Experimental neurotoxicity of the anorectic fenfluramine

Summary Fenfluramine, an amphophilic compound which is a halogenated derivative of amphetamine, is still used as an anorectic agent for weight reduction, as it acts on the satiety center of the hypothalamus. Holtzman strain rats aged 6 days were daily injected s.c. fenfluramine hydrochloride at the dose of 75 mg/kg body weight. The animals were killed at different time intervals between days 7 and 40, and different parts of the brain were examined by light and electron microscopy. About half of the animals showed intralysosomal membrano-cytoplasmic bodies in the oligodendroglia, neurons, and neuropil, maximally in the animals receiving 8–19 injections. They were seen as concentrically arranged, single-layered lamellae; small dense bodies; or larger heterogeneous bodies. The mechanism of production of such inclusions could be the formation of complexes of this amphophilic compound with tissue phospholipids, or some enzyme-inhibiting action. A marked prominence of dark cells, predominantly oligodendroglia, was also noticed in the brains of experimental animals. Some of these cells appeared to be dark neurons, probably resulting from the serotonin-depleting effect of fenfluramine. A few dark cells were identified as resting microglial cells, while macrophagic reactive microglia were detected in the brains of very young animals. Fenfluramine appears to provide a model for studying neuroglial reactions.Paper presented at the Erwin Riesch symposium on Lysosomal Disorders of the Nervous System, Berlin (Convenor, Prof. Cervos-Navarro); and as poster-talk at the 9th International Congress of Neuropathology, Vienna, September 1982     

Variation in acute fluid resuscitation among pediatric burn centers

BackgroundAccurate resuscitation of pediatric patients with large thermal injury is critical to achieving optimal outcomes. The goal of this project was to describe the degree of variability in resuscitation guidelines among pediatric burn centers and the impact on fluid estimates.MethodsFive pediatric burn centers in the Pediatric Injury Quality Improvement Collaborative (PIQIC) contributed data from patients with ≥15% total body surface area (TBSA) burns treated from 2014 to 2018. Each center's resuscitation guidelines and guidelines from the American Burn Association were used to calculate estimated 24-h fluid requirements and compare these values to the actual fluid received.ResultsDifferences in the TBSA burn at which fluid resuscitation was initiated, coefficients related to the Parkland formula, criteria to initiate dextrose containing fluids, and urine output goals were observed. Three of the five centers’ resuscitation guidelines produced statistically significant lower mean fluid estimates when compared with the actual mean fluid received for all patients across centers (4.53 versus 6.35 ml/kg/% TBSA, p < 0.001), (4.90 versus 6.35 ml/kg/TBSA, p = 0.002) and (3.38 versus 6.35 ml/kg/TBSA, p < 0.0001).ConclusionsThis variation in practice patterns led to statistically significant differences in fluid estimates. One center chose to modify its resuscitation guidelines at the conclusion of this study.     

Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method

Objective : The aim of this study was to investigate the inter-relationship between urinary excretion of alpha-1-microglobulin (AIM), retinol-binding protein (RBP) and albumin in term and premature neonates, with urine collected into cotton wool balls and extracted by a novel method. Subjects and methods : Sixty-four infants were studied on the first day of life; 26 had been born at term (37–42 weeks gestation) and 38 prematurely (24–28 weeks n = 16, 29–36 weeks n = 22). Urine collected into cotton wool balls was analysed following a new detergent extraction method, which resulted in a recovery rate of 94–107% for albumin, AIM, RBP and creatinine. Results : Urinary protein excretion, expressed as a ratio to urinary creatinine, decreased significantly with increasing gestational age (24–28 weeks, 29–36 weeks, 37–42 weeks: albuminxreatinine ratio mg/mmol mean 96.9, 31.7, 19.3; AIM: creatinine ratio mg/mmol mean 99.3, 37.0, 7.8; RBP: creatinine ratio mg/mmol mean 16.2, 3.8, and <0.01, below the limit of detection, respectively). When results were corrected for birthweight, this gestation-associated effect was still present for A1M and RBP, but not for albumin. In premature infants there was a significant positive correlation between AIM: creatinine ratio and RBP: creatinine ratio ( r = 0.85), and also between albumin and both AIM and RBP ( r = 0.82 and 0.77). Conclusion : Increased excretion of AIM, RBP and albumin at earlier gestational ages is probably due to proximal tubular immaturity, although tubular damage and also glomerular dysfunction cannot be excluded as possible explanations.     

A Short Series of Case Reports of COVID-19 in Immunocompromised Patients

Immunocompromised individuals are at risk of prolonged SARS-CoV-2 infection due to weaker immunity, co-morbidities, and lowered vaccine effectiveness, which may evolve highly mutated variants of SARS-CoV-2. Nonetheless, limited data are available on the immune responses elicited by SARS-CoV-2 infection, reinfections, and vaccinations with emerging variants in immunocompromised patients. We analyzed clinical samples that were opportunistically collected from eight immunocompromised individuals for mutations in SARS-CoV-2 genomes, neutralizing antibody (NAb) titers against different SARS-CoV-2 variants, and the identification of immunoreactive epitopes using a high-throughput coronavirus peptide array. The viral genome analysis revealed two SARS-CoV-2 variants (20A from a deceased patient and an Alpha variant from a recovered patient) with an eight amino-acid (aa) deletion within the N-terminal domain (NTD) of the surface glycoprotein. A higher NAb titer was present against the prototypic USA/WA1/2020 strain in vaccinated immunocompromised patients. NAb titer was absent against the Omicron variant and the cultured virus of the 20A variant with eight aa deletions in non-vaccinated patients. Our data suggest that fatal SARS-CoV-2 infections may occur in immunocompromised individuals even with high titers of NAb post-vaccination. Moreover, persistent SARS-CoV-2 infection may lead to the emergence of newer variants with additional mutations favoring the survival and fitness of the pathogen that include deletions in NAb binding sites in the SARS-CoV-2 surface glycoprotein.     

Effect of rGO with BaCuO3 perovskite on the thermal decomposition of AP and NTO

In this study, the syntheses of a BaCuO₃ perovskite-structured oxide and rGO were conducted using a sol–gel method and ultrasonication process, respectively. Their physico-chemical characteristics were studied by powder X-ray diffraction (PXRD), Raman spectroscopy, and ultraviolet-visible (UV-vis) spectroscopy analyses. The perovskite type particles were found to present as a cubic crystal system with a crystal size in the range of 10–60 nm. Their catalytic performance was investigated using differential thermal analysis (DTA) measurements at varying heating rates via the thermal decomposition of ammonium perchlorate (AP) and 3-nitro-1,2,4-triazol-5-one (NTO). The kinetics and thermodynamics parameters, such as the average activation energy, pre-exponential factor, entropy, and Gibbs free energy, were also investigated, which showed a decrease in the decomposition peak temperature of AP and NTO in the presence of the catalysts rGO, BaCuO₃, and rGO + BaCuO₃ compared to pure AP and NTO.

The thermal decomposition of AP and NTO was investigated in the presence of rGO, a perovskite structured BaCuO₃ catalyst, and composite rGO + BaCuO₃ using DTA analysis. These catalysts highly decreased the decomposition peak temperature of AP and NTO compared to pure AP and NTO.     

Modification of nano-silver bioactivity by adsorption on carbon nanotubes and graphene oxide

Abstract

Objective: The toxicity of silver nanomaterials in various forms has been extensively evaluated, but the toxicity of silver nanocarbon composites is less well understood. Therefore, silver-carbon nanotube composites (Ag-MWCNT-COOH) and silver-graphene oxide composites (Ag-GO) were synthesized by microwave irradiation and evaluated in two in vitro cell models.

Materials/Methods: Toxicity of silver nanosphere (Ag), Ag-MWCNT-COOH and Ag-GO were analyzed by MTS assay and LDH assay in primary C57BL/6 murine alveolar macrophages and human THP-1 cells. Activation of NLRP3 inflammasome by particle variants in these models was done by proxy using LPS co-culture and IL-1β release.

Results: The results depended on the model, as the amount of Ag on the modified carbon resulted in slightly increased toxicity for the murine cells, but did not appear to affect toxicity in the human cell model. IL-1β release from carbon particle-exposures was decreased by the presence of Ag in both cell models. Suspensions of Ag-MWCNT-COOH, Ag-GO and Ag in artificial lysosomal fluid were prepared and ICP-MS was used to detect Ag ions concentration in three silver suspension/solutions. The amount of Ag ions released from Ag-MWCNT-COOH and Ag-GO were similar, which were both lower than that of Ag nanospheres.

Conclusions: The results suggest the bioactivity of silver composites may be related to the amount of Ag ions released, which can be dependent on the cell model under investigation.     

Recurrent ulnar nerve entrapment at the elbow: Correlation of surgical findings and 3-Tesla magnetic resonance neurography

The authors describe the correlation between 3-Tesla magnetic resonance neurography (MRN) and surgical findings in two patients who underwent multiple previous failed ulnar nerve surgeries. MRN correctly localized the site of the abnormality. Prospectively observed MRN findings of perineural fibrosis, ulnar nerve re-entrapment abnormalities, medial antebrachial cutaneous neuroma and additional median nerve entrapment were confirmed surgically.