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1.
Int J Mol Sci ; 22(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33805070

RESUMO

Lipedema is an adipose tissue disorder characterized by the disproportionate increase of subcutaneous fat tissue in the lower and/or upper extremities. The underlying pathomechanism remains unclear and no molecular biomarkers to distinguish the disease exist, leading to a large number of undiagnosed and misdiagnosed patients. To unravel the distinct molecular characteristic of lipedema we performed lipidomic analysis of the adipose tissue and serum of lipedema versus anatomically- and body mass index (BMI)-matched control patients. Both tissue groups showed no significant changes regarding lipid composition. As hyperplastic adipose tissue represents low-grade inflammation, the potential systemic effects on circulating cytokines were evaluated in lipedema and control patients using the Multiplex immunoassay system. Interestingly, increased systemic levels of interleukin 11 (p = 0.03), interleukin 28A (p = 0.04) and interleukin 29 (p = 0.04) were observed. As cytokines can influence metabolic activity, the metabolic phenotype of the stromal vascular fraction was examined, revealing significantly increased mitochondrial respiration in lipedema. In conclusion, despite sharing a comparable lipid profile with healthy adipose tissue, lipedema is characterized by a distinct systemic cytokine profile and metabolic activity of the stromal vascular fraction.

2.
Sci Rep ; 11(1): 4854, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649405

RESUMO

We investigated sex-related differences in the prognosis of patients with hypertrophic cardiomyopathy (HCM) using the Korea National Health Insurance Service database. From 2010 to 2016, 9524 patients diagnosed with HCM and had more than 1-year follow-up period were analyzed. The primary endpoint was the composite of cardiovascular death or new-onset heart failure (HF) admission. Propensity score-matching analysis was performed to adjust for different baseline characteristics. With a 4.4-years' median follow-up interval (range 2.0-6.6 years) and male predominance (77.6%), women with HCM were older (52.6 ± 9.7 vs. 51.4 ± 9.1, p < 0.001), had lower incomes, more comorbidities based on Charlson comorbidity index. Women with HCM had a higher incidence of the primary endpoint than men (incidence rate: 34.15 vs. 22.83 per 1000 person-years, log-rank p < 0.001). Multivariable Cox analysis showed that female sex was a poor prognostic factor for the primary endpoint (HR 1.43, 95% CI 1.24-1.64, p < 0.001). This was mainly driven by a higher incidence of new-onset HF admission (HR 1.55, 95% CI 1.34-1.80). However, there was no difference in the incidence of cardiovascular death between the sexes. This result was concordant in the propensity score-matched cohort. In conclusion, women with HCM have worse prognosis, which was mainly driven by a higher new-onset HF admission.

3.
J Diabetes Investig ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33662172

RESUMO

AIMS/INTRODUCTION: We estimated the hazards of cardiovascular diseases (CVDs) and early all-cause mortality in Korean adults according to the presence of recently diagnosed type 2 diabetes (type 2 diabetes for <5 years) and insulin use. MATERIALS AND METHODS: We used the Korean National Health Insurance Service-National Sample Cohort database (2002-2015) for this longitudinal population-based study. Among adults aged ≥40 years without baseline CVD, individuals without diabetes or with recently diagnosed type 2 diabetes were selected (N = 363,919). The hazard ratios (HRs) for myocardial infarction (MI), stroke, and all-cause mortality during follow-up were analyzed according to three groups categorized by the presence of type 2 diabetes and insulin use. RESULTS: Within a mean 7.8 years, there were 5,275 MIs, 7,220 strokes, and 15,834 deaths. The hazards for outcomes were higher in the insulin-treated type 2 diabetes group than in the non-diabetes group [HR (95% CI): 2.344 (1.870-2.938) for MI, 2.420 (1.993-2.937) for stroke, and 3.037 (2.706-3.407) for death], higher in the non-insulin-treated type 2 diabetes group than in the non-diabetes group [HR (95% CI): 1.284 (1.159-1.423) for MI, 1.435 (1.320-1.561) for stroke, and 1.135 (1.067-1.206) for death], and higher in the insulin-treated type 2 diabetes group than in the non-insulin-treated type 2 diabetes group [HR (95% CI): 1.914 (1.502-2.441) for MI, 1.676 (1.363-2.060) for stroke, and 2.535 (2.232-2.880) for death]. CONCLUSIONS: Recently diagnosed type 2 diabetes patients showed increased risks of incident CVDs and premature mortality, and insulin-treated group demonstrated an additional increase in the risks of these outcomes in adults with recently diagnosed type 2 diabetes, suggesting the need for intensified cardio-protective interventions for adults with insulin-treated type 2 diabetes.

4.
Sci Rep ; 11(1): 2878, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536553

RESUMO

We conducted a nationwide population-based cohort study to identify the risk factors associated with failure of total ankle arthroplasty (TAA). We included 2,914 subjects who underwent primary TAA between January 1, 2010, and December 31, 2016, utilizing the database of the Korean National Health Insurance Service. Failure of TAA was defined as revision TAA or arthrodesis procedures. An increased risk of TAA failure was observed in the < 65 age group versus the ≥ 75 age group [adjusted hazard ratios (aHR) 2.273, 95% confidence interval (CI) 1.223-4.226 in the 60-64 age group; aHR 2.697, 95% CI 1.405-5.178 in the 55-59 age group; aHR 2.281, 95% CI 1.145-4.543 in the 50-54 age group; aHR 2.851, 95% CI 1.311-6.203 in the < 50 age group]. Conversely, the ≥ 65 age group displayed no increase in the risk of TAA failure. The risk of TAA failure was increased in the severely obese group with body mass index (BMI) of ≥ 30 kg/m2 versus the normal BMI group (aHR 1.632; 95% CI 1.036-2.570). This population-based longitudinal study demonstrated that age < 65 years and BMI of ≥ 30 kg/m2 were associated with increased risk of TAA failure.

6.
J Tissue Eng Regen Med ; 15(1): 88-98, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33459498

RESUMO

Adipose stem cells (ASCs) possess the capacity to proliferate, to differentiate into various cells types, and they are able to secrete growth factors. These characteristics are supposed to contribute to their potential for regenerative medicine approaches. In order to advance the therapeutic effects of ASCs, different modulatory procedures have been examined. In this context, the endocannabinoid system (ECS) represents an interesting possibility, since the increased availability of cannabinoids and the underlying molecular pathways of the ECS are of relevance for the development of new regenerative strategies. The effects of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were investigated on ASC metabolic activity, quantified by PrestoBlue conversion, and cell numbers, evaluated by crystal violet staining. enzyme-linked immunosorbent assay (ELISA) measures were performed to determine cytokine release, and differentiation was assessed by specific labeling techniques. AEA increased the metabolic activity, while 2-AG decreased it in a concentration dependent manner. AEA significantly enhanced OilRed O staining after adipogenic differentiation by over 100%, and both compounds significantly increased cresolphthalein staining after osteogenic differentiation. By contrast, they did not affect sphere diameter or safranin O staining after chondrogenic differentiation. Both substances significantly increased the release of insulin-like growth factor-1 and hepatocyte growth factor, while only AEA enhanced transforming growth factor-ß secretion. The results demonstrated that stimulating the ECS exerted significant effects on the biology of ASCs. Exposure to endocannabinoids modulated viability, induced release of regenerative growth factors, and promoted adipogenic and osteogenic differentiation. Our findings could be of specific relevance in ASC based therapies for regenerative medicine.

7.
Burns ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33288334

RESUMO

INTRODUCTION: A need exists to improve the efficiency of clinical trials in burn care. The objective of this study was to validate "Persistent Organ Dysfunction" plus death as endpoint in burn patients and to demonstrate its statistical efficiency. METHODS: This secondary outcome analysis of a dataset from a prospective international multicenter RCT (RE-ENERGIZE) included patients with burned total body surface area >20% and a 6-month follow-up. Persistent organ dysfunction was defined as persistence of organ dysfunction with life-supportiing technologies and ICU care. RESULTS: In the 539 included patients, the prevalence of 0p p+ pdeath was 40% at day 14 and of 27% at day 28. At both timepoints, survivors with POD (vs. survivors without POD) had a higher mortality rate, longer ICU- and hospital-stays, and a reduced quality of life. POD + death as an endpoint could result in reduced sample size requirements for clinical trials. Detecting a 25% relative risk reduction in 28-day mortality would require a sample size of 4492 patients, whereas 1236 patients would be required were 28-day POD + death used. CONCLUSIONS: POD + death represents a promising composite outcome measure that may reduce the sample size requirements of clinical trials in severe burns patients. Further validation in larger clinical trials is warranted. STUDY TYPE: Prospective cohort study, level of evidence: II.

8.
J Burn Care Res ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33137191

RESUMO

BACKGROUND: Electrical injuries are rare, but very destructive with high morbidity and mortality, prolonged hospital length of stay and need for repeated procedures. The aim of study was to investigate characteristics and management electrical injuries and predisposing factors for mortality and prolonged length of stay. METHODS: Patient charts were reviewed retrospectively to identify patients admitted with electrical injuries at the Zurich Burns Center (2005-2019). Patient characteristics, management and outcome were analyzed and risk factors for mortality and prolonged hospitalization assessed. RESULTS: 89 patients were included, mostly males (86.5%), between 21-40-years (50.6%), with high-voltage (74.2%) occupational injuries (66.3%). Median intensive care unit and hospital stays were 6 (1st and 3rd IQR: 2.0; 30.0) and 18 (9.0; 48.0) days. Low-voltage patients had a median of 2 (1.5; 3.0) procedures, compared to 4 (2.0; 10.8) in high-voltage. Amputation rate was 13.5%, and a total of 46 flaps required. Fifty-four patients had at least one serious complication. Mortality was 18% in high-voltage patients, mostly after multiple organ failure (35%). High TBSA, renal failure and cardiovascular complications were risk factors for mortality (p<0.001) in multivariate regression models. Determinants for prolonged hospital stay were TBSA and sepsis (p<0.01), and additionally abdominal complications and limb loss for intensive care unit stay (p<0.05). CONCLUSIONS: Electrical injuries are still cause of significant morbidity and mortality, mostly involve young men in their earning period. Several risk factors for in-hospital mortality and prolonged stay were identified and can support physicians in the management and decision-making in these patients.

9.
Pharmacol Rep ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026642

RESUMO

BACKGROUND: The inflammatory sequence is the first phase of wound healing. Macrophages (MPhs) and mesenchymal stromal cells (MSCs) respond to an inflammatory microenvironment by adapting their functional activity, which polarizes them into the pro-inflammatory phenotypes M1 and MSC1. Prolongation of the inflammatory phase results in the formation of chronic wounds. The endocannabinoid system (ECS) possesses immunomodulatory properties that may impede this cellular phenotypic switch. METHODS: We investigated the immunosuppressive influence of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) on the M1 and MSC1 cytokine secretion. Lipopolysaccharides (LPS) were used as inflammagen to stimulate MPhs and MSCs. Both inflammatory phenotypes were co-exposed to AEA or 2-AG, the specific cannabinoid receptor CB2 agonist JWH-133 served as reference. The inflammatory responses were detected by CD80/163 immuno-labelling and by ELISA measures of secreted IL-6, IL-8, MIF, TNF-α, TGF-ß, and VEGF. RESULTS: M1 cells were found positive for CD80 expression and secreted less IL-6 and IL-8 than MSC1 cells, while both cell types produced similar amounts of MIF. TNF-α release was increased by M1, and growth factors were secreted by MSC1, only. Cannabinoid receptor ligands efficiently decreased the inflammatory response of M1, while their impact was less pronounced in MSC1. CONCLUSIONS: The ECS down-regulated the inflammatory responses of MPhs and MSCs by decreasing the cytokine release upon LPS treatment, while CB2 appeared to be of particular importance. Hence, stimulating the ECS by manipulation of endo- or use of exogenous cannabinoids in vivo may constitute a potent therapeutic option against inflammatory disorders.

10.
PLoS One ; 15(10): e0239517, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33021999

RESUMO

Vascularized lymph node (VLN) transfer is an emerging strategy to re-establish lymphatic drainage in chronic lymphedema. However, the biological processes underlying lymph node integration remain elusive. This study introduces an experimental approach facilitating the analysis of short-term molecular and cellular effects of ischemia/reperfusion on VLN flaps. Lymph node flaps were dissected pedicled on the lateral thoracic vessels in 44 Lewis rats. VLN flaps were exposed to 45 or 120 minutes ischemia by in situ clamping of the vascular pedicle with subsequent reperfusion for 24 hours. Flaps not exposed to ischemia/reperfusion served as controls. Lymph nodes and the perinodal adipose tissue were separately analyzed by Western blot for the expression of lymphangiogenic and angiogenic growth factors. Moreover, morphology, microvessel density, proliferation, apoptosis and immune cell infiltration of VLN flaps were further assessed by histology and immunohistochemistry. Ischemia for 120 minutes was associated with a markedly reduced cellularity of lymph nodes but not of the perinodal adipose tissue. In line with this, ischemic lymph nodes exhibited a significantly lower microvessel density and an increased expression of VEGF-D and VEGF-A. However, VEGF-C expression was not upregulated. In contrast, analyses of the perinodal adipose tissue revealed a more subtle decrease of microvessel density, while only the expression of VEGF-D was increased. Moreover, after 120 minutes ischemia, lymph nodes but not the perinodal adipose tissue exhibited significantly higher numbers of proliferating and apoptotic cells as well as infiltrated macrophages and neutrophilic granulocytes compared with non-ischemic flaps. Taken together, lymph nodes of VLN flaps are highly susceptible to ischemia/reperfusion injury. In contrast, the perinodal adipose tissue is less prone to ischemia/reperfusion injury.


Assuntos
Linfonodos/irrigação sanguínea , Linfonodos/cirurgia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Retalhos Cirúrgicos , Animais , Apoptose , Linfonodos/citologia , Microvasos/fisiopatologia , Estresse Oxidativo , Ratos , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/cirurgia
11.
Plast Reconstr Surg ; 146(2): 309-320, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32740581

RESUMO

BACKGROUND: Adipose-derived stem cells are considered as candidate cells for regenerative plastic surgery. Measures to influence cellular properties and thereby direct their regenerative potential remain elusive. Hyperbaric oxygen therapy-the exposure to 100% oxygen at an increased atmospheric pressure-has been propagated as a noninvasive treatment for a multitude of indications and presents a potential option to condition cells for tissue-engineering purposes. The present study evaluates the effect of hyperbaric oxygen therapy on human adipose-derived stem cells. METHODS: Human adipose-derived stem cells from healthy donors were treated with hyperbaric oxygen therapy at 2 and 3 atm. Viability before and after each hyperbaric oxygen therapy, proliferation, expression of surface markers and protein contents of transforming growth factor (TGF)-ß, tumor necrosis factor-α, hepatocyte growth factor, and epithelial growth factor in the supernatants of treated adipose-derived stem cells were measured. Lastly, adipogenic, osteogenic, and chondrogenic differentiation with and without use of differentiation-inducing media (i.e., autodifferentiation) was examined. RESULTS: Hyperbaric oxygen therapy with 3 atm increased viability, proliferation, and CD34 expression and reduced the CD31/CD34/CD45 adipose-derived stem cell subset and endothelial progenitor cell population. TGF-ß levels were significantly decreased after two hyperbaric oxygen therapy sessions in the 2-atm group and decreased after three hyperbaric oxygen therapy sessions in the 3-atm group. Hepatocyte growth factor secretion remained unaltered in all groups. Although the osteogenic and chondrogenic differentiation were not influenced, adipogenic differentiation and autodifferentiation were significantly enhanced, with osteogenic autodifferentiation significantly alleviated by hyperbaric oxygen therapy with 3 atm. CONCLUSION: Hyperbaric oxygen therapy with 3 atm increases viability and proliferation of adipose-derived stem cells, alters marker expression and subpopulations, decreases TGF-ß secretion, and skews adipose-derived stem cells toward adipogenic differentiation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.


Assuntos
Adipogenia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Engenharia Celular/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Oxigênio/administração & dosagem , Tecido Adiposo/citologia , Adulto , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Células-Tronco Mesenquimais/fisiologia , Pessoa de Meia-Idade , Pressão , Cultura Primária de Células/métodos
12.
PLoS One ; 15(8): e0238185, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857776

RESUMO

BACKGROUND: Recent studies have reported that after the introduction of rotavirus vaccine the incidence of intussusception did not change among infants, or slightly increased at the age immediately after the first dose. The rotavirus vaccines were introduced in Korea for private market use in 2007-2008. We investigated the incidence of intussusception before (2002-2006) and after (2009-2015) the vaccine introduction in Korea. METHODS: We conducted an interrupted time series study that used data from the Korean National Health Insurance database to identify infants (<12 months of age) who were diagnosed with intussusception and underwent non-invasive or invasive reduction from 2002 to 2015. According to the recommended ages for immunization, the annual intussusception incidence and the incidence rate ratios were calculated among three age groups, 6-14, 15-24, and 25-34 weeks. RESULTS: The annual incidences in infants have decreased over time from 241.7 per 100,000 infants (pre-vaccine period) to 160.1-205.2 per 100,000 infants (post-vaccine period). The incidence rate ratio during the post-vaccine period ranged from 0.66 to 0.85. The incidences of intussusception in all three infant age groups have decreased in post-vaccine period compared to pre-vaccine period (incidence rate ratio range: 0.31-0.65, 0.47-0.75, and 0.68-0.94 in 6-14, 15-24, and 25-34 weeks, respectively). CONCLUSIONS: The incidence of intussusception in infants did not increase after the rotavirus vaccine introduction in Korea, but rather decreased over the past decades. Since the incidence of intussusception varies according to country or region, continuous monitoring the incidence of intussusception in infants is necessary in each county or region.


Assuntos
Intussuscepção/epidemiologia , Vacinas contra Rotavirus/administração & dosagem , Humanos , Incidência , Lactente , República da Coreia/epidemiologia , Infecções por Rotavirus/prevenção & controle
13.
Sci Rep ; 10(1): 10947, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32616854

RESUMO

Lipedema is a chronic adipose tissue disorder characterized by the disproportional subcutaneous deposition of fat and is commonly misdiagnosed as lymphedema or obesity. The molecular determinants of the lipedema remain largely unknown and only speculations exist regarding the lymphatic system involvement. The aim of the present study is to characterize the lymphatic vascular involvement in established lipedema. The histological and molecular characterization was conducted on anatomically-matched skin and fat biopsies as well as serum samples from eleven lipedema and ten BMI-matched healthy patients. Increased systemic levels of vascular endothelial growth factor (VEGF)-C (P = 0.02) were identified in the serum of lipedema patients. Surprisingly, despite the increased VEGF-C levels no morphological changes of the lymphatic vessels were observed. Importantly, expression analysis of lymphatic and blood vessel-related genes revealed a marked downregulation of Tie2 (P < 0.0001) and FLT4 (VEGFR-3) (P = 0.02) consistent with an increased macrophage infiltration (P = 0.009), without changes in the expression of other lymphatic markers. Interestingly, a distinct local cytokine milieu, with decreased VEGF-A (P = 0.04) and VEGF-D (P = 0.02) expression was identified. No apparent lymphatic anomaly underlies lipedema, providing evidence for the different disease nature in comparison to lymphedema. The changes in the lymphatic-related cytokine milieu might be related to a modified vascular permeability developed secondarily to lipedema progression.


Assuntos
Lipedema/patologia , Sistema Linfático/patologia , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/patologia , Linfócitos T/imunologia , Fator C de Crescimento do Endotélio Vascular/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Lipedema/imunologia , Lipedema/metabolismo , Macrófagos/imunologia
14.
Thyroid ; 30(10): 1496-1504, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32524894

RESUMO

Background: The association of metabolic syndrome and its components with the risk of thyroid cancer is unclear. Thus, we conducted a large-scale, nationwide, population-based, cohort study to investigate this relationship. Methods: We studied 9,890,917 adults without thyroid cancer from the Korean National Health Insurance health checkup database from January 1 to December 31, 2009. Individuals with at least three of the following five components were diagnosed with metabolic syndrome: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein-cholesterol levels, elevated blood pressure, and hyperglycemia. Multivariate Cox proportional hazards models were used to estimate thyroid cancer risk. Results: During the average 7.2 years of follow-up, 77,133 thyroid cancer cases were newly identified. The thyroid cancer risk was higher in the metabolic syndrome group than in the nonmetabolic syndrome group (hazard ratio [HR] 1.15 [95% confidence interval, CI 1.13-1.17]). The association between metabolic syndrome and thyroid cancer risk was significant in the obese group (HR 1.10 [CI 1.07-1.13]) and not in the nonobese group (HR 1.002 [CI 0.98-1.03]). The effect of metabolic syndrome on the risk of thyroid cancer differs according to obesity (p for interaction = 0.017). People with all five components of metabolic syndrome had a 39% higher risk than those without any components (HR 1.39 [CI 1.33-1.44]). The higher risk of thyroid cancer in people with all five components was significant in the obese group (HR 1.29 [CI 1.21-1.38]), but not in the nonobese group (HR 1.06 [CI 0.98-1.14]). There was a significant interaction between the number of metabolic syndrome components and obesity (p for interaction <0.0001). For the combined effect of obesity and metabolic syndrome on the risk of thyroid cancer, obese men with metabolic syndrome had the highest risk of thyroid cancer compared with those without (HR 1.58 [CI 1.52-1.64]), but obese women with metabolic syndrome did not. Conclusions: Metabolic syndrome was associated with an increased risk of thyroid cancer in the Korean general population. Metabolic syndrome had a more significant risk of thyroid cancer in the obese group. Metabolic syndrome and obesity were associated with a higher risk of thyroid cancer in men but not in women.

15.
Diabetes Res Clin Pract ; 165: 108237, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32473297

RESUMO

OBJECTIVE: It remains unclear which specific combinations of metabolic syndrome (MetS) components confer a higher risk of type 2 diabetes mellitus (T2DM). This study examined the relation of each and combinations of MetS components with the risk of T2DM. METHODS: We studied the records of 19,475,643 adults aged ≥ 20 years with no history of T2DM from the database of the Korean National Health Insurance Service covering 2009 to 2012. The hazard ratios (HRs) and confidence intervals (CIs) of T2DM were estimated using Cox proportional hazards models. RESULTS: During a median follow-up of 5.13 years, 1,906,963 individuals were diagnosed with T2DM. The multivariable-adjusted HRs for T2DM were 1.86 for MetS, 1.821 for elevated fasting plasma glucose (FPG), 1.484 for elevated triglycerides, 1.415 for reduced high-density lipoprotein (HDL) cholesterol, 1.413 for elevated blood pressure (BP), and 1.17 for abdominal obesity compared with those without. In the combinations of two components excluding elevated FPG, subjects with elevated triglycerides and reduced HDL cholesterol had the highest risk of T2DM (HR 1.71; 95% CI, 1.695-1.725). In three components, the highest risk combination was elevated FPG, elevated triglycerides, and reduced HDL cholesterol (HR 3.342; 95% CI, 3.308-3.376). CONCLUSIONS: The combination of elevated triglycerides and reduced HDL cholesterol were more strongly associated with an increased risk of T2DM than other combinations except for elevated FPG.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Síndrome Metabólica/complicações , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
16.
J Plast Surg Hand Surg ; 54(3): 137-144, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32281469

RESUMO

Background: The macrophage migration inhibitory factor (MIF) has been determined as a cytokine exerting a multitude of effects in inflammation and angiogenesis. Earlier studies have indicated that MIF may also be involved in wound healing and flap surgery. Methods: We investigated the effect of MIF in an excisional wound model in wildtype, Mif-/- and recombinant MIF treated mice. Wound closure rates as well as the macrophage marker Mac-3, the pro-inflammatory cytokine tumor necrosis factor α (TNFα) and the pro-angiogenic factor von Willebrand factor (vWF) were measured. Finally, we used a flap model in Mif-/- and WT mice with an established perfusion gradient to identify MIF's contribution in flap perfusion. Results: In the excision wound model, we found reduced wound healing after MIF injection, whereas Mif deletion improved wound healing. Furthermore, a reduced expression of Mac-3, TNFα and vWF in Mif-/- mice was seen when compared to WT mice. In the flap model, Mif-/- knockout mice showed mitigated flap perfusion with lower hemoglobin content and oxygen saturation as measured by O2C measurements when compared to WT mice. Conclusions: Our data suggest an inhibiting effect of MIF in wound healing with increased inflammation and perfusion. In flaps, by contrast, MIF may contribute to flap vascularization.

17.
J Plast Reconstr Aesthet Surg ; 73(6): 1075-1080, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32317232

RESUMO

INTRODUCTION: Numerous techniques have been proposed for the plastic surgical treatment of hypertrophic breasts. Challenges of the procedure include the preservation of vascular supply and sensitivity of the nipple areola complex (NAC), breast feeding, and an esthetically pleasing result. OBJECTIVES: In the present preliminary report, we introduce a new technique called the three-block L-wing reduction mammaplasty that addresses the aforementioned difficulties. MATERIALS AND METHODS: The three-block L-wing reduction mammaplasty with a thick hemispheric superiorly based NAC pedicle and a medial as well as lateral pillar was performed in a total of 60 patients. RESULTS: Our technique increases both, vascular safety and the sensory supply to the NAC, as it conceptually decreases the need for dissection of breast tissue and skin. The incidence of fat necrosis and wound healing disorders may be reduced with this technique. Because the ducts of the breast-gland underneath the NAC are not dissected, this technique also promises a higher probability of regular breast-feeding. Finally, our technique permits a cosmetically pleasing round-shaped mound of the breast. CONCLUSION: The three-block modification simplifies the procedure of the superior pedicle L-wing mammaplasty markedly. It may increase the esthetic as well as the functional outcome and decrease postoperative complications.


Assuntos
Cicatriz/prevenção & controle , Mamoplastia/métodos , Adolescente , Adulto , Idoso , Mama/cirurgia , Feminino , Humanos , Mamoplastia/efeitos adversos , Pessoa de Meia-Idade , Mamilos/cirurgia , Retalhos Cirúrgicos/cirurgia , Adulto Jovem
18.
Exp Cell Res ; 389(1): 111881, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32006556

RESUMO

Human adipose tissue includes large quantities of mesenchymal stromal cells (atMSCs), which represent an abundant cell source for therapeutic applications in the field of regenerative medicine. Adipose tissue secrets various soluble factors including endocannabinoids, and atMSCs express the cannabinoid receptors CB1 and CB2. This indicates that adipose tissue possesses an endocannabinoid system (ECS). The ECS is also ascribed great significance for wound repair, e.g. by modulating inflammation. However, the exact effects of CB1/CB2 activation in human atMSCs have not been investigated, yet. In the present study, we stimulated human atMSCs with increasing concentrations (1-30 µM) of the unspecific cannabinoid receptor ligand WIN55,212-2 and the specific CB2 agonist JWH-133, either alone or co-applied with the receptor antagonist Rimonabant (CB1) or AM 630 (CB2). We investigated the effects on metabolic activity, cell number, differentiation and cytokine release, which are important processes during tissue regeneration. WIN decreased metabolic activity and cell number, which was reversed by Rimonabant. This suggests a CB1 dependent mechanism, whereas the number of atMSCs was increased after CB2 ligation. WIN and JWH increased the release of VEGF, TGF-ß1 and HGF. Adipogenesis was enhanced by WIN, which could be reversed by blocking CB1. There was no effect on osteogenesis, and only WIN increased chondrogenic differentiation. Our results indicate that definite activation of the cannabinoid receptors exerted different effects in atMSCs, which could be of specific value in cell-based therapy for wound regeneration.


Assuntos
Tecido Adiposo/citologia , Autorrenovação Celular , Células-Tronco Mesenquimais/fisiologia , Receptor CB1 de Canabinoide/fisiologia , Receptor CB2 de Canabinoide/fisiologia , Regeneração , Benzoxazinas/farmacologia , Canabinoides/farmacologia , Diferenciação Celular/efeitos dos fármacos , Autorrenovação Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Endocanabinoides/agonistas , Endocanabinoides/antagonistas & inibidores , Endocanabinoides/farmacologia , Humanos , Indóis/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Morfolinas/farmacologia , Naftalenos/farmacologia , Cultura Primária de Células , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB2 de Canabinoide/agonistas , Receptor CB2 de Canabinoide/antagonistas & inibidores , Regeneração/efeitos dos fármacos , Regeneração/fisiologia , Rimonabanto/farmacologia
19.
FASEB J ; 34(3): 4219-4233, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31961019

RESUMO

Sepsis is a leading cause of death worldwide and recent studies have shown white adipose tissue (WAT) to be an important regulator in septic conditions. In the present study, the role of the inflammatory cytokine macrophage migration inhibitory factor (MIF) and its structural homolog D-dopachrome tautomerase (D-DT/MIF-2) were investigated in WAT in a murine endotoxemia model. Both MIF and MIF-2 levels were increased in the peritoneal fluid of LPS-challenged wild-type mice, yet, in visceral WAT, the proteins were differentially regulated, with elevated MIF but downregulated MIF-2 expression in adipocytes. Mif gene deletion polarized adipose tissue macrophages (ATM) toward an anti-inflammatory phenotype while Mif-2 gene knockout drove ATMs toward a pro-inflammatory phenotype and Mif-deficiency was found to increase fibroblast viability. Additionally, we observed the same differential regulation of these two MIF family proteins in human adipose tissue in septic vs healthy patients. Taken together, these data suggest an inverse relationship between adipocyte MIF and MIF-2 expression during systemic inflammation, with the downregulation of MIF-2 in fat tissue potentially increasing pro-inflammatory macrophage polarization to further drive adipose inflammation.

20.
Clin Plast Surg ; 47(1): 139-145, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31739890

RESUMO

Fat grafting is as a unique regenerative filler with soluble factors and progenitor cells that may remodel scar tissue in an easy yet effective way. A combination of microfat grafting, lipococoncentrate injection, scar subcision, and platelet-rich plasma supplementation may be used to treat the majority of facial scars. The lipoconcentrate technique condenses the lipoaspirate to a progenitor cell-rich fluid of low volume by a combination of centrifugation and emulsification steps. In this article, the authors' methods for scar treatment by fat grafting are discussed. Choice of technique for facial scars, precise indications, and contraindications are introduced.


Assuntos
Tecido Adiposo/transplante , Cicatriz/cirurgia , Traumatismos Faciais/cirurgia , Lipectomia/métodos , Plasma Rico em Plaquetas , Cicatriz/etiologia , Traumatismos Faciais/complicações , Humanos , Rejuvenescimento , Células-Tronco
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