Pharmacological and structural characterization of a novel phospholipase A2 from Micrurus dumerilii carinicauda venom.

We have isolated a new phospholipase A2 (MiDCA1) from the venom of the coral snake Micrurus dumerilii carinicauda. This toxin, which had a molecular mass of 15,552Da, shared high sequence homology with the PLA2 toxins MICNI A and B from Micrurus nigrocinctus venom (77.7% and 73.1%, respectively). In chick biventer cervicis preparations, MiDCA1 produced concentration- and time-dependent neuromuscular blockade that reached 100% after 120 min (2.4 microM, n = 6); contractures to exogenously applied carbachol (8 microM) and KCl (13 mM) were still seen after complete blockade. In mouse phrenic-nerve diaphragm preparations, MiDCA1 (2.4 microM; n = 6) caused triphasic changes followed by partial neuromuscular blockade. Intracellular recordings of end-plate potentials (EPPs) and miniature end-plate potentials (MEPPs) from mouse diaphragm preparations showed that MiDCA1 increased the quantal content by 386+/-12% after 10 min (n = 14; p<0.05) and caused a triphasic change in the frequency of MEPPs. MiDCA1 also decreased the resting membrane potential, an effect that was prevented by tetrodotoxin and/or low extracellular calcium, but not by d-tubocurarine. The toxin increased the amplitude of mouse sciatic-nerve compound action potentials by 30+/-9% (0.6 microM; p<0.05). Potassium currents elicited in freshly dissociated dorsal root ganglia neurones were blocked by 31+/-1% (n = 4; p<0.05) in the presence of 2.4 microM MiDCA1. These results show that MiDCA1 is a new presynaptic phospholipase A2 that produces neuromuscular blockade in vertebrate nerve-muscle preparations. The triphasic effects seen in mammalian preparations and the facilitatory response were probably caused mainly by the activation of sodium channels, complemented by the blockade of nerve terminal potassium channels. The inability of d-turocurarine to prevent the depolarization by MiDCA1 indicated that cholinergic nicotinic receptors were not involved in this phenomenon.     

Dual-Port 2D and 3D Endoscopy: Expanding the Limits of the Endonasal Approaches to Midline Skull Base Lesions with Lateral Extension

Objective To investigate a novel dual-port endonasal and subtemporal endoscopic approach targeting midline lesions with lateral extension beyond the intracavernous carotid artery anteriorly and the Dorello canal posteriorly. Methods Ten dual-port approaches were performed on five cadaveric heads. All specimens underwent an endoscopic endonasal approach from the sella to middle clivus. The endonasal port was combined with an anterior or posterior endoscopic extradural subtemporal approach. The anterior subtemporal port was placed directly above the middle third of the zygomatic arch, and the posterior port was placed at its posterior root. The extradural space was explored using two-dimensional and three-dimensional endoscopes. Results The anterior subtemporal port complemented the endonasal port with direct access to the Meckel cave, lateral sphenoid sinus, superior orbital fissure, and lateral and posterosuperior compartments of the cavernous sinus; the posterior subtemporal port enhanced access to the petrous apex. Endoscopic dissection and instrument maneuverability were feasible and performed without difficulty in both the anterior and posterior subtemporal ports. Conclusion The anterior and posterior subtemporal ports enhanced exposure and control of the region lateral to the carotid artery and Dorello canal. Dual-port neuroendoscopy is still minimally invasive yet dramatically increases surgical maneuverability while enhancing visualization and control of anatomical structures.     

Functional analysis of gene expression in risperidone treated cells provide new insights in molecular mechanism and new candidate genes for pharmacogenetic studies

Risperidone is a potent antagonist of both dopamine and serotonin receptors. However, little is known about the underlying molecular mechanism by which risperidone acts. Although a number of genetic variants have been observed to correlate with treatment response there are no definitive predictors of response. We performed a genome-wide gene expression analysis (Human Genome U219 Array Plate) of a human neuroblastoma cell line (SK-N-SH) exposed to risperidone to identify molecular mechanisms involved in the cellular response to risperidone and thus identify candidate genes for pharmacogenetic studies. Our results revealed that cellular risperidone treatment is associated with a range of gene expression changes, which are time (6–48 h) and dose related (0.1–10 μM). We found that functional clusters of these changes correspond to Gene Ontology categories related to neural cell development functions, and synaptic structure and functions. We also identified Canonical Pathways related to these functional categories: neurogenesis and axon guidance; synaptic vesicle; and neurotransmitter signaling (dopamine, serotonin and glutamate). Finally, we identified candidate genes for pharmacogenetic studies related to the main risperidone secondary effects: motor disorders, cardiovascular disorders and metabolic disorders. Our results suggest that risperidone treatment affects the neurogenesis and neurotransmission of neuroblastoma cells, which is in agreement with the “initiation and adaptation” model to explain the mechanism of action of psychotropic drugs.     

Sleep-Related Breathing Disorders: When CPAP Is Not Enough

Three decades ago, continuous positive airway pressure (CPAP) was introduced to treat obstructive sleep apnea (OSA). Shortly after, bilevel positive airway pressure devices (BPAP) that independently adjusted inspiratory and expiratory positive airway pressure were developed to treat complex sleep-related breathing disorders unresponsive to CPAP. Based on the bilevel positive airway pressure platform (hardware) governed by propriety algorithms (software), advanced modes of noninvasive ventilation (NIV) were developed to address complex cardiorespiratory pathophysiology beyond OSA. This review summarizes key aspects of different bilevel PAP therapies (BPAP with/without backup rate, adaptive servoventilation, and volume-assured pressure support) to treat common sleep-related hypoventilation disorders, treatment-emergent central sleep apnea, and central sleep apnea syndromes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-020-00955-x.Key Words: Bilevel positive airway pressure (BPAP), Adaptive servoventilation (ASV), Volume-assured pressure support (VAPS), Sleep-related hypoventilation, Treatment-emergent central apnea, Central sleep apnea     

Fascitis craneal: caso clínico y revisión de la literatura

Cranial fasciitis is an uncommon, rapidly-growing, benign, non-tumoural, myofibroblastic lesion of the skull, found mainly among young children in their first year of life. It is histologically similar to nodular fasciitis and pseudosarcomatous fasciitis. It may mimic more aggressive pathologies, such as sarcomatosis or histiocytosis, due to its rapid, nodular growth in subcutaneous tissue. Complete resection is considered curative and, therefore, entails a low risk of metastases or malignant recurrences.We present the clinical, radiological and pathological findings in a 4-year-old boy with cranial fasciitis in the deep, subcutaneous, soft tissue, with erosion of the outer table of the cranium, which also produced periosteal reaction, while respecting the inner table and meninges. The objective of this article is to highlight the absence of radiotherapeutic or chemotherapeutic adjuvant treatment. In addition, an exhaustive review of the literature is also presented.     

Prevalence of drug interactions in hospital healthcare

Aim of the review To study the prevalence of drug interactions in hospital healthcare by reviewing literature. Method A review was carried out of studies written in Spanish and English on the prevalence of drug interactions in hospital care published in Pubmed between January 1990 and September 2008. The search strategy combined free text and MeSH terms, using the following keywords: ??Drug interaction??, ??prevalence?? and ??hospital??. For each article, we classified independent variables (pathology, age of population, whether patients were hospitalized or not, geographical location, etc.) and dependent variables (number of interactions per 100 patients studied, prevalence of patients with interactions, most common drug interactions, and others). Results The search generated 436 articles. Finally, 47 articles were selected for the study, 3 provided results about drug interactions with real clinical consequences, 42 about potential interactions, and 2 described both. The prevalence of patients with interactions was between 15 and 45?% and the number of interactions per 100 patients was between 37 and 106, depending on the group of studies analyzed. There was a considerable increase in these rates in patients with heart diseases and elderly persons. Conclusion There is a large number of studies on the prevalence of drug interactions in hospitals but they report widely varying results. The prevalence is higher in patients with heart diseases and elderly people.     

Living donor liver transplantation in Brazil—current state

Currently in Brazil, living donor liver transplantation (LDLT) represents 8.5% of liver transplantation (LT), being the majority pediatric one. Up to now, according to Brazilian Organ Transplantation Association (ABTO) annual report, 2,086 procedures have been done nationwide, most of them in southeast and south regions. Based on national centers reports, biliary complication is the most common recipient postoperative complication (14.5–20.6%), followed by hepatic artery thrombosis (3.1–10.7%) and portal vein thrombosis (2.3–9.1%). Patient and graft overall 5-y survival correspond to 76% and 74%, respectively. Regarding the donor, morbidity rate ranges from 12.4% to 28.3%, with a national mortality rate of 0.14%. In conclusion, Brazilian LDLT programs enhance international experience that this is a feasible and safe procedure, as well as an excellent alternative strategy to overcome organs shortage.