White Adipose Tissue Expansion in Multiple Symmetric Lipomatosis Is Associated with Upregulation of CK2, AKT and ERK1/2.

Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by overgrowing lipomatous tissue (LT) in the subcutaneous adipose tissue (SAT). What LT is and how it expands are not completely understood; previous data suggested that it could derive from brown AT precursors. In six MSL type I patients, we compared LT morphology by histological and immunohistochemistry (IHC) analysis, gene expression, by qPCR, kinase activity, by Western Blot and in vitro assay to paired-control SAT using AT from patients with pheochromocytoma as a human browning reference. In the stromal vascular fraction (SVF), we quantified adipose stem cells (ASCs) by flow cytometry, the proliferation rate, white and beige adipogenic potential and clonogenicity and adipogenicity by a limiting dilution assay. LT displayed white AT morphology and expression pattern and did not show increased levels of the brown-specific marker UCP1. In LT, we evidenced AKT, CK2 and ERK1/2 hyperactivation. LT-SVF contained increased ASCs, proliferated faster, sprouted clones and differentiated into adipocytes better than the control, displaying enhanced white adipogenic potential but not increased browning compared to SAT. In conclusion, LT is a white AT depot expanding by hyperplasia through increased stemness and enhanced white adipogenesis upregulating AKT, CK2 and ERK1/2, which could represent new targets to counteract MSL.

Effect of mild hypothermic cardiopulmonary bypass on the amplitude of somatosensory-evoked potentials.

BACKGROUND: Several neurophysiological techniques are used to intraoperatively assess cerebral functioning during surgery and intensive care, but the introduction of hypothermia as a means of intraoperative neuroprotection has brought their reliability into question. The present study aimed to evaluate the effect of mild hypothermia on somatosensory-evoked potentials' (SSEPs) amplitude and latency in a cohort of cardiopulmonary bypass (CPB) patients as the temperature reached the steady-state. MATERIALS AND METHODS: The amplitude and latency of 4 different SSEP signals--N9, N13, P14/N18 interpeak, and N20/P25--were evaluated retrospectively in 84 patients undergoing CPB during normothermic (36°C±0.43°C) and mild hypothermic (32°C±1.38°C) conditions. SSEPs were recorded in normothermia immediately after the induction of anesthesia and in hypothermia as the temperature reached its steady-state, specifically, when the nasopharyngeal temperature was equivalent to the rectal temperature (±0.5°C). A paired-samples t test was performed for each SSEP to test the differences in latencies and amplitudes between normothermic and hypothermic conditions. RESULTS: Compared with normothermia, hypothermia not only significantly increased the latency of all SSEPs, N9 (P<0.001), N13 (P<0.001), P14/N18 (P<0.001), and N20/P25 (P<0.001), but also the amplitude of N9 (P<0.001) and N20/P25 (P<0.001). CONCLUSIONS: The increased amplitude in particularly of cortical SSEPs (N20/P25), detected specifically during steady-state hypothermia, seems to support the clinical utility of this methodology in monitoring the brain function not only during cardiac surgery with CPB, but also in other settings like therapeutic hypothermia procedures in an intensive care unit.

Brain emboli distribution and differentiation during cardiopulmonary bypass.

OBJECTIVE: Cardiopulmonary bypass (CPB) is a lifesaving practice in cardiac surgery, but its use frequently is associated with cerebral injury and neurocognitive dysfunctions. Despite the involvement of numerous factors, microembolism occurring during CPB seems to be one of the main mechanisms leading to such alterations. The aim of the present study was to characterize the occurrence of cerebral microembolism with reference to microembolic amount, nature, and distribution in different combinations of cardiac procedures and CPB on the microembolic load. DESIGN: A retrospective observational clinical study. SETTING: A single-center regional hospital. PARTICIPANTS: Fifty-five patients undergoing elective cardiac surgery with CPB. INTERVENTIONS: Bilateral detection of the patients' middle cerebral arteries using a multifrequency transcranial Doppler. MEASUREMENTS AND MAIN RESULTS: Patients were divided into 3 groups depending on the CPB circuit used (open, open with vacuum, or closed). There was a significant difference between the number of solid and gaseous microemboli (p<0.001), with the solid lower than the gaseous ones. The number of solid microemboli was affected by group (p< 0.05), CPB phase (p<0.001), and laterality (p<0.01). The number of gaseous microemboli was affected only by group (p<0.05) and CPB phase (p<0.001). Generally, the length of CPB phase did not affect the number of microemboli. CONCLUSIONS: Surgical procedures combined with CPB circuits, but not the CPB phase length, affected the occurrence, nature, and laterality of microemboli.

Tsg101 interacts with herpes simplex virus 1 VP1/2 and is a substrate of VP1/2 ubiquitin-specific protease domain activity.

Ubiquitination/deubiquitination of key factors represent crucial steps in the biogenesis of multivesicular body (MVB) and sorting of transmembrane proteins. We and others previously demonstrated that MVB is involved in herpes simplex virus 1 (HSV-1) envelopment and budding. Here, we report that the HSV-1 large tegument protein, VP1/2, interacts with and regulates the ubiquitination of Tsg101, a cellular protein essential in MVB formation, thus identifying the first cellular substrate of a herpesviral deubiquitinating enzyme.

Pump flow changes do not impair sublingual microcirculation during cardiopulmonary bypass.

OBJECTIVE: The flow rate of the cardiopulmonary bypass (CPB) pump used in cardiac surgery often undergoes inherent fluctuations ranging from 10% to 20% of its theoretic value. However, the effects of such alterations remain unknown. In the present study, the authors investigated whether such variations could induce changes in the microvascular flow, which is considered a primary indicator of poor perfusion. DESIGN: A prospective, observational, clinical study. SETTING: A university-affiliated teaching hospital. PARTICIPANTS: Thirty adult patients undergoing elective cardiac surgery with CPB. INTERVENTIONS: Analysis of the sublingual microcirculation during CPB using a pump flow rate of 80% or 100% of the theoretic value. MEASUREMENTS AND MAIN RESULTS: Sidestream dark field (SDF) imaging was used to record 2 video clips of the sublingual microcirculation in each patient. The videos were recorded at the same site at 80% and 100% of the theoretic flow rate. Microvascular analysis displaying the De Backer score, the microvascular flow index, the total vessel density, the perfused vessel density, and the proportion of perfused vessels was performed. Moreover, the mean arterial pressure (MAP), SvO(2), and PaCO(2) were evaluated. No significant changes in the measured parameters were noted at the 2 different flow rates. CONCLUSIONS: Changes in the CPB pump flow rate within 20% (80%-100%) of its theoretic value do not alter the sublingual microcirculation. Thereafter, it is conceivable that during perioperative adjustments of the CPB pump rate, blood flow autoregulation mechanisms are activated so that limited changes in the pump flow can be considered safe not only at the sublingual site but also for the entire microcirculation.

Relação entre carga glicêmica da dieta e acne: [revisão] / Relationship between dietïs glycemic load and acne: [review]

Objetivos: revisar a bibliografia científica existente com o intuito de identificar o efeito da carga glicêmica da dieta no tratamento da acne vulgar.Fonte de dados: foram revisados artigos científicos originais e de revisão, indexados nas bases de dados do SciELO, PubMed, Lilacs e Medline, nos idiomas inglês, espanhol e português, publicados a partir de 1990. Também foram feitas pesquisas em livros do acervo das bibliotecas da Pontifícia Universidade Católica do Rio Grande do Sul e da Universidade Federal do Rio Grande do Sul.Síntese dos dados: a acne vulgar é uma dermatose crônica, específica dos folículos pilossebáceos, causada por fatores genéticos, hormonais, dietéticos e psicológicos. A dieta habitual exerce influência sobre o desenvolvimento dessa dermatose, principalmente em função da carga glicêmica, a qual pode gerar alterações em parâmetros bioquímicos e endócrinos relacionados ao desenvolvimento da acne.Conclusão: alterações na dieta podem melhorar a acne e seus fatores associados.

Aims: To review the scientific bibliography in order to identify the effect of the diet?s glycemic load in acne vulgaris treatment.Source of data: original and review articles indexed in databases SciELO, Lilacs, PubMed and Medline, written in English, Spanish and Portuguese, and published from 1990, were reviewed. The review included books from the collection of Pontifícia Universidade Católica do Rio Grande do Sul and Universidade Federal do Rio Grande do Sul libraries.Summary of findings: Acne vulgaris is a chronic skin condition, specific of the pilosebaceous follicles, caused by genetic, hormonal, dietary and psychological factors. Usual diet influences the development of this condition, mainly due to the glycemic load, which can cause changes in endocrine and biochemical parameters related to the development of acne.Conclusion: Changes in diet can improve acne and its associated factors.

Intracellular trafficking and maturation of herpes simplex virus type 1 gB and virus egress require functional biogenesis of multivesicular bodies.

The biogenesis of multivesicular bodies (MVBs) is topologically equivalent to virion budding. Hence, a number of viruses exploit the MVB pathway to build their envelope and exit from the cell. By expression of dominant negative forms of Vps4 and Vps24, two components of the MVB pathway, we observed an impairment in infectious herpes simplex virus (HSV) assembly/egress, in agreement with a recent report showing the involvement in HSV envelopment of Vps4, the MVB-specific ATPase (C. M. Crump, C. Yates, and T. Minson, J. Virol. 81:7380-7387). Furthermore, HSV infection resulted in morphological changes to MVBs. Glycoprotein B (gB), one of the most highly conserved glycoproteins across the Herpesviridae family, was sorted to MVB membranes. In cells expressing the dominant negative form of Vps4, the site of intracellular gB accumulation was altered; part of gB accumulated as an endoglycosidase H-sensitive immature form at a calreticulin-positive compartment, indicating that gB traffic was dependent on a functional MVB pathway. gB was ubiquitinated in both infected and transfected cells. Ubiquitination was in part dependent on ubiquitin lysine 63, a signal for cargo sorting to MVBs. Partial deletion of the gB cytoplasmic tail resulted in a dramatic reduction of ubiquitination, as well as of progeny virus assembly and release to the extracellular compartment. Thus, HSV envelopment/egress and gB intracellular trafficking are dependent on functional MVB biogenesis. Our data support the view that the sorting of gB to MVB membranes may represent a critical step in HSV envelopment and egress and that modified MVB membranes constitute a platform for HSV cytoplasmic envelopment or that MVB components are recruited to the site(s) of envelopment.