Numerical Study of Hyper-Thermic Laser Lipolysis With 1,064 nm Nd:YAG Laser in Human Subjects.

BACKGROUND AND OBJECTIVES: The aim of this study was to develop a numerical model for hyperthermic laser lipolysis in human subjects to improve understanding of the procedure and find optimal therapeutic parameters. STUDY DESIGN/MATERIALS AND METHODS: A numerical model of hyperthermic laser lipolysis (HTLL) on human subjects was developed that is based on light and heat transport, including the effects of blood perfusion and forced air cooling. Tissue damage was evaluated using the Arrhenius model. Three irradiation scenarios were considered: single skin area irradiation without and with forced air cooling, and sequential heating of four adjacent skin areas in a cyclical manner. An evaluation of the numerical model was made by comparing the recorded skin surface temperature evolution during an experimental HTLL procedure performed on the abdomen of ten human volunteers using a 1,064 nm Nd:YAG laser irradiation. RESULTS: A good agreement was obtained between the simulated skin surface temperatures and that as measured during the HTLL procedure. The temperature difference between the simulations and experiments was in the range of 0.2-0.4°C. The model parameters, which were fitted to the experiment were the perfusion parameter (0.36-0.79 and 0.18-0.49 kg/m 3 ·s for dermis and subcutis) and the subcutaneous tissue absorption coefficient (0.17-0.21 cm -1 ). By using the developed HTLL model and the determined parameters, temperature depth distributions and the resulting thermal injury to adipocytes were simulated under different treatment conditions. Optimal ranges of the HTTL treatment parameters were determined for different skin types, damaging adipocytes while preserving skin cells. The target subcutaneous temperatures were in the range of 43-47°C, which has been found to lead to programmed adipocyte death. The optimal treatment parameters were further used to define a range of recommended protocols for safe and effective multiarea cycled HTLL treatment of large body surfaces. Specifically, for the set of chosen optimal treatment parameters (4-5 treatment cycles, 1.2 W/cm 2 radiant exposure, and 60-130 W/cm 2 forced air heat-transfer coefficient) the threshold surface temperature during irradiation was found to be in the range of 31-38°C, depending on the skin type and heat-transfer coefficient. CONCLUSIONS: The developed numerical model allows for the calculation of the temperature distribution and the resulting injury to adipocyte cells within deeper lying fatty tissues under different clinical treatment conditions. It is demonstrated that by measuring the temporal evolution of the skin surface temperature and by stopping the laser irradiation at predefined skin surface threshold temperatures, it may be possible to monitor and control the effects of the HTLL procedure deeper within the tissue. As such, the model provides a better insight into the HTLL, and may become a tool for defining the range of safe and effective HTLL treatment protocols for patients with different skin types. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Sub-Scarpa's Lipectomy in Abdominoplasty: An Analysis of Risks and Rewards in 723 Consecutive Patients.

BACKGROUND: During the course of performing abdominoplasties, a plastic surgeon will encounter a certain body habitus characterized by a thick, tethered, and excessively redundant upper skin flap. Often these patients also demonstrate diffuse and substantial fascial laxity. One approach to this problem involves direct thinning and release of the flap by resection of the sub-Scarpa's fat pad. In theory, this resection should be safe from a flap perfusion standpoint. However, the safety of the sub-Scarpa's resection has not been completely documented. OBJECTIVES: The author sought to assess the safety and efficacy of sub-Scarpa's lipectomy in abdominoplasty. METHODS: A total 723 patients were retrospectively examined and divided into 2 groups: those with (Group B) and those without (Group A) a sub-Scarpa's lipectomy component to the abdominoplasty. Because of differences in the baseline characteristics between the 2 groups, data analysis was performed with a logistic regression model and with propensity score matching. RESULTS: The sub-Scarpa's lipectomy technique allowed for substantial thinning of the flap: the average weight of the resected fat pad was 411 g. Wide undermining allowed for substantial fascial correction, and excellent results were obtainable even in challenging cases. The sub-Scarpa's lipectomy group did not demonstrate an increase in either minor (<5 cm2) or major (>5 cm2) flap necrosis. However, there was a statistically significant increase in fat necrosis and seroma formation in Group B compared with Group A. In both groups, an increasing body mass index was a risk factor for fat necrosis and major flap necrosis. CONCLUSIONS: The implementation of a sub-Scarpa's lipectomy during abdominoplasty is a useful technique to consider for selected abdominoplasty candidates. The risks of minor and major flap loss do not seem to be increased compared to the standard abdominoplasty, but the risks of fat necrosis and seroma formation may be greater.

Effect of liraglutide on dietary lipid-induced insulin resistance in humans.

AIMS: To test whether liraglutide suppresses postprandial elevations in lipids and thus protects against high saturated fatty acid (SFA) diet-induced insulin resistance. METHODS: In a randomized placebo-controlled crossover study, 32 participants with normal or mildly impaired glucose tolerance received liraglutide and placebo for 3 weeks each. Insulin suppression tests (IST) were conducted at baseline and after a 24-hour SFA-enriched diet after each treatment. Plasma glucose, insulin, triglycerides and non-esterified fatty acids (NEFA) were measured over the initial 8 hours (breakfast and lunch) on the SFA diet. A subset of participants underwent ex vivo measurements of insulin-mediated vasodilation of adipose tissue arterioles and glucose metabolism regulatory proteins in skeletal muscle. RESULTS: Liraglutide reduced plasma glucose, triglycerides and NEFA concentrations during the SFA diet (by 50%, 25% and 9%, respectively), and the SFA diet increased plasma glucose during the IST (by 36%; all P < .01 vs placebo). The SFA diet-induced impairment of vasodilation on placebo (-9.4% vs baseline; P < .01) was ameliorated by liraglutide (-4.8%; P = .1 vs baseline). In skeletal muscle, liraglutide abolished the SFA-induced increase in thioredoxin-interacting protein (TxNIP) expression (75% decrease; P < .01 vs placebo) and increased 5'AMP-activated protein kinase (AMPK) phosphorylation (50% vs -3%; P = .04 vs placebo). CONCLUSIONS: Liraglutide blunted the SFA-enriched diet-induced peripheral insulin resistance. This effect may be related to improved microvascular function and modulation of TxNIP and AMPK pathways in skeletal muscle.

Upregulation of cathepsin C expression contributes to endothelial chymase activation in preeclampsia.

Chymase is an ACE (angiotensin-converting enzyme)-independent angiotensin II-forming enzyme whose expression is increased in the maternal vascular endothelium in preeclampsia. However, mechanisms underlying chymase activation in preeclampsia remain unclear. Cathepsin C is a key enzyme in the activation of several serine proteases including chymase. In this study, we determined whether increased cathepsin C expression/activity might be responsible for the upregulation of chymase expression in preeclampsia. Maternal vascular cathepsin C, chymase and ACE expression were examined through immunohistochemical staining of subcutaneous fat tissue sections of normal and preeclamptic pregnant women. The role of cathepsin C in endothelial chymase and ACE expression was determined in cells treated with cathepsin C. Consequences of chymase activation were then determined by measurement of angiotensin II production in cells treated with the ACE inhibitor captopril and the chymase inhibitor chymostatin, separately and in combination. Expression of both cathepsin C and chymase, but not ACE expression, was markedly increased in the maternal vascular endothelium in subjects with preeclampsia compared with normal pregnant controls. Exogenous cathepsin C induced a dose-dependent increase in expression of mature cathepsin C and chymase, but not ACE, in endothelial cells. Moreover, angiotensin II production was significantly inhibited in cells treated with captopril or chymostatin alone and was further inhibited in cells treated with both inhibitors. These results suggest that cathepsin C upregulation induces chymase activation and subsequently promotes angiotensin II generation in endothelial cells. These data also provide evidence of upregulation of the cathepsin C-chymase-angiotensin signaling axis in maternal vasculature in preeclampsia.

Insulin Plays a Permissive Role for the Vasoactive Effect of GIP Regulating Adipose Tissue Metabolism in Humans.

CONTEXT AND OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) in combination with hyperinsulinemia increases blood flow and triglyceride (TAG) clearance in subcutaneous (sc) abdominal adipose tissue in lean humans. The present experiments were performed to further investigate the role of insulin for the vasoactive effect of GIP in adipose tissue metabolism and whether the vasodilatory effect of GIP is dependent on C-peptide. METHODS: Six lean healthy subjects were studied. The sc abdominal adipose tissue metabolism was assessed by Fick's principle during GIP infusion (1.5 pmol/kg/min) in combination with 1) euglycemic-high insulinemic clamp (Eugluc-Hiinsu), raising plasma insulin concentrations to postprandial levels, 2) hyperglycemic-euinsulinemic clamp (Hygluc-Euinsu), and 3) hyperglycemic-hyperinsulinemic clamp, raising plasma insulin concentrations to supraphysiological levels. During the hyperglycemic clamps, endogenous insulin and C-peptide secretion were inhibited by infusion of the somatostatin analogue octreotide. RESULTS: During GIP infusion, Eugluc-Hiinsu, and hyperglycemic-hyperinsulinemic clamps, sc abdominal adipose tissue blood flow (ATBF) was similar and increased from 2.1 ± 0.2 and 2.2 ± 0.4 ml min(-1) (100 g tissue)(-1) to 7.1 ± 0.6 and 7.6 ± 0.1 ml min(-1) (100 g tissue)(-1), respectively (P < .01). ATBF remained virtually constant (2.7 ± 0.4 ml min(-1) [100 g tissue](-1)) during Hygluc-Euinsu and GIP infusion. In addition, adipose tissue TAG clearance increased significantly (P = .03), whereas free fatty acid output (P = .01), glycerol output (P = .02) and free fatty acid/glycerol release ratio (P = .04) decreased during the Eugluc-Hiinsu clamp compared to Hygluc-Euinsu clamp with GIP. CONCLUSION: In healthy lean humans, insulin is permissive for GIP to induce an increase in blood flow and TAG clearance in sc abdominal adipose tissue. This effect is independent of C-peptide.

FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance.

OBJECTIVE: To study effects of dexamethasone on gene expression in human adipose tissue aiming to identify potential novel mechanisms for glucocorticoid-induced insulin resistance. MATERIALS/METHODS: Subcutaneous and omental adipose tissue, obtained from non-diabetic donors (10 M/15 F; age: 28-60 years; BMI: 20.7-30.6 kg/m²), was incubated with or without dexamethasone (0.003-3 µmol/L) for 24 h. Gene expression was assessed by microarray and real time-PCR and protein expression by immunoblotting. RESULTS: FKBP5 (FK506-binding protein 5) and CNR1 (cannabinoid receptor 1) were the most responsive genes to dexamethasone in both subcutaneous and omental adipose tissue (~7-fold). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots. The gene product, FKBP51 protein, was 10-fold higher in the omental than in the subcutaneous depot, whereas the mRNA levels were similar. Higher FKBP5 gene expression in omental adipose tissue was associated with reduced insulin effects on glucose uptake in both depots. Furthermore, FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter and negatively with plasma HDL-cholesterol. FKBP5 SNPs were found to be associated with type 2 diabetes and diabetes-related phenotypes in large population-based samples. CONCLUSIONS: Dexamethasone exposure promotes expression of FKBP5 in adipose tissue, a gene that may be implicated in glucocorticoid-induced insulin resistance.

Cyclooxygenase inhibition improves endothelial vasomotor dysfunction of visceral adipose arterioles in human obesity.

OBJECTIVE: The purpose of this study was to determine whether cyclooxygenase inhibition improves vascular dysfunction of adipose microvessels from obese humans. DESIGN AND METHODS: In 20 obese subjects (age 37 ± 12 years, BMI 47 ± 8 kg/m²), subcutaneous and visceral fat were collected during bariatric surgery and characterized for adipose depot-specific gene expression, endothelial cell phenotype, and microvascular function. Vasomotor function was assessed in response to endothelium-dependent agonists using videomicroscopy of small arterioles from fat. RESULTS: Arterioles from visceral fat exhibited impaired endothelium-dependent, acetylcholine-mediated vasodilation, compared to the subcutaneous depot (P < 0.001). Expression of mRNA transcripts relevant to the cyclooxygenase pathway was upregulated in visceral compared to subcutaneous fat. Pharmacological inhibition of cyclooxygenase with indomethacin improved endothelium-dependent vasodilator function of arterioles from visceral fat by twofold (P = 0.01), whereas indomethacin had no effect in the subcutaneous depot. Indomethacin increased activation via serine-1177 phosphorylation of endothelial nitric oxide synthase in response to acetylcholine in endothelial cells from visceral fat. Inhibition of endothelial nitric oxide synthase with N(ω)-nitro-L-arginine methyl ester abrogated the effects of cyclooxygenase-inhibition suggesting that vascular actions of indomethacin were related to increased nitric oxide bioavailability. CONCLUSIONS: Our findings suggest that cyclooxygenase-mediated vasoconstrictor prostanoids partly contribute to endothelial dysfunction of visceral adipose arterioles in human obesity.

Glucose-dependent insulinotropic polypeptide has impaired effect on abdominal, subcutaneous adipose tissue metabolism in obese subjects.

OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) appears to have a role in lipid metabolism. Recently, we showed that GIP in combination with hyperinsulinemia and hyperglycemia increases triglyceride uptake in abdominal, subcutaneous adipose tissue in lean humans. It has been suggested that increased GIP secretion in obesity will promote lipid deposition in adipose tissue. In light of the current attempts to employ GIP antagonists in the treatment and prevention of human obesity, the present experiments were performed in order to elucidate whether the adipose tissue lipid metabolism would be enhanced or blunted during a GIP, hyperinsulinemic and hyperglycemic (HI-HG) clamp in obese subjects with either normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). DESIGN: Sixteen obese (BMI>30 kg m(-2)) subjects were divided into two groups, based on their plasma glucose response to an oral glucose challenge: (i) NGT and (ii) IGT. Abdominal, subcutaneous adipose tissue lipid metabolism was studied by conducting measurements of arteriovenous concentrations of metabolites and regional adipose tissue blood flow (ATBF) during GIP (1.5 pmol kg(-1) min(-1)) in combination with a HI-HG clamp. RESULTS: In both groups, ATBF responses were significantly lower than what we have found previously in healthy, lean subjects (P<0.0001). The flow response was significantly lower in the IGT group than in the NGT group (P=0.03). It was not possible to show any increase in the lipid deposition in adipose tissue under the applied experimental conditions and likewise the circulating triglyceride (TAG) concentrations remained constant. CONCLUSION: The applied GIP, HI-HG clamp did not induce any changes in TAG uptake in adipose tissue in obese subjects. This may be due to a blunted increase in ATBF. These experiments therefore suggest that GIP does not have a major role in postprandial lipid metabolism in obese subjects.

The dynamics of the microcirculation in the subcutaneous adipose tissue is impaired in the postprandial state in type 2 diabetes.

UNLABELLED: Postprandially, the blood flow and uptake of non-esterified fatty acids increase concomitantly in the abdominal subcutaneous adipose tissue in healthy subjects. In insulin-resistant subjects, this postprandial blood flow increase is blunted. We have previously found that the postprandial adipose tissue blood flow (ATBF) increase is accompanied by capillary recruitment in healthy subjects. The aim of the present study was to investigate whether the postprandial capillary recruitment in adipose tissue is affected in type 2 diabetes mellitus. Eight type 2 diabetic overweight male subjects and eight age- and weight-matched healthy subjects were studied. Contrast-enhanced ultrasound imaging was applied to study the microvascular volume in abdominal subcutaneous adipose tissue and in forearm skeletal muscle in the fasting state and 60, 120 and 180 min after a 75-g oral glucose load. Abdominal subcutaneous ATBF was measured using (133) Xenon washout technique, and forearm skeletal muscle blood flow was assessed by venous occlusion plethysmography. In the healthy, overweight subjects, ATBF increased and concomitantly capillary recruitment took place after glucose ingestion. No significant changes were found in the ATBF or in capillary recruitment in the type 2 diabetic subjects. There was no significant blood flow or microvascular blood volume changes in forearm skeletal muscle in either of the groups. CONCLUSION: After an oral glucose load, the abdominal ATBF and microvascular blood volume changes in abdominal subcutaneous adipose tissue are impaired in overweight type 2 diabetic subjects compared to weight-matched healthy subjects.

Lipolytic effects of B-type natriuretic peptide 1-32 in adipose tissue of heart failure patients compared with healthy controls.

OBJECTIVES: Our goal was to examine the role of B-type natriuretic peptide (BNP) in lipolysis regulation in heart failure (HF) patients. BACKGROUND: Enhanced adipose tissue lipolysis can contribute to myocardial lipid overload, insulin resistance, and cachexia in advanced HF. Natriuretic peptides were recently recognized to stimulate lipolysis in healthy subjects. METHODS: Ten nondiabetic HF patients (New York Heart Association functional class III, 50% nonischemic etiology) and 13 healthy subjects (control subjects) of similar age, sex, and body composition underwent a microdialysis study of subcutaneous abdominal adipose tissue. Four microdialysis probes were simultaneously perfused with 0.1 µM BNP(1-32,) 10 µM BNP(1-32), 10 µM norepinephrine (NE) or Ringer's solution. Outgoing dialysate glycerol concentration (DGC) was measured as an index of lipolysis. RESULTS: Spontaneous lipolysis was higher in HF patients compared with control subjects (DGC: 189 ± 37 µmol/l vs. 152 ± 35 µmol/l, p < 0.01). Response to NE was similar (p = 0.35) in HF patients and control subjects (DGC increase of 1.7 ± 0.2-fold vs. 1.7 ± 0.4-fold). BNP(1-32) 10 µM markedly increased lipolysis in both HF patients and control subjects (DGC increase of 2.8 ± 0.5-fold vs. 3.2 ± 0.3-fold), whereas the response to 0.1 µM BNP(1-32) was more pronounced in HF patients (p = 0.02). In HF patients, spontaneous lipolysis positively correlated with insulin resistance and the response to BNP(1-32) negatively correlated with adiposity. CONCLUSIONS: BNP(1-32) exerts strong lipolytic effects in humans. Despite marked elevation of plasma immunoreactive BNP, the responsiveness of adipose tissue to BNP(1-32) is not attenuated in HF, possibly reflecting a deficiency of endogenous bioactive BNP. Lipolytic effects of BNP can contribute to excessive fatty acid mobilization in advanced HF.

Age-associated adaptations in murine adipose tissues.

Ageing is associated with an increase in visceral obesity in men and women. Although wild-type mice with a C57Bl/6 genetic background are extensively used in studies on obesity and metabolism, little information is available on age-associated changes in their adipose tissues. We have evaluated development and composition of subcutaneous (SC) and gonadal (GON) adipose tissue in male C57Bl/6 mice at the ages of 10 weeks, 12 months or 24 months, while kept on normal chow. Total body weight as well as SC and GON fat mass significantly increased between 10 weeks and 12 months, but markedly decreased again up to 24 months of age. Adipocyte size in both fat depots and blood vessel size in GON fat followed this trend. Plasma leptin levels correlated positively with body weight and SC or GON fat mass. Both 12 and 24 months old mice displayed better insulin sensitivity as compared to 10 weeks old counterparts, reflected by significantly decreased plasma levels of insulin and/or glucose. Thus, ageing of C57Bl/6 male mice is associated with a biphasic pattern (increase up to 12 months followed by a decrease up to 24 months) of body weight, SC and GON fat mass, adipocyte and blood vessel size.

Real-time contrast-enhanced ultrasound determination of microvascular blood volume in abdominal subcutaneous adipose tissue in man. Evidence for adipose tissue capillary recruitment.

The adipose tissue metabolism is dependent on its blood perfusion. During lipid mobilization e.g. during exercise and during lipid deposition e.g. postprandial, adipose tissue blood flow is increased. This increase in blood flow may involve capillary recruitment in the tissue. We investigated the basic and postprandial microvascular volume in adipose tissue using real-time contrast-enhanced ultrasound (CEU) imaging in healthy normal weight subjects. In nine subjects, CEU was performed in abdominal subcutaneous adipose tissue and in the underlying skeletal muscle after a bolus injection of ultrasound contrast agent to establish the reproducibility of the technique. In nine subjects, the effect of an oral glucose load on blood flow and microvascular volume was measured in abdominal subcutaneous adipose tissue and forearm skeletal muscle. ¹³³Xe washout and venous occlusion strain-gauge plethysmography was used to measure the adipose tissue and forearm blood flow, respectively. Ultrasound signal intensity of the first plateau phases was 27 ± dB in the abdominal subcutaneous adipose tissue and 18 ± 2 dB (P < 0.05) in the underlying skeletal muscle. The reproducibility of the measurements was good with a 4% coefficient of variation in both tissues. Blood flow and the change in signal intensity as a measure of the microvascular volume increased significantly and simultaneously in abdominal subcutaneous adipose tissue after glucose intake. The forearm blood flow and muscle signal intensity remained constant. It is concluded that the microvascular volume and changes in volume in abdominal subcutaneous adipose tissue can be assessed using CEU with good reproducibility. Postprandial capillary recruitment takes place in abdominal subcutaneous adipose tissue.

Morphological characteristics of abdominal adipose tissue in normal-weight and obese women of different metabolic profiles.

BACKGROUND AND AIMS: Morphological changes in adipose tissue reflect functional disorders that correlate with cardiometabolic complications of obesity. The metabolic risks vary among the obese individuals. Furthermore, normal-weight individuals are not necessarily metabolically healthy. Therefore, the aim of this study was to analyze morphological characteristics of the abdominal adipose tissue in normal-weight and obese individuals in regards to metabolic risks. METHODS AND RESULTS: The study group consisted of 30 overweight or obese and 20 normal-weight women undergoing elective surgery. Women of each group were divided into metabolically healthy and metabolically obese, based on the homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride, total-, LDL- and HDL-cholesterol levels. The size and numerical density of adipocytes, as well as volume density of blood vessels in subcutaneous and visceral adipose tissue were compared among subgroups. The results showed hypertrophy of adipocytes of visceral adipose tissue in metabolically obese normal-weight women. At the same time, metabolically healthy obese women had smaller adipocytes in both depots in comparison with "at risk" obese women. The lowest volume density of blood vessels correlated with the largest diameter of adipocytes in "at risk" obese women indicating hypoxic changes in visceral adipose tissue. The observed differences of the adipose tissue morphology did not correlate with considerable phenotypic differences within either the normal-weight or obese women group. CONCLUSION: Changes in adipocyte size, cellular and vascular density of adipose tissue in relation with metabolic disorders, regardless of nutritional level, suggest limited capacity of fat deposition and adipose tissue response to hypoxia.

Effect of insulin catheter wear-time on subcutaneous adipose tissue blood flow and insulin absorption in humans.

BACKGROUND: Insertion of an insulin catheter for continuous subcutaneous insulin infusion into the subcutaneous adipose tissue (SAT) causes a tissue trauma that may have consequences for insulin absorption. We evaluated the importance of insulin catheter wear-time on subcutaneous adipose tissue blood flow (ATBF) and absorption of the rapid-acting insulin analog insulin aspart over a period of 4 days. METHODS: Teflon insulin catheters (Medtronic, Minneapolis, MN) were inserted into the abdominal SAT of 10 healthy men without diabetes (mean +/- SEM age, 23.0 +/- 1.1 years; body mass index, 22.1 +/- 0.7 kg/m(2)) and connected to an insulin pump delivering a constant rate of isotonic saline for 4 days. Subjects participated in four study days (days 0, 1, 2, and 4) during which ATBF around the catheter tip was measured by (133)Xe clearance and absorption of an insulin aspart bolus (0.1 U/kg) was measured for 4 h. RESULTS: ATBF increased from day 0 to day 2 after catheter insertion (2.6 +/- 0.6 to 4.5 +/- 0.8 mL/100 g/min; P = 0.030). By day 4, ATBF had returned to day 0 level. Time to peak plasma insulin aspart concentration after bolus administration decreased with catheter wear-time from 55 +/- 3 min on day 0 to 45 +/- 4 min on day 4 (P = 0.019). Neither peak plasma concentration nor area under the curve of insulin aspart changed significantly. CONCLUSIONS: Insertion of a Teflon insulin catheter into the SAT results in increased ATBF and faster absorption of insulin aspart in a period of 4 days without any change in the total amount of insulin aspart absorbed.

Banking a hemi-abdominal DIEP flap: a pilot report of indications, technique, and utility.

We present a pilot report of "banking" the contralateral hemi-abdominal deep inferior epigastric perforator (DIEP) flap under the abdominal closure in patients undergoing unilateral autologous breast reconstruction when a hemi-abdominal flap suffices. Four patients undergoing unilateral autologous breast reconstruction with a hemi-abdominal DIEP or superficial inferior epigastric artery flap had their contralateral hemi-abdominal flap left in position, or "banked," under their abdominal closure to be used in case of failure. This novel method may be of assistance when a free microvascular hemi-abdominal flap is felt to be threatened or suspect. It provides a life-boat for the younger and experienced surgeon alike, and most importantly, for the breast cancer survivor. Economic analysis of the technique reveals that the contralateral hemi-abdominal flap should be banked more often than intuition alone would suggest.

RANTES release by human adipose tissue in vivo and evidence for depot-specific differences.

Obesity is associated with elevated inflammatory signals from various adipose tissue depots. This study aimed to evaluate release of regulated on activation, normal T cell expressed and secreted (RANTES) by human adipose tissue in vivo and ex vivo, in reference to monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) release. Arteriovenous differences of RANTES, MCP-1, and IL-6 were studied in vivo across the abdominal subcutaneous adipose tissue in healthy Caucasian subjects with a wide range of adiposity. Systemic levels and ex vivo RANTES release were studied in abdominal subcutaneous, gastric fat pad, and omental adipose tissue from morbidly obese bariatric surgery patients and in thoracic subcutaneous and epicardial adipose tissue from cardiac surgery patients without coronary artery disease. Arteriovenous studies confirmed in vivo RANTES and IL-6 release in adipose tissue of lean and obese subjects and release of MCP-1 in obesity. However, in vivo release of MCP-1 and RANTES, but not IL-6, was lower than circulating levels. Ex vivo release of RANTES was greater from the gastric fat pad compared with omental (P = 0.01) and subcutaneous (P = 0.001) tissue. Epicardial adipose tissue released less RANTES than thoracic subcutaneous adipose tissue in lean (P = 0.04) but not obese subjects. Indexes of obesity correlated with epicardial RANTES but not with systemic RANTES or its release from other depots. In conclusion, RANTES is released by human subcutaneous adipose tissue in vivo and in varying amounts by other depots ex vivo. While it appears unlikely that the adipose organ contributes significantly to circulating levels, local implications of this chemokine deserve further investigation.

Neutrophils, but not lymphocytes or monocytes, infiltrate maternal systemic vasculature in women with preeclampsia.

OBJECTIVE: Leukocytes are activated in women with preeclampsia, but the class of leukocytes that infiltrates the maternal vasculature and, therefore, is most likely to cause vascular dysfunction is not known. METHODS: Subcutaneous fat biopsies were obtained at Cesarean section or abdominal surgery from 7 normal non-pregnant women, 7 women with normal pregnancies, and 7 women with preeclampsia. Tissues were immunohistochemically stained for CD14, a monocyte/macrophage antigen, CD99, a lymphocyte antigen, and CD66b, a neutrophil antigen. RESULTS: CD14 stained cells were found infiltrated into fat tissue but were not present in vessels for any of the groups. CD99-stained cells were present in approximately 20% to 30% of vessels with no difference among groups. CD66b-stained cells were present in all groups with a significantly greater percentage of vessels stained for preeclamptic than normal pregnant or normal non-pregnant women (70 +/- 6 vs. 43 +/- 9 vs. 21 +/- 5%, respectively, p < 0.01). CD66b cells were the most abundant cell type that infiltrated vessels of preeclamptic women. CONCLUSIONS: 1) A significantly greater number of neutrophils adhered to endothelium and infiltrated into the intimal space in the maternal systemic vasculature of preeclamptic women than in that of normal pregnant women or normal non-pregnant women; 2) No significant difference in lymphocyte infiltration was observed among the patient groups, and lymphocytes were present in much lower numbers than-neutrophils; 3) Monocytes/macrophages were found in fat tissue but not in vessels. We speculate that neutrophils are the class of leukocytes that cause the majority of vascular cell dysfunction in women with preeclampsia.

Amyloid precursor protein expression is upregulated in adipocytes in obesity.

The aim of this study was to determine whether amyloid precursor protein (APP) is expressed in human adipose tissue, dysregulated in obesity, and related to insulin resistance and inflammation. APP expression was examined by microarray expression profiling of subcutaneous abdominal adipocytes (SAC) and cultured preadipocytes from obese and nonobese subjects. Quantitative real-time PCR (QPCR) was performed to confirm differences in APP expression in SAC and to compare APP expression levels in adipose tissue, adipocytes, and stromal vascular cells (SVCs) from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) specimens. Adipose tissue samples were also examined by western blot and immunofluorescence confocal microscopy. Microarray studies demonstrated that APP mRNA expression levels were higher in SAC (approximately 2.5-fold) and preadipocytes (approximately 1.4) from obese subjects. Real-time PCR confirmed increased APP expression in SAC in a separate group of obese compared with nonobese subjects (P=0.02). APP expression correlated to in vivo indices of insulin resistance independently of BMI and with the expression of proinflammatory genes, such as monocyte chemoattractant protein-1 (MCP-1) (R=0.62, P=0.004), macrophage inflammatory protein-1alpha (MIP-1alpha) (R=0.60, P=0.005), and interleukin-6 (IL-6) (R=0.71, P=0.0005). Full-length APP protein was detected in adipocytes by western blotting and APP and its cleavage peptides, Abeta40 and Abeta42, were observed in SAT and VAT by immunofluorescence confocal microscopy. In summary, APP is highly expressed in adipose tissue, upregulated in obesity, and expression levels correlate with insulin resistance and adipocyte cytokine expression levels. These data suggest a possible role for APP and/or Abeta in the development of obesity-related insulin resistance and adipose tissue inflammation.

Enterostatin inhibition of angiogenesis: possible role of pAMPK and vascular endothelial growth factor A (VEGF-A).

INTRODUCTION: We utilized a genomic analysis of the response of neuronal GT1-7 cells to enterostatin to identify pathways responsive to this peptide. This information, together with reported properties of the enterostatin receptor, suggested that enterostatin may have an effect on angiogenesis. METHOD: To investigate this hypothesis, we studied the effect of enterostatin as an antiangiogenic agent in two angiogenic tissue culture model systems. RESULTS: Enterostatin induced a 50% or greater inhibition in the angiogenic response of human fat cells and had a U-shaped bimodal dose-response effect in inhibiting angiogenesis in a human placental vein angiogenesis model. To further understand this response, we tested enterostatin's effect in a human hepatoma cell line (HepG2 cells) that was subjected to glucose deprivation, a condition known to induce angiogenesis in other tumor cell lines. Phosphorylated AMP kinase (pAMPK) levels and vascular endothelial growth factor A (VEGF-A) mRNA expression were elevated robustly after incubation of HepG2 cells in the absence of glucose for 4 h, but 15 min incubation with enterostatin dramatically inhibited this pAMPK activation and reduced VEGF-A gene expression after 1 h incubation with enterostatin. The AMPK activator 5-aminoimidazole-4-carboximide ribonucleoside (AICAR) induced VEGF-A expression. SUMMARY: These data suggest that enterostatin has an antiangiogenic effect and suggest that it regulates VEGF-A gene expression through inhibition of AMPK activity.

Acute dilatation to phytoestrogens and estrogen receptor subtypes expression in small arteries from women with coronary heart disease.

We tested if endothelial function and estrogen receptor (ER) expression differs between resistance arteries in subcutaneous circulation from postmenopausal women with coronary heart disease (CHD, congruent with 1 year after myocardial infarction, n=12) and aged matched controls (n=14); and if acute effects of phytoestrogens (genistein, resveratrol) could be of relevance for vascular protection. We utilized ex vivo small artery ( congruent with 350 microm) bioassays and found no difference in bradykinin (BK)-mediated dilatation between the groups. One-hour incubation with phytoestrogens (natural ER beta agonists), propyl-pyrazole-triol-trisphenol (PPT-selective ER alpha agonist) and 17beta-estradiol (17beta-E(2)-ER alpha/beta agonist) at 0.01 microM/L had no effect on BK-induced responses. Concentration-response curves (0.01-30 microM/L) to investigated compounds were also obtained and compared in separate arteries. We found that dilatation to phytoestrogens was enhanced in CHD if compared to controls (p<0.05), while responses to 17beta-E(2) remained similar. The dilatation to phytoestrogens was also higher if compared to 17beta-E(2) (p<0.05) in CHD. In controls, only responses to PPT, but not to phytoestrogens, were enhanced in comparison to 17beta-E(2) (p<0.05). Inhibition of NO synthase had no effect on dilatation induced by increasing concentrations of investigated compounds. ER beta expression was enhanced in the vascular wall from CHD women, while ER alpha predominated in the controls (p<0.05). We suggest that diet supplementation by phytoestrogens may provide cardiovascular benefit for postmenopausal women with CHD. The selective targeting of one of the ER subtype may have implications for women's cardiovascular health.