RESUMO
Tocopherols (TOH) are lipophilic antioxidants which require the phenolic OH group for their redox activity. In contrast, non-redox active esters of α-TOH with succinate (α-TOS) were shown to possess proapoptotic activity in cancer cells. It was suggested that this activity is mediated via mitochondrial inhibition with subsequent O2(-) production triggering apoptosis and that the modification of the linker between the succinate and the lipophilic chroman may modulate this activity. However, the specific mechanism and the influence of the linker are not clear yet on the level of the mitochondrial respiratory chain. Therefore, this study systematically compared the effects of α-TOH acetate (α-TOA), α-TOS and α-tocopheramine succinate (α-TNS) in cells and submitochondrial particles (SMP). The results showed that not all cancer cell lines are highly sensitive to α-TOS and α-TNS. In HeLa cells α-TNS did more effectively reduce cell viability than α-TOS. The complex I activity of SMP was little affected by α-TNS and α-TOS while the complex II activity was much more inhibited (IC50=42±8µM α-TOS, 106±8µM α-TNS, respectively) than by α-TOA (IC50 >1000µM). Also the complex III activity was inhibited by α-TNS (IC50=137±6µM) and α-TOS (IC50=315±23µM). Oxygen consumption of NADH- or succinate-respiring SMP, involving the whole electron transfer machinery, was dose-dependently decreased by α-TOS and α-TNS, but only marginal effects were observed in the presence of α-TOA. In contrast to the similar inhibition pattern of α-TOS and α-TNS, only α-TOS triggered O2(-) formation in succinate- and NADH-respiring SMP. Inhibitor studies excluded complex I as O2(-) source and suggested an involvement of complex III in O2(-) production. In cancer cells only α-TOS was reproducibly able to increase O2(-) levels above the background level but neither α-TNS nor α-TOA. Furthermore, the stability of α-TNS in liver homogenates was significantly lower than that of α-TOS. In conclusion, this suggests that α-TNS although it has a structure similar to α-TOS is not acting via the same mechanism and that for α-TOS not only complex II but also complex III interactions are involved.
Assuntos
Antineoplásicos/farmacologia , Mitocôndrias/efeitos dos fármacos , Succinatos/farmacologia , Superóxidos/metabolismo , Vitamina E/análogos & derivados , alfa-Tocoferol/farmacologia , Antineoplásicos/química , Antineoplásicos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Complexo I de Transporte de Elétrons/antagonistas & inibidores , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/antagonistas & inibidores , Complexo II de Transporte de Elétrons/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Radicais Livres/metabolismo , Células HeLa , Humanos , Mitocôndrias/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Partículas Submitocôndricas/efeitos dos fármacos , Partículas Submitocôndricas/metabolismo , Succinatos/química , Succinatos/metabolismo , Células Tumorais Cultivadas , Vitamina E/química , Vitamina E/metabolismo , Vitamina E/farmacologia , alfa-Tocoferol/química , alfa-Tocoferol/metabolismoRESUMO
Background: Bilateral mastectomy for both therapeutic and prophylactic reasons is becoming increasingly important. To achieve good results after mastectomy, synthetic meshes are often used as an alternative to acellular dermal matrices (ADMs). The aim of this study is to analyze the results of subcutaneous mastectomies and direct-to-implant breast reconstruction using SERASYNTHâ MESH BR. Methods: In this work, data from mastectomies (n = 32) in 22 patients without prior radiation after breast reconstruction with SERASYNTHâ MESH BR from a single center were retrospectively analyzed with 1 year follow-up. Complications were categorized as serious (need for revision surgery) and minor events. Statistical analysis was performed using the t-test in SPSS. Data were compared with the existing literature. Results: Major complications occurred in 15.6% (n = 5). Two out of five revisions were due to hematoma. In three cases, a seroma followed by other complications (e.g., infections, necrosis) necessitated revision. Minor complications occurred in 12.5% of cases. Due to the safety aspect, implants were replaced in each revision. There was no significant difference in complication rates between prophylactic and therapeutic mastectomies (p = 0.3815, SE = 0.171). There was no statistically significant difference in esthetic outcomes (p = 0.3846). Conclusion: The application of the absorbable polymer poly-p-dioxanone SERASYNTHâ MESH BR has complication rates comparable to those reported in the existing literature. Careful patient selection is paramount in order to limit the complication rate. SERASYNTHâ MESH BR can be considered a safe tool to achieve esthetic results in combination with direct-to-implant breast reconstruction.
RESUMO
The aim of this study is the evaluation of three selected osseous pelvic features in modern anatomical specimen - the sacral preauricular extension, the preauricular sulcus and pits on the dorsal side of the pubic bone laterally to the symphysis. The specificity and significance of these features are under debate and their genesis is largely unclear. Descriptive data of specific soft tissue structures surrounding the anterior sacroiliac joint gap and the pubic symphysis were generated by assessing 20 fresh pelves and 12 embalmed hemipelves from human body donors. Computed tomography (CT) was performed on all specimens and three-dimensional (3D) surface models were generated and analysed. Afterwards, all the specimens underwent anatomical dissection and finally maceration. During dissection, it became apparent that the anterior sacroiliac ligament, due to its position, shape and potential impact on the sacroiliac joint and adjacent osseous structures, requires a detailed analysis of its dimension. The most promising result, in terms of the sacral preauricular extension, was that the measurements of the triangular part of the anterior sacroiliac ligament were significantly longer in females than in males. Pelvic floor muscle fibres and fascial parts were directly connected to this ligament in some specimens, which is an important starting point for a larger in-depth study. The evaluation of the anatomic structures in connection to dorsal pitting refutes the assumption that the pelvic floor muscles or fasciae could exert influence on its formation. A histological evaluation of the ligaments of the pubic symphysis, especially the dorsal pubic ligament, would be expedient to clarify the etiology of this feature.
Assuntos
Osso Púbico , Sínfise Pubiana , Feminino , Corpo Humano , Humanos , Ligamentos Articulares , Masculino , Articulação Sacroilíaca/diagnóstico por imagemRESUMO
OBJECTIVES: The vestibulo-medial temporal lobe (MTL) axis model proposes that the vestibular system and the MTL are tightly linked both structurally and functionally so that alterations of one structure should entail disturbances in the other. Accordingly, patients with temporal lobe epilepsy (TLE) with their functional and possible structural temporal lobe pathology should show deficits in vestibular-related behaviour. This study aimed at assessing behavioural deficits related to a suspected disturbance of the vestibulo-MTL axis in patients with TLE. METHODS: Twenty patients with TLE (46.7±15.1 years, seven females) and their age-matched and gender-matched controls (46.7±15.1, seven females) underwent three test batteries that challenged vestibular and MTL functions: balancing, path integration (triangle completion test) and rotational memory. In addition, participants underwent a structural MRI for grey matter analysis using voxel-based morphometry. RESULTS: Compared with controls, patients with TLE showed significantly inferior performance in all three behavioural tests, with large effect sizes. There were no significant grey matter differences between the two groups. CONCLUSION: These results indicate a potential disturbance in the vestibulo-MTL axis in TLE; these are to be verified by future large-scale studies. In the current study, these behavioural deficits emerged without evidence of any brain volume differences between the patients and their controls as depicted by high-resolution MRI. This speaks for a dissociation between functional and structural alterations in TLE.
RESUMO
Feline immunodeficiency virus (FIV) causes progressive immunodeficiency in domestic cats, with clinical course dependent on virus strain. For example, clade A FIV-PPR is predominantly neurotropic and causes a mild disease in the periphery, whereas clade C FIV-C36 causes fulminant disease with CD4(+) T-cell depletion and neutropenia but no significant pathology in the central nervous system. In order to map pathogenic determinants, chimeric viruses were prepared between FIV-C36 and FIV-PPR, with reciprocal exchanges involving (i) the 3' halves of the viruses, including the Vif, OrfA, and Env genes; (ii) the 5' end extending from the 5' long terminal repeat (LTR) to the beginning of the capsid (CA)-coding region; and (iii) the 3' LTR and Rev2-coding regions. Ex vivo replication rates and in vivo replication and pathologies were then assessed and compared to those of the parental viruses. The results show that FIV-C36 replicates ex vivo and in vivo to levels approximately 20-fold greater than those of FIV-PPR. None of the chimeric FIVs recapitulated the replication rate of FIV-C36, although most replicated to levels similar to those of FIV-PPR. The rates of chloramphenicol acetyltransferase gene transcription driven by the FIV-C36 and FIV-PPR LTRs were identical. Furthermore, the ratios of surface glycoprotein (SU) to capsid protein (CA) in the released particles were essentially the same in the wild-type and chimeric FIVs. Tests were performed in vivo on the wild-type FIVs and chimeras carrying the 3' half of FIV-C36 or the 3' LTR and Rev2 regions of FIV-C36 on the PPR background. Both chimeras were infectious in vivo, although replication levels were lower than for the parental viruses. The chimera carrying the 3' half of FIV-C36 demonstrated an intermediate disease course with a delayed peak viral load but ultimately resulted in significant reductions in neutrophil and CD4(+) T cells, suggesting potential adaptation in vivo. Taken together, the findings suggest that the rapid-growth phenotype and pathogenicity of FIV-C36 are the result of evolutionary fine tuning throughout the viral genome, rather than being properties of any one constituent.
Assuntos
Síndrome de Imunodeficiência Adquirida Felina/virologia , Vírus da Imunodeficiência Felina/química , Animais , Capsídeo/metabolismo , Gatos , Cloranfenicol O-Acetiltransferase/metabolismo , Genoma Viral , Vírus da Imunodeficiência Felina/metabolismo , Infecções , Rim/metabolismo , Cinética , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/virologia , Fenótipo , Ligação Proteica , Receptores OX40/biossíntese , Sequências Repetidas TerminaisRESUMO
PURPOSE: Correctly performed basic life support (BLS) and early defibrillation are the most effective measures to treat sudden cardiac arrest. Audiovisual feedback improves BLS. Automated external defibrillators (AED) with feedback technology may play an important role in improving CPR quality. The aim of this simulation study was to investigate if an AED with audiovisual feedback improves CPR parameters during standard BLS performed by trained laypersons. METHODS: With ethics committee approval and informed consent, 68 teams (2 flight attendants each) performed 12 min of standard CPR with the AED's audiovisual feedback mechanism enabled or disabled. We recorded CPR quality parameters during resuscitation on a manikin in this open, prospective, randomized controlled trial. Between the feedback and control-group we measured differences in compression depth and rate as main outcome parameters and effective compressions, correct hand position, and incomplete decompression as secondary outcome parameters. An effective compression was defined as a compression with correct depth, hand position, and decompression. RESULTS: The feedback-group delivered compression rates closest to the recommended guidelines (101 ± 9 vs. 109 ± 15/min, p=0.009), more effective compressions (20 ± 18 vs. 5 ± 6%, p<0.001), more compressions with correct hand position (96 ± 13 vs. 88 ± 16%, p<0.001), and less leaning (21 ± 31 vs. 77 ± 33%, p<0.001). However, only the control-group adhered to the recommended compression depth (44 ± 7 mm vs. 39 ± 6, p=0.003). CONCLUSION: Use of an AED's audiovisual feedback system improved some CPR-quality parameters, thus confirming findings of earlier studies with the notable exception of decreased compression depth, which is a key parameter that might be linked to reduced cardiac output.