Improved HDL cholesterol efflux capacity in morbidly obese individuals after bariatric surgery

Improved HDL cholesterol efflux capacity in morbidly obese individuals after bariatric surgeryBackground. Obesity has become a global epidemic and carries excess cardiovascular (CV) morbidity and mortality. Bariatric surgery was shown to improve significantly CV outcome. HDL cholesterol efflux capacity (CEC) was shown to be inversely correlated with cardiovascular risk (CVR), both in the acute and the chronic phases. Our aim is to assess if HDL CEC is improved 6 months post bariatric surgery in comparison to baseline, as a surrogate marker for the increased CVR reduction in the morbidly obese population. Methods. HDL CEC via ATP-binding cassette A1 (ABCA1), ATP-binding cassette G1 (ABCG1) and scavenger receptor BI (SR-BI) was measured for morbidly obese individuals prior to and 6 months after bariatric surgery. HDL CEC was measured using radioactive cell-based assays. Results. Plasma from 36 morbidly obese patients was analyzed. The mean age of the patients was 43.2±12.2 years, 30.6% of the patients were males, 61.1% had undergone sleeve gastrectomy (SG) and 38.9% Roux-en-Y gastric bypass. HDL CEC improved 6 months post-bariatric surgery in comparison to baseline for all 3 transporters as well as unstimulated total CEC; efflux via ABCA1 increased by 9.5% (14.35±1.85 vs. 13.1±2.63, P=0.004), via ABCG1 by 14% (4.38±0.95 vs. 3.84±0.84, P=0.001), via SR-BI by 14.1% (5.96±0.99 vs. 5.23±0.89, P<0.001) and unstimulated total efflux increased by 14.8% (8.82±1.3 vs. 7.68±0.93, P<0.001). Discussion. In the current study, we found that HDL CEC through ABCA1, ABCG1 and SR-BI improved significantly in morbidly obese individuals 6 months after bariatric surgery. Efflux is an ongoing process, hence even a small improvement in CEC can have a substantial effect on the atherosclerotic plaque. Given that HDL CEC has an inverse correlation with CVR, these findings may explain, at least in part, the improvement in CVR in morbidly obese patients post-bariatric surgery. Conclusion. HDL CEC improves after bariatric surgery, and may play an important role in the favorable CV outcome seen in obese patients post-bariatric surgery. If the same is proven in larger clinical studies, decreased HDL CEC might serve as another indication for bariatric surgery in obese individuals.L'amélioration de la capacité d'efflux du cholestérol LHD chez les personnes obèses morbides après la chirurgie bariatriqueContexte. L'obésité est devenue une épidémie mondiale et entraîne un excès de morbidité et de mortalité cardiovasculaire (CV). Il a été démontré que la chirurgie bariatrique améliore de manière significative les issues CV. La capacité d'efflux du cholestérol LHD (CEC) s'est révélée inversement corrélée au risque cardiovasculaire (RCV), tant dans les phases aiguës que chroniques. Notre objectif est d'évaluer s'il y a amélioration de la CEC LHD 6 mois après chirurgie bariatrique par rapport au niveau de base, et d'utiliser la CEC LHD comme un marqueur de substitution pour la réduction du RCV dans la population de personnes atteintes d'obésité morbide. Méthodes. La CEC LHD via l'ATP-binding cassette A1 (ABCA1), l'ATP-binding cassette G1 (ABCG1) et le scavenger receptor BI (SR-BI) a été mesurée à l'aide des tests cellulaires radioactifs chez 36 personnes obèses morbides avant et 6 mois après la chirurgie bariatrique. Résultats. Le plasma des 36 patients atteints d'obésité morbide a été analysé. L'âge moyen des patients était de 43,2 ± 12,2 ans, 30,6% des patients étaient des hommes, 61,1% ont subi une gastrectomie longitudinale et 38,9% ont subi un by-pass gastrique par une anastomose en Roux-en-Y. Comparé au niveau de base, la CEC LHD a augmenté 6 mois après la chirurgie bariatrique pour tous les 3 transporteurs, de même que la CEC non-stimulée. L'efflux via l'ABCA1 a augmenté de 9,5% (14,35 ± 1,85 vs 13,1 ± 2,63, P =0,004), via l'ABCG1 de 14% (4,38 ± 0,95 vs 3,84 ± 0,84, P =0,001), via le SR-BI de 14,1% (5,96 ± 0,99 vs 5,23 ± 0,89, P <0,001) et l'efflux total non stimulé a augmenté de 14,8% (8,82 ± 1,3 vs 7,68 ± 0,93, P <0,001). Discussion. Dans la présente étude, nous avons démontré que la CEC LHD par l'ABCA1, l'ABCG1 et le SR-BI s'améliore de façon significative 6 mois après la chirurgie bariatriques chez les individus atteints d'obésité morbide. L'efflux est un processus continu, donc même une petite amélioration de la CEC peut avoir un effet marqué sur la plaque d'athérome. Étant donné que la CEC LHD a une corrélation inverse avec le RCV, ces résultats peuvent expliquer, au moins en partie, l'amélioration du RCV chez les patients obèses morbides post-chirurgie bariatrique. Conclusion. La CEC LHD s'améliore après une chirurgie bariatrique, et peut jouer un rôle important au niveau des issues CV favorables vues chez les patients obèses post-chirurgie bariatrique. Si notre hypothèse est prouvée dans de plus grandes études cliniques, la diminution de la CEC LHD pourrait servir comme une autre indication pour la chirurgie bariatrique

The Biochemical Diagnosis of Acromegaly

Background: The diagnosis of acromegaly still poses a clinical challenge, and prolonged diagnostic delay is common. The most important assays for the biochemical diagnosis and management of acromegaly are growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Objective: Discuss the role of IGF-1, basal serum GH, and nadir GH after oral glucose tolerance test (OGTT) for the diagnosis, management, and treatment of patients with acromegaly. Methods: We performed a narrative review of the published data on the biochemical diagnosis and monitoring of acromegaly. An English-language search for relevant studies was conducted on PubMed from inception to 1 January 2021. The reference lists of relevant studies were also reviewed. Results: Serum IGF-1 levels, basal GH values, and nadir GH after OGTT play a major role in the diagnosis, management, and treatment of patients with acromegaly. Measurement of IGF-1 levels is the key factor in the diagnosis and monitoring of acromegaly, but basal and nadir GH following OGTT are also important. However, several factors may significantly influence the concentrations of these hormones, including assay methods, physiologic and pathologic factors. In some cases, discordant GH and IGF-1 levels may be challenging and usually requires additional data and monitoring. Conclusion: New GH and IGF-1 standards are much more precise and provide more accurate tools to diagnose and monitor patients with acromegaly. However, all these biochemical tools have their limitations, and these should be taken under consideration, along with the history, clinical features and imaging studies, when assessing patients for acromegaly

Correction: Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells.

[This corrects the article DOI: 10.1371/journal.pone.0149723.]

Structure and coupling chemistry of Au-modified MWCNTs.

<p><b>A.</b> Scanning electron microscopy (SEM) images of COOH-functionalized Au-labeled Thiol-Carbon derived bionanofluids, at two different magnifications. Au particles have defined spherical structures, highlighted by the arrowhead. <b>B.</b> EDC-NHS coupling chemistry to attach bio-affinity molecules, whether antibody or protein/mitogen to the Thiol-PEG-CNT. PEGylation of the Thiol-CNT is described in the Materials and Methods.</p

Bionanofluid conjugate stability assessment.

<p><b>A</b>. α-TSHR- and Thyrogen-Thiol-PEG-CNT conjugates were prepared on day 1 and kept at 4°C for up to 21 days. Conjugates activity was assessed by cell killing assay of BCPAP cells (as described above). <b>B.</b> Similarly, α-TSHR- and Thyrogen-Thiol-PEG-CNT conjugates were prepared on day 1 and were kept at -20°C or -80°C for up to 6 weeks. Conjugates activity was assessed by cell killing assay at day 5, day 7, and every week for up to 6 weeks.</p

Concentration and time optimization of TSHR targeting bionanofluid to BCPAP cells.

<p>Included in these experimental conditions are, α-THSR-, Thyrogen-, and purified Thyrotropin-Thiol-PEG-CNT conjugates. Control conditions included PBS and CNT alone. <b>A.</b> Determination of optimal cell to conjugate BioNanofluid ratio to achieve specific maximum targeted BCPAP cell killing. Laser exposure time was 30 seconds for all conditions. Ratios are represented as volume:volume ratios, thus for a 1:1 ratio, 100 μL of cells (of 250,000–350,000 cells per ml) were mixed with 100 μL of Conjugated-BioNanofluid of 2 μg/mL concentration. <b>B.</b> Optimal exposure time determination experiment. BCPAP cells were exposed to laser treatment for 20, 30, and 40 seconds, at a 2:1 cell:conjugated- or unconjugated-Thiol-PEG CNT ratio.</p

Selective cell killing of BCPAP TSHR-positive vs NSC-34 TSHR-negative cells with TSHR-targeted bionanofluid.

<p><b>A.</b> TSHR expression of BCPAP and NSC-34 cells was determined by Western blot analysis, using TSHR specific antibody. BCPAP were positive for TSHR expression, whereas NSC-34 cells were null. B-ACTIN was used as a loading control. <b>B.</b> BCPAP and NSC-34 cell were incubated α-THSR-, Thyrogen-, and purified Thyrotropin-Thiol-PEG-CNT conjugates. Control conditions included IgG-thiol-PEG-CNTs, PBS and CNT alone. All conditions were performed in 2:1 cell:bionanofluid ratio and 30 second laser exposure. The BCPAP cells showed ~60% to ~73% cell killing with all TSHR targeted bionanofluid conjugates, whereas minimal cell death was observed with the control other conditions. The NSC-34 cell line showed negligible cell death in all conditions.</p

Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing&rsquo;s Disease: Does Size Matter?

Background: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Objective: Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing for Cushing&rsquo;s disease (CD) in a clinical trial and a systematic review. A second aim was to evaluate differences between macroadenomas with and without cavernous and sphenoid sinus invasion. Methods: Retrospective charts review of patients with CD, treated at Rabin Medical Center between 2000 and 2020 or at Maccabi Healthcare Services in Israel between 2005 and 2017. Clinical and biochemical factors were compared between patients with corticotroph microadenomas and macroadenomas. We have also performed a systematic review of all studies (PRISMA guidelines) comparing corticotroph microadenomas with macroadenomas up to 31 November 2021. Results: The cohort included 105 patients (82 women, 78%; mean age, 41.5 &plusmn; 14.5 years), including 80 microadenomas (mean size, 5.2 &plusmn; 2.2 mm) and 25 macroadenomas (mean size, 18.0 &plusmn; 7.7 mm). Other baseline characteristics were similar between groups. Most common presentation suggestive for hypercortisolemia among patients with both micro- and macroadenomas were weight gain (46.3% vs. 48.0%, p = NS) and Cushingoid features (27.5% vs. 20.0%, p = NS). Mean 24 h urinary free cortisol (5.2 &plusmn; 5.4 &times; ULN vs. 7.8 &plusmn; 8.7 &times; ULN) and serum cortisol following low-dose dexamethasone (372.0 &plusmn; 324.5 vs. 487.6 &plusmn; 329.8 nmol/L), though higher for macroadenomas, were not significant. Levels of ACTH were greater for macroadenomas (1.9 &plusmn; 1.2 &times; ULN vs. 1.3 &plusmn; 0.8 &times; ULN, respectively, p = 0.01). Rates of recurrent/persistent disease were similar, as were rates of post-operative adrenal insufficiency and duration of post-operative glucocorticoid replacement. Macroadenomas with sphenoid or cavernous sinus invasion were associated with higher ACTH, 24 h free urinary cortisol, and serum cortisol following low-dose dexamethasone, compared with suprasellar or intrasellar macroadenomas. Conclusions: While ACTH-secreting macroadenomas exhibit higher plasma ACTH than microadenomas, there was no association between tumor size with cortisol hypersecretion or clinical features of hypercortisolemia. Though overall rare, increased awareness is needed for patients with CD with tumor extension in the cavernous or sphenoid sinus, which displays increased biochemical burden, highlighting that extent/location of the adenoma may be more important than size per se. Our systematic review, the first on this topic, highlights differences and similarities with our study