Surgical treatment of pulmonary venous baffle obstruction after modified Senning procedure

Paciente de 13 anos de idade, sexo masculino, submetido à correção de estenose de túnel das veias pulmonares (ETVP) após cirurgia de Senning modificada realizada aos 5 meses. O quadro clínico era de congestão pulmonar e broncopneumonias de repetição e o ecocardiograma confirmou ETVP. Uma angioplastia com balão foi realizada previamente à correção cirúrgica com circulação extracorpórea. A placa de pericárdio bovino empregada para ampliação do átrio direito retraiu-se e calcificou, levando a ETVP. A placa foi removida e o átrio direito foi ampliado com um retalho de politetrafluoretileno. O ecocardiograma transesofágico intraoperatório demonstrou redução significativa da estenose.A 13-year-old male was admitted to undergoing correction of a pulmonary venous baffle stenosis (PVBS) after a modified Senning procedure was performed by the age of five months. Recurrent Pulmonary congestion and pneumonia episodes were followed by echocardiography and cardiac catheterization that confirmed PVBS. Previous catheter balloon angioplasty was attempted, and a surgical revision was done under cardiopulmonary bypass. The bovine pericardial patch used for augmentation of the right atrium, retracted and calcified producing PVBS. Stenotic area was excised and enlargement was done with polytetrafluoroethylene membrane. Intraoperative transesophageal echocardiogram showed relief of stenosis

Optical Control of GABAA Receptors with a Fulgimide-Based Potentiator

Optogenetic and photopharmacological tools to manipulate neuronal inhibition have limited efficacy and reversibility. We report the design, synthesis, and biological evaluation of Fulgazepam, a fulgimide derivative of benzodiazepine that behaves as a pure potentiator of ionotropic γ-aminobutyric acid receptors (GABA A Rs) and displays full and reversible photoswitching in vitro and in vivo. The compound enables high-resolution studies of GABAergic neurotransmission, and phototherapies based on localized, acute, and reversible neuroinhibition

A Photoswitchable Antimetabolite for Targeted Photoactivated Chemotherapy

The efficacy and tolerability of systemically administered anticancer agents are limited by their off-target effects. Precise spatiotemporal control over their cytotoxic activity would allow improving chemotherapy treatments, and light-regulated drugs are well suited to this purpose. We have developed phototrexate, the first photoswitchable inhibitor of the human dihydrofolate reductase (DHFR), as a photochromic analogue of methotrexate, a widely prescribed chemotherapeutic drug to treat cancer and psoriasis. Quantification of the light-regulated DHFR enzymatic activity, cell proliferation, and in vivo effects in zebrafish show that phototrexate behaves as a potent antifolate in its photoactivated cis configuration and that it is nearly inactive in its dark-relaxed trans form. Thus, phototrexate constitutes a proof-of-concept to design light-regulated cytotoxic small molecules and a step forward to develop targeted anticancer photochemotherapies with localized efficacy and reduced adverse effect

Subunit-specific photocontrol of glycine receptors by azobenzene-nitrazepam photoswitcher

© 2021 Maleeva et al. Photopharmacology is a unique approach that through a combination of photochemistry methods and advanced life science techniques allows the study and control of specific biological processes, ranging from intracellular pathways to brain circuits. Recently, a first photochromic channel blocker of anion-selective GABAA receptors, the azobenzene-nitrazepam-based photochromic compound (Azo-NZ1), has been described. In the present study, using patch-clamp technique in heterologous system and in mice brain slices, site-directed mutagenesis and molecular modeling we provide evidence of the interaction of Azo-NZ1 with glycine receptors (GlyRs) and determine the molecular basis of this interaction. Glycinergic synaptic neurotransmission determines an important inhibitory drive in the vertebrate nervous system and plays a crucial role in the control of neuronal circuits in the spinal cord and brain stem. GlyRs are involved in locomotion, pain sensation, breathing, and auditory function, as well as in the development of such disorders as hyperekplexia, epilepsy, and autism. Here, we demonstrate that Azo-NZ1 blocks in a UV-dependent manner the activity of a2 GlyRs (GlyR2), while being barely active on a1 GlyRs (GlyR1). The site of Azo-NZ1 action is in the chloride-selective pore of GlyR at the 2’ position of transmembrane helix 2 and amino acids forming this site determine the difference in Azo-NZ1 blocking activity between GlyR2 and GlyR1. This subunit-specific modulation is also shown on motoneurons of brainstem slices from neonatal mice that switch during development from expressing “fetal” GlyR2 to “adult” GlyR1 receptors

Trait anxiety is associated with attentional brain networks

Trait anxiety is a well-established risk factor for anxiety and depressive disorders, yet its neural correlates are not clearly understood. In this study, we investigated the neural correlates of trait anxiety in a large sample (n = 179) of individuals who completed the trait and state versions of the State-Trait Anxiety Inventory and underwent resting-state functional magnetic resonance imaging. We used independent component analysis to characterize individual resting-state networks (RSNs), and multiple regression analyses to assess the relationship between trait anxiety and intrinsic connectivity. Trait anxiety was significantly associated with intrinsic connectivity in different regions of three RSNs (dorsal attention network, default mode network, and auditory network) when controlling for state anxiety. These RSNs primarily support attentional processes. Notably, when state anxiety was not controlled for, a different pattern of results emerged, highlighting the importance of considering this factor in assessing the neural correlates of trait anxiety. Our findings suggest that trait anxiety is uniquely associated with resting-state brain connectivity in networks mainly supporting attentional processes. Moreover, controlling for state anxiety is crucial when assessing the neural correlates of trait anxiety. These insights may help refine current neurobiological models of anxiety and identify potential targets for neurobiologically-based interventions

Optical Control of Cardiac Function with a Photoswitchable Muscarinic Agonist

Light-triggered reversible modulation of physiological functions offers the promise of enabling on-demand spatiotemporally controlled therapeutic interventions. Optogenetics has been successfully implemented in the heart, but significant barriers to its use in the clinic remain, such as the need for genetic transfection. Herein, we present a method to modulate cardiac function with light through a photoswitchable compound and without genetic manipulation. The molecule, named PAI, was designed by introduction of a photoswitch into the molecular structure of an M2 mAChR agonist. In vitro assays revealed that PAI enables light-dependent activation of M2 mAChRs. To validate the method, we show that PAI photoisomers display different cardiac effects in a mammalian animal model, and demonstrate reversible, real-time photocontrol of cardiac function in translucent wildtype tadpoles. PAI can also effectively activate M2 receptors using two-photon excitation with near-infrared light, which overcomes the scattering and low penetration of short-wave-length illumination, and offers new opportunities for intravital imaging and control of cardiac function

Adrenergic Modulation With Photochromic Ligands

© 2020 Wiley-VCH GmbH Adrenoceptors are ubiquitous and mediate important autonomic functions as well as modulating arousal, cognition, and pain on a central level. Understanding these physiological processes and their underlying neural circuits requires manipulating adrenergic neurotransmission with high spatio-temporal precision. Here we present a first generation of photochromic ligands (adrenoswitches) obtained via azologization of a class of cyclic amidines related to the known ligand clonidine. Their pharmacology, photochromism, bioavailability, and lack of toxicity allow for broad biological applications, as demonstrated by controlling locomotion in zebrafish and pupillary responses in mice

Three-Dimensional Printing Model in Double-Outlet Right Ventricle to Simplify Intraventricular Repair

Introduction: Three-dimensional (3D) printing of anatomical structures is gaining interest in congenital heart surgery. We report the case of a 6 year-old boy with double-outlet right ventricle, tetralogy of Fallot subtype, who underwent surgical repair with intracardiac patch. This procedure was performed with the support of two 3D printed models: one of the heart and another of the tunnel patch. Materials and Methods: Transthoracic color Doppler echocardiography, cardiac catheterization, and multi-detector row computed tomography angiography with 3D reconstruction were performed as preoperative evaluation. The 3D models of the heart and the patch –virtually designed to create the intracardiac tunnel– were printed to evaluate possibilities and strategies during the repair. Both 3D models were sterilized for intraoperative use. Results: The 3D heart accurately showed the position of the ventricular septal defect regarding adjacent structures, including the pulmonary, tricuspid, and aortic valves. The virtual planning, simulation, and 3D-printed patch model were useful for making the sutured patch for the tunnel. Postoperative color Doppler echocardiography revealed an effective repair with no residual obstruction. Conclusions: Three-dimensional printing models of the intracardiac anatomy, together with simulation and patch printing, using multi-detector row computed tomography angiography, could provide valuable information for preoperative planning in patients with double-outlet right ventricle, tetralogy of Fallot subtype. The 3D-printed patch models could also be useful to simplify and increase the efficacy of complex procedures.Introducción: La impresión tridimensional (3D) de estructuras anatómicas está ganando interés en cirugía de cardiopatías congénitas. Reportamos el caso de un niño de 6 años con doble vía de salida del ventrículo derecho, subtipo Fallot, que fue sometido a reparación quirúrgica con parche intracardíaco. Este procedimiento se realizó con asistencia de dos modelos impresos 3D: uno del corazón y otro del parche para el túnel. Material y métodos: La evaluación preoperatoria se realizó mediante ecocardiograma Doppler color transtorácico, cateterismo cardíaco y angiotomografía computarizada multidetectores con reconstrucción 3D. Los modelos tridimensionales del corazón y el parche virtualmente diseñados para crear el túnel intracardíaco fueron impresos, para evaluar posibilidades y estrategias en la reparación. Ambos modelos 3D fueron esterilizados para uso intraoperatorio. Resultados: El corazón 3D mostró en forma precisa la posición de la comunicación interventricular con respecto a las estructuras adyacentes, incluidas las válvulas pulmonar, tricúspide y aorta. La planificación virtual, simulación e impresión 3D del molde del parche fue útil para la confección del parche suturado para el túnel. El ecocardiograma Doppler color posoperatorio evidenció una reparación efectiva sin obstrucción residual. Conclusiones: Los modelos cardíacos impresos 3D de la anatomía intracardíaca junto con la simulación e impresión de parches, usando angiotomografia computarizada multidetectores, podrían brindar valiosa información para la planificación preoperatoria en pacientes con doble vía de salida de ventrículo derecho tipo Fallot. Los modelos 3D impresos del parche también podrían ser útiles para simplificar e incrementar la eficacia de procedimientos complejos.