CZT SPECT Imaging: Is It Ready for Clinical Use?

Purpose of Review

Myocardial blood flow (MBF) quantification with positron emission tomography (PET) is well validated and has established diagnostic and prognostic value for patient management. New cardiac dedicated solid-state single-photon emission tomography (SPECT) cameras using cadmium-zinc-telluride (CZT) crystals have better temporal and spatial resolution and increased count sensitivity than conventional SPECT systems and can measure MBF. We review recent validation studies using CZT technology for measurement of MBF and assess its readiness for clinical application.

Recent Findings

One preclinical study showed the accuracy of MBF measured using the CZT technology and conventional radiotracers versus microsphere data. Clinical studies have demonstrated the feasibility in patients and excellent correlations with coronary angiography and flow-wire studies, and PET imaging.

Summary

Measurement of MBF is possible with SPECT CZT systems and has been validated. Further studies are necessary to confirm the incremental value of MBF measurements with SPECT CZT to standard relative perfusion imaging for diagnostic accuracy and risk stratification.

     

Remote ischemic preconditioning improves the survival of rat random-pattern skin flaps

Random-pattern flap transfer is one of the most popular procedures for covering soft tissue defects. Ischemic preconditioning is a protective endogenous mechanism capable of reducing ischemia-reperfusion injury, and it has been shown that preconditioning by proximal pedicle clamping can improve flap survival. However, the method is not suitable for random-pattern flap transfer in the clinical setting. The present study evaluates the effect of ischemic preconditioning of Wistar rat hind limbs upon dorsal random-pattern skin flap survival. Ischemic preconditioning was induced by ischemia of the right hind limb during 10 min, followed by 30 min of reperfusion. Thirty-two animals were divided in two groups. In group 1, a dorsal random-pattern skin flap measuring 2 × 7 cm was raised immediately after the induction of ischemic preconditioning. The animals in group 2 (controls) received the same treatment, but without ischemic preconditioning. The survival area was defined as the surface of the viable tissue (square centimeter) on the fifth postoperative day. The average survival area was 6.57 ± 0.18 cm² in group 1 and 4.44 ± 0.21 cm² in group 2. All preconditioned animals presented significantly higher flap survival areas than the controls (p ≤ 0.01, Student’s t test). Our findings show that flap necrosis was reduced by the induction of ischemic preconditioning in a body area distant from the flap harvest site, and that ischemic preconditioning has a systemic protective effect on dorsal random-pattern skin flaps and increase survival. A better understanding of the mechanism involved may improve the clinical condition of patients requiring random-pattern skin flap transfer, especially in high-risk groups.     

Natural and Prosthetic Heart Valve Calcification: Morphology and Chemical Composition Characterization

Calcification is the most common cause of damage and subsequent failure of heart valves. Although it is a common phenomenon, little is known about it, and less about the inorganic phase obtained from this type of calcification. This article describes the scanning electron microscopy (SEM)/energy dispersive X‐ray spectroscopy and Ca K‐edge X‐ray absorption near edge structure (XANES) characterization performed in natural and bioprosthetic heart valves calcified in vivo (in comparison to in vitro‐calcified valves). SEM micrographs indicated the presence of deposits of similar morphology, and XANES results indicate, at a molecular level, that the calcification mechanism of both types of valves are probably similar, resulting in formation of poorly crystalline hydroxyapatite deposits, with Ca/P ratios that increase with time, depending on the maturation state. These findings may contribute to the search for long‐term efficient anticalcification treatments.     

Polyclonal antibodies against properly folded Dengue virus NS1 protein expressed in E. coli enable sensitive and early dengue diagnosis

The non-structural 1 (NS1) protein plays an important role in dengue diagnosis because it has been detected as a soluble serum antigen in both primary and secondary infections. The NS1 protein was expressed in Escherichia coli cells, and the efficiency of four different refolding protocols was tested. All of the protocols generated dimeric NS1 in a conformation similar to that of the protein expressed by eukaryotic cells. A polyclonal antibody produced from the properly folded E. coli recombinant NS1 (rNS1) protein proved to be a useful tool for the diagnosis of Dengue virus because it detected 100% of the Dengue virus 2 (DENV2) in infected patients’ sera and 60% of the DENV IgM-positive sera not detected by commercial NS1-based diagnostic kits. These data suggest a high-efficiency method for correctly folding rNS1 that maintains its structural and immunogenic properties. In addition, a detection method using the polyclonal antibody against correctly folded rNS1 seemed to be more sensitive and efficient for NS1 detection in serum, highlighting its usefulness for developing a high-sensitivity diagnostic kit.     

Role of DC-SIGN and L-SIGN receptors in HIV-1 vertical transmission

The innate immune system acts in the first line of host defense against pathogens. One of the mechanisms used involves the early recognition and uptake of microbes by host professional phagocytes, through pattern recognition receptors (PRRs). These PRRs bind to conserved microbial ligands expressed by pathogens and initiate both innate and adaptative immune responses. Some PRRs located on the surface of dendritic cells (DCs) and other cells seem to play an important role in human immunodeficiency virus type 1 (HIV-1) transmission. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin, CD209 (DC-SIGN) and its homolog, DC-SIGN-related (DC-SIGNR or L-SIGN) receptors are PPRs able to bind the HIV-1 gp120 envelope protein and, because alterations in their expression patterns also occur, they might play a role in both horizontal and vertical transmission as well as in disseminating the virus within the host. This review aims to explore the involvement of the DC-SIGN and L-SIGN receptors in HIV-1 transmission from mother to child.     

Prospects in Lyophilization of Bovine Pericardium

Almost 30 years after the introduction of heart valve prostheses patients worldwide are benefiting from the implant of these devices. Among the various types of heart valves, the ones made of treated bovine pericardium have become a frequently used replacement of the heart's native valve. Lyophilization, also known as freeze-drying, is an extremely useful technique for tissue storage for surgical applications. This article gives a brief overview on the current bovine pericardium lyophilization development, including the chemical modification to improve physical–chemical characteristics and the advanced technologies used to guarantee a high-quality product. It was shown that lyophilization process can be successfully applied as a method of bovine pericardium preservation and also as a technological tool to prepare new materials obtained by chemical modification of native tissues.       

Configuration-dependent diffusion can shift the kinetic transition state and barrier height of protein folding

We show that diffusion can play an important role in protein-folding kinetics. We explicitly calculate the diffusion coefficient of protein folding in a lattice model. We found that diffusion typically is configuration- or reaction coordinate-dependent. The diffusion coefficient is found to be decreasing with respect to the progression of folding toward the native state, which is caused by the collapse to a compact state constraining the configurational space for exploration. The configuration- or position-dependent diffusion coefficient has a significant contribution to the kinetics in addition to the thermodynamic free-energy barrier. It effectively changes (increases in this case) the kinetic barrier height as well as the position of the corresponding transition state and therefore modifies the folding kinetic rates as well as the kinetic routes. The resulting folding time, by considering both kinetic diffusion and the thermodynamic folding free-energy profile, thus is slower than the estimation from the thermodynamic free-energy barrier with constant diffusion but is consistent with the results from kinetic simulations. The configuration- or coordinate-dependent diffusion is especially important with respect to fast folding, when there is a small or no free-energy barrier and kinetics is controlled by diffusion. Including the configurational dependence will challenge the transition state theory of protein folding. The classical transition state theory will have to be modified to be consistent. The more detailed folding mechanistic studies involving phi value analysis based on the classical transition state theory also will have to be modified quantitatively.