Search

Epigenetic regulation of histone H3K27 methylation has recently emerged as a key step during alternative immunoregulatory M2-like macrophage polarization; known to impact cardiac repair after Myocardial Infarction (MI). We hypothesized that EZH2, responsible for H3K27 methylation, could act as an epigenetic checkpoint regulator during this process. We demonstrate for the first time an ectopic EZH2, and putative, cytoplasmic inactive localization of the epigenetic enzyme, during monocyte differentiation into M2 macrophages in vitro as well as in immunomodulatory cardiac macrophages in vivo in the post-MI acute inflammatory phase. Moreover, we show that pharmacological EZH2 inhibition, with GSK-343, resolves H3K27 methylation of bivalent gene promoters, thus enhancing their expression to promote human monocyte repair functions. In line with this protective effect, GSK-343 treatment accelerated cardiac inflammatory resolution preventing infarct expansion and subsequent cardiac dysfunction in female mice post-MI in vivo. In conclusion, our study reveals that pharmacological epigenetic modulation of cardiac-infiltrating immune cells may hold promise to limit adverse cardiac remodeling after MI. Modulating pro-inflammatory immune cell kinetics after myocardial infarction is a critical step to prevent heart dysfunction. In this study, the authors show that Ezh2 pharmacological inhibition, acting as an epigenetic checkpoint in monocytes and macrophages, prevents myocardial infarction-induced cardiac dysfunction. [ABSTRACT FROM AUTHOR]

We examined health insurance coverage among U.S. and Mexican/Central American (M/CA) born labor workers living in the U.S. Using data from the 2010-2015 National Health Interview Survey, we employed logistic regression models to examine health insurance coverage and covariates among U.S. and M/CA born labor workers. Prevalence ratios between U.S. and M/CA born workers were also obtained. U.S. born workers had double the prevalence of insurance coverage. Regarding private insurance coverage, U.S. born workers had a higher prevalence of coverage compared to their M/CA born counterparts. Among foreign born workers with U.S. citizenship, the odds of having insurance coverage was greater than that of noncitizens. Additionally, those who had lived in the U.S. for 10 or more years had higher odds of having health insurance coverage. Disparities in health care coverage exist between U.S. born and foreign born labor workers. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the performance of F- l-dihydroxyphenylalanine (F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. Methods: We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. Results: F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. Conclusion: F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by F-DOPA PET/CT. [ABSTRACT FROM AUTHOR]

Therapeutic angiogenesis has yet to fulfill its promise for the clinical treatment of ischemic diseases. Given the impact of macrophages during pathophysiological angiogenesis, we asked whether macrophages may similarly modulate vascular responses to targeted angiogenic therapies. Mouse matrigel plug assay and rat myocardial infarction (MI) model were used to assess angiogenic therapy with either VEGF-A or FGF-2 with HGF (F+H) delivered locally via albumin-alginate microcapsules. The infiltration of classical M1-type and alternative M2-like macrophages was assessed. Clodronate was used to prevent macrophage recruitment, and the VEGFR2 blocking antibody, DC101, to prevent VEGF-A signaling. At 3 weeks after matrigel implantation, the combination therapy (F+H) led to increased total, and specifically M2-like, macrophage infiltration versus control and VEGF-A plugs, correlating with the angiogenic response. In contrast, VEGF-A preferential recruited M1-type macrophages. In agreement with a direct role of M2-like macrophages in F+H-induced vessel growth, clodronate radically decreased angiogenesis. Further, DC101 reduced F+H-induced angiogenesis, without altering macrophage infiltration, revealing macrophage-derived VEGF-A as a crucial determinant of tissue responsiveness. Similarly, increased cardiac M2-like macrophage infiltration was found following F+H therapy post-MI, with strong correlation between macrophage levels and angiogenic and arteriogenic responses. In conclusion, M2-like macrophages play a decisive role, linked to VEGF-A production, in regulation of tissue responsiveness to angiogenic therapies including the combination of F+H. Our data suggest that future attempts at therapeutic revascularization in ischemic patients might benefit from coupling targeted growth factor delivery with either direct or indirect approaches to recruit pro-angiogenic macrophages in order to maximize therapeutic angiogenic/arteriogenic responses. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to evaluate, in mild primary hyperparathyroidism (pHPT) patients, the quality of life (QoL) using the SF-36 questionnaire before and after parathyroidectomy and to detect preoperatively patients who benefit the most from surgery. Most pHPT patients present a mild pHPT defined by calcemia ≤11.4 mg/dL. For these patients, there is debate about whether they should be managed with surveillance, medical therapy, or surgery. Methods: A prospective multicenter study investigated QoL (SF-36) in patients with mild pHPT before and after parathyroidectomy in four university hospitals. Laboratory results and SF-36 scores were obtained preoperatively and postoperatively (3, 6, and 12 months). Results: One hundred sixteen patients were included. After surgery, the biochemical cure rate was 98%. Preoperatively, the mental component summary and the physical component summary (PCS) were 38.69 of 100 and 39.53 of 100, respectively. At 1 year, the MCS and the PCS were 41.29 of 100 and 42.03 of 100. The subgroup analysis showed a more significant improvement in patients < 70 years and with calcemia ≥10.4 mg/dL. Postoperative PCS was correlated with age and preoperative PCS: variation = 32.11 − 0.21 × age − 0.4 × preoperative PCS. Men did not improve their MCS postoperatively. Only women with a preoperative MCS <43.6 of 100 showed postoperative improvement. Conclusions: This study showed, in patients with mild pHPT, an improvement of QoL 1 year after parathyroidectomy. Patients <70 years and with calcemia ≥10.4 mg/dL had a more significant improvement. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate intra- and interobserver reproducibility of shear wave elastography (SWE) for breast masses. Methods: For intraobserver reproducibility, each observer obtained three consecutive SWE images of 758 masses that were visible on ultrasound. 144 (19%) were malignant. Weighted kappa was used to assess the agreement of qualitative elastographic features; the reliability of quantitative measurements was assessed by intraclass correlation coefficients (ICC). For the interobserver reproducibility, a blinded observer reviewed images and agreement on features was determined. Results: Mean age was 50 years; mean mass size was 13 mm. Qualitatively, SWE images were at least reasonably similar for 666/758 (87.9%). Intraclass correlation for SWE diameter, area and perimeter was almost perfect (ICC ≥ 0.94). Intraobserver reliability for maximum and mean elasticity was almost perfect (ICC = 0.84 and 0.87) and was substantial for the ratio of mass-to-fat elasticity (ICC = 0.77). Interobserver agreement was moderate for SWE homogeneity (κ = 0.57), substantial for qualitative colour assessment of maximum elasticity (κ = 0.66), fair for SWE shape (κ = 0.40), fair for B-mode mass margins (κ = 0.38), and moderate for B-mode mass shape (κ = 0.58), orientation (κ = 0.53) and BI-RADS assessment (κ = 0.59). Conclusions: SWE is highly reproducible for assessing elastographic features of breast masses within and across observers. SWE interpretation is at least as consistent as that of BI-RADS ultrasound B-mode features. Key Points: • Shear wave ultrasound elastography can measure the stiffness of breast tissue • It provides a qualitatively and quantitatively interpretable colour-coded map of tissue stiffness • Intraobserver reproducibility of SWE is almost perfect while intraobserver reproducibility of SWE proved to be moderate to substantial • The most reproducible SWE features between observers were SWE image homogeneity and maximum elasticity [ABSTRACT FROM AUTHOR]

The concept of surgical invasiveness cannot be limited to the length or to the site of the skin incision. It must be extended to all structures dissected during the procedure. Therefore, MIT or MIP should properly be defined as operations through a short and discrete incision that permits direct access to the thyroid or parathyroid gland, resulting in a focused dissection. Parathyroid glands are particularly suitable for minimally invasive surgery as most parathyroid tumors are small and benign. MIP are performed through a limited or discrete incision when compared to classic open transverse cervical incision and are targeted on one specific parathyroid gland. The concept of these limited explorations is based on the fact that 85% of patients will have single-gland disease. MIP must be proposed only for patients with sporadic hyperparathyroidism in whom a single adenoma has been clearly localized by preoperative imaging studies. The minimal access approaches to the thyroid gland may be broadly classified into three groups: the mini-open lateral approach via a small incision, minimally invasive video-assisted thyroidectomy via the midline and various endoscopic techniques. Endoscopic extracervical approaches have the main advantage of leaving no scar in the neck but cannot reasonably be described as minimally invasive as they require more dissection than conventional open surgery. Initially the indications for MIT were a solitary thyroid nodule of less than 3 cm in diameter in an otherwise normal gland. Today, MIT are also proposed in patients with small nodular goiters, Graves's diseases and low risk papillary thyroid cancers. Some concern remains about the radicality of MIT in this latter group but preliminary results are comparable to those of conventional surgery both in terms of I-131 uptake and serum thyroglobuline levels. Demonstrating the advantages of MIT and MIP over conventional surgery is not easy. Main complications, such as nerve injury, hypoparathyroidism, or hemorrhage, are the same as in conventional surgery. Several studies comparing conventional surgery with minimally invasive techniques using a cervical access have shown a diminution of postoperative pain, and better cosmetic results with minimally invasive techniques. MIP and MIT seem overall to be an advance but only randomized studies will demonstrate the real benefit. [ABSTRACT FROM AUTHOR]

Reoperation for primary hyperparathyroidism (PHPT) remains a major challenge for both the patient and surgeons. Before considering reoperation, the surgeon must confirm the diagnosis of PHPT and assess patient risk factors. The goal of reoperative surgery is to excise the abnormal parathyroid gland(s) and limit exploration to help minimize the potential complications. At least two positive and concordant localizing studies should be available before reoperation, but the surgeon must keep in mind that the operative and histology reports from previous operation are the first localization techniques. A thorough knowledge of the anatomy and an understanding of the embryonic development of the parathyroid glands are also the keys to successful localization. According to the case history and the results of localization studies, the surgeon must clearly establish whether or not there is a suspicion of multiglandular disease (MGD). If the lesion sought is a solitary adenoma, an open-focused approach can be proposed. Conversely, if there is a confirmation or strong suspicion of MGD, revision of the transverse cervicotomy is recommended. In case of suspicion of local recurrence, an extensive local resection or en bloc resection may be indicated. Intraoperative QPTH assay is recommended to rule out MGD. In some cases, cryopreservation of parathyroid tissue and judicious use of parathyroid transplantation can be useful. With experienced parathyroid surgeons, the success rate of reoperations can be as high as 95%. It has been estimated that about 5% to 10% of initial operations for PHPT result in recurrent or persistent disease. It is too early to evaluate the real risk of persistent or recurrent disease following minimally invasive techniques, but any attempt to limit the extent of the primary procedure will be insignificant if the risk of persistent or recurrent disease is increased. [ABSTRACT FROM AUTHOR]

Postoperative cosmesis in the neck is often a major concern of patients, particularly women, undergoing thyroid or parathyroid surgery. Therefore, a reduction in the length of the cervical incision, and even more so, having no scar in the neck, is particularly appealing to these patients. Over the last years, many different so-called minimally invasive procedures have been proposed for the treatment of thyroid and parathyroid diseases, the primary aim being to improve the cosmetic results. Nevertheless, the concept of surgical invasiveness cannot be limited to the length or to the site of the skin incision. It must be extended to all structures dissected during the procedure. Therefore, minimally invasive thyroidectomy or minimally invasive parathyroidectomy should properly be defined as operations through a short, less than 3 cm, and discrete incision that permits direct access to the thyroid or parathyroid gland, resulting in a focused dissection. In addition, type of anesthesia, duration of the operation, postoperative pain, complication and success rates, and long-term outcome should also be taken into account to assess surgical invasiveness. Thyroid and parathyroid operations that minimize the incision but keep it in the neck may be considered minimally invasive not only in respect of the size of the skin incision but also, and above all, in respect of the accessibility of the operative field and extent of dissection. These operations have some advantages over conventional cervicotomy in terms of postoperative pain and cosmetic results. Until now, there is no evidence to state that morbidity of these new approaches is at least equal to the conventional equivalent. Operations that employ an extracervical approach, which have the advantage of leaving no scar in the neck, cannot reasonably be described as minimally invasive, as they require more dissection than conventional open surgery. [ABSTRACT FROM AUTHOR]

Secretion of hormones and other bioactive substances is a fundamental process for virtually all multicellular organisms. Using total internal reflection fluorescence microscopy (TIRFM), we have studied the calcium-triggered exocytosis of single, fluorescently labeled large, dense core vesicles in the human neuroendocrine BON cell line. Three types of exocytotic events were observed: (1) simple fusions (disappearance of a fluorescent spot by rapid diffusion of the dye released to the extracellular space), (2) “orphan” fusions for which only rapid dye diffusion, but not the parent vesicle, could be detected, and (3) events with incomplete or multi-step disappearance of a fluorescent spot. Although all three types were reported previously, only the first case is clearly understood. Here, thanks to a combination of two-color imaging, variable angle TIRFM, and novel statistical analyses, we show that the latter two types of events are generated by the same basic mechanism, namely shape retention of fused vesicle ghosts which become targets for sequential fusions with deeper lying vesicles. Overall, ∼25% of all exocytotic events occur via sequential fusion. Secondary vesicles, located 200–300 nm away from the cell membrane are as fusion ready as primary vesicles located very near the cell membrane. These findings call for a fundamental shift in current models of regulated secretion in endocrine cells. Previously, sequential fusion had been studied mainly using two-photon imaging. To the best of our knowledge, this work constitutes the first quantitative report on sequential fusion using TIRFM, despite its long running and widespread use in studies of secretory mechanisms. [ABSTRACT FROM AUTHOR]

Both increase in cardiac arrhythmia incidence and decrease in heart rate variability (HRV) have been described following human and experimental animal exposures to air pollutants. However, the potential causal relationship between these two factors remains unclear. Incidence of ventricular arrhythmia and HRV were evaluated during and after a 3 h period of Diesel engine exhaust exposure in ten healthy and ten chronic ischemic heart failure (CHF, 3 months after coronary ligation) Wistar rats using implantable ECG telemetry. Air pollutants were delivered to specifically designed whole body individual exposure chambers at particulate matter concentrations similar to those measured inside cabins of cars inserted in congested urban traffic. Recordings were obtained from unrestraint and unsedated vigil rats. Immediate decrease in RMSSD was observed in both healthy (6.64 ± 2.62 vs. 4.89 ± 1.67 ms, P < 0.05) and CHF rats (8.01 ± 0.89 vs. 6.6 ± 1.37 ms, P < 0.05) following exposure. An immediate 200–500% increase in ventricular premature beats was observed in CHF rats only. Whereas HRV progressively returned to baseline values within 2.5 h after exposure start, the proarrhythmic effect persisted as late as 5 h after exposure termination in CHF rats. Persistence of ventricular proarrhythmic effects after HRV normalization suggests that HRV reduction is not the mechanism of cardiac arrhythmias in this model. Our methodological approach, closely reflecting the real clinical situations, appeared to be a unique tool to provide further insight into the pathophysiological mechanisms of traffic related airborne pollution health impact. [ABSTRACT FROM AUTHOR]

Background and aims: Postoperative haematoma formation is a fortunately rare but potentially life-threatening complication of thyroid surgery. This paper aims to identify potential aetiological factors, describe surgical techniques and newer haemostatic agents that may be used to minimise the risk of haematoma formation and propose surgical strategies to deal with haematoma formation. Materials and methods: An extensive literature search as well as own considerable experience in a tertiary referral centre endocrine surgical unit was drawn upon to review this topic. Conclusions: Postoperative haematoma may have a multifactorial aetiology. Numerous manoeuvres and surgical haemostatic agents may be employed to minimise the risk of haematoma formation but are no substitute for meticulous haemostasis. In the event of haematoma formation, early surgical re-intervention is strongly advocated with due care given to at risk structures. [ABSTRACT FROM AUTHOR]

Background: Parathyroid cysts (PCs) are rare, and their origin is a subject of debate. They have been described as either functional, causing hyperparathyroidism, or non-functional in eucalcaemic patients. Patients and methods: We have performed a 25-year departmental review of PCs. Features studied included the clinical presentation and intra-operative findings, and a histological review was performed. Cases of cystic degeneration of parathyroid adenomas and pseudocystic change were excluded. Results: Over 25 years, 22,009 thyroidectomies and 2,505 parathyroidectomies were performed in our department. Amongst these, 38 non-functional PCs were documented in 37 patients. The mode of presentation included incidental findings on routine chest x-ray, compressive symptoms or an asymptomatic palpable neck mass. Aspiration was the initial treatment in 14 patients and was curative in 10 of these. Four out of 14 patients underwent surgical procedures for recurrence of the cyst that occurred 6 to 48 months after aspiration. In 27 patients, surgery was performed and all identified PCs were localized in the inferior parathyroid glands. Histologically, the cyst wall consisted in associations of lymphoid, muscular, thymic, salivary, adipose and mesenchymal tissues. Conclusions: PCs are rare but should be included within the differential diagnosis of a neck lump. True PCs are non-functional. Pathological and immunohistochemical findings are suggestive of a branchial origin. Fine-needle aspiration may be curative and is diagnostic due to the characteristic appearance of the fluid and high PTH levels on assay. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism is the most common manifestation of MEN 1 syndrome. The management of these patients is complex due to the underlying disease process, which predisposes patients to persistent and recurrent disease. The surgical treatment of patients with MEN 1 and hyperparathyroidism can therefore be considered to be palliative in nature. The basic principles of surgery include (1) obtaining and maintaining normocalcaemia for the longest time possible, avoiding persistent/recurrent hypercalcaemia, (2) avoiding surgically induced hypocalcaemia, and (3) facilitating future surgery for recurrent disease. Two approaches have been described as the best practice for patients with hyperparathyroidism in MEN 1: subtotal parathyroidectomy, leaving a remnant of no more than 60 mg in the neck, and total parathyroidectomy with immediate autotransplantation of 10–20 1 mm3 pieces of parathyroid tissue. Both approaches should be combined with efforts to exclude supernumerary glands and ectopic parathyroid tissue by including resection of fatty tissue from the central neck compartment and thymectomy in all patients. Cryopreservation of parathyroid tissue should be performed whenever facilities are available. In patients with persistent or recurrent disease, an attempt to obtain total elimination of cervical parathyroid tissue is justified, combined with cryopreservation of parathyroid tissue. As radical as surgery is for hyperparathyroidism in MEN 1, the surgeon must take steps to avoid permanent hypoparathyroidism, which in young patients may be worse than the disease itself. [ABSTRACT FROM AUTHOR]

Enterochromaffin-like (ECL) cells regulate gastric acid secretion through vesicular release of histamine. Until now, the molecular machinery of human ECL cells involved in the formation and release of vesicles is largely unknown. We analyzed tissue samples obtained from normal human gastric mucosa ( n=4) and ECLomas ( n=5) immunohistochemically using the APAAP method or double immunofluorescence confocal laser microscopy. Human pheochromocytomas ( n=5) were investigated in parallel and compared to ECL cells. Secretory pathways were characterized using antibodies specific for marker proteins of large dense-core vesicles (LDCVs; islet cell antigen 512, chromogranin A, pancreastatin, and vesicular monoamine transporter 2) and small synaptic vesicle (SSV) analogues (synaptophysin). Tissues were also analyzed for expression of the peptide hormone processing enzymes, carboxypeptidase E and prohormone convertase 1, as well as the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, 25-kDa synaptosome-associated protein (SNAP25), syntaxin, and synaptobrevin. Immunoreactivity for markers of LDCVs and SSV analogues were detected in normal ECL cells and ECLomas. Both tissues also showed expression of carboxypeptidase E and prohormone convertase 1. Analysis of vesicular SNARE (v-SNARE) and target membrane SNARE (t-SNARE) proteins revealed the presence of SNAP25, syntaxin, and synaptobrevin in normal and neoplastic ECL cells. Our data suggest that ECL cells possess the two vesicle types of regulated neuroendocrine secretory pathways, LDCVs and SSV analogues. Since ECL cells also contain typical SNARE proteins, the molecular machinery underlying secretory processes in this cell type appears to be identical to the secretory apparatus of neuroendocrine cells and neurons. In addition, our findings suggest that the secretory apparatus of ECL cells is maintained during neoplastic transformation. [ABSTRACT FROM AUTHOR]

We estimate a factor requirement frontier for European railways using a panel data approach in which technical efficiency is assumed to be endogeneously determined. This approach has two main outcomes. On one hand, it allows the identification of factors influencing technical efficiency, and on the other hand, it allows the estimation of alternative efficiency indicators free of these influences. In the case under study, a particular attention is devoted to an autonomy indicator representing the managerial freedom, with respect to public authorities, experienced by firms, that appears to be positively correlated with technical efficiency. [ABSTRACT FROM AUTHOR]

Copyright of Paläontologische Zeitschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper deals with the urban traffic queue modelling and estimation. A general formulation of delays on a road section is used to link measured speeds at its entrance to the current queue state. This measurement model is applied to correct a posteriori the queue state distribution whose a priori evolution is ruled by a time varying Markov chain. The resulting predictor-corrector is tested with a microscopic simulation tool. Results in fixed plan control show that for long road sections (200 meters) the estimation error is unacceptable whereas for short road sections (50–100 meters) the average quadratic error is about 1 vehicle2. In real time control conditions, in spite of a significant increase of the estimation quadratic error, results show a delay benefit of 15% with respect to the fixed plan control. [ABSTRACT FROM AUTHOR]

A voltage-dependent cationic channel of large conductance is observed in phospholipid bilayers formed at the tip of microelectrodes from proteoliposomes derived from mitochondrial membranes. This channel was blocked by a 13-residue peptide with the sequence of the amino terminal extremity of the nuclear-coded subunit IV of cytochrome c oxidase. The blockade was reversible, voltage- and dose-dependent. The peptide did not affect the activity of a Torpedo chloride channel observed under the same conditions. From experiments with phospholipid monolayers, it is unlikely that the peptide inserts into bilayers under the experimental conditions used. The blockade was observed from both sides of the membrane, being characterized by more frequent transitions to the lower conductance states, and a maximum effect was observed around 0 mV. Channels, the gating mechanism of which had been eliminated by exposure to trypsin, were also blocked by the peptide. For trypsinized channels, the duration of the closure decreased and the blockade saturated at potentials below −30 mV. These observations are consistent with a translocation of the peptide through the channel. Dynorphin B, which has the same length and charge as the peptide, had some blocking activity. Introduction of negative charges in the peptide by succinylation suppressed the activity. [ABSTRACT FROM AUTHOR]

Although optimal therapy for myocardial infarction includes reperfusion to restore blood flow to the ischemic region, ischemia/reperfusion (IR) also initiates an inflammatory response likely contributing to adverse left ventricular (LV) extracellular matrix (ECM) remodeling. Galectin-3 (Gal-3), a β-galactoside-binding-lectin, promotes cardiac remodeling and dysfunction. Our aim is to investigate whether Gal-3 pharmacological inhibition using modified citrus pectin (MCP) improves cardiac remodeling and functional changes associated with IR. Wistar rats were treated with MCP from 1 day before until 8 days after IR (coronary artery ligation) injury. Invasive hemodynamics revealed that both LV contractility and LV compliance were impaired in IR rats. LV compliance was improved by MCP treatment 8 days after IR. Cardiac magnetic resonance imaging showed decreased LV perfusion in IR rats, which was improved with MCP. There was no difference in LV hypertrophy in MCP-treated compared to untreated IR rats. However, MCP treatment decreased the ischemic area as well as Gal-3 expression. Gal-3 blockade paralleled lower myocardial inflammation and reduced fibrosis. These novel data showing the benefits of MCP in compliance and ECM remodeling in IR reinforces previously published data showing the therapeutic potential of Gal-3 inhibition. [ABSTRACT FROM AUTHOR]

The article reflects on potentially malignant adrenal tumors. According to the classification of World Health Organization (WHO), malignancy of pheochromocytomas (PCCs) and paragangliomas (PGLs) is considered by the presence of metastases at nonchromaffin. It also mentions that both pheochromocytomas and paragangliomas are associated with germline succinate dehydrogenase B (SDHB) mutations.