Toxicity, inflammation, and anti-human immunodeficiency virus type 1 activity following exposure to chemical moieties of C31G.

C31G, which has potent activity against the human immunodeficiency virus type 1 (HIV-1) and an established record of safety in animal studies and human trials, is a microbicidal agent comprised of a buffered equimolar mixture of two amphoteric, surface-active agents: an alkyl amine oxide (C14AO) and an alkyl betaine (C16B). Studies of long-term in vitro exposure to C31G and its constituents have suggested that the components of C31G may contribute differentially to its toxicity and efficacy. In the present studies, in vitro assays of cytotoxicity and anti-HIV-1 activity demonstrated that C16B was slightly less cytotoxic compared to either C31G or C14AO, whereas the anti-HIV-1 activities of C31G and its individual constituents were similar. In the murine model of cervicovaginal microbicide toxicity, in vivo exposure to C14AO resulted in severe cervical inflammation followed by a delayed disruption of the columnar epithelium. In contrast, exposure to C16B caused severe cervical epithelial disruption and a secondary, less intense inflammatory response. These results demonstrate that (i) there are both mechanistic and temporal differences in toxicity associated with the components of C31G not necessarily predicted by in vitro assessments of cytotoxicity and (ii) contributions of each component to the anti-HIV-1 activity of C31G appear to be equal. In addition, these findings indicate that direct and indirect mechanisms of in vivo toxicity can be observed as separate but interrelated events. These results provide further insight into the activity of C31G, as well as mechanisms potentially associated with microbicide toxicity.     

Myxopapillary ependymoma of lumbosacral region with metastasis to both cerebellopontine angles: report of a rare case

Introduction Myxopapillary ependymomas are low grade tumours that are known to recur locally even after complete excision, but metastasis to distant sites is extremely uncommon. Case report We report an unusual case of lumbo-sacral myxopapillary ependymoma in a 13-year-old boy with metastasis to both cerebellopontine angles. To the best of our knowledge, this is the youngest patient of metastatic myxopapillary ependymoma.     

Genetic variability of begomoviruses associated with cotton leaf curl disease originating from India

Summary. Cotton leaf curl disease (CLCuD) causing viruses belong to the Begomovirus genus of the family Geminiviridae. Most begomoviruses are bipartite with two molecules of circular single stranded DNA (A and B) encapsidated in icosahedral geminate particles. However, the begomoviruses associated with CLCuD have DNA- instead of DNA-B. In this communication we report the complete genomic sequence of DNA-A component of two CLCuD-causing begomoviruses, cotton leaf curl Kokhran virus-Dabawali (CLCuKV-Dab), tomato leaf curl Bangalore virus-Cotton [Fatehabad] (ToLCBV-Cotton [Fat]) and partial sequences of two other isolates cotton leaf curl Rajasthan virus-Bangalore (CLCuRV-Ban) and cotton leaf curl Kokhran virus-Ganganagar (CLCuKV-Gang). A phylogenetic analysis of these isolates along with other related begomoviruses showed that ToLCBV-Cotton [Fat] isolate was closest to the tomato leaf curl Bangalore virus-5 (ToLCBV-Ban5) where as CLCuKV-Dab isolate was close to the cotton leaf curl Kokhran virus-Faisalabad1 (CLCuKV-Fai1), cotton leaf curl Kokhran virus-72b (CLCuKV-72b) and cotton leaf curl Kokhran virus-806b (CLCuKV-806b) isolates from Pakistan. The phylogenetic analysis further showed that the ToLCBV-Cotton [Fat] and CLCuKV-Dab isolates along with CLCuKV-Fai1, CLCuKV-72b and CLCuKV-806b are closer to the ToLCBV, tomato leaf curl Gujarat virus (ToLCGV), tomato leaf curl Gujarat virus-Varanasi (ToLCGV-Var) and tomato leaf curl Sri Lanka virus (ToLCSLV) isolates, where as cotton leaf curl Alabad virus-804a (CLCuAV-804a), cotton leaf curl Multhan virus (CLCuMV) cluster with the isolates from cotton leaf curl Rajasthan virus (CLCuRV) and okra yellow vein mosaic virus (OYVMV). These results demonstrate the extensive variability observed in this group of viruses. The AC4 ORF is the least conserved among these viruses. In order to further asses the variability in the CLCuD-causing begomoviruses, the region showing minimum similarity in the DNA-A sequence was first determined by a comparison of segments of different lengths of the aligned sequences. The results indicated that region 2411–424 (771nt) was the least conserved. A phylogenetic tree constructed using the sequences of all the CLCuD causing begomoviruses, corresponding to the least conserved region showed that they form two distinct clusters.     

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.