Cisplatin is a platinum-based chemotherapeutic agent that induces peripheral neuropathy in 30% of patients. Peripheral neuropathy is the dose limiting side effect, which has no preventative therapy. We have previously shown that cisplatin induces apoptosis in dorsal root ganglion (DRG) sensory neurons by covalently binding to nuclear DNA (nDNA), resulting in DNA damage, subsequent p53 activation and Bax-mediated apoptosis via the mitochondria. We now demonstrate that cisplatin also directly binds to mitochondrial DNA (mtDNA) with the same binding affinity as nDNA. Cisplatin binds 1 platinum molecule per 2166 mtDNA base pairs and 1 platinum molecule per 3800 nDNA base pairs. Furthermore, cisplatin treatment inhibits mtDNA replication as detected by 5-bromo-2'-deoxy-uridine (BrdU) incorporation and inhibits transcription of mitochondrial genes. The relative reduction in mtDNA transcription is directly related to the distance the gene is located from the transcription initiation point, which implies that randomly formed platinum adducts block transcription. Cisplatin treated DRG neurons exhibit mitochondrial vacuolization and degradation in vitro and in vivo. Taken together, this data suggests that direct mtDNA damage may provide a novel, distinct mechanism for cisplatin-induced neurotoxicity separate from the established nDNA damage pathway.
This study confirms the presence of distinct subcutaneous fat compartments and provides evidence for an individual behavior when soft-tissue fillers are applied: inferior displacement of the superficial nasolabial, middle cheek, and jowl compartments, in contrast to an increase in volume without displacement (i.e., an increase in projection) of the medial cheek, lateral cheek, and both superficial temporal compartments.
Background:
Injection of soft-tissue fillers into the facial fat compartments is frequently performed to ameliorate the signs of facial aging. This study was designed to investigate the functional anatomy of the deep facial fat compartments and to provide information on the effects of injected material in relation to age and gender differences.
Methods:
Forty fresh frozen cephalic specimens of 17 male and 23 female Caucasian body donors (mean age, 76.9 ± 13.1 years; mean body mass index, 23.6 ± 5.3 kg/m2) were investigated. Computed tomographic and magnetic resonance imaging procedures were carried out using colored contrast-enhanced materials with rheologic properties similar to commercially available soft-tissue fillers. Anatomical dissections were performed to guide conclusions.
Results:
No statistically significant influences of age or gender were detected in the investigated sample. Increased amounts of injected contrast agent did not correlate with inferior displacement of the material in any of the investigated compartments: deep pyriform, deep medial cheek, deep lateral cheek, deep nasolabial (located within the premaxillary space), and the medial and lateral sub–orbicularis oculi fat.
Conclusions:
Increasing volume in the deep midfacial fat compartments did not cause inferior displacement of the injected material. This underscores the role of deep soft-tissue filler injections (i.e., in contact with the bone) in providing support for overlying structures and resulting in anterior projection.
Summary
Background
Myocardial native T1 and T2 mapping are promising techniques for quantitative assessment of diffuse myocardial pathologies; however, due to conflicting data regarding normal values, routine clinical implementation of this method is still challenging.
Methods
To evaluate this situation during daily clinical practice the characteristics of normal values obtained in 60 healthy volunteers who underwent magnetic resonance imaging (MRI) scans on 1.5T and 3T scanners were studied. The T1 modified look-locker inversion recovery (MOLLI; 5(3)3; modified for higher heart rates) and T2 navigator gated black-blood prepared gradient-spin-echo (GraSE) sequences were used.
Results
While age and body mass index did not affect relaxation times, a gender and heart rate dependency was found showing higher T1 and T2 values in females, whereas at higher heart rates a prolongation of T1 and a shortening of T2 relaxation times was found. Particularly prone to artifacts were T2 measurements at 3T and the inferolateral wall. In the individual setting mean relaxation times for T1 were 995.8 ± 30.9 ms at 1.5T and 1183.8 ± 37.5 ms at 3T and 55.8 ± 2.8 ms at 1.5T and 51.6 ± 3 ms at 3T for T2 indicating a high dependency of reference values on MRI protocol when compared to the literature. Furthermore, as presumed mean T1 and T2 values correlated in the same individual.
Conclusions
The T1 and T2 relaxation times depend on physiological factors and especially on MRI protocols. Therefore, reference values should be validated individually in every radiological institution before implementing mapping protocols in daily clinical practice. Correlation of mean T1 and T2 values in the same proband at both field strengths indicates intraindividual reproducibility.
The results presented in this study increase the understanding of the forehead anatomy. Understanding the presence of the superficial and the deep forehead compartments allows one to change the signs of frontal aging. The deep forehead compartments are in general avascular planes and permit blunt dissection for access to the supraorbital region.
This work provides detailed information on the course of the facial vein in relation to neighboring structures. The presented clinically relevant anatomical observations and descriptions of landmarks will serve as helpful information for plastic, reconstructive, and aesthetic surgeons.
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