Pressurized intra-peritoneal aerosol chemotherapy (PIPAC): increased intraperitoneal pressure does not affect distribution patterns but leads to deeper penetration depth of doxorubicin in a sheep model.

BACKGROUND: Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is an innovative treatment against peritoneal carcinomatosis. Doxorubicin is a common intra-venous chemotherapy used for peritoneal carcinomatosis and for PIPAC. This study evaluated the impact of increased PIPAC intraperitoneal pressure on the distribution and cell penetration of doxorubicin in a sheep model. METHODS: Doxorubicin was aerosolized using PIPAC into the peritoneal cavity of 6 ewes (pre-alpes breed): N = 3 with 12 mmHg intraperitoneal pressure ("group 12") and N = 3 with 20 mmHg ("group 20"). Samples from peritoneum (N = 6), ovarian (N = 1), omentum (N = 1) and caecum (N = 1) were collected for each ewe. The number of doxorubicin positive cells was determined using the ratio between doxorubicine fluorescence-positive cell nuclei (DOXO+) over total number of DAPI positive cell nuclei (DAPI+). Penetration depth (µm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei over the total number of cell nuclei that were stained with DAPI. Penetration depth (µm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei. RESULTS: DOXO+ nuclei were identified in 87% of samples. All omental samples, directly localized in front of the nebulizer head, had 100% DOXO+ nuclei whereas very few nuclei were DOXO+ for caecum. Distribution patterns were not different between the two groups but penetration depth in ovary and caecum samples was significantly deeper in group 20. CONCLUSIONS: This study showed that applying a higher intra-peritoneal pressure during PIPAC treatment leads to a deeper penetration of doxorubicin in ovarian and caecum but does not affect distribution patterns.

Analytic comparison of talc in commercially available baby powder and in pelvic tissues resected from ovarian carcinoma patients.

OBJECTIVE: Measure the size and shape of talc particles in talcum powder and compare this data to the size and shape of talc particles found in surgically resected tissues from patients with ovarian carcinoma. METHODS: Using polarized light microscopy (PLM) and scanning electron microscopy (SEM), we measured the size and shape of talc particles in samples of talc-containing baby powder (TCBP) and surgically resected pelvic tissues (hysterectomies) from talc-exposed patients with ovarian carcinoma. RESULTS: The most frequent class of particles in TCBP can be unequivocally identified as talc, using both polarized light microscopy and scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX). The talc particles found in resected tissues from ovarian carcinoma patients are similar in size and shape to the most abundant morphological class of particles in TCBP. CONCLUSIONS: This finding, combined with previous epidemiological literature and tissue-based analytical studies, provides further evidence that the small, isodiametric particles that dominate TCBP can migrate from the perineum and become lodged in distal structures in the female reproductive tract, where they may lead to an increased risk of developing ovarian carcinoma.

Topical purified omental lipid formulations in the prevention of skin ulcers: a narrative review.

The omentum is a large peritoneal fold. Its main function is to protect abdominal organs, exerting a defensive action against infective agents. The tissue promotes repair after several types of injury. An extensive vascularisation is the key characteristic of this tissue and the omentum has the highest level of production and content of vascular endothelial growth factor (VEGF). A component of omentum is the lipid compound, which carries out important activities for the organism. Omentum is rich in neutral glycerides, phospholipids, glycolipids and gangliosides. Dermatological products containing purified omental lipids are commercially available and topical omental extracts have been useful in the softening, moisturising and smoothing of skin. Animal-derived omental lipids could be use in topical products with different textures (creams, fluids, emulsions and cleansers) and at different concentrations (10-25%) for the treatment of fragile skin or skin conditions causing risk of ulcer formation. This review summarises the pharmacological rationale of purified omental lipids in topical formulations for use in fragile skin conditions, the clinical efficacy data available in the scientific literature and the potential future perspectives. Efficacy of topical purified omental lipids have been demonstrated in numerous clinical controlled trials involving a total of 320 subjects. These studies demonstrated that this product helps prevent the formation of pressure ulcers (PU) in hospitalised high-risk subjects, improves wound healing process, normalises skin hydration in diabetic subjects with moderate-severe skin xerosis and improve the clinical evolution of diabetic foot. Therefore, purified omental lipid could be an effective tool for the management of fragile skin and the skin at high risk of PU formation.

Selected Case From the Arkadi M. Rywlin International Pathology Slide Club: Peritoneal Lipofuscinosis and Deciduosis in Pregnancy.

Peritoneal lipofuscinosis is a very rarely recognized condition occurring during pregnancy characterized by brown pigmentation of the omentum and peritoneum, a decidual reaction and benign mesothelial cells. The iron negative pigment, which is likely to be confused with hemosiderin in the hematoxylin and eosin stain, is lipofuscin. The seminar case, apparently the third published, arose in a 37-year-old woman who presented in October 2015 at 24 weeks pregnancy with abdominal pain. Investigations revealed a ruptured left ovarian cyst and rising serum carcinoembryonic antige levels. At laparotomy, there was no free intraperitoneal blood but the omentum and uterine serosa were black. Histology showed lipofuscinosis and a decidual reaction. The patient delivered a normal baby in February 2016 and was clinically well after delivery. A left ovarian endometriotic cyst was removed in February 2017. The patient made a good recovery with no clinically apparent symptoms from the liposuscinosis. We postulate that the endometriotic cyst had ruptured and released blood into the peritoneal cavity in 2015. The iron from the red cells breakdown was then rapidly resorbed because of the pregnancy requirements for iron, leaving lipofuscin in peritoneal macrophages.

Biodistribution and Clearance of Stable Superparamagnetic Maghemite Iron Oxide Nanoparticles in Mice Following Intraperitoneal Administration.

Nanomedicine is an emerging field with great potential in disease theranostics. We generated sterically stabilized superparamagnetic iron oxide nanoparticles (s-SPIONs) with average core diameters of 10 and 25 nm and determined the in vivo biodistribution and clearance profiles. Healthy nude mice underwent an intraperitoneal injection of these s-SPIONs at a dose of 90 mg Fe/kg body weight. Tissue iron biodistribution was monitored by atomic absorption spectroscopy and Prussian blue staining. Histopathological examination was performed to assess tissue toxicity. The 10 nm s-SPIONs resulted in higher tissue-iron levels, whereas the 25 nm s-SPIONs peaked earlier and cleared faster. Increased iron levels were detected in all organs and body fluids tested except for the brain, with notable increases in the liver, spleen, and the omentum. The tissue-iron returned to control or near control levels within 7 days post-injection, except in the omentum, which had the largest and most variable accumulation of s-SPIONs. No obvious tissue changes were noted although an influx of macrophages was observed in several tissues suggesting their involvement in s-SPION sequestration and clearance. These results demonstrate that the s-SPIONs do not degrade or aggregate in vivo and intraperitoneal administration is well tolerated, with a broad and transient biodistribution. In an ovarian tumor model, s-SPIONs were shown to accumulate in the tumors, highlighting their potential use as a chemotherapy delivery agent.

Short communication: in vivo deposition of [1-13C]vaccenic acid and the product of its Δ9-desaturation, [1-13C]rumenic acid, in the body tissues of lactating goats fed oils.

This study was conducted in lactating goats with the aim of measuring the deposition of trans-11 18:1 (vaccenic acid, VA) and the product of its Δ(9)-desaturation, cis-9, trans-11 18:2 (rumenic acid, RA), in the major tissues that are involved in lipid metabolism in the lactating ruminant (i.e., mammary secretory tissue, liver, and omental and perirenal adipose tissues) and examining its potential link with variations in the expression of genes encoding Δ(9)-desaturase [stearoyl-CoA desaturases 1 and 5 (SCD1 and SCD5)]. Eight lactating goats were fed a diet supplemented with sunflower oil (n=4) or sunflower oil plus fish oil and additional starch (n=4), based on the hypothesis that these dietary treatments could affect Δ(9)-desaturase gene expression in specific tissues. A chemical tracer, 1.5 g of [1-13C]VA as nonesterified fatty acid, was delivered by jugular injection. Goats were slaughtered 4 d later, and tissue samples were collected for the measurement of [13C]VA and [13C]RA enrichment and SCD1 and SCD5 expression. The addition of fish oil and additional starch to a diet containing sunflower oil was associated with several changes in [13C]VA and [13C]RA enrichment. These results support previous studies suggesting that mammary secretory tissue is the primary site of Δ(9)-desaturation in lactating goats. In adipose tissues, the [13C]VA + [13C]RA enrichment was consistent with a net uptake of circulating fatty acids to reconstitute body reserves at the end of the lactation cycle. The putative uptake of [13C]RA synthesized by other tissues precludes any conclusion from being drawn regarding potential Δ(9)-desaturation in the liver of goats, despite the detection of SCD1 and SCD5 mRNA in this tissue. Finally, no significant effect of dietary treatment was observed for SCD1 or SCD5 mRNA abundance in the mammary secretory tissue or other body tissues.

Biomarker expression in pelvic high-grade serous carcinoma: comparison of ovarian and omental sites.

Neoadjuvant therapy has an emerging role in the treatment of high-stage ovarian carcinoma. Some ovarian carcinoma subtypes do not respond well to standard chemotherapy, making accurate subtype diagnosis before starting therapy important. This diagnosis is frequently based on omental biopsy specimens. In particular, with very small biopsies, immunostaining for diagnostic biomarkers may be needed. To assess intratumoral heterogeneity of biomarker expression in pelvic high-grade serous carcinoma, we compared the expression of a set of 10 biomarkers between ovarian and omental sites. Tissue microarrays were constructed from 123 high-grade serous carcinomas with paired ovarian and omental tumor samples. These samples were stained with biomarkers that have been used in ovarian carcinoma subtype diagnosis (WT1, TP53/p53, MUC16/CA125, CDKN2A/p16), and with biomarkers of the tumor microenvironment (CD8, CD163, SPARC, PDGFRB), cell adhesion (CDH1/E-Cadherin), and proliferation (Ki67) as well. Expression frequencies in samples from the 2 sites were compared, as was concordance at the 2 sites for individual tumors. The 2 markers of desmoplastic stromal response (PDGFRB, SPARC) were more frequently expressed in the omentum compared with the ovary (P<0.001; McNemar test). The other 8 markers did not show a significant difference in the frequency of expression between sites. Within individual cases, some markers such as Ki67 and CDKN2A showed variability, indicating that these markers are affected by intratumoral heterogeneity. The intratumoral variability for MUC16, TP53, and WT1 was modest. Commonly used diagnostic markers, such as TP53 and WT1, show little variability between ovarian and omental sites, suggesting that they can be successfully used in small biopsy specimens from extraovarian sites. In contrast, markers of host stromal response do vary between sites, suggesting a biologic difference of the microenvironment at different sites that should be taken into account when tissue-based research is carried out.

Morphological hallmarks facilitating distinction of omental milky spots and lymph nodes: an exploratory study on their discriminative capacity.

BACKGROUND: Omental milky spots (OMSs) are the primary lymphoid structures of the greater omentum. However, the presence of lymph nodes (LNs) has occasionally been mentioned as well. Understanding which lymphoid structures are present is of significance, especially in gastric tumor metastasis; tumor deposits in omental LNs suggest local lymphatic spread, whereas tumor deposits in OMSs suggest peritoneal spread and hence extensive disease. Since LNs and OMSs share morphological characteristics and OMSs might be wrongly identified as LNs, reliable hallmarks facilitating easy discrimination are needed. MATERIALS AND METHOD: A series of microscopic morphological hallmarks unique to LNs were selected as potential candidates and were assessed for their discriminative capacity: 1) capsule, 2) trabeculae, 3) subcapsular sinus, 4) afferent lymphatic vessels, 5) distinct B- and T cell regions, and 6) a layered organization with, from the outside in a capsule, cortex, paracortex, and medulla. These hallmarks were visualized by multiple staining techniques. RESULTS: Hallmarks 1, 2 5 and 6 were shown to be the most efficient as these were consistent and discriminative. They were best visualized by Picrosirius red, smooth muscle actin and a B-cell / T-cell double staining. CONCLUSION: The presence of a capsule, trabeculae, distinct B- and T-cell regions and a layered organization represent consistent and reliable morphological features which allow to easily distinguish LNs from OMSs, especially when applied in combination.

Osteopontin involvement in granuloma formation and in the severity of Paracoccidioides brasiliensis infection.

The participation of osteopontin (OPN) in Paracoccidioides brasiliensis infected mice, its association to granulomatogenesis, severity of infection, pattern of lesions, nitric oxide (NO) levels and fungal load were evaluated in this investigation. Immunohistochemistry analysis showed marked OPN staining in extracellular matrix and in macrophages and multinucleated giant cells at the center of lesions, suggesting a possible role of OPN in the distribution of these cells within the granulomas. At 15 days post-infection with a virulent P. brasiliensis isolate, OPN+ cells were more numerous and intensely immunostained in the loose granulomas of susceptible mice than in those of resistant mice. In addition, high fungal loads and low NO levels were observed in susceptible mice. At 120 days after infection, resistant mice had increased total OPN levels (ELISA) and OPN positivity in compact granulomas, higher NO levels and lower fungal loads than susceptible mice. Residual lesions associated with low OPN levels, high NO and control of fungal dissemination were observed in both mouse strains at 120 days post-infection with the slightly virulent fungal isolate. Therefore, OPN could be associated with higher severity of the disease in an early phase of infection and with a degree of control of the progressive infection.

Proteomic biomarkers for the diagnosis and risk stratification of polycystic ovary syndrome: a systematic review.

BACKGROUND: The exact causes of polycystic ovary syndrome (PCOS) are uncertain, and treatment could be improved. Discovery-based approaches like 'proteomics' may result in faster insights into the causes of PCOS and improved treatment. OBJECTIVES: To identify the number and nature of proteomic biomarkers found in PCOS so far and to identify their diagnostic and therapeutic potential. SEARCH STRATEGY: All published studies on proteomic biomarkers in women with PCOS identified through the MEDLINE (1966-2008), EMBASE (1980-2008) and the ISI web of knowledge (v4.2) databases. SELECTION CRITERIA: The terms 'polycystic ovary syndrome' and 'proteomic', 'proteomics', 'proteomic biomarker' or 'proteomics biomarker' without any limits/restrictions were used. DATA COLLECTION AND ANALYSIS: Original data were abstracted where available and summarised on a separate Microsoft Excel (2007) database for analysis. MAIN RESULTS: Seventeen articles were identified, of which 6 original papers and 1 review article contained original data. Tissues investigated included serum, omental biopsies, ovarian biopsies, follicular fluid and T lymphocytes. Sample sizes ranged from 3 to 30 women. One hundred and forty-eight biomarkers were identified. The biomarkers were involved in many pathways, for example the regulation of fibrinolysis and thrombosis, insulin resistance, immunity/inflammation and the antioxidant pathway. Eleven groups of biomarkers appeared to be independently validated. The individual sensitivities for the diagnosis of PCOS were reported for 11 named biomarkers and ranged from 57 to 100%. AUTHOR'S CONCLUSIONS: Proteomic biomarker discovery in PCOS offers great potential. Current challenges include reproducibility and data analysis. The establishment of a PCOS-specific biomarker data bank and international consensus on the framework of systematic reviews in this field are required.

Identification of biomarkers, pathways and potential therapeutic agents for white adipocyte insulin resistance using bioinformatics analysis.

For the better understanding of insulin resistance (IR), the molecular biomarkers in IR white adipocytes and its potential mechanism, we downloaded two mRNA expression profiles from Gene Expression Omnibus (GEO). The white adipocyte samples in two databases were collected from the human omental adipose tissue of IR obese (IRO) subjects and insulin-sensitive obese (ISO) subjects, respectively. We identified 86 differentially expressed genes (DEGs) between the IRO and ISO subjects using limma package in R software. Gene Set Enrichment Analysis (GSEA) provided evidence that the most gene sets enriched in kidney mesenchyme development in the ISO subjects, as compared with the IRO subjects. The Gene Ontology (GO) analysis indicated that the most significantly enriched in cellular response to interferon-gamma. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the DEGs were most significantly enriched in cytokine-cytokine receptor interaction. Protein-Protein Interaction (PPI) network was performed with the STRING, and the top 10 hub genes were identified with the Cytohubba. CMap analysis found several small molecular compounds to reverse the altered DEGs, including dropropizine, aceclofenac, melatonin, and so on. Our outputs could empower the novel potential targets to treat omental white adipocyte insulin resistance, diabetes, and diabetes-related diseases.

Age-related changes in fatty acids from different adipose depots in rat and their association with adiposity and insulin.

OBJECTIVE: We studied age-related changes in fatty acids (FAs) from serum and adipose tissue in rats by comparing different adipose regions and analyzed their relations to adiposity and insulin function. METHODS: Female weaned rats were fed on a high-fat diet until 6, 14, and 20 mo of age (n = 12, n = 6, n = 10, respectively). Body weight, adiposity, serum insulin, serum glucose, and homeostatic model assessment index were measured. FA compositions from serum and interscapular brown, periovarian, mesenteric, and subcutaneous tissues were determined by gas chromatography. RESULTS: Body weight and adiposity increased with age; visceral depots grew by hypertrophy, whereas subcutaneous depots grew by hyperplasia and in a higher ratio. Initially, the mesenteric tissue showed greater saturated and trans-FA contents, whereas brown tissue had higher polyunsaturated FA (PUFA) proportions. Aging resulted in a lower saturation degree in adipose tissue, attenuating earlier differences among depots. There was an elevation in omega-6 PUFAs with age, mainly because of C18:2omega-6, whereas omega-3 long-chain PUFAs, C20:5omega-3 and C22:6omega-3, tended to decrease in serum and adipose tissue. Adiposity was associated positively with monounsaturated FAs and inversely with PUFAs; insulin-related variables correlated negatively with serum omega-6 PUFA but positively with serum monounsaturated FAs and subcutaneous depot trans-FAs. CONCLUSION: The mesenteric tissue showed the least favorable FA profile compared with the other depots, but differences among adipose regions diminished with age. In rats fed a high-fat diet, aging resulted in a lower saturation degree, with increased values in the cardiometabolic risk factor omega-6/omega-3 ratio in serum and adipose tissue.

Clinical value of bioelectrical properties of cancerous tissue in advanced epithelial ovarian cancer patients.

Currently, there are no valid pre-operatively established biomarkers or algorithms that can accurately predict surgical and clinical outcome for patients with advanced epithelial ovarian cancer (EOC). In this study, we suggest that profiling of tumour parameters such as bioelectrical-potential and metabolites, detectable by electronic sensors, could facilitate the future development of devices to better monitor disease and predict surgical and treatment outcomes. Biopotential was recorded, using a potentiometric measurement system, in ex vivo paired non-cancerous and cancerous omental tissues from advanced stage EOC (n = 36), and lysates collected for metabolite measurement by microdialysis. Consistently different biopotential values were detected in cancerous tissue versus non-cancerous tissue across all cases (p < 0.001). High tumour biopotential levels correlated with advanced tumour stage (p = 0.048) and tumour load, and negatively correlated with stroma. Within our EOC cohort and specifically the high-grade serous subtype, low biopotential levels associated with poorer progression-free survival (p = 0.0179, p = 0.0143 respectively). Changes in biopotential levels significantly correlated with common apoptosis related pathways. Lactate and glucose levels measured in paired tissues showed significantly higher lactate/glucose ratio in tissues with low biopotential (p < 0.01, n = 12). Our study proposes the feasibility of biopotential and metabolite monitoring as a biomarker modality profiling EOC to predict surgical and clinical outcomes.

ECM-based macroporous sponges release essential factors to support the growth of hematopoietic cells.

The success of hematopoietic stem cells (HSCs) transplantation is limited due to the low number of HSCs received from donors. In vivo, HSCs reside within a specialized niche inside the 3D porous spongy bone. The natural environment in the niche is composed of structural proteins, glycosaminoglycans (GAGs) and soluble factors that control cells fate. However, the designed scaffolds for in vitro culture do not fairly recapitulate this microenvironment and cannot efficiently control HSCs fate. Here we report on the development of new omental ECM-based 3D macroporous sponges for hematopoietic cell culture. The scaffolds' structure, porosity and stability were characterized and optimized. Analysis of the biochemical content revealed that they were composed of collagens and GAGs, including sulfated GAGs. This morphology and composition enabled growth factors interaction with the sulfated GAGs, as indicated by the high loading capacity and release profile of three different hematopoietic niche factors. Finally, the ability of the ECM-based scaffolds to efficiently support the growth of hematopoietic cells by releasing stem cell factor (SCF) was demonstrated.

Early loss of proliferative potential of human peritoneal mesothelial cells in culture: the role of p16INK4a-mediated premature senescence.

Much has been learned about the mechanisms underlying cellular senescence. The pathways leading to senescence appear to vary, depending on the cell type and cell culture conditions. In this respect, little is known about senescence of human peritoneal mesothelial cells (HPMC). Previous studies have significantly differed in the reported proliferative lifespan of HPMC. Therefore, in the present study, we have examined how HPMC enter state of senescence under conditions typically used for HPMC culture. HPMC were isolated from omentum and grown into senescence. The cultures were assessed for the growth rate, the presence of senescence markers, activation of cell-cycle inhibitors, and the oxidative stress. HPMC were found to reach, on average, six population doublings before senescence. The terminal growth arrest was associated with decreased expression of Ki67 antigen, increased percentage of cells in the G1 phase, reduced early population doubling level cDNA-1 mRNA expression, and the presence of senescence-associated beta-galactosidase. Compared with early-passage cells, the late-passage HPMC exhibited increased expression of p16INK4a but not of p21Cip1. In addition, these cells generated more reactive oxygen species and displayed increased presence of oxidatively modified DNA (8-hydroxy-2'-deoxyguanosine). These results demonstrate that early onset of senescence in omentum-derived HPMC may be associated with oxidative stress-induced upregulation of p16INK4a.

Omental and subcutaneous adipose tissue steroid levels in obese men.

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8-62.2 years (average BMI value of 46.3 +/- 12.7 kg/m(2)). Abdominal adipose tissue biopsies were obtained during general or obesity surgery. Omental and subcutaneous adipose tissue steroid levels were measured by gas chromatography and chemical ionization mass spectrometry after appropriate extraction procedures. BMI and waist circumference were negatively correlated with plasma testosterone (r = -0.49 and -0.50, respectively, p < 0.01) and dihydrotestosterone (r = -0.58 and -0.56, respectively, p < 0.01), and positively associated with estrone levels (r = 0.64 and 0.62, respectively, p < 0.001). Regional differences in adipose tissue steroid levels were observed for dihydrotestosterone (p < 0.005), androstenedione (p < 0.0001) and dehydroepiandrosterone levels (p < 0.05), which were all significantly more concentrated in omental versus subcutaneous fat. Positive significant associations were found between circulating level of a steroid and its concentration in omental and subcutaneous adipose tissue, for estrone (r = 0.72 and 0.57, respectively, p < 0.01), testosterone (r = 0.66 and 0.58, respectively, p < 0.01) and dihydrotestosterone (r = 0.58 and 0.45, respectively, p < 0.05). Positive correlations were observed between plasma dehydroepiandrosterone-sulfate and omental (r = 0.56, p < 0.01) as well as subcutaneous adipose tissue dehydroepiandrosterone level (r = 0.38, p = 0.05). Positive significant associations were found between omental adipocyte responsiveness to positive lipolytic stimuli (isoproterenol, dibutyryl cyclic AMP and forskolin) and plasma or omental fat tissue androgen levels. In conclusion, although plasma androgen or estrogen levels are strong correlates of adipose tissue steroid content both in the omental and subcutaneous fat depots, regional differences may be observed. Androgen concentration differences in omental versus subcutaneous adipose tissue suggest a depot-specific impact of these hormones on adipocyte function and metabolism.

Chemerin activation in human obesity.

OBJECTIVE: Chemerin is an inflammatory adipokine, whose activity is regulated by successive proteolytic cleavages at its C-terminus. It is secreted as an inactive precursor (chem163S); cleavage at Lys158 converts it to chem158K with modest activity. Chem157S is the most potent form and chem155A is inactive. The aim of this study was to determine if chemerin was activated in samples from patients with obesity. METHODS: Using specific ELISAs for different chemerin forms and a pan-chemerin ELISA, chemerin forms in human obesity were characterized. RESULTS: Plasma chemerin from patients with obesity (BMI 44.3 ± 1.3 kg/m(2) , n = 29) was significantly higher than in lean controls (BMI 20.9 ± 0.7 kg/m(2) , n = 10) (160 ± 11 vs. 76.2 ± 5.5 ng/mL, respectively, P < 0.0001). This increase in chemerin was due to increased previously unattributed chemerin, with further C-terminal truncation demonstrated by mass spectrometry, accounting for ∼35% of total plasma chemerin. Chemerin forms in adipose tissue showed a different profile, with minimal chem163S and significant levels of chem157S. Chem155A was present in omental but not in subcutaneous adipose tissue. Unattributed chemerin forms were undetectable in adipose tissue. CONCLUSIONS: Chemerin is activated in adipose tissue of subjects with obesity, and further C-terminal processing occurs during the disposition of chemerin from adipose tissue, resulting in substantial levels of novel degraded forms in plasma that correlate with obesity.

Distribution of persistent organic pollutants in serum, omental, and parietal adipose tissue of French women with deep infiltrating endometriosis and circulating versus stored ratio as new marker of exposure.

Several studies have assessed the potential role of environmental chemicals in the onset, growth, and/or physiopathology of endometriosis. However, their contour in terms of considered exposure markers remains limited. The present study aimed to characterize the internal exposure levels of 78 persistent organic pollutants (POPs, including dioxins, polychlorobiphenyls, brominated flame retardants and organochlorine pesticides) in a set of 113 adult French women (45 controls, 68 cases), and to characterize the distribution of these POPs within three biological compartments (omental adipose tissue, parietal adipose tissue, and serum). For all targeted substances, the correlation between the concentrations measured in omental versus parietal adipose tissue was found strongly significant (p<0.0001). An equivalence of the measures performed in parietal and omental adipose tissue was moreover observed with median levels of 6.4 vs. 7.4pg/gl.w. for WHO-TEQ2005 PCDD/F, 4.5 vs. 4.7pg/gl.w. for WHO-TEQ2005 dl-PCB, 137.1 vs. 147.9ng/gl.w. for sum of 6 ndl-PCB, and 2.1 vs. 2.0ng/gl.w. for sum of 7 i-PBDE, respectively. The same observation was made for individual targeted OCs compounds. Significant correlations were also observed between these concentrations determined in adipose tissue and those measured in serum for dioxins (WHO-TEQ2005 PCDD/F=6.1pg/gl.w), PCBs (WHO-TEQ2005 dl-PCB=3.6pg/gl.w., sum of 6 ndl-PCB=81.1ng/gl.w.), and brominated flame-retardants (sum of 7 i-PBDE=0.9ng/gl.w.). The circulating versus stored ratio of some exposure markers (Sum PCDDs, 1,2,3,6,7,8-HxCDF, slightly versus highly chlorinated PCBs ratio, PBDE 99 and PBB 153) was found statistically different for control and case individuals. These extended exposure data from deep infiltrating endometriosis patients are the first ones available for France and give a new insight about the equilibrium of chemicals between storage and circulating compartments that should be further considered as new marker of exposure in the context of exposure-health relationship studies.

Inhibitory effect of high concentration of glucose on relaxations to activation of ATP-sensitive K+ channels in human omental artery.

OBJECTIVE: The present study was designed to examine in the human omental artery whether high concentrations of D-glucose inhibit the activity of ATP-sensitive K+ channels in the vascular smooth muscle and whether this inhibitory effect is mediated by the production of superoxide. METHODS AND RESULTS: Human omental arteries without endothelium were suspended for isometric force recording. Changes in membrane potentials were recorded and production of superoxide was evaluated. Glibenclamide abolished vasorelaxation and hyperpolarization in response to levcromakalim. D-glucose (10 to 20 mmol/L) but not l-glucose (20 mmol/L) reduced these vasorelaxation and hyperpolarization. Tiron and diphenyleneiodonium, but not catalase, restored vasorelaxation and hyperpolarization in response to levcromakalim in arteries treated with D-glucose. Calphostin C and Gö6976 simultaneously recovered these vasorelaxation and hyperpolarization in arteries treated with D-glucose. Phorbol 12-myristate 13 acetate (PMA) inhibited the vasorelaxation and hyperpolarization, which are recovered by calphostin C as well as Gö6976. D-glucose and PMA, but not l-glucose, significantly increased superoxide production from the arteries, whereas such increased production was reversed by Tiron. CONCLUSIONS: These results suggest that in the human visceral artery, acute hyperglycemia modulates vasodilation mediated by ATP-sensitive K+ channels via the production of superoxide possibly mediated by the activation of protein kinase C.

Omentum ECM-based hydrogel as a platform for cardiac cell delivery.

Cardiovascular diseases remain the number one killer in Western countries. Despite recent advances and promising results in cardiac cell-based therapy, one of the remaining challenges is poor cell retention in the desired site. As a solution, cell delivery systems are developed to ensure that a sufficient number of viable cells reach the infarct area. These delivery systems are based on biomaterials that provide a surrogate microenvironment for the encapsulated cells, retaining them in the desired location post-delivery. Injectable thermoresponsive ECM-based hydrogels have been developed to achieve this goal. Unfortunately, the use of allogeneic or xenogeneic ECM may hamper the treatment due to an immune response to residual cellular content from the host. In this work, we have developed an omentum-based hydrogel capable of self-assembly under physiological conditions. Although in this study the omentum was obtained from porcine sources, it can be easily and safely extracted from the patient, serving as an autologous protective vehicle for the transported cells. We have characterized the biochemical composition, mechanical properties, and gelation and degradation kinetics of the processed biomaterial. Furthermore, the ability of the hydrogel to encapsulate cardiac cells and support their culture was evaluated. We envision that the newly developed platform may open new opportunities for personalized cell delivery to the heart and other tissues.